Search results for: therapeutic exercises

Authors: Fuad Abdullah Alatawi

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Microbial infections-based diseases are a significant public health issue around the world, mainly when antibiotic-resistant bacterium types evolve. In this research, we explored the anti-bacterial and anti-cancer potency of iron-oxide (Fe₂O₃) nanoparticles prepared from F. macrocarpa fruit extract. The chemical composition of F. macrocarpa fruit extract was used as a reducing and capping agent for nanoparticles’ synthesis was examined by GC-MS/MS analysis. Then, the prepared nanoparticles were confirmed by various biophysical techniques, including X-ray powder diffraction (XRD), Fourier-transform infrared spectroscopy (FTIR), UV-Vis Spectroscopy, and Transmission Electron Microscopy (TEM) and Energy Dispersive Spectroscopy (EDAX), and Dynamic Light Scattering (DLS). Also, the antioxidant capacity of fruit extract was determined through 2,2-diphenyl-1-picrylhydrazyl (DPPH), 2,2'-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid (ABTS), Fluorescence Recovery After Photobleaching (FRAP), Superoxide Dismutase (SOD) assays. Furthermore, the cytotoxicity activities of Fe₂O₃ NPs were determined using the (3-(4, 5-dimethylthiazolyl-2)-2, 5-diphenyltetrazolium bromide) (MTT) test on MCF-7 cells. In the antibacterial assay, lethal doses of the Fe₂O₃NPs effectively inhibited the growth of gram-negative and gram-positive bacteria. The surface damage, ROS production, and protein leakage are the antibacterial mechanisms of Fe₂O₃NPs. Concerning antioxidant activity, the fruit extracts of F. macrocarpa had strong antioxidant properties, which were confirmed by DPPH, ABTS, FRAP, and SOD assays. In addition, the F. microcarpa-derived iron oxide nanomaterials greatly reduced the cell viability of (MCF-7). The GC-MS/MS analysis revealed the presence of 25 main bioactive compounds in the F. microcarpa extract. Overall, the finding of this research revealed that F. microcarpa-derived Fe₂O₃ nanoparticles could be employed as an alternative therapeutic agent to cure microbial infection and breast cancer in humans.

Keywords: ficus microcarpa, iron oxide, antibacterial activity, cytotoxicity

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Authors: R. Raudonis, L. Raudonė, V. Janulis, P. Viškelis

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Pharmacological and clinical studies demonstrated that phenolic compounds particularly flavonoids and phenolic acids are responsible for a wide spectrum of therapeutic activities. Flavonoids and phenolic acids are regarded as natural antioxidants that play an important role in protecting cells from oxidative stress. Qualitatively prepared dry extracts possess high stability and concentration of bio active compounds, facility of standardization and quality control. The aim of this work was to determine the phenolic and antioxidant profiles of Hippophaë rhamnoides L., Betula pendula Roth., Tilia cordata Mill., Sorbus aucuparia L. leaves dry extracts and to identify markers of antioxidant activity. Extracts were analyzed using high-performance liquid chromatography (HPLC) with FRAP post-column assay. Dry extracts are versatile forms possessing wide area of applications, final product ensure consistent phytochemical and functional properties. Seven flavonoids: rutin, hyperoside, isorhamnetin 3-O-rutinoside, isorhamnetin 3-O-glucoside, quercetin, kaempferol, isorhamnetin were identified in dry extract of Hippophaë rhamnoides L. leaves. Predominant compounds were flavonol glycosides which were chosen as markers for quantitative control of dry extracts. Chlorogenic acid, hyperoside, rutin, quercetin, isorhamnetin were prevailing compounds in Betula pendula Roth. leaves extract, whereas strongest ferric reducing activity was determined for chlorogenic acid and hyperoside. Notable amounts of protocatechuic acid and flavonol glycosides, rutin, hyperoside, quercitrin, isoquercitrin were identified in the chromatographic profile of Tilia cordata Mill. Neochlorogenic and chlorogenic acids were significantly dominant compounds in antioxidant profile in dry extract of Sorbus aucuparia L. leaves. Predominant compounds of antioxidant profiles could be proposed as functional markers of quality of phenolic rich raw materials. Dry extracts could be further used for manufacturing of pharmaceutical and nutraceuticals.

Keywords: dry extract, FRAP, antioxidant activity, phenolic

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Authors: Asif Khaliq, Sayeeda A. Sayed

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The drug information centers provide drug related information to the requesters that include physicians, pharmacist, nurses and other allied health care professionals. The International Pharmacist Federation (FIP) describes basic functions of a drug and poison information centers as drug evaluation, therapeutic counseling, pharmaceutical advice, research, pharmaco-vigilence and toxicology. Continuous advancement in the field of medicine has expanded the medical literature, which has increased demand of a drug and poison information center for the guidance, support and facilitation of physicians. The objective of the study is to determine the need of drug and poison information centers in public and private hospitals of Karachi, Pakistan. A cross sectional study was conducted during July 2013 to April 2014 using a self-administered, multi-itemed questionnaire. Non Probability Convenient sampling was used to select the study participants. A total of 307 physicians from public and private hospitals of Karachi participated in the study. The need for 24/7 Drug and poison information center was highlighted by 92 % of physicians and 67% physicians suggested opening a drug information center at the hospital. It was reported that 70% physicians take at least 15 minutes for searching the information about the drug while managing a case. Regarding the poisoning case management, 52% physicians complaint about the unavailability of medicines in hospitals; and mentioned the importance of medicines for safe and timely management of patients. Although 73% physicians attended continued medical education (CME) sessions, 92 % physicians insisted on the need of 24/7 Drug and poison information center. The scarcity of organized channel for obtaining the information about drug and poisons is one of the most crucial problems for healthcare workers in Pakistan. The drug and poison information center is an advisory body that assists health care professional and patients in provision of appropriate drug and hazardous substance information. Drug and poison information center is one of the integral needs for running an effective health care system. Provision of a 24 /7 drug information centers with specialized staff offer multiple benefits to the hospitals while reducing treatment delays, addressing awareness gaps of all stakeholders and ensuring provision of quality health care.

Keywords: drug and poison information centers, Pakistan, physicians, public and private hospitals

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Authors: Dorottya Horváth, Andras Lang, Diana Varro-Horvath

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This research activity and study is part of a major research effort to gain an integrative, neuropsychological, and personality psychological understanding of Attention Deficit Hyperactivity Disorder (ADHD) and thus improve the specification of diagnostic and therapeutic care. In the past, the neuropsychology section has investigated working memory, executive function, attention, and behavioural manifestations in children. Currently, we are looking for personality psychological protective factors for ADHD and its symptomatic exacerbation. We hypothesise that secure attachment, adaptive emotion regulation, and high resilience are protective factors. The aim of this study is to measure and report the results of a Hungarian sample of the Cognitive Emotion Regulation Questionnaire for Children (CERQ-k) because before studying groups with different developmental differences, it is essential to know the average scores of groups with neurotypical devel-opment. Until now, there was no Hungarian version of the above test, so we used our own translation. This questionnaire has been developed to assess children's thoughts after experiencing negative life events. It consists of 4-4 items per subscale, for a total of 36 items. The response categories for each item range from 1 (almost never) to 5 (almost always). The subscales were self-blame, blaming others, acceptance, planning, positive refocusing, rumination or thought-focusing, positive reappraisal, putting into perspective, and catastrophizing. The data for this study were collected from 120 children aged 9-14 years. It was analysed using descriptive statistical analysis, where the mean and standard deviation values for each age group, as well as the Cronbach's alpha value, were significant in testing the reliability of the questionnaire. The results showed that the questionnaire is a reliable and valid measuring instrument also on a Hungarian sample. These developments and results will allow the use of a version of the Cognitive Emotion Regulation Questionnaire for children in Hungarian and pave the way for the study of different developmental groups such as children with learning disabilities and/or with ADHD.

Keywords: neurotypical development, emotion regulation, negative life events, CERQ-k, Hungarian average scores

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Authors: Shamas Ul Hassan, Nasir Mukhtar, Sajjad Ur Rehman, Asghar Ali Mian, Iftikhar Hussain, Muhammad Safdar Anjum

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The Mycoplasma gallisepticum (MG) is the major cause of economic looses in birds which is transmitted by free flying birds in the environment. These demands for improving the biosecurity measures at farm level including proper disposal of farm mortality and other wastes along with the inclusion of zoos and wild life parks in the MG surveillance programme. For the purpose of doing surveillance of MG in different pet, game and free flying birds a total of 12 samples each of peacocks, pheasants, ducks, pigeons, parrots, and house crows were included in the first ever study of its nature in Pakistan. During the study, the relevant samples along with recording clinical and postmortem findings were subjected to sero-prevalence, culture isolation and PCR system. Further PCR being more sensitive proves to be a better epidemiological tool. Seropositive findings revealed in peacocks, pheasants, ducks, pigeons, parrots, and crows were 66.7%, 58.3%, 41.7%, 41.7%, 16.7% and 16.7% respectively with some free flying birds giving ambiguous reactions. Whereas in the same order the culture/isolation positive results were recorded as 25%, 16.7%, 8.3%, 16.7%, 16.7%, and 25%. The samples were further confirmed on the basis of 732 bp product in PCR system. High rate of prevalence of MG in the pet, game and free flying birds regardless to their clinical findings demands to improve the biosecurity measures at the farm level with the minimum interaction of these birds with commercial poultry. Further the proper and timely disposal of all sorts of carcasses contaminated litter and wasted feed in such ways that the free flying birds are denied of picking up at those wastages. Moreover, MG surveillance system including the advances diagnostic techniques in wildlife parks and zoos be devised with proper timely preventive and therapeutic measures. The study proves that a variety of birds other then chicken either with or without clinical exhibitions carry MG organism which could be the potential source of infection for commercial poultry. The routine surveillance will be done to reduce the economic losses in poultry production.

Keywords: epidemiology, Mycoplasma gallisepticum (MG), free flying birds, surveillance, PCR

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Authors: Wenjie Wu, Peng Cheng, Zehua Zhang, Fei Luo, Feng Wu, Min Zhong, Jianzhong Xu

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Background: There has been limited research into the therapeutic efficacy of rapid diagnosis of spinal tuberculosis complicated with pulmonary tuberculosis. We attempted to discover whether the utilization of a DNA microarray assay to detect multidrug-resistant spinal tuberculosis complicated with pulmonary tuberculosis can improve clinical outcomes. Methods: A prospective study was conducted from February 2006 to September 2015. One hundred and forty-three consecutive culture–confirmed, clinically and imaging diagnosed MDR-TB patients with spinal tuberculosis complicated by pulmonary tuberculosis were enrolled into the study. The initial time to treatment for MDR-TB, the method of infection control, radiological indicators of spinal tubercular infectious foci, culture conversion, and adverse drug reactions were compared with the standard culture methods. Results: Of the total of 143 MDR-TB patients, 68 (47.6%) were diagnosed by conventional culture methods and 75 (52.4%) following the implementation of detection using the DNA microarray. Patients in the microarray group began rational use of the second-line drugs schedule more speedily than sufferers in the culture group (17.3 vs. 74.1 days). Among patients were admitted to a general tuberculosis ward, those from the microarray group spent less time in the ward than those from the culture group (7.8 vs. 49.2 days). In those patients with six months follow-up (n=134), patients in the microarray group had a higher rate of sputum negativity conversion at six months (89% vs. 73%). In the microarray group, the rate of drug adverse reactions was significantly lower (22.2% vs. 67.7%). At the same time, they had a more obvious reduction of the area with spinal tuberculous lesions in radiological examinations (77% vs. 108%). Conclusions: The application of the CapitalBio™ DNA Microarray assay caused noteworthy clinical advances including an earlier time to begin MDR-TB treatment, increased sputum culture conversion, improved infection control measures and better radiographical results

Keywords: tuberculosis, multidrug-resistant, tuberculous spondylitis, DNA microarray, clinical outcomes

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Authors: F. Polito, M. Cucinotta, A. Conti, C. Lo Giudice, C. Tomasello, F. Angileri, D. La Torre, M. Aguennouz

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Glioblastoma multiforme (GBM) is the most aggressive form of brain tumors, with an extremely poor prognosis. Telomeres lenght is associated with tumor progression in several type of human cancers and telomere elongation is a common molecular feature of advanced malignancies. Among the telomeric shelterin proteins PTOP is required for telomeric protein complex assembly, telomerase recruitment and activity, and telomere length regulation through a PTOP-telomerase interaction. Previous studies suggest that PTOP upregulation is involved in radioresistance and telomere lengthening in colorectal cancer cells. Moreover, in human osteosarcoma cells PTOP deletion led to telomere shortening, increased apoptosis and radiation sensitivity enhancement. However, to date, little is known about the role of PTOP in progression of glioma cancers. In light of this background aim of the study is to investigate the expression of PTOP in different grades of human glioma and its correlation with the pathological grade of gliomas, grades of malignancy, proliferative activity and apoptosis. Fifteen Low Grade Astrocytomas (LGA), 18 Anaplastic Astrocytomas (AA) and 26 Glioblastoma Multiforme (GBM) samples were analyzed. Three samples of normal brain tissue (NBT) were used as controls. The expression levels of PTOP, h-TERT, BIRC1 and cyclin D1 were determined by real time PCR and/or western blot. Results obtained shows that PTOP expression in glioma tissues is tightly correlated with clinical grade ( p < 0.01 ). No correlation was found between PTOP expression and other clinicopathologic parameters. The expression of PTOP was positively correlated with the expression of hTERT and TERF1. Furthermore PTOP positively correlates with cyclin D1 and negatively correlates with the expression of BIRC1. Our findings indicate that PTOP might play key role in the progression of glioma regulating telomerase activity and likely through regulation of cell cycle and apoptosis. In conclusion results obtained prompted us to speculate that PTOP might represents a potential molecular bio marker and a therapeutic target for the treatment of glioblastoma tumors.

Keywords: glioblastoma, PTOP, telomere, brain tumors

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Authors: John Masani Nduko, Joseph Wafula Matofari

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Many spontaneously fermented milk products are produced in Kenya, where they are integral to the human diet and play a central role in enhancing food security and income generation via small-scale enterprises. Fermentation enhances product properties such as taste, aroma, shelf-life, safety, texture, and nutritional value. Some of these products have demonstrated therapeutic and probiotic effects although recent reports have linked some to death, biotoxin infections, and esophageal cancer. These products are mostly processed from poor quality raw materials under unhygienic conditions resulting to inconsistent product quality and limited shelf-lives. Though very popular, research on their processing technologies is low, and none of the products has been produced under controlled conditions using starter cultures. To modernize the processing technologies for these products, our study aims at describing the microbiology and biochemistry of a representative Kenyan spontaneously fermented milk product, Mursik using modern biotechnology (DNA sequencing) and their chemical composition. Moreover, co-creation processes reflecting stakeholders’ experiences on traditional fermented milk production technologies and utilization, ideals and senses of value, which will allow the generation of products based on common ground for rapid progress will be discussed. Knowledge of the value of clean starting raw material will be emphasized, the need for the definition of fermentation parameters highlighted, and standard equipment employment to attain controlled fermentation discussed. This presentation will review the available information regarding traditional fermented milk (Mursik) and highlight our current research work on the application of molecular approaches (metagenomics) for the valorization of Mursik production process through starter culture/ probiotic strains isolation and identification, and quality and safety aspects of the product. The importance of the research and future research areas on the same subject will also be highlighted.

Keywords: lactic acid bacteria, high throughput biotechnology, spontaneous fermentation, Mursik

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Authors: Dar-Bin Shieh, Gwo-Bin Lee, Chen-Ming Chang, Chen Sheng Yeh, Chih-Chia Huang, Tsung-Ju Li

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Mitochondrial defects have a significant impact in many human diseases and aging associated phenotypes. The pathogenic mitochondrial DNA (mtDNA) mutations are diverse and usually present as heteroplasmic. mtDNA 4977bps deletion is one of the common mtDNA defects, and the ratio of mutated versus normal copy is significantly associated with clinical symptoms thus their quantitative detection has become an important unmet needs for advanced disease diagnosis and therapeutic guidelines. This study revealed a Micro-electro-mechanical-system (MEMS) enabled automatic microfluidic chip that only required minimal sample. The system integrated multiple laboratory operation steps into a Lab-on-a-Chip for high-sensitive and prompt measurement. The entire process including magnetic nanoparticle based mtDNA extraction in chip, mutation selective photonic DNA cleavage, and nanoparticle accelerated photonic quantitative polymerase chain reaction (qPCR). All subsystems were packed inside a miniature three-dimensional micro structured system and operated in an automatic manner. Integration of magnetic beads with microfluidic transportation could promptly extract and enrich the specific mtDNA. The near infrared responsive magnetic nanoparticles enabled micro-PCR to be operated by pulse-width-modulation controlled laser pulsing to amplify the desired mtDNA while quantified by fluorescence intensity captured by a complementary metal oxide system array detector. The proportions of pathogenic mtDNA in total DNA were thus obtained. Micro capillary electrophoresis module was used to analyze the amplicone products. In conclusion, this study demonstrated a new magnetophotonic based qPCR MEMS system that successfully detects and quantify specific disease related DNA mutations thus provides a promising future for rapid diagnosis of mitochondria diseases.

Keywords: mitochondrial DNA, micro-electro-mechanical-system, magnetophotonics, PCR

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Authors: Bruno Biagianti, Angela Tseng, Kathy Wannaviroj, Allison Corlett, Megan DuBois, Kyu Lee, Suma Jacob

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Background: ASD is characterized by pervasive Sensory Processing Abnormalities (SPA) and social cognitive deficits that persist throughout the course of the illness and have been linked to functional abnormalities in specific neural systems that underlie the perception, processing, and representation of sensory information. SPA and social cognitive deficits are associated with difficulties in interpersonal relationships, poor development of social skills, reduced social interactions and lower academic performance. Importantly, they can hamper the effects of established evidence-based psychological treatments—including PEERS (Program for the Education and Enrichment of Relationship Skills), a parent/caregiver-assisted, 16-weeks social skills intervention—which nonetheless requires a functional brain capable of assimilating and retaining information and skills. As a matter of fact, some adolescents benefit from PEERS more than others, calling for strategies to increase treatment response rates. Objective: We will present interim data on CICADAS (Care Improving Cognition for ADolescents on the Autism Spectrum)—a clinician-assisted, closed-loop technology mobile application for adolescents with ASD. Via ten mobile assessments, CICADAS captures data on sensory processing abnormalities and associated cognitive deficits. These data populate a machine learning algorithm that tailors the delivery of ten neuroplasticity-based social cognitive training (NB-SCT) exercises targeting sensory processing abnormalities. Methods: In collaboration with the Autism Spectrum and Neurodevelopmental Disorders Clinic at the University of Minnesota, we conducted a fully remote, three-arm, randomized crossover trial with adolescents with ASD to document the acceptability of CICADAS and evaluate its potential as a stand-alone treatment or as a treatment enhancer of PEERS. Twenty-four adolescents with ASD (ages 11-18) have been initially randomized to 16 weeks of PEERS + CICADAS (Arm A) vs. 16 weeks of PEERS + computer games vs. 16 weeks of CICADAS alone (Arm C). After 16 weeks, the full battery of assessments has been remotely administered. Results: We have evaluated the acceptability of CICADAS by examining adherence rates, engagement patterns, and exit survey data. We found that: 1) CICADAS is able to serve as a treatment enhancer for PEERS, inducing greater improvements in sensory processing, cognition, symptom reduction, social skills and behaviors, as well as the quality of life compared to computer games; 2) the concurrent delivery of PEERS and CICADAS induces greater improvements in study outcomes compared to CICADAS only. Conclusion: While preliminary, our results indicate that the individualized assessment and treatment approach designed in CICADAS seems effective in inducing adaptive long-term learning about social-emotional events. CICADAS-induced enhancement of processing and cognition facilitates the application of PEERS skills in the environment of adolescents with ASD, thus improving their real-world functioning.

Keywords: ASD, social skills, cognitive training, mobile app

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Authors: Frida Carrillo Morales, Maria Maricela Carrasco Yépez, Saúl Rojas Hernández

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Naegleria fowleri is the causative agent of primary amebic meningoencephalitis, this disease is acute and fulminant that affects humans. It has been reported that despite the existence of therapeutic options against this disease, its mortality rate is 97%. Therefore, the need arises to have vaccines that confer protection against this disease and, in addition to developing adjuvants to enhance the immune response. In this regard, in our work group, we obtained a peptide designed from the membrane protein MP2CL5 of Naegleria fowleri called Smp145 that was shown to be immunogenic; however, it would be of great importance to enhance its immunological response, being able to co-administer it with a non-toxic adjuvant. Therefore, the objective of this work was to carry out the bioinformatic design of a peptide of the Naegleria fowleri membrane protein MP2CL5 conjugated with a non-toxic modified adjuvant from the native A1 structure of Cholera Toxin. For which different bioinformatics tools were used to obtain a model with a modification in amino acid 61 of the A1 subunit of the CT (CTA1), to which the Smp145 peptide was added and both molecules were joined with a 13-glycine linker. As for the results obtained, the modification in CTA1 bound to the peptide produces a reduction in the toxicity of the molecule in in silico experiments, likewise, the prediction in the binding of Smp145 to the receptor of B cells suggests that the molecule is directed in specifically to the BCR receptor, decreasing its native enzymatic activity. The stereochemical evaluation showed that the generated model has a high number of adequately predicted residues. In the ERRAT test, the confidence with which it is possible to reject regions that exceed the error values was evaluated, in the generated model, a high score was obtained, which determines that the model has a good structural resolution. Therefore, the design of the conjugated peptide in this work will allow us to proceed with its chemical synthesis and subsequently be able to use it in the mouse meningitis protection model caused by N. fowleri.

Keywords: immunology, vaccines, pathogens, infectious disease

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Authors: I-Hui Hsieh, Yu-Hsuan Hu

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The powerful effect of music is often associated with changes in physiological responses such as heart rate and respiration. Previous studies demonstrate that Mayer waves of blood pressure, the spontaneous rhythm occurring at 0.1 Hz, corresponds to a progressive crescendo of the musical phrase. However, music contain dynamic changes in temporal and spectral features. As such, it remains unclear which aspects of musical structures optimally affect synchronization of cardiovascular rhythms. This study investigates the independent contribution of spectral pattern, temporal pattern, and dissonance level on synchronization of cardiovascular rhythms. The regularity of acoustical patterns occurring at a periodic rhythm of 0.1 Hz is hypothesized to elicit the strongest coherence of cardiovascular rhythms. Music excerpts taken from twelve pieces of Western classical repertoire were modulated to contain varying degrees of pattern regularity of the acoustic envelope structure. Three levels of dissonance were manipulated by varying the harmonic structure of the accompanying chords. Electrocardiogram and photoplethysmography signals were recorded for 5 minutes of baseline and simultaneously while participants listen to music excerpts randomly presented over headphones in a sitting position. Participants were asked to indicate the pleasantness of each music excerpt by adjusting via a slider presented on screen. Analysis of the Fourier spectral power of blood pressure around 0.1 Hz showed a significant difference between music excerpts characterized by spectral and temporal pattern regularity compared to the same content in random pattern. Phase coherence between heart rate and blood pressure increased significantly during listening to spectrally-regular phrases compared to its matched control phrases. The degree of dissonance of the accompanying chord sequence correlated with level of coherence between heart rate and blood pressure. Results suggest that low-level auditory features of music can entrain coherence of autonomic physiological variables. These findings have potential implications for using music as a clinical and therapeutic intervention for regulating cardiovascular functions.

Keywords: cardiovascular rhythms, coherence, dissonance, pattern regularity

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Authors: Fadia Gafri, Kathryn Mckintosh, Louise Young, Alan Harvey, Simon Mackay, Andrew Paul, Robin Plevin

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Nuclear factor-kappa B (NF-κB) is a ubiquitous transcription factor found originally to play a key role in regulating inflammation. However considerable evidence links this pathway to the suppression of apoptosis, cellular transformation, proliferation and invasion (Aggarwal et al., 2006). Moreover, recent studies have also linked inflammation to cancer progression making NF-κB overall a promising therapeutic target for drug discovery (Dobrovolskaia & Kozlov, 2005). In this study we examined the effect of the natural product canthin-6-one (SU182) as part of a CRUK small molecule drug discovery programme for effects upon the NF-κB pathway. Initial studies demonstrated that SU182 was found to have good potency against the inhibitory kappa B kinases (IKKs) at 30M in vitro. However, at concentrations up to 30M, SU182 had no effect upon TNFα stimulated loss in cellular IκBα or p65 phosphorylation in the keratinocyte cell line NCTC2544. Nevertheless, 30M SU182 reduced TNF-α / PMA-induced NF-κB-linked luciferase reporter activity to (22.9 ± 5%) and (34.6± 3 %, P<0.001) respectively, suggesting an action downstream of IKK signalling. Indeed, SU182 neither decreased NF-κB-DNA binding as assayed by EMSA nor prevented the translocation of p65 (NF-κB) to the nucleus assessed by immunofluorescence and subcellular fractionation. In addition to the inhibition of transcriptional activity of TNFα-induced NF-κB reporter activity SU182 significantly reduced PMA-induced AP-1-linked luciferase reporter activity to about (48± 9% at 30M, P<0.001) . This mode of inhibition was not sufficient to prevent the activation of NF-κB dependent induction of other proteins such as COX-2 and iNOS, or activated MAP kinases (p38, JNK and ERK1/2) in LPS stimulated RAW 264.7 macrophages. Taken together these data indicate the potential for SU182 to interfere with the transcription factors NF-κB and AP-1 at transcriptional level. However, no potential anti-inflammatory effect was indicated, further investigation for other NF-κB dependent proteins linked to survival are also required to identify the exact mechanism of action.

Keywords: Canthin-6-one, NF-κB, AP-1, phosphorylation, Nuclear translocation, DNA-binding activity, inflammatory proteins.

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Authors: Cenza Rhoda, Falone Sunda, Elvis Kidzeru, Nonhlanhla P. Khumalo, Afolake Arowolo

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Introduction: The human FAM111B gene mutations are associated with POIKTMP, a rare multi-organ fibrosing disease. Recent studies also reported the overexpression of FAM111B in specific cancers. However, the role of FAM111B in these pathologies, particularly fibrosarcoma, remains unknown. Materials and Methods: FAM111B RNA expression in some cancer cell lines was assessed in silico and validated in vitro in these cell lines and skin fibroblasts derived from the South African family member affected by POIKTMP with the heterozygous FAM111B gene mutation: NM_198947.4: c.1861T>G (p. Tyr621Asp or Y621D) by qPCR and western blot. The cellular function of FAM111B was also studied in HT1080 using various cell-based functional assays and a simple and cost-effective PCR-RFLP method for genotyping/screening FAM111B gene mutations described. Results: Expression studies showed upregulated FAM111B mRNA and protein in the cancer cells. High FAM111B expression with robust nuclear localization occurred in HT1080. Additionally, expression data and cell-based assays indicated that FAM111B led to the upregulation of cell migration and decreased cell apoptosis and cell proliferation modulation. FAM111B Y621D mutation showed similar effects on cell migration but minimal impact on cell apoptosis. FAM111B mRNA and protein expression were markedly downregulated (p ≤ 0.05) in the patient's skin-derived fibroblasts. Lastly, the PCR-RFLP method successfully genotyped FAM111B Y621D gene mutation. Discussion: FAM111B is a cancer-associated nuclear protein: Its modulation by mutations may enhance cell migration and proliferation and decrease apoptosis, as seen in cancers and POIKTMP/fibrosis, thus representing a viable therapeutic target in these disorders. Furthermore, the PCR-RFLP method could prove a valuable tool for FAM111B mutation validation or screening in resource-constrained laboratories.

Keywords: FAM111B, POIKTMP, cancer, fibrosis, PCR-RFLP

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Authors: Abdulbaset Mazarzaei

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Natural killer (NK) cells are innate immune effectors that play a pivotal role in combating tumors and infected cells. In recent years, the therapeutic potential of NK cells has gained significant attention due to their remarkable cytotoxic ability. This study focuses on investigating the cytotoxic effect of expanded NK cells enriched with interleukin 12 (IL12) and interleukin 15 (IL15), derived from the leukoreduction filter, on the K562 cell line. Firstly, NK cells were isolated from whole blood samples obtained from healthy volunteers. These cells were subsequently expanded ex vivo using a combination of feeder cells, IL12, and IL15. The expanded NK cells were then harvested and assessed for their cytotoxicity against K562, a well-established human chronic myelogenous leukemia cell line. The cytotoxicity was evaluated using flow cytometry assay. Results demonstrate that the expanded NK cells significantly exhibited enhanced cytotoxicity against K562 cells compared to non-expanded NK cells. Interestingly, the expanded NK cells derived specifically from IL12 and IL15-enriched leukoreduction filters showed a robust cytotoxic effect similar to the whole blood-derived NK cells. These findings suggest that IL12 and IL15 in the leukoreduction filter are crucial in promoting NK cell cytotoxicity. Furthermore, the expanded NK cells displayed relatively similar cytotoxicity profiles to whole blood-derived NK cells, indicating their comparable capability in targeting and eliminating tumor cells. This observation is of significant relevance as expanded NK cells from the leukoreduction filter could potentially serve as a readily accessible and efficient source for adoptive immunotherapy. In conclusion, this study highlights the significant cytotoxic effect of expanded NK cells enriched with IL12 and IL15 obtained from the leukoreduction filter on the K562 cell line. Moreover, it emphasizes that these expanded NK cells exhibit comparable cytotoxicity to whole blood-derived NK cells. These findings reinforce the potential clinical utility of using expanded NK cells from the leukoreduction filter as an effective strategy in adoptive immunotherapy for the treatment of cancer. Further studies are warranted to explore the broader implications of this approach in clinical settings.

Keywords: natural killer (NK) cells, Cytotoxicity, Leukoreduction filter, IL-12 and IL-15 Cytokines

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Authors: Samaneh Abedini, Diana Coholic

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The transition from adolescence into adulthood involves many changes that result in increased vulnerability to psychological challenges. This developmental stage can be especially stressful for female youth living in underserviced regions. If mental health problems are left untreated in socially marginalized youth, these challenges can extend into adulthood. We know that a lack of access to mental health services and supports can influence adolescents’ psycho-social development and well-being, while resilience and emotion regulation can help them cope with these challenges. Feasible therapeutic programs can play a significant role in assisting youth in developing these characteristics and skills. Mindfulness-Based Cognitive Therapy for Children (MBCT-C) and Holistic Art-Based Program (HAP) are two examples of mindfulness-based interventions (MBIs) that address emotion regulation, coping strategies, and resilience in marginalized youth. While each program’s beneficial effects have been documented, there is a lack of research comparing MBIs with youth, within underserviced geographical locations, and across different cultures. In this study, the sample was 42 female youth between the ages of 12 and 17 years from Iran. 42 female youth from the Elm o Honar High School, located in rural parts of Iran, Isfahan province, have been enrolled in the study. The participants were assigned to one of the MBIs (three MBCT-C experimental groups (n=20) and three HAP experimental groups (n=22)). All participants completed measures including the Child and Youth Resilience Measure-28 (CYRM-28), Child and Adolescent Mindfulness Measure (CAMM), and Difficulties in Emotion Regulation Scale (DERS) at baseline and post-intervention. At the end of intervention, the MBCT-C and HAP experimental groups showed significant changes in resilience and emotion regulation. However, the changes in resilience in HAP groups were not significant; the participants in MBCT-C experimental groups showed significant improvement in resilience. The study provided initial evidence that mindfulness-based intervention can be potentially beneficial for improving mental health status in marginalized Iranian female youth living in the middle east culture.

Keywords: benefits, female, marginalized, mindfulness, youth

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Authors: A. Aslihan Gokaltun, Martin L. Yarmush, Ayse Asatekin, O. Berk Usta

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Poly(dimethylsiloxane) (PDMS) is one of the most widely used materials in the fabrication of microfluidic devices. It is easily patterned and can replicate features down to nanometers. Its flexibility, gas permeability that allows oxygenation, and low cost also drive its wide adoption. However, a major drawback of PDMS is its hydrophobicity and fast hydrophobic recovery after surface hydrophilization. This results in significant non-specific adsorption of proteins as well as small hydrophobic molecules such as therapeutic drugs limiting the utility of PDMS in biomedical microfluidic circuitry. While silicon, glass, and thermoplastics have been used, they come with problems of their own such as rigidity, high cost, and special tooling needs, which limit their use to a smaller user base. Many strategies to alleviate these common problems with PDMS are lack of general practical applicability, or have limited shelf lives in terms of the modifications they achieve. This restricts large scale implementation and adoption by industrial and research communities. Accordingly, we aim to tailor biocompatible PDMS surfaces by developing a simple and one step bulk modification approach with novel smart materials to reduce non-specific molecular adsorption and to stabilize long-term cell analysis with PDMS substrates. Smart polymers that blended with PDMS during device manufacture, spontaneously segregate to surfaces when in contact with aqueous solutions and create a < 1 nm layer that reduces non-specific adsorption of organic and biomolecules. Our methods are fully compatible with existing PDMS device manufacture protocols without any additional processing steps. We have demonstrated that our modified PDMS microfluidic system is effective at blocking the adsorption of proteins while retaining the viability of primary rat hepatocytes and preserving the biocompatibility, oxygen permeability, and transparency of the material. We expect this work will enable the development of fouling-resistant biomedical materials from microfluidics to hospital surfaces and tubing.

Keywords: cell culture, microfluidics, non-specific protein adsorption, PDMS, smart polymers

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Authors: Phill-Seung Jung, Dae-Yeon Kim

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Objectives: In young, especially nulliparous women, it is not easy to decide on excisional therapy for cervical intraepithelial neoplasia (CIN). We aimed to evaluate how effective topical imiquimod is in the treatment of high-grade CIN so that excisional therapy can be avoided in young women. Methods: Patients with CIN were allocated to this pilot study. They did not want excisional therapy and agreed with topical imiquimod therapy, which required once-a-week hospital visit for 8 weeks for the application of imiquimod to the cervix by a gynecologic oncologist. If the lesion got worse during treatment, it was decided to convert imiquimod therapy to excisional therapy. Results: A total of 36 patients with a median age of 29 years (range, 22–41 years) agreed to receive topical imiquimod therapy. Of these, 32 patients (88.9%) were positive for high-risk human papillomavirus (HR HPV). Twenty-five patients (69.4%) had low-grade squamous intraepithelial lesion (LSIL), and 11 (30.6%) had high-grade squamous intraepithelial lesion (HSIL) on their initial LBC. Twenty-eight patients underwent punch biopsy, which showed CIN 1 in 7 (19.4%), CIN 2 in 11 (30.6%), and CIN 3 in 10 (27.8%) patients. Twenty patients finished the 8-week imiquimod therapy. Among them, 14 patients had CIN 2 or 3, and 6 patients had CIN 1. HR HPV was positive in 12 patients. On the last examination, 14 patients (70.0%) had negative intraepithelial lesions, 3 (15.0%) had atypical squamous cells of undetermined significance, and 1 (5.0%) had LSIL. Two patients had persistent HSIL: 1 patient underwent loop electrosurgical excision procedure, resulting in CIN 3 with positive resection margin, and the other patient underwent punch biopsy, resulting in intermediate cells and restarted imiquimod therapy. Only 7 patients were negative for HR HPV. Conclusions: This study showed that topical imiquimod therapy was effective for the treatment of high-grade CIN, with a histologic regression rate of 85.7% (14/20) and HPV eradication rate of 25.0% (8/32). Based on our findings, topical imiquimod therapy might have a successful therapeutic effect in young women with CIN 2-3 so that they can avoid excisional therapy. In addition, it could be a more reassuring treatment option for CIN 1 than just follow-up after few months. To confirm its efficacy, a phase II study with larger cohort would be needed.

Keywords: Imiquimod, Cervical Intraepthelial Neoplasia, Cervical Dysplasia, Human Papillomavirus

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Authors: Simone F. Medeiros, Jessica M. Fonseca, Gizelda M. Alves, Danilo M. Santos, Sérgio P. Campana-Filho, Amilton M. Santos

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Stimuli responsive and biocompatible hydrogel nanoparticles have gained special attention as systems for potential applications in controlled release of drugs to improve their therapeutic efficacy while minimizing side effects. In this work, novel solid dispersions based on thermo- and pH-responsive poly(N-vinylcaprolactam-co-itaconic acid-co-ethylene- glycol dimethacrylate) hydrogel nanoparticles embedded in chitosan matrices were prepared via spray drying for controlled release of ketoprofen. Firstly, the hydrogel nanoparticles containing ketoprofen were prepared via precipitation polymerization and their stimuli-responsive behavior, thermal properties, chemical composition, encapsulation efficiency and morphology were characterized. Then, hydrogel nanoparticles with different particles size were embedded into chitosan matrices via spray-drying. Scanning electron microscopy (SEM) analyses were performed to investigate the particles size, dispersity and morphology. Finally, ketoprofen release profiles were studied as a function of pH and temperature. Chitosan/poly(NVCL-co-IA-co-EGDMA)-ketoprofen microparticles presented spherical shape, rough surface and pronounced agglomeration, indicating that hydrogels nanoparticles loaded with ketoprofen modified the surface of chitosan matrix. The maximum encapsulation efficiency of ketoprofen into hydrogel nanoparticles was 57.8% and the electrostatic interactions between amino groups from chitosan and carboxylic groups from hydrogel nanoparticles were able to control ketoprofen release. The hydrogel nanoparticles themselves were capable to retard the release of ketoprofen-loaded until 48h of in vitro release tests, while their incorporation into chitosan matrix achieved a maximum percentage of drug release of 45%, using a mass ratio of chitosan: poly(NVCL-co-IA-co-EGDMA equal to 10:7, and 69%, using a mass ratio of chitosan: poly(NVCL-co-IA-co-EGDMA equal to 5:2.

Keywords: hydrogel nanoparticles, poly(N-vinylcaprolactam-co-itaconic acid-co-ethylene- glycol dimethacrylate), chitosan, ketoprofen, spray-drying

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Authors: Shanker Kalakotla, Krishna Mohan Gottumukkala

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Diabetes is a metabolic disorder characterized by hyperglycemia, carbohydrates, altered lipids and proteins metabolism. In recent research nanotechnology is a blazing field for the researchers; latterly there has been prodigious excitement in the nanomedicine and nano pharmacological area for the study of silver nanoparticles synthesis using natural products. Biological methods have been used to synthesize silver nanoparticles in presence of medicinally active antidiabetic plants, and this intention made us assess the biologically synthesized silver nanoparticles from the seed extract of Psoralea corylfolia using 1 mM silver nitrate solution. The synthesized herbal mediated silver nanoparticles (HMSNP’s) then subjected to various characterization techniques such as XRD, SEM, EDX, TEM, DLS, UV and FT-IR respectively. In current study, the silver nanoparticles tested for in-vitro anti-diabetic activity and possible toxic effects in healthy female albino mice by following OECD guidelines-425. Herbal mediated silver nanoparticles were successfully obtained from bioreduction of silver nitrate using Psoralea corylifolia plant extract. Silver nanoparticles have been appropriately characterized and confirmed using different types of equipment viz., UV-vis spectroscopy, XRD, FTIR, DLS, SEM and EDX analysis. From the behavioral observations of the study, the female albino mice did not show sedation, respiratory arrest, and convulsions. Test compounds did not cause any mortality at the dose level tested (i.e., 2000 mg/kg body weight) doses till the end of 14 days of observation and were considered safe. It may be concluded that LD50 of the HMSNPs was 2000mg/kg body weight. Since LD50 of the HMSNPs was 2000mg/kg body weight, so the preferred dose range for HMSNPs falls between the levels of 200 and 400 mg/kg. Further In-vivo pharmacological models and biochemical investigations will clearly elucidate the mechanism of action and will be helpful in projecting the currently synthesized silver nanoparticles as a therapeutic target in treating chronic ailments.

Keywords: herbal mediated silver nanoparticles, HMSNPs, toxicity of silver nanoparticles, PTP1B in-vitro anti-diabetic assay female albino mice, 425 OECD guidelines

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Authors: Farah Naja, Mohamad Alameddine

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Background: The difficulty of compliance to therapeutic and lifestyle management of type 2 diabetes mellitus (T2DM) encourages patients to use complementary and alternative medicine (CAM) therapies. Little is known about the prevalence and mode of CAM use among diabetics in the Eastern Mediterranean Region in general and Lebanon in particular. Objective: To assess the prevalence and modes of CAM use among patients with T2DM residing in Beirut, Lebanon. Methods: A cross-sectional survey of T2DM patients was conducted on patients recruited from two major referral centers - a public hospital and a private academic medical center in Beirut. In a face-to-face interview, participants completed a survey questionnaire comprised of three sections: socio-demographic, diabetes characteristics and types and modes of CAM use. Descriptive statistics, univariate and multivariate logistic regression analyses were utilized to assess the prevalence, mode and correlates of CAM use in the study population. The main outcome in this study (CAM use) was defined as using CAM at least once since diagnosis with T2DM. Results: A total of 333 T2DM patients completed the survey (response rate: 94.6%). Prevalence of CAM use in the study population was 38%, 95% CI (33.1-43.5). After adjustment, CAM use was significantly associated with a “married” status, a longer duration of T2DM, the presence of disease complications, and a positive family history of the disease. Folk foods and herbs were the most commonly used CAM followed by natural health products. One in five patients used CAM as an alternative to conventional treatment. Only 7 % of CAM users disclosed the CAM use to their treating physician. Health care practitioners were the least cited (7%) as influencing the choice of CAM among users. Conclusion: The use of CAM therapies among T2DM patients in Lebanon is prevalent. Decision makers and care providers must fully understand the potential risks and benefits of CAM therapies to appropriately advise their patients. Attention must be dedicated to educating T2DM patients on the importance of disclosing CAM use to their physicians especially patients with a family history of diabetes, and those using conventional therapy for a long time.

Keywords: nutritional supplements, type 2 diabetes mellitus, complementary and alternative medicine (CAM), conventional therapy

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Authors: Sena Park

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Background: The concurrent presentation with colorectal cancer in the inguinal hernia has been extremely rare. Due to its rarity, its presentation may lead to diagnostic and therapeutic dilemmas. We aim to review all the reported cases on colorectal cancer incarcerated in the inguinal hernia in the last 20 years, and discuss the operative approaches. Methods: We identified all case reports on colorectal cancer within inguinal hernia using PUBMED (2002-2022) and MEDLINE (2002-2022). The search strategy included the following keywords: colorectal cancer (title/abstract) AND inguinal hernia (title/abstract) OR incarceration (title/abstract). The search did not include letters, book chapters, systemic reviews, meta-analysis and editorials. Results: In the last 20 years, a total of 19 cases on colorectal cancer within the inguinal hernia were identified. The age of the patients ranged between 48 and 89. Majority of the patients were male (95%). Most commonly involved part of the large intestine was sigmoid colon (79%). Of all the cases, 79 percent of patients received open procedure and 21 percent had laparoscopic procedure. Discussion: Inguinal hernias are common with an incidence of approximately 1.7 percent. Colorectal cancer is the one of the leading causes of cancer-related mortality worldwide. However, their concurrent presentation has been extremely rare. In the last 20 years, 19 cases on concurrent presentation of colorectal cancer and inguinal hernia have been reported. Most patients who had open procedures had two incisions of groin incision and a midline laparotomy. There were 4 cases where the oncological resection was performed laparoscopically. The advantages of laparoscopic resection include reduced blood lost, reduced post-operative pain, reduced length of hospital stay and similar number of lymph nodes taken. From the review of the cases in the last 20 years, both open and laparoscopic approaches seemed to be safe and achieve adequate oncological resections. Conclusion: This is a brief overview of reported cases of colorectal cancer presenting with inguinal hernia concurrently. Due to its rarity, there are no current guidelines on operative approach in clinical practice. The experience in the last 20 years supports both open and laparoscopic approach.

Keywords: colorectal cancer, inguinal hernia, incarceration, operative approach

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Authors: Begona del Pino, Beatriz Prieto, Alberto Prieto

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Two opposite approaches to teaching can be considered: in-class learning (teacher-oriented) versus virtual learning (student-oriented). The most known example of the latter is Massive Online Open Courses (MOOCs). Both methodologies have pros and cons. Nowadays there is an increasing trend towards combining both of them. Blending learning is considered a valuable tool for improving learning since it combines student-centred interactive e-learning and face to face instruction. The aim of this contribution is to exchange and share the experience and research results of a blended-learning project that took place in the University of Granada (Spain). The research objective was to prove how combining didactic resources of a MOOC with in-class teaching, interacting directly with students, can substantially improve academic results, as well as student acceptance. The proposed methodology is based on the use of flipped learning technics applied to the subject ‘Fundamentals of Computer Science’ of the first course of two degrees: Telecommunications Engineering, and Industrial Electronics. In this proposal, students acquire the theoretical knowledges at home through a MOOC platform, where they watch video-lectures, do self-evaluation tests, and use other academic multimedia online resources. Afterwards, they have to attend to in-class teaching where they do other activities in order to interact with teachers and the rest of students (discussing of the videos, solving of doubts and practical exercises, etc.), trying to overcome the disadvantages of self-regulated learning. The results are obtained through the grades of the students and their assessment of the blended experience, based on an opinion survey conducted at the end of the course. The major findings of the study are the following: The percentage of students passing the subject has grown from 53% (average from 2011 to 2014 using traditional learning methodology) to 76% (average from 2015 to 2018 using blended methodology). The average grade has improved from 5.20±1.99 to 6.38±1.66. The results of the opinion survey indicate that most students preferred blended methodology to traditional approaches, and positively valued both courses. In fact, 69% of students felt ‘quite’ or ‘very’ satisfied with the classroom activities; 65% of students preferred the flipped classroom methodology to traditional in-class lectures, and finally, 79% said they were ‘quite’ or ‘very’ satisfied with the course in general. The main conclusions of the experience are the improvement in academic results, as well as the highly satisfactory assessments obtained in the opinion surveys. The results confirm the huge potential of combining MOOCs in formal undergraduate studies with on-campus learning activities. Nevertheless, the results in terms of students’ participation and follow-up have a wide margin for improvement. The method is highly demanding for both students and teachers. As a recommendation, students must perform the assigned tasks with perseverance, every week, in order to take advantage of the face-to-face classes. This perseverance is precisely what needs to be promoted among students because it clearly brings about an improvement in learning.

Keywords: blended learning, educational paradigm, flipped classroom, flipped learning technologies, lessons learned, massive online open course, MOOC, teacher roles through technology

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Authors: Eric Lacoste

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Laboratory animals are currently widely used as a model of human pathologies in dermatology such as atopic dermatitis (AD). These models provide a better understanding of the pathophysiology of this complex and multifactorial disease, the discovery of potential new therapeutic targets and the testing of the efficacy of new therapeutics. However, confirmation of the correct development of AD is mainly based on histology from skin biopsies requiring invasive surgery or euthanasia of the animals, plus slicing and staining protocols. However, there are currently accessible imaging technologies such as Optical Coherence Tomography (OCT), which allows non-invasive visualization of the main histological structures of the skin (like stratum corneum, epidermis, and dermis) and assessment of the dynamics of the pathology or efficacy of new treatments. Briefly, female immunocompetent hairless mice (SKH1 strain) were sensitized and challenged topically on back and ears for about 4 weeks. Back skin and ears thickness were measured using calliper at 3 occasions per week in complement to a macroscopic evaluation of atopic dermatitis lesions on back: erythema, scaling and excoriations scoring. In addition, OCT was performed on the back and ears of animals. OCT allows a virtual in-depth section (tomography) of the imaged organ to be made using a laser, a camera and image processing software allowing fast, non-contact and non-denaturing acquisitions of the explored tissues. To perform the imaging sessions, the animals were anesthetized with isoflurane, placed on a support under the OCT for a total examination time of 5 to 10 minutes. The results show a good correlation of the OCT technique with classical HES histology for skin lesions structures such as hyperkeratosis, epidermal hyperplasia, and dermis thickness. This OCT imaging technique can, therefore, be used in live animals at different times for longitudinal evaluation by repeated measurements of lesions in the same animals, in addition to the classical histological evaluation. Furthermore, this original imaging technique speeds up research protocols, reduces the number of animals and refines the use of the laboratory animal.

Keywords: atopic dermatitis, mouse model, oxzolone model, histology, imaging

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Authors: S. Sreeja, Radhakrishnan R. Nair, Noble Gracious, Sreeja S. Nair, M. Radhakrishna Pillai

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Background: Tacrolimus is a potent immunosuppressant clinically used for the long term treatment of antirejection of transplanted organs in liver and kidney transplant recipients though dose optimization is poorly managed. However, So far no study has been carried out on the South Indian kidney transplant patients. The objective of this study is to evaluate the potential influence of a functional polymorphism in CYP3A5*3 gene on tacrolimus physiological availability/dose ratio in South Indian renal transplant patients. Materials and Methods: Twenty five renal transplant recipients receiving tacrolimus were enrolled in this study. Their body weight, drug dosage, and therapeutic concentration of Tacrolimus were observed. All patients were on standard immunosuppressive regime of Tacrolimus-Mycophenolate mofetil along with steroids on a starting dose of Tac 0.1 mg/kg/day. CYP3A5 genotyping was performed by PCR followed with RFLP. Conformation of RFLP analysis and variation in the nucleotide sequence of CYP3A5*3 gene were determined by direct sequencing using a validated automated generic analyzer. Results: A significant association was found between tacrolimus per dose/kg/d and CYP3A5 gene (A6986G) polymorphism in the study population. The CYP3A5 *1/*1, *1/*3 and *3/*3 genotypes were detected in 5 (20 %), 5 (20 %) and 15 (60 %) of the 25 graft recipients, respectively. CYP3A5*3 genotypes were found to be a good predictor of tacrolimus Concentration/Dose ratio in kidney transplant recipients. Significantly higher L/D was observed among non-expressors 9.483 ng/mL(4.5- 14.1) as compared with the expressors 5.154 ng/mL (4.42-6.5 ) of CYP3A5. Acute rejection episodes were significantly higher for CYP3A5*1 homozygotes compared to patients with CYP3A5*1/*3 and CYP3A5*3/*3 genotypes (40 % versus 20 % and 13 %, respectively ). The dose normalized TAC concentration (ng/ml/mg/kg) was significantly lower in patients having CYP3A5*1/*3 polymorphism. Conclusion: This is the first study to extensively determine the effect of CYP3A5*3 genetic polymorphism on tacrolimus pharmacokinetics in South Indian renal transplant recipients and also shows that majority of our patients carry mutant allele A6986G in CYP3A5*3 gene. Identification of CYP3A5 polymorphism prior to transplantation could contribute to evaluate the appropriate initial dosage of tacrolimus for each patient.

Keywords: kidney transplant patients, CYP3A5 genotype, tacrolimus, RFLP

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Authors: Milada Krejci, Martin Hill, Vaclav Hosek, Dobroslava Jandova, Jiri Kajzar, Pavel Blaha

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The paper declares effects of exercise intervention of the research project “Basic research of balance changes in seniors”, granted by the Czech Science Foundation. The objective of the presented study is to define predictors, which influence bio-psycho-social consequences and effects of balance ability in senior 65 years old and above. We focused on the Fall-Efficacy Scale changes evaluation in seniors. Comprehensive hypothesis of the project declares, that motion uncertainty (dyskinesia) can negatively affect the well-being of a senior in bio-psycho-social context. In total, random selection and testing of 100 seniors (30 males, 70 females) from Prague and Central Bohemian region was provided. The sample was divided by stratified random selection into experimental and control groups, who underwent input and output testing. For diagnostics the methods of Medical Anamnesis, Functional anthropological examinations, Tinetti Balance Assessment Tool, SF-36 Health Survey, Anamnestic comparative self-assessment scale were used. Intervention method called "Life in Balance" based on yoga techniques was applied in four-week cycle. Results of multivariate regression were verified by repeated measures ANOVA: subject factor, phase of intervention (between-subject factor), body fluid (within-subject factor) and phase of intervention × body fluid interaction). ANOVA was performed with a repetition involving the factors of subjects, experimental/control group, phase of intervention (independent variable), and x phase interaction followed by Bonferroni multiple comparison assays with a test strength of at least 0.8 on the probability level p < 0.05. In the paper results of the first-year investigation of the three years running project are analysed. Results of balance tests confirmed no significant difference between females and males in pre-test. Significant improvements in balance and walking ability were observed in experimental group in females comparing to males (F = 128.4, p < 0.001). In the females control group, there was no significant change in post- test, while in the female experimental group positive changes in posture and spine flexibility in post-tests were found. It seems that females even in senior age react better to incentives of intervention in balance and spine flexibility. On the base of results analyses, we can declare the significant improvement in social balance markers after intervention in the experimental group (F = 10.5, p < 0.001). In average, seniors are used to take four drugs daily. Number of drugs can contribute to allergy symptoms and balance problems. It can be concluded that static balance and walking ability of seniors according Tinetti Balance scale correlate significantly with psychic and social monitored markers.

Keywords: exercises, balance, seniors 65+, health, mental and social balance

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Authors: Misty Attwood, Helgi Schioth

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Transmembrane proteins are important components in many essential cell processes such as signal transduction, cell-cell signalling, transport of solutes, structural adhesion activities, and protein trafficking. Due to their involvement in diverse critical activities, transmembrane proteins are implicated in different disease pathways and hence are the focus of intense interest in understanding functional activities, their pathogenesis in disease, and their potential as pharmaceutical targets. Further, as the structure and function of proteins are correlated, investigating a group of proteins with the same tertiary structure, i.e., the same number of transmembrane regions, may give understanding about their functional roles and potential as therapeutic targets. In this in silico bioinformatics analysis, we identify and comprehensively characterize the previously unstudied group of proteins with five transmembrane-spanning regions (5TM). We classify nearly 60 5TM proteins in which 31 are members of ten families that contain two or more family members and all members are predicted to contain the 5TM architecture. Furthermore, nine singlet proteins that contain the 5TM architecture without paralogues detected in humans were also identifying, indicating the evolution of single unique proteins with the 5TM structure. Interestingly, more than half of these proteins function in localization activities through movement or tethering of cell components and more than one-third are involved in transport activities, particularly in the mitochondria. Surprisingly, no receptor activity was identified within this family in sharp contrast with other TM families. Three major 5TM families were identified and include the Tweety family, which are pore-forming subunits of the swelling-dependent volume regulated anion channel in astrocytes; the sidoreflexin family that acts as mitochondrial amino acid transporters; and the Yip1 domain family engaged in vesicle budding and intra-Golgi transport. About 30% of the proteins have enhanced expression in the brain, liver, or testis. Importantly, 60% of these proteins are identified as cancer prognostic markers, where they are associated with clinical outcomes of various tumour types, indicating further investigation into the function and expression of these proteins is important. This study provides the first comprehensive analysis of proteins with 5TM regions and provides details of the unique characteristics and application in pharmaceutical development.

Keywords: 5TM, cancer prognostic marker, drug targets, transmembrane protein

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Authors: Endris Yibru Hanurry, Wei-Hsin Hsu, Hsieh-Chih Tsai

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In recent years, the discovery of small interfering RNAs (siRNAs) has got great attention for the treatment of cancer and other diseases. However, the therapeutic efficacy of siRNAs has been faced with many drawbacks because of short half-life in blood circulation, poor membrane penetration, weak endosomal escape and inadequate release into the cytosol. To overcome these drawbacks, we designed a non-viral vector by conjugating polyamidoamine generation 4.5 dendrimer (PDG4.5) with diethylenetriamine (DETA)- and tetraethylenepentamine (TEPA) followed by binding with siRNA to form polyplexes through electrostatic interaction. The result of 1H nuclear magnetic resonance (NMR), 13C NMR, correlation spectroscopy, heteronuclear single–quantum correlation spectroscopy, and Fourier transform infrared spectroscopy confirmed the successful conjugation of DETA and TEPA with PDG4.5. Then, the size, surface charge, morphology, binding ability, stability, release assay, toxicity and cellular internalization were analyzed to explore the physicochemical and biological properties of PDG4.5-DETA and PDG4.5-TEPA polyplexes at specific N/P ratios. The polyplexes (N/P = 8) exhibited spherical nanosized (125 and 85 nm) particles with optimum surface charge (13 and 26 mV), showed strong siRNA binding ability, protected the siRNA against enzyme digestion and accepted biocompatibility to the HeLa cells. Qualitatively, the fluorescence microscopy image revealed the delocalization (Manders’ coefficient 0.63 and 0.53 for PDG4.5-DETA and PDG4.5-TEPA, respectively) of polyplexes and the translocation of the siRNA throughout the cytosol to show a decent cellular internalization and intracellular biodistribution of polyplexes in HeLa cells. Quantitatively, the flow cytometry result indicated that a significant (P < 0.05) amount of siRNA was internalized by cells treated with PDG4.5-DETA (68.5%) and PDG4.5-TEPA (73%) polyplexes. Generally, PDG4.5-DETA and PDG4.5-TEPA were ideal nanocarriers of siRNA in vitro and might be used as promising candidates for in vivo study and future pharmaceutical applications.

Keywords: non-viral carrier, oligoalkylamine, poly(amidoamine) dendrimer, polyplexes, siRNA

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Authors: Kyra Kannen, Sonja D. Roelen, Sebastian Schnieder, Jarek Krajewski, Steffen Holsteg, André Karger, Johanna Askeridis, Celina Slawik, Philip Mildner, Jens Piesk, Ruslan David, Holger Kürten, Benjamin Oster, Robert Malzan, Mike Ludemann

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Virtual Reality (VR) is increasingly recognized for its potential in transforming mental disorder treatment, offering advantages such as cost-effectiveness, time efficiency, accessibility, reduced stigma, and scalability. While the application of VR in the context of anxiety disorders has been extensively evaluated and demonstrated to be effective, the utilization of VR as a therapeutic treatment for depression remains under-investigated. Our goal is to pioneer immersive VR therapy modules for treating major depression, alongside a web-based system for home use. We develop a modular digital therapy platform grounded in psychodynamic therapy interventions which addresses stress reduction, exploration of social situations and relationship support, social skill training, avoidance behavior analysis, and psychoeducation. In addition, an automated depression monitoring system, based on acoustic voice analysis, is implemented in the form of a speech-based diary to track the affective state of the user and depression severity. The use of immersive VR facilitates patient immersion into complex and realistic interpersonal interactions with high emotional engagement, which may contribute to positive treatment acceptance and satisfaction. In a proof-of-concept study, 45 depressed patients were assigned to VR or web-platform modules, evaluating user experience, usability and additional metrics including depression severity, mindfulness, interpersonal problems, and treatment satisfaction. The findings provide valuable insights into the effectiveness and user-friendliness of VR and web modules for depression therapy and contribute to the refinement of more tailored digital interventions to improve mental health.

Keywords: virtual reality therapy, digital health, depression, psychotherapy

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Authors: Buhari Samaila, Buhari Maidamma

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Background: The use of ionizing radiation in medical diagnostics and treatment is indispensable for accurate imaging and effective cancer therapies. However, radiation exposure carries inherent risks, necessitating strict protection measures to safeguard both patients and healthcare workers. This review critically examines the existing radiation protection measures in diagnostic radiology and radiotherapy, highlighting technological advancements, regulatory frameworks, and challenges. Objective: The objective of this review is to critically evaluate the effectiveness of current radiation protection measures in diagnostic and therapeutic radiology, focusing on minimizing patient and staff exposure to ionizing radiation while ensuring optimal clinical outcomes and propose future directions for improvement. Method: A comprehensive literature review was conducted, covering scientific studies, regulatory guidelines, and international standards on radiation protection in both diagnostic radiology and radiotherapy. Emphasis was placed on ALARA principles, dose optimization techniques, and protective measures for both patients and healthcare workers. Results: Radiation protection measures in diagnostic radiology include the use of shielding devices, minimizing exposure times, and employing advanced imaging technologies to reduce dose. In radiotherapy, accurate treatment planning and image-guided techniques enhance patient safety, while shielding and dose monitoring safeguard healthcare personnel. Challenges such as limited infrastructure in low-income settings and gaps in healthcare worker training persist, impacting the overall efficacy of protection strategies. Conclusion: While significant advancements have been made in radiation protection, challenges remain in optimizing safety, especially in resource-limited settings. Future efforts should focus on enhancing training, investing in advanced technologies, and strengthening regulatory compliance to ensure continuous improvement in radiation safety practices.

Keywords: radiation protection, diagnostic radiology, radiotherapy, ALARA, patient safety, healthcare worker safety

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