Search results for: expressive therapies

Authors: Khushbu Priyadarshi, Chandramani Pathak

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Cancer cells can develop resistance to conventional therapies especially chemotherapeutic drugs. Resistance to chemotherapy is another challenge in cancer therapeutics. Therefore, it is important to address this issue. Gallic acid (GA) is a natural plant compound that exhibits various biological properties including anti-proliferative, anti-inflammatory, anti-oxidant and anti-bacterial. Despite of the wide spectrum biological properties GA has cytotoxic response and low bioavailability. To overcome this problem, GA was conjugated with the Polyamidoamine(PAMAM) dendrimer for improving the bioavailability and efficient delivery in drug-resistant HCT-116 Colon Cancer cells. Gallic acid was covalently linked to 4.0 G PAMAM dendrimer. PAMAM dendrimer is well established nanocarrier but has cytotoxicity due to presence of amphiphilic nature of amino group. In our study we have modified surface of PAMAM dendrimer with Gallic acid and examine their anti-proliferative effects in drug-resistant HCT-116 cells. Further, drug-resistant colon cancer cells were established and thereafter treated with different concentration of PAMAM-GA to examine their anti-proliferative potential. Our results show that PAMAM-GA conjugate induces apoptotic cell death in HCT-116 and drug-resistant cells observed by Annexin-PI staining. In addition, it also shows that multidrug-resistant drug transporter P-gp protein expression was downregulated with increasing the concentration of GA conjugate. After that we also observed the significant difference in Rh123 efflux and accumulation in drug sensitive and drug-resistant cancer cells. Thus, our study suggests that conjugation of anti-cancer agents with PAMAM could improve drug resistant property and cytotoxic response to treatment of cancer.

Keywords: drug resistance, gallic acid, PAMAM dendrimer, P-glycoprotein

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Authors: Melanie Macgregor-Ramiasa, Isabel Hopp, Patricia Murray, Krasimir Vasilev

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Stem cells based therapies are one of the greatest promises of new-age medicine due to their potential to help curing most dreaded conditions such as cancer, diabetes and even auto-immune disease. However, establishing suitable in vitro culture materials allowing to control the fate of stem cells remain a challenge. Amongst the factor influencing stem cell behavior, substrate chemistry and nanotopogaphy are particularly critical. In this work, we used plasma assisted surface modification methods to produce model substrates with tailored nanotopography and controlled chemistry. Three different sizes of gold nanoparticles were bound to amine rich plasma polymer layers to produce homogeneous and gradient surface nanotopographies. The outer chemistry of the substrate was kept constant for all substrates by depositing a thin layer of our patented biocompatible polyoxazoline plasma polymer on top of the nanofeatures. For the first time, protein adsorption and stem cell behaviour (mouse kidney stem cells and mesenchymal stem cells) were evaluated on nanorough plasma deposited polyoxazoline thin films. Compared to other nitrogen rich coatings, polyoxazoline plasma polymer supports the covalent binding of proteins. Moderate surface nanoroughness, in both size and density, triggers cell proliferation. In association with polyoxazoline coating, cell proliferation is further enhanced on nanorough substrates. Results are discussed in term of substrates wetting properties. These findings provide valuable insights on the mechanisms governing the interactions between stem cells and their growth support.

Keywords: nanotopography, stem cells, differentiation, plasma polymer, oxazoline, gold nanoparticles

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Authors: Aba-Carina Pârlog

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On translating, reading against the grain results in a wrong effect in the TL. Quine’s ocular irradiation plays an important part in the process of understanding and translating a text. The various types of textual radiation must be rendered by the translator by paying close attention to the types of field that produce it. The literary work must be seen as an indirect cause of an expressive effect in the TL that is supposed to be similar to the effect it has in the SL. If the adaptive transformative codes are so flexible that they encourage the translator to repeatedly leave out parts of the original work, then a subversive pattern emerges which changes the entire book. In this case, the translator is a writer per se who decides what goes in and out of the book, how the style is to be ciphered and what elements of ideology are to be highlighted. Figurative language must not be flattened for the sake of clarity or naturalness. The missing figurative elements make the translated text less interesting, less challenging and less vivid which reflects poorly on the writer. There is a close connection between style and the writer’s person. If the writer’s style is very much changed in a translation, the translation is useless as the original writer and his / her imaginative world can no longer be discovered. Then, a different writer appears and his / her creation surfaces. Changing meaning considered as a “negative shift” in translation defines one of the faulty transformative codes used by some translators. It is a dangerous tool which leads to adaptations that sometimes reflect the original less than the reader would wish to. It contradicts the very essence of the process of translation which is that of making a work available in a foreign language. Employing speculative aesthetics at the level of a text indicates the wish to create manipulative or subversive effects in the translated work. This is generally achieved by adding new words or connotations, creating new figures of speech or using explicitations. The irradiation patterns of the original work are neglected and the translator creates new meanings, implications, emphases and contexts. Again s/he turns into a new author who enjoys the freedom of expressing his / her ideas without the constraints of the original text. The stimulus meaning of a text is very important for a translator which is why reading against the grain is unadvisable during the process of translation. By paying attention to the waves of the SL input, a faithful literary work is produced which does not contradict general knowledge about foreign cultures and civilizations. Following personal common sense is essential in the field of translation as well as everywhere else.

Keywords: stimulus meaning, substance of expression, transformative code, translation

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Authors: Alieh Farshbaf

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Introduction: Current anti-retroviral drugs have some restrictions for treatment of HIV-1 infection. The efficacy of retroviral drugs is not same in different infected patients and the virus rebound from latent reservoirs after stopping them. Recently, the engineering of stem cells and gene therapy provide new approaches to eliminate some drug problems by induction of resistance to HIV-1. Literature review: Up to now, AIDS-restriction genes (ARGs) were suitable candidate for gene and cell therapies, such as cc-chemokine receptor-5 (CCR5). In this manner, CCR5 provide effective cure in Berlin and Boston patients by inducing of HIV-1 resistance with allogeneic stem cell transplantation. It is showed that Zinc Finger Nuclease (ZFN) could induce HIV-1 resistance in stem cells of infected patients by homologous recombination or non-end joining mechanism and eliminate virus loading after returning the modified cells. Then, gene modification by HIV restriction factors, as TRIM5, introduced another gene candidate for HIV by interfering in infection process. These gene modifications/editing provided by stem cell futures that improve treatment in refractory disease such as HIV-1. Conclusion: Although stem cell transplantation has some complications, but in compare to retro-viral drugs demonstrated effective cure by elimination of virus loading. On the other hand, gene therapy is cost-effective for an infected patient than retroviral drugs payment in a person life-long. The results of umbilical cord blood stem cell transplantation showed that gene and cell therapy will be applied easier than previous treatment of AIDS with high efficacy.

Keywords: stem cell, AIDS, gene modification, cell engineering

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Authors: F. Bosca, F. Foglietta, F. Turci, E. Calcio Gaudino, S. Mana, F. Dosio, R. Canaparo, L. Serpe, A. Barge

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In recent years, medical science has improved chemotherapy, radiation therapy and adjuvant therapy and has developed newer targeted therapies as well as refining surgical techniques for removing cancer. However, the chances of surviving the disease depend greatly on the type and location of the cancer and the extent of the disease at the start of treatment. Moreover, mainstream forms of cancer treatment have side effects which range from the unpleasant to the fatal. Therefore, the continuation of progress in anti-cancer therapy may depend on placing emphasis on other existing but less thoroughly investigated therapeutic approaches such as Sonodynamic Therapy (SDT). SDT is based on the local activation of a so called 'sonosensitizer', a molecule able to be excited by ultrasound, the radical production as a consequence of its relaxation processes and cell death due to different mechanisms induced by radical production. The present work deals with synthesis, characterization and preliminary in vitro test of Single Walled Carbon Nanotubes (SWCNT) decorated with porphyrins and biological vectors. The SWCNT’s surface was modified exploiting 1, 3-dipolar cycloaddition or Dies Alder reactions. For this purpose, different porphyrins scaffolds were ad-hoc synthesized using also non-conventional techniques. To increase cellular specificity of porphyrin-conjugated SWCNTs and to improve their ability to be suspended in aqueous solution, the modified nano-tubes were grafted with suitable glutamine or hyaluronic acid derivatives. These nano-sized sonosensitizers were characterized by several methodologies and tested in vitro on different cancer cell lines.

Keywords: sonodynamic therapy, porphyrins synthesis and modification, SWNCT grafting, hyaluronic acid, anti-cancer treatment

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Authors: Younis Elhaddad, Alfonso Ortega

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Oil production by means of gas lift is a standard technique in oil production industry. To optimize the total amount of oil production in terms of the amount of gas injected is a key question in this domain. Different methods have been tested to propose a general methodology. Many of them apply well-known numerical methods. Some of them have taken into account the power of evolutionary approaches. Our goal is to provide the experts of the domain with a powerful automatic searching engine into which they can introduce their knowledge in a format close to the one used in their domain, and get solutions comprehensible in the same terms, as well. These proposals introduced in the genetic engine the most expressive formal models to represent the solutions to the problem. These algorithms have proven to be as effective as other genetic systems but more flexible and comfortable for the researcher although they usually require huge search spaces to justify their use due to the computational resources involved in the formal models. The first step to evaluate the viability of applying our approaches to this realm is to fully understand the domain and to select an instance of the problem (gas lift optimization) in which applying genetic approaches could seem promising. After analyzing the state of the art of this topic, we have decided to choose a previous work from the literature that faces the problem by means of numerical methods. This contribution includes details enough to be reproduced and complete data to be carefully analyzed. We have designed a classical, simple genetic algorithm just to try to get the same results and to understand the problem in depth. We could easily incorporate the well mathematical model, and the well data used by the authors and easily translate their mathematical model, to be numerically optimized, into a proper fitness function. We have analyzed the 100 curves they use in their experiment, similar results were observed, in addition, our system has automatically inferred an optimum total amount of injected gas for the field compatible with the addition of the optimum gas injected in each well by them. We have identified several constraints that could be interesting to incorporate to the optimization process but that could be difficult to numerically express. It could be interesting to automatically propose other mathematical models to fit both, individual well curves and also the behaviour of the complete field. All these facts and conclusions justify continuing exploring the viability of applying the approaches more sophisticated previously proposed by our research group.

Keywords: evolutionary automatic programming, gas lift, genetic algorithms, oil production

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Authors: Debasmita Mukhopadhyay, Manika Pal Bhadra

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MiRNAs contribute to oncogenesis either as tumor suppressors or oncogenes. Hence, discovery of miRNA-based therapeutics are imperative to ameliorate cancer. Modulation of miRNA maturation is accomplished via several therapeutic agents, including small molecules and oligonucleotides. Due to the attractive pharmacokinetic properties of small molecules over oligonucleotides, we set to identify small molecule inhibitors of a metastasis-inducing microRNA. Cytotoxicity profile of aza-flavanone C1 was analyzed in a panel of breast cancer cells employing the NCI-60 screen protocols. Flow cytometry, immunofluorescence and western blotting of apoptotic or EMT markers were performed to analyze the effect of C1. A dual luciferase assay unequivocally suggested that C1 repressed endogenous miR-10b in MDA-MB-231 cells. A derivative of aza-flavanone C1 is shown as a strong inhibitor miR-10b. Blockade of miR-10b by C1 resulted in decreased expression of miR-10b targets in an aggressive breast cancer cell line model, MDA-MB-231. Abrogation of TWIST1, an EMT-inducing transcription factor also contributed to C1 mediated apoptosis. Moreover C1 exhibited a specific and selective down-regulation of miR-10b and did not function as a general inhibitor of miRNA biogenesis or other oncomiRs of breast carcinoma. Aza-flavanone congener C1 functions as a potent inhibitor of the metastasis-inducing microRNA, miR-10b. Our present study provides evidence for targeting metastasis-inducing microRNA, miR-10b with a derivative of Aza-flavanone. Better pharmacokinetic properties of small molecules place them as attractive agents compared to nucleic acids based therapies to target miRNA. Further work, in generating analogues based on aza-flavanone moieties will significantly improve the affinity of the small molecules to bind miR-10b. Finally, it is imperative to develop small molecules as novel miRNA-therapeutics in the fight against cancer.

Keywords: breast cancer, microRNA, metastasis, EMT

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Authors: Sanjay Singh, Swati Jaiswal, Prashant Mishra

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Nanoparticle based formulations of drug delivery systems have shown their potential in improving the performance of existing drugs and have opened avenues for new therapies. Calendula extract is a low cost, wide spectrum bioactive material that has been used for a long term therapy of various infections. Aim: The aim of this study was to develop Calendula officinalis extract based nanoformulations and to study the antibacterial activity of either Calendula extract loaded chitosan nanoparticles or Calendula extract coated silver nanoparticles for increased bioavailability and their long term effect. Methods: Chitosan nanoparticles were prepared by the process of ionotropic gelation, based on interaction between the negative groups of tri polyphosphate (TPP) and positively charged amino groups of chitosan. The size of the Calendula extract-loaded chitosan particles was determined using dynamic light scattering and scanning electron microscopy. Antibacterial activities of these formulations were determined based on minimum inhibitory concentration and time kill studies. In addition, silver nanoparticles were also synthesized in the presence of Calendula extract and characterized by UV visible spectrum, DLS and XRD. Experiments were conducted on 96-plates against two Gram-positive bacteria; Staphylococcus aureus and Bacillus subtilis two Gram-negative bacteria; Escherichia coli and Pseudomonas aeruginosa. Results: Results demonstrated time dependent antibacterial activity against different microbes studied. Both Calendula extract and Calendula extract loaded chitosan nanoparticles have shown good antimicrobial activity against both Gram positive and Gram negative bacteria. Conclusion: Calendula extract loaded chitosan nanoparticles and calendula extract coated silver nanoparticles are potential antibacterial for their long term antibacterial effects.

Keywords: antibacterial, Calendula extract, chitosan nanoparticles, silver nanoparticles

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Authors: Sultan Çağırıcı, Arsida Bajrami, Beyza Aslan, Hacı Ali Erdoğan, Nejla Sözer Topçular, Dilek Bozkurt, Vildan Yayla

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Objective: Corticobasal syndrome (CBS) is phenotypically characterized by asymmetric rigidity, apraxia, alien-limb phenomenon, cortical sensory loss, dystonia and myoclonus. The underlying pathologies consists of corticobasal degeneration (CBD), progressive supra nuclear palsy, Alzheimer's, Creutzfeldt-Jakob and frontotemporal degeneration. CBD is a degenerative disease with clinical symptoms related to the prominent involvement of cerebral cortex and basal ganglia. CBD is a pathological diagnosis and antemortem clinical diagnosis may change many times. In this paper, we described the clinical features and discussed a cases diagnosed with symmetric CBS because of its rarity. Case: Seventy-five-year-old woman presented with a three years history of difficulty in speaking and reading. Involuntary hand jerks and slowness of movement also had began in the last six months. In the neurological examination the patient was alert but not fully oriented. The speech was non-fluent, word finding difficulties were present. Bilateral limited upgaze, bradimimia, bilateral positive cogwheel' rigidity but prominent in the right side, postural tremor and negative myoclonus during action on the left side were detected. Receptive language was normal but expressive language and repetition were impaired. Acalculia, alexia, agraphia and apraxia were also present. CSF findings were unremarkable except for elevated protein level (75 mg/dL). MRI revealed bilateral symmetric cortical atrophy prominent in the frontoparietal region. PET showed hypometabolism in the left caudate nucleus. Conclusion: The increase of data related to neurodegenerative disorders associated with dementia, movement disorders and other findings results in an expanded range of diagnosis and transitions between clinical diagnosis. When considered the age of onset, clinical symptoms, imaging findings and prognosis of this patient, clinical diagnosis was CBS and pathologic diagnosis as probable CBD. Imaging of CBD usually consist of typical asymmetry between hemispheres. Still few cases with clinical appearance of CBD may show symmetrical cortical cerebral atrophy. It is presented this case who was diagnosed with CBD although we found symmetrical cortical cerebral atrophy in MRI.

Keywords: symmetric cortical atrophy, corticobasal degeneration, corticobasal syndrome

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Authors: Catarina Ramos Pereira, Jorge Rodrigues, Natália Oliveira, Jorge Machado, Maria Begoña Criado, Jorge Machado, Henri J. Greten

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Background: Parkinson's disease is a multi-system neurodegenerative disorder characterized by motor and non-motor symptoms. To slow disorder progression, different treatment options are now available, but in most cases, these therapeutic strategies also involve the presence of important side effects. This has led many patients to pursue complementary therapies, such as acupuncture, to alleviate PD symptoms. Therefore, an update on the efficacy of this treatment for patients of PD is of great value. This work presents a systematic review of the efficacy of acupuncture treatments in relieving PD symptoms. Methods: EMBASE, Medline, Pubmed, Science Direct, The Cochrane Library, Cochrane Central Register of Controlled Trials (Central), and Scielo databases were systematically searched from January 2011 through July 2021. Randomized controlled trials (RCTs) published in English with all types of acupuncture treatment were included. The selection and analysis of the articles were conducted by two blinding authors through the Rayyan application. Results: 720 potentially relevant articles were identified; 52 RCTs met our inclusion criteria. After the exclusion of 35, we found 17 eligible. The included RCTs reported positive effects for acupuncture plus conventional treatment compared with conventional treatment alone in the UPDRS score. Conclusions: Additional evidence should be supported by rigorous methodological strategies. Although firm conclusions cannot be drawn, acupuncture treatment, in the framework of an interdisciplinary care team, appears to have positive effects on PD symptoms.

Keywords: systematic review, Parkinson disease, acupuncture, traditional Chinese medicine

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Authors: Deborah García-Magna

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When a person goes through the criminal justice system, either as a suspect, arrested, prosecuted or convicted, certain personal data are recorded, and a wide range of persons and organizations may have access to it. The recording of data can have a great impact on the daily life of the person concerned during the period of time determined by the legislation. In addition, this registered information can refer to various aspects not strictly related directly to the alleged or actually committed infraction. In some areas, the Spanish legislation does not clearly determine the cancellation period of the registers nor what happens when they are cancelled since some of the files are not really erased and remain recorded, even if their consultation is no more allowed or it is stated that they should not be taken into account. Thus, access to the recorded data of arrested or convicted persons may reduce their possibilities of reintegration into society. In this research, some of the areas in which data recording has a special impact on the lives of affected persons are analyzed in a critical manner, taking into account Spanish legislation and jurisprudence, and the influence of the European Court of Human Rights, the Council of Europe and other supranational instruments. In particular, the analysis cover the scope of video-surveillance in public spaces, the police record, the recording of personal data for the purposes of police investigation (especially DNA and psychological profiles), the registry of administrative and minor offenses (especially as they are taken into account to impose aggravating circumstaces), criminal records (of adults, minors and legal entities), and the registration of special circumstances occurred during the execution of the sentence (files of inmates under special surveillance –FIES–, disciplinary sanctions, special therapies in prison, etc.).

Keywords: ECHR jurisprudence, formal and informal criminal control, privacy, disciplinary sanctions, social reintegration

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Authors: B. J. Mahen, N. E. Lloyd-Gale, S. Johnson, W. P. Rakowicz, M. J. Harris, A. D. Miller

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Background: Migraine is a leading cause of disability in the world. Calcitonin gene-related peptide (CGRP) receptor antagonists offer an approach to migraine prophylaxis by inhibiting the inflammatory and vasodilatory effects of CGRP. In recent years, NICE licensed the use of three CGRP-receptor antagonists: Fremanezumab, Galcanezumab, and Erenumab. Here, we present the outcomes of CGRP-antagonist treatment in a cohort of patients who suffer from episodic or chronic migraine and have failed at least three oral prophylactic therapies. Methods: We offered CGRP antagonists to 86 patients who met the NICE criteria to start therapy. We recorded the number of headache days per month (HDPM) at 0 weeks, 3 months, and 12 months. Of those, 26 patients were switched to an alternative treatment due to poor response or side effects. Of the 112 total cases, 9 cases did not sufficiently maintain their headache diary, and 5 cases were not followed up at 3 months. We have therefore included 98 sets of data in our analysis. Results: Fremanezumab achieved a reduction in HDPM by 51.7% at 3 months (p<0.0001), with 63.7% of patients meeting NICE criteria to continue therapy. Patients trialed on Galcanezumab attained a reduction in HDPM by 47.0% (p=0.0019), with 51.6% of patients meeting NICE criteria to continue therapy. Erenumab, however, only achieved a reduction in HDPM by 17.0% (p=0.29), and this was not statistically significant. Furthermore, 34.4%, 9.7%, and 4.9% of patients taking Fremanezumab, Galcanezumab, and Erenumab, respectively, continued therapy beyond 12 months. Of those who attempted drug holidays following 12 months of treatment, migraine symptoms relapsed in 100% of cases. Conclusion: We observed a significant improvement in HDPM amongst episodic and chronic migraine patients following treatment with Fremanezumab or Galcanezumab.

Keywords: migraine, CGRP, fremanezumab, galcanezumab, erenumab

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Authors: Hsiu-Tsu Cho

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Collective efficacy refers to a group’s sense of its capacity to complete a task successfully or to reach objectives. Little effort has been expended on investigating the relationship between the emotion expression of a leader and collective efficacy. In this study, we examined the impact of the different emotions and emotion expression of a group leader on collective efficacy and explored whether the emotion–expressive effects differed under conditions of negative and positive emotions. A total of 240 undergraduate and graduate students recruited using Facebook and posters at a university participated in this research. The participants were separated randomly into 80 groups of four persons consisting of three participants and a confederate. They were randomly assigned to one of five conditions in a 2 (pride vs. guilt) × 2 (emotion expression of group leader vs. no emotion expression of group leader) factorial design and a control condition. Each four-person group was instructed to get the reward in a group competition of solving the five-disk Tower of Hanoi puzzle and making decisions on an investment case. We surveyed the participants by employing the emotional measure revised from previous researchers and collective efficacy questionnaire on a 5-point scale. To induce an emotion of pride (or guilt), the experimenter announced whether the group performance was good enough to have a chance of getting the reward (ranking the top or bottom 20% among all groups) after group task. The leader (confederate) could either express or not express a feeling of pride (or guilt) following the instruction according to the assigned condition. To check manipulation of emotion, we added a control condition under which the experimenter revealed no results regarding group performance in maintaining a neutral emotion. One-way ANOVAs and post hoc pairwise comparisons among the three emotion conditions (pride, guilt, and control condition) involved assigning pride and guilt scores (pride: F(1,75) = 32.41, p < .001; guilt: F(1,75) = 6.75, p < .05). The results indicated that manipulations of emotion were successful. A two-way between-measures ANOVA was conducted to examine the predictions of the main effects of emotion types and emotion expression as well as the interaction effect of these two variables on collective efficacy. The experimental findings suggest that pride did not affect collective efficacy (F(1,60) = 1.90, ns.) more than guilt did and that the group leader did not motivate collective efficacy regardless of whether he or she expressed emotion (F(1,60) = .89, ns.). However, the interaction effect of emotion types and emotion expression was statistically significant (F(1,60) = 4.27, p < .05, ω2 = .066); the effects accounted for 6.6% of the variance. Additional results revealed that, under the pride condition, the leader enhanced group efficacy when expressing emotion, whereas, under the guilt condition, an expression of emotion could reduce collective efficacy. Overall, these findings challenge the assumption that the effect of expression emotion are the same on all emotions and suggest that a leader should be cautious when expressing negative emotions toward a group to avoid reducing group effectiveness.

Keywords: collective efficacy, group leader, emotion expression, pride, guilty

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Authors: Jungbin Lim, Bohee Kang, Heelim Lee, Sunjin Kim, GeumHee Choi, Jae-Suk Jung, Suk Ji

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Nonsurgical periodontal therapies have, for several decades, been the basis of periodontal treatment concepts. The aim of this paper is to investigate the effectiveness of non-surgical periodontal therapy according to the severity of periodontitis disease. Methods: Retrospective data of patients who visited Department of periodontics in Ajou University Medical Center from 2016 to 2022 were collected. Among the patients, those who took full mouth examination of clinical parameters and non-surgical periodontal therapy were chosen for this study. Selected patients were divided into initial, moderate, and severe periodontitis based on severity and complexity of management (2018 World Workshop EFP/AAP consensus). Recall visits with clinical periodontal examination were scheduled for 1,2,3 months or 1,3,6 months after the treatment. The results were evaluated by recordings of mean probing pocket depth (mean PD), mean clinical attachment levels (mean CAL), bleeding on probing (BOP%), mean gingival index (mean GI), mean regression, mean sulcus bleeding index (mean SBI), mean plaque scores (mean PI). All statistical analyses were performed with R software, version 4.3.0. A level of significance, P<0.05, was considered to be statistically significant. Results: A total of 92 patients were included in this study. 15 patients were diagnosed as initial periodontitis, 14 moderate periodontitis, and 63 severe periodontitis. The all parameters except for mean recession decreased over time in all groups. The amount of mean PD decreased were the greatest in severe periodontitis group followed by moderate and initial, which was found to be statistically significant. The changes of mean PD were 0.15±0.05 mm, 0.37±0.06 mm, and 1.01±0.07 mm (initial, moderate, and severe, respectively, P<0.001). When comparing before and after treatment, the reductions in BOP(%), mean GI, mean SBI, and mean PI were statistically significant. Conclusion: All patients who received non-surgical periodontal therapy showed periodontal healing in terms of improvements in clinical parameters, and it was greater in the severe group.

Keywords: periodontology, clinical periodontology, oral treatment, comprehensive preventive dentistry, non-surgical periodontal therapy

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Authors: Sabrina Barsky, Ashley Monks

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In humans, exercise improves symptoms of various pathological states, although exercise adaptations seem to differ in response to sex. Skeletal muscle anabolism is thought to be regulated by androgen receptor (AR) through poorly specified mechanisms. Interactions of AR and exercise on muscle phenotype remain inconclusive in males, and undetermined in females. We hypothesized that sex differences in exercise adaptations are regulated by the androgenic system and the type of exercise performed. Here we examined interactions between a muscle-specific AR overexpression transgene (HSA-AR) and forced aerobic exercise paradigm on muscle and adipose exercise adaptation in male and female rats. We used dual-energy X-ray absorptiometry (DXA) to examine body composition adaptations post 9-week exercise protocol. We replicated the effects of HSA-AR on body composition, with males only having increased % lean mass and reduced % fat mass (P<0.05). Aerobic exercise improved lean body phenotype significantly, with lesser indices of total and % fat mass (P<0.01) in both sexes. Sex-specific effects of exercise included decreased total body mass (P<0.01) in males and increased lean mass % (P<0.001) in females. Surprisingly, neither AR manipulation nor exercise affected bone parameters in either sex. This varied response in total mass and lean mass according to exercise presents a sexually dimorphic response to exercise. Neither sex showed an interaction between HSA-AR and forced aerobic exercise on body composition. Future work is proposed to examine the effects of exercise type (aerobic versus resistance) and the role of gonadal androgens in sexually dimorphic exercise-mediated mitochondrial adaptations. This work implicates the development of sex-specific exercise therapies.

Keywords: androgen receptor, forced exercise, muscle physiology, sexual dimorphism

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Authors: Sasan Khademnematolahi, Kevine Kamga Silihe, Katarína Pružinská, Martina Chrastina, Elisabeth Louise Ndjengue Mindang, František Dráfi, Katarína Bauerová

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Background: In ethnomedicine, plant parts and compounds are traditionally utilized to treat many disorders. Azadirachta indica, known as Neem, has been traditionally used in medicinal practices. Due to the presence of bioactive substances such as nimbolide, azadirachtin, and gedunin, Neem offers a variety of medicinal properties, including anti-inflammatory and antioxidant properties. Through its effect on pathological inflammatory processes, supplementation with it could alleviate the symptoms of rheumatoid arthritis (RA). Methods: This research aimed to assess Neem seed oil's impact on rats with adjuvant arthritis. Three doses in monotherapy and two in combination with methotrexate (MTX) have been studied, and their effect was compared. Neem p.o. doses of 100, 200, and 300 mg/kg and MTX p.o. doses of 0.3 mg/kg were examined. After clinical parameters assessment, biochemical analysis was performed in plasma. Results: During the acute phase of the experimental arthritis (Day21), levels of MMP-9, MCP-1, and cytokines IL-1beta and IL-17A were measured. The positive results of inflammatory mediators evaluation in plasma encourage additional analysis also in related tissues to prove if Neem seed oil can be used as an adjuvant therapy for RA. Conclusion: In this study, the combination therapy of Neem with MTX was the most effective of all therapies investigated. Acknowledgement: SAIA PROJECT of Kevine Kamga Silihe, Slovakia-Cameroon 2023: “The effect of Crocus sativus L (Saffron), Azadirachta indica (Neem) and their main bioactives compounds in combinatory treatment with methotrexate on experimental arthritis”, VEGA 2/0079/24, VEGA 2/0136/20, VEGA 2/0126/23 and VEGA 2/0091/23.

Keywords: adjuvant, Neem, methotrexate, arthritis

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Authors: Priya Saha, Sourav Dey Roy Jr., Debotosh Bhattacharjee, Mita Nasipuri, Barin Kumar De, Mrinal Kanti Bhowmik

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Biometric face recognition technology (FRT) has gained a lot of attention due to its extensive variety of applications in both security and non-security perspectives. It has come into view to provide a secure solution in identification and verification of person identity. Although other biometric based methods like fingerprint scans, iris scans are available, FRT is verified as an efficient technology for its user-friendliness and contact freeness. Accurate facial feature localization plays an important role for many facial analysis applications including biometrics and emotion recognition. But, there are certain factors, which make facial feature localization a challenging task. On human face, expressions can be seen from the subtle movements of facial muscles and influenced by internal emotional states. These non-rigid facial movements cause noticeable alterations in locations of facial landmarks, their usual shapes, which sometimes create occlusions in facial feature areas making face recognition as a difficult problem. The paper proposes a new hybrid based technique for automatic landmark detection in both neutral and expressive frontal and near frontal face images. The method uses the concept of thresholding, sequential searching and other image processing techniques for locating the landmark points on the face. Also, a Graphical User Interface (GUI) based software is designed that could automatically detect 16 landmark points around eyes, nose and mouth that are mostly affected by the changes in facial muscles. The proposed system has been tested on widely used JAFFE and Cohn Kanade database. Also, the system is tested on DeitY-TU face database which is created in the Biometrics Laboratory of Tripura University under the research project funded by Department of Electronics & Information Technology, Govt. of India. The performance of the proposed method has been done in terms of error measure and accuracy. The method has detection rate of 98.82% on JAFFE database, 91.27% on Cohn Kanade database and 93.05% on DeitY-TU database. Also, we have done comparative study of our proposed method with other techniques developed by other researchers. This paper will put into focus emotion-oriented systems through AU detection in future based on the located features.

Keywords: biometrics, face recognition, facial landmarks, image processing

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Authors: Ragy Raafat Gaber Attaalla

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For cardiovascular illness, oral P2Y12 inhibitors including clopidogrel, prasugrel, and ticagrelor are frequently recommended. Each of these medications has advantages and disadvantages. In the absence of genotyping, it has been demonstrated that the stronger platelet aggregation inhibitors prasugrel and ticagrelor are superior than clopidogrel at preventing significant adverse cardiovascular events following an acute coronary syndrome and percutaneous coronary intervention (PCI). Both, nevertheless, come with a higher risk of bleeding unrelated to a coronary artery bypass. As a prodrug, clopidogrel needs to be bioactivated, principally by the CYP2C19 enzyme. A CYP2C19 no function allele and diminished or absent CYP2C19 enzyme activity are present in about 30% of people. The reduced exposure to the active metabolite of clopidogrel and reduced inhibition of platelet aggregation among clopidogrel-treated carriers of a CYP2C19 no function allele likely contributed to the reduced efficacy of clopidogrel in clinical trials. Clopidogrel's pharmacogenetic results are strongest when used in conjunction with PCI, but evidence for other indications is growing. One of the most typical examples of clinical pharmacogenetic application is CYP2C19 genotype-guided antiplatelet medication following PCI. Guidance is available from expert consensus groups and regulatory bodies to assist with incorporating genetic information into P2Y12 inhibitor prescribing decisions. Here, we examine the data supporting genotype-guided P2Y12 inhibitor selection's effects on clopidogrel response and outcomes and discuss tips for pharmacogenetic implementation. We also discuss procedures for using genotype data to choose P2Y12 inhibitor therapies as well as any unmet research needs. Finally, choosing a P2Y12 inhibitor medication that optimally balances the atherothrombotic and bleeding risks may be influenced by both clinical and genetic factors.

Keywords: inhibitors, cardiovascular events, coronary intervention, pharmacogenetic implementation

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Authors: Alexandra Kennedy

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Making use of the notion of ‘epodic spaces’ this paper presents a reconsideration of non-objective art practices, proposing alternatives to established materialist, formalist, process-based conceptualist approaches to such work. In his Neo-Concrete Manifesto (1959) Ferreira Gullar (1930-2016) sought to create a distinction between various forms of non-objective art. He distinguished the ‘geometric’ arts of neoplasticism, constructivism, and suprematism – which he described as ‘dangerously acute rationalism’ – from other non-objective practices. These alternatives, he proposed, have an expressive potential lacking in the former and this formed the basis for their categorisation as neo-concrete. Gullar prioritized the phenomenological over the rational, with an emphasis on the role of the spectator (a key concept of minimalism). Gullar highlighted the central role of sensual experience, colour and the poetic in such work. In the early twentieth century, Russian Cosmism – an esoteric philosophical movement – was highly influential on Russian avant-garde artists and can account for suprematist artists’ interest in, and approach to, planar geometry and four-dimensional space as demonstrated in the abstract paintings of Kasimir Malevich (1879-1935). Nikolai Fyodorov (1823-1903) promoted the idea of anti-gravity and cosmic space as the field for artistic activity. The artist and writer Kuzma Petrov-Vodkin (1878-1939) wrote on the concept of Euclidean space, the overcoming of such rational conceptions of space and the breaking free from the gravitational field and the earth’s sphere. These imaginary spaces, which also invoke a bodily experience, present a poetic dimension to the work of the suprematists. It is a dimension that arguably aligns more with Gullar’s formulation of his neo-concrete rather than that of his alignment of Suprematism with rationalism. While found in experiments with planar geometry, the interest in forms suggestive of an experience of breaking free–both physically from the earth and conceptually from rational, mathematical space (in a pre-occupation with non-Euclidean space and anti-geometry) and in their engagement with the spatial properties of colour, Suprematism presents itself as imaginatively epodic. The paper discusses both historical and contemporary non-objective practices in this context, drawing attention to the manner in which the category of the non-objective is used to categorise art works which are, arguably, qualitatively different.

Keywords: anti-gravity, neo-concrete, non-Euclidian geometry, non-objective painting

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Authors: Setareh Yousife

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Introduction: Studies suggest that Extramarital Infidelity (EMI) variants, such as sexual and emotional infidelities are increasing in marriage relationships. To our knowledge, less is known about what therapies and mental-hygiene factors can prevent more effective this behavior and address it. Spiritual and cognitive-behavioural health have proven to reduce marital conflict, Increase marital satisfaction and commitment. Objective: This study aims to discuss the effectiveness of spiritual counseling combined with Cognitive-behavioural techniques in addressing Extramarital Infidelity. Method: Descriptive, analytical, and intervention articles indexed in SID, Noormags, Scopus, Iranmedex, Web of Science and PubMed databases, and Google Scholar were searched. We focused on Studies in which Women with extramarital relationships, including heterosexual married couples-only studies and spirituality/religion and CBT as coping techniques used as EMI therapy. Finally, the full text of all eligible articles was prepared and discussed in this review. Results: 25 publications were identified, and their textual analysis facilitated through four thematic approaches: The nature of EMI in Women, the meaning of spirituality in the context of mental health and human behavior as well as psychotherapy; Spirituality integrated into Cognitive-Behavioral approach, The role of Spirituality as a deterrent to EMI. Conclusions: The integration of the findings discussed herein suggests that the application of cognitive and behavioral skills in addressing these kinds of destructive family-based relationships is inevitable. As treatments based on religion/spirituality or cognition/behavior do not seem adequately effective in dealing with EMI, the combination of these approaches may lead to higher efficacy in fewer sessions and a shorter time.

Keywords: spirituality, religion, cognitive behavioral therapy, extramarital relation, infidelity

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Authors: Svetlana Guryeva, Inna Kornienko, Elena Petersen

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At present, translational medicine is a rapidly developing branch of biomedicine. The main idea of translational medicine is a practical application of fundamental research. One of the possible applications for translational medicine is researching therapies that improve human age-related organism condition. To fill the gap between experiments and clinical practice, it is necessary to create the standardized system for the investigation of different effects on cellular aging models. In this study, primary human fibroblasts derived from patients of different ages were used as a cellular aging model. The senescence-associated β-galactosidase activity, lipofuscin, γ-H2AX, the reactive oxygen species level, and cell death markers (annexin V/propidium iodide) were used as biomarkers of the cell functional state. The effects of damaging exposures (oxidative stress and heat shock), potential positive factors (metformin and acetaminophen), and their combinations were investigated using the described biomarkers. Oxidative stress and heat shock caused the increase in the levels of all biomarkers, and only the cells from young patients partly coped with stress 3 days after the exposures. Metformin improved the state of pretreatment cells from young and old patients. The acetaminophen did not show significant changes in the biomarker levels compare to the action of metformin. This study proved the opportunity to develop a standardized screening system based on biomarkers of the cell functional state to identify potential positive or negative effects of some physical and chemical exposures. Moreover, such a system can be useful for the aims of regenerative medicine to determine the effect of cell pretreatment before transplantation.

Keywords: biomarkers, primary fibroblasts, regenerative medicine, senescence, test system, translational medicine

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Authors: Domenica Tambasco, Riina Bray, Sophia Jaworski, Gillian Grant, Celeste Corkery

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Fibromyalgia is a chronic condition characterized by widespread musculoskeletal pain, fatigue, and reduced function. Management of symptoms include medications, physical treatments and mindfulness therapies. Myofascial Release is a modality that has been successfully applied in var-ious musculoskeletal conditions. However, to the author’s best knowledge, it is not yet recog-nized as a self-management therapy option in Fibromyalgia. In this study, we investigated whether Self-applied Myofascial Release (SMR) is associated with overall improved function and symptoms in Fibromyalgia. Methods: Eligible adult patients with a confirmed diagnosis of Fibromyalgia at Women’s College Hospital were recruited to SMR. Sessions ran for 1 hour once a week for 7 weeks, led by the same two Physiotherapists knowledgeable in this physical treat-ment modality. The main outcome measure was an overall impact score for function and symp-toms based on the validated assessment tool for Fibromyalgia, the Revised Fibromyalgia Impact Questionnaire (FIQR), measured pre and post-intervention. Both descriptive and analytical methods were applied and reported. Results: We analyzed results using a paired t-test to deter-mine if there was a statistically significant difference in mean FIQR scores between initial (pre-intervention) and final (post-intervention) scores. A clinically significant difference in FIQR was defined as a reduction in score by 10 or more points. Conclusions: Our pilot study showed that SMR appeared to be a safe and effective intervention for our Fibromyalgia participants and the overall impact on function and symptoms occurred in only 7 weeks. Further studies with larger sample sizes comparing SMR to other physical treatment modalities (such as stretching) in an RCT are recommended.

Keywords: fibromyalgia, myofascial release, physical therapy, FIQR

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Authors: Amna J. Ghith, Khaled Abu Zid, Khairia Youssef, Nasser Saad

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Backgrounds: The multikinase and vascular endothelial growth factor (VEGF) receptor inhibitors interrupt the pathway by which angiogenesis becomes established and promulgated, resulting in the inadequate nourishment of metastatic disease. VEGFR-2 has been the principal target of anti-angiogenic therapies. We disclose the new thieno pyrimidines as inhibitors of VEGFR-2 designed by a molecular modeling approach with increased synergistic activity and decreased side effects. Purpose: 2-substituted thieno pyrimidines are designed and synthesized with anticipated anticancer activity based on its in silico molecular docking study that supports the initial pharmacophoric hypothesis with a same binding mode of interaction at the ATP-binding site of VEGFR-2 (PDB 2QU5) with high docking score. Methods: A series of compounds were designed using discovery studio 4.1/CDOCKER with a rational that mimic the pharmacophoric features present in the reported active compounds that targeted VEGFR-2. An in silico ADMET study was also performed to validate the bioavailability of the newly designed compounds. Results: The Compounds to be synthesized showed interaction energy comparable to or within the range of the benzimidazole inhibitor ligand when docked with VEGFR-2. ADMET study showed comparable results most of the compounds showed absorption within (95-99) zone varying according to different substitutions attached to thieno pyrimidine ring system. Conclusions: A series of 2-subsituted thienopyrimidines are to be synthesized with anticipated anticancer activity and according to docking study structure requirement for the design of VEGFR-2 inhibitors which can act as powerful anticancer agents.

Keywords: docking, discovery studio 4.1/CDOCKER, heterocycles based anticancer agents, 2-subsituted thienopyrimidines

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Authors: A. D. Zikiryahodjaev, L. V. Bolotina, A. S. Sukhotko

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Purpose. To evaluate the expediency and timeliness of performance of surgical treatment as a component of multi-therapy treatment of patients with stage IV breast cancers. Materials and Methods. This investigation comparatively analyzed the results of complex treatment with or without surgery in patients with metastatic breast cancer. We analyzed retrospectively treatment experience of 196 patients with generalized breast cancer in the department of oncology and breast reconstructive surgery of P.A. Herzen Moscow Cancer Research Institute from 2000 to 2012. The average age was (58±1,1) years. Invasive ductul carcinoma was verified in128 patients (65,3%), invasive lobular carcinoma-33 (16,8%), complex form - 19 (9,7%). Complex palliative care involving drug and radiation therapies was performed in two patient groups. The first group includes 124 patients who underwent surgical intervention as complex treatment, the second group includes 72 patients with only medical therapy. Standard systemic therapy was given to all patients. Results. Overall, 3-and 5-year survival in fist group was 43,8 and 21%, in second - 15,1 and 9,3% respectively [p=0,00002 log-rank]. Median survival in patients with surgical treatment composed 32 months, in patients with only systemic therapy-21. The factors having influencing an influence on the prognosis and the quality of life outcomes for of patients with generalized breast cancer were are also studied: hormone-dependent tumor, Her2/neu hyper-expression, reproductive function status (age, menopause existence). Conclusion.Removing primary breast tumor in patients with generalized breast cancer improve long-term outcomes. Three- and five-year survival increased by 28,7 and 16,3% respectively, and median survival–for 11 months. These patients may benefit from resection of the breast tumor. One explanation for the effect of this resection is that reducing the tumor load influences metastatic growth.

Keywords: breast cancer, combination therapy, factors of prognosis, primary tumor

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Authors: Tahira Hyder, Saima Quraeshi, Zohaib Akram

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Salvadora Persica (SP) is known to have anti-inflammatory, antioxidant, anti-coagulant and anti-bacterial properties that may provide therapeutic benefits in the treatment of chronic periodontitis (CP). The current clinical trial was designed to investigate the clinical and anti-microbial effects of SP gel as an adjunct to scaling and root planning (SRP) in subjects with generalized CP. Sixty-six subjects with CP were randomized allocated into two groups: SRP + SP gel (test group) and SRP only (control group). Clinical parameters (periodontal pocket depth, gingival recession, clinical attachment level, bleeding score and plaque score) were recorded at baseline before SRP and at 6 weeks. At baseline and 6 weeks subgingival plaque samples were collected and periodontopathogen Porphyromonas Gingivalis (Pg) quantified using Real-time Polymerase Chain Reaction (RT-PCR). Both therapies reduced the mean periodontal pocket depth (PPD), plaque score (PS) and bleeding score (BOP) and improved the mean clinical attachment level (CAL) between baseline and 6 weeks. In subjects receiving adjunctive SP gel a statistically significant improvement was observed in BOP at follow-up compared to control group (15.01±3.47% and 22.81±6.81% respectively, p=0.001), while there was no statistically significant difference in periodontal pocket depth, gingival recession, clinical attachment level and plaque score between both groups. The test group displayed significantly greater Pg reduction compared to the control group after 6 weeks. The current study establishes that local delivery of SP gel into periodontal pocket in CP stimulated a significant reduction in bacteria Pg level and an improvement in gingival health, as evident from a reduced bleeding score, when used as an adjunct to SRP.

Keywords: miswak, scaling and root planing, porphyromonas gingivalis, chronic periodontitis

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Authors: Dawid Sołoducha, Tomasz Borowski, Agata Markowska-Szczupak, Aneta Wesołowska, Marian Kordas, Rafał Rakoczy

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Many studies report varied effects of the magnetic field in medicine, but applications are still missing. Also, essential oils (EOs) were historically used in healing therapies, food preservation and the cosmetic industry due to their wound healing and antioxidant properties and antimicrobial activity. Unfortunately, the chemical characterization of EOs activates its antibacterial action only at a fairly high concentration. They can cause skin reactions, e.g., irritation (irritant contact dermatitis) or allergic contact dermatitis; therefore, they should always be used with caution. However, the administration of EOs to achieve the desired antimicrobial activity and stability with long-term medical usage in low concentration is challenging. The aim of this work was to investigate the antimicrobial activity of commercial Pinus sylvestris L. essential oil from Polish company Avicenna-Oil® under Rotating Magnetic Field (RMF) at f = 1 – 50 Hz. The novel construction of the magnetically assisted self-constructed reactor (MAP) was applied for this study. The chemical composition of essential pine oil was determined by gas chromatography coupled with mass spectrometry (GC-MS). Model bacteria Escherichia coli K12 (ATCC 25922) was used. Different concentrations of pine oil was prepared: 100% 50%, 25%, 12.5% and 6.25%. The disc diffusion and MIC test were done. To examine the effect of essential pine oil and rotating magnetic field RMF on antibacterial performance agar plate method was used. Pine oil consist of α-pinene (28.58%), β-pinene (17.79%), δ-3-carene (14.17%) and limonene (11.58%). The present study indicates the exposition to the RMF, as compared to the unexposed controls causing an increase in the efficacy of antibacterial properties of pine oil. We have shown that the rotating magnetic fields (RMF) at a frequency, f, between 25 Hz to 50 Hz, increase the antimicrobial efficiency of oil at lower than 50% concentration. The new method can be applied in many fields e.g. aromatherapy, medicine as a component of dressing, or as food preservatives.

Keywords: rotating magnetic field, pine oil, antimicrobial activity, Escherichia coli

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Authors: Leticia Lengler, Jefferson Oliveira, Vania Estivalete, Jordana Marques Kneipp, Lucia Regina Da Rosa Gama Madruga

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The way social entrepreneurs act and can positively impact on our society engages the interest of academics, companies and governments, who seek solutions to solve or alleviate issues related to the abuse of natural resources, as well as the increase of poverty (social aspects). Studies on social entrepreneurship have been characterized by diverse ramifications and their transdisciplinary character, permeating various disciplines and approaches. Different bibliometric studies were conducted within the theme of social entrepreneurship. In this context, because it is a topic in development and multifaceted, the aim of this article is to present the main interfaces of the studies on the Social Entrepreneur figure in relation to the social concern of sustainability, highlighting the relevant researches and their trends, as well as their relationship with the organizations. Aiming to achieve this purpose, the specific goals are: to identify the most cited authors and articles, to verify the authors and journals with the greatest number of publications and their approaches and to point out their affiliations, countries, and languages of publications. It is still a secondary objective to identify the emerging trends in relation to the social entrepreneur and his social concern stemming from the discussions on sustainability. This way, we analyzed articles from two international databases (Scopus and Web of Science), from 2004 to 2016. The main results were the increase in the number of publications, with most of them in English language, coming mainly from the United States institutions (such as Indiana University and Harvard University) and the United Kingdom (whose main institutions are University of London and Robert Gordon University). Although publications in Spanish and Portuguese are the least expressive in quantity, some tendencies point to publications that discuss the social entrepreneur in terms of gender (that relates to female entrepreneurship) and social class (that relates to the need of building communities that contemplate the Social entrepreneur at the base of the pyramid). It should be noted that the trends of the themes emerged from the analysis of the publication titles only in Portuguese, since this is the native language of the authors who carry out their studies mainly in Brazil. When considering articles in Portuguese (57 indicated by WOS and 9 by Scopus), a previous analysis of the titles was carried out to identify how researchers were approaching the theme social entrepreneur in a joint way to the social dimension of sustainability. However, the analysis of the titles themselves brought a limitation to our study, since it was felt a need to carry out a qualitative study, in which it could be possible to consider the abstracts of the available articles.

Keywords: base of pyramid, social dimension, social entrepreneur, sustainability

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Authors: Chaoran Liu

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Bioactive polysaccharides and polysaccharide-protein complex derived from mushrooms and fungi have a wide range of immunomodulatory activity with low side-effects and have therefore the potential to be developed as an adjuvant in cancer therapies. Mushrooms sclerotium is rich in polysaccharides and the polysaccharides isolated from the sclerotium of Polyporus rhinocerus have shown potent in vivo and in vitro immunomodulatory effects. Macrophages are considered to be an important component of the innate immune response against bacterial infection and cancer. To better understanding the immunomodulatory effects and its underlying mechanisms of sclerotial water-soluble polysaccharides extracted from P. rhinocerus on macrophages, the objectives of this study are to purify the water-soluble novel sclerotial polysaccharides and to characterize the structure and properties as well as to study the detailed molecular mechanisms of the in vitro immunomodulating effects in murine macrophages. The hot water-soluble fraction PRW from the sclerotium of P. rhinocerus was obtained using solvent extraction. PRW was further fractionated by membrane ultrafiltration to a give a fraction (PRW1) with molecular mass less than 50 kDa. PRW1 was characterized to be a polysaccharide-protein complex composed of 45.7% polysaccharide and 44.2% protein. The chemical structure of the carbohydrate moiety of PRW1 was elucidated by GC and FTIR to be mainly beta-D-glucan with trace amount of galactose and mannose. The immunomodulatory effects of PRW1 on murine RAW 264.7 macrophages were demonstrated in terms of the increase in nitric oxide production and cytokine production. Mechanistically, PRW1 initiates ERK phosphorylation to activate macrophages within 15 min and significantly improves the expression level of inducible NOS (iNOS) from 6 h after treatment. In summary, this study indicates that PRW1 is a potent immunomodulatory agent for macrophages and suggests that mushroom sclerotia from Polyporus rhinocerus requires for further investigation in cancer research.

Keywords: Polyporus rhinocerus, mushroom sclerotia, Polysaccharide-Protein Complex, macrophage activation

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Authors: Nathalie Bolding, Marta Montero, Joaquim Cevallos, Juan F. Martin-Lazaro

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Background: Inhaled epoprostenol (iEPO) have been shown to improve PaO2:FiO2 (PF) in combination with bronchodilators (BD). However, there is not an available device to deliver these two therapies concomitantly. We describe a new method to provide this therapy successfully. Objective: To evaluate the response to continuous nebulization of iEPO and intermittent nebulization of Salbutamol/Ipratropium bromide in adults with severe respiratory failure through a double mesh nebulisation in tandem. Methods: This observational study included two mechanical ventilated adults under hourly ventilatory, gasometrical and clinical measurements during 48h. Both had severe respiratory failure treated with continuous iEPO (50 – 200 micrograms/h) and BD (Salbutamol 2.5 mg and Ipratropium bromide 500 mcg every 6 hours) through double mesh nebulisation (Aerogen solo®) placed in tandem in the dry side of the humidificator. The primary endpoints were the variables associated with a positive response to this tandem nebulised therapy (PaFiO2 index, ROX index). Secondary endpoints were laboratory (ABG) clinical and ventilatory variables. Statistical analysis (SPSS v29) included linear regression and ANOVA. Results: The patients included (n=2) survived, both extubated, one after ECMO therapy. Severe acute respiratory failure had a positive response rate to continuous iEPO and intermittent BD: PaFiO2 increased (7.40 to 30.91; P75: 27%) as well as ROX index (2.91 to 11.43; P75: 33%). There was a linear correlation of improvement between iEPO with PaFiO2 (ANOVA, r=0.393, p<0.002) and ROX (r=0.419, p<0.001). iEPO+BD therapy did not show any complications. Conclusion: Continuous and intermittent mesh tandem nebulisation can be effectively delivered with this method with a positive effect in ventilatory parameters without observed complications. Randomised studies will be able to provide reassurance in this new therapy.

Keywords: tandem, mesh, nebulisers, pulmonary, vasoldilators, bronchodilators, respiratory, failure

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Authors: Babak Bahri, Fatemeh Yassaee Meybodi, Changiz Eslahchi

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In the pursuit of effective cancer therapies, the exploration of combinatorial drug regimens is crucial to leverage synergistic interactions between drugs, thereby improving treatment efficacy and overcoming drug resistance. However, identifying synergistic drug pairs poses challenges due to the vast combinatorial space and limitations of experimental approaches. This study introduces ClusterSyn, a machine learning (ML)-powered framework for classifying anti-cancer drug synergy scores. ClusterSyn employs a two-step approach involving drug clustering and synergy score prediction using a fully connected deep neural network. For each cell line in the training dataset, a drug graph is constructed, with nodes representing drugs and edge weights denoting synergy scores between drug pairs. Drugs are clustered using the Markov clustering (MCL) algorithm, and vectors representing the similarity of drug pairs to each cluster are input into the deep neural network for synergy score prediction (synergy or antagonism). Clustering results demonstrate effective grouping of drugs based on synergy scores, aligning similar synergy profiles. Subsequently, neural network predictions and synergy scores of the two drugs on others within their clusters are used to predict the synergy score of the considered drug pair. This approach facilitates comparative analysis with clustering and regression-based methods, revealing the superior performance of ClusterSyn over state-of-the-art methods like DeepSynergy and DeepDDS on diverse datasets such as Oniel and Almanac. The results highlight the remarkable potential of ClusterSyn as a versatile tool for predicting anti-cancer drug synergy scores.

Keywords: drug synergy, clustering, prediction, machine learning., deep learning

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