Search results for: orthotopic brain tumor

Authors: Sara Assi, Berthe Hayar, Claudio Pisano, Nadine Darwiche, Walid Saad

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Nanomedicine, the application of nanotechnology to medicine, is an emerging discipline that has gained significant attention in recent years. Current breakthroughs in nanomedicine have paved the way to develop effective drug delivery systems that can be used to target cancer. The use of nanotechnology provides effective drug delivery, enhanced stability, bioavailability, and permeability, thereby minimizing drug dosage and toxicity. As such, the use of nanoparticle (NP) formulations in drug delivery has been applied in various cancer models and have shown to improve the ability of drugs to reach specific targeted sites in a controlled manner. Cancer is one of the major causes of death worldwide; in particular, colorectal cancer (CRC) is the third most common type of cancer diagnosed amongst men and women and the second leading cause of cancer related deaths, highlighting the need for novel therapies. Retinoids, consisting of natural and synthetic derivatives, are a class of chemical compounds that have shown promise in preclinical and clinical cancer settings. However, retinoids are limited by their toxicity and resistance to treatment. To overcome this resistance, various synthetic retinoids have been developed, including the adamantyl retinoid ST1926, which is a potent anti-cancer agent. However, due to its limited bioavailability, the development of ST1926 has been restricted in phase I clinical trials. We have previously investigated the preclinical efficacy of ST1926 in CRC models. ST1926 displayed potent inhibitory and apoptotic effects in CRC cell lines by inducing early DNA damage and apoptosis. ST1926 significantly reduced the tumor doubling time and tumor burden in a xenograft CRC model. Therefore, we developed ST1926-NPs and assessed their efficacy in CRC models. ST1926-NPs were produced using Flash NanoPrecipitation with the amphiphilic diblock copolymer polystyrene-b-ethylene oxide and cholesterol as a co-stabilizer. ST1926 was formulated into NPs with a drug to polymer mass ratio of 1:2, providing a stable formulation for one week. The contin ST1926-NP diameter was 100 nm, with a polydispersity index of 0.245. Using the MTT cell viability assay, ST1926-NP exhibited potent anti-growth activities as naked ST1926 in HCT116 cells, at pharmacologically achievable concentrations. Future studies will be performed to study the anti-tumor activities and mechanism of action of ST1926-NPs in a xenograft mouse model and to detect the compound and its glucuroconjugated form in the plasma of mice. Ultimately, our studies will support the use of ST1926-NP formulations in enhancing the stability and bioavailability of ST1926 in CRC.

Keywords: nanoparticles, drug delivery, colorectal cancer, retinoids

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Authors: Sarpong Boateng, Rohit Balasundaram, Akua Afrah Amoah

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Introduction: Racial and Gender disparities have been found to be independently associated with Salivary Gland Cancers (SGCs) survival; however, to our best knowledge, there are no previous studies on the interplay of these social determinants on the prognosis of SGCs. The objective of this study was to examine the joint effect of race and gender on the survival of SGCs. Methods: We analyzed survival outcomes of 13,547 histologically confirmed cases of SGCs using the Surveillance Epidemiology and End Results (SEER) database (2004 to 2015). Multivariable Cox regression analysis and Kaplan-Meier curves were used to estimate hazard ratios (HR) after controlling for age, tumor characteristics, treatment type and year of diagnosis. Results: 73.5% of the participants were whites, 8.5% were blacks, 10.1% were Hispanics and 58.5% were males. Overall, males had poorer survival than females (HR = 1.16, p=0.003). In the adjusted multivariable model, there were no significant differences in survival by race. However, the interaction of gender and race was statistically significant (p=0.01) in Hispanic males. Thus, compared to White females (reference), Hispanic females had significantly better survival (HR=0.53), whiles Hispanic males had worse survival outcomes (HR=1.82) for SGCs. Conclusions: Our results show significant interactions between race and gender, with racial disparities varying across the different genders for SGCs survival. This study indicates that racial and gender differences are crucial factors to be considered in the prognostic counseling and management of patients with SGCs. Biologic factors, tumor genetic characteristics, chemotherapy, lifestyle, environmental exposures, and socioeconomic and dietary factors are potential yet proven reasons that could account for racial and gender differences in the survival of SGCs.

Keywords: salivary, cancer, survival, disparity, race, gender, SEER

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Authors: Mohammad Hadi Mahmoodi, Soroor Zekrati

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The aim of this study was to investigate the relationship between hemispheric dominance and intonation learning of Iranian EFL students. In order to gain this goal, 52 female students from three levels of beginner, elementary and intermediate in Paradise Institute, and 18 male university students at Bu-Ali Sina University constituted the sample. In order to assist students learn the correct way of applying intonation to their everyday speech, the study proposed an interactive approach and provided students with visual aid through which they were able to see the intonation pattern on computer screen using 'Speech Analyzer' software. This software was also used to record subjects’ voice and compare them with the original intonation pattern. Edinburg Handedness Questionnaire (EHD), which ranges from –100 for strong left-handedness to +100 for strong right-handedness was used to indicate the hemispheric dominance of each student. The result of an independent sample t-test indicated that girls learned intonation pattern better than boys, and that right brained students significantly outperformed the left brained ones. Using one-way ANOVA, a significant difference between three proficiency levels was also found. The posthoc Scheffer test showed that the exact difference was between intermediate and elementary, and intermediate and beginner levels, but no significant difference was observed between elementary and beginner levels. The findings of the study might provide researchers with some helpful implications and useful directions for future investigation into the domain of the relationship between mind and second language learning.

Keywords: intonation, hemispheric dominance, visual aid, language learning, second language learning

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Authors: Farhan Sohail, Gul Shahnaz Irshad Hussain, Shoaib Sarwar, Ibrahim Javed, Zajif Hussain, Akhtar Nadhman

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The present study was aimed to develop a hybrid nanocarrier (NC) system with enhanced membrane permeability, bioavailability and targeted delivery of Docetaxel (DTX) in breast cancer. Hybrid NC’s based on folic acid (FA) grafted thiolated chitosan (TCS) enveloped liposomes were prepared with DTX and evaluated in-vitro and in-vivo for their enhanced permeability and bioavailability. Physicochemical characterization of NC’s including particle size, morphology, zeta potential, FTIR, DSC, PXRD, encapsulation efficiency and drug release from NC’s was determined in vitro. Permeation enhancement and p-gp inhibition were performed through everted sac method on freshly excised rat intestine which indicated that permeation was enhanced 5 times as compared to pure DTX and the hybrid NC’s were strongly able to inhibit the p-gp activity as well. In-vitro cytotoxicity and tumor targeting was done using MDA-MB-231 cell line. The stability study of the formulations performed for 3 months showed the improved stability of FA-TCS enveloped liposomes in terms of its particles size, zeta potential and encapsulation efficiency as compared to TCS NP’s and liposomes. The pharmacokinetic study was performed in vivo using rabbits. The oral bioavailability and AUC0-96 was increased 10.07 folds with hybrid NC’s as compared to positive control. Half-life (t1/2) was increased 4 times (58.76 hrs) as compared to positive control (17.72 hrs). Conclusively, it is suggested that FA-TCS enveloped liposomes have strong potential to enhance permeability and bioavailability of hydrophobic drugs after oral administration and tumor targeting.

Keywords: docetaxel, coated liposome, permeation enhancement, oral bioavailability

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Authors: Mojtaba Barzegar, Alireza Shirazi, Saied Rabi Mahdavi

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Intraoperative radiation therapy (IORT) is an innovative treatment modality that the delivery of a large single dose of radiation to the tumor bed during the surgery. The radiotherapy success depends on the absorbed dose delivered to the tumor. The achievement better accuracy in patient treatment depends upon the measured dose by standard dosimeter such as ionization chamber, but because of the high density of electric charge/pulse produced by the accelerator in the ionization chamber volume, the standard correction factor for ion recombination Ksat calculated with the classic two-voltage method is overestimated so the use of dose/pulse independent dosimeters such as chemical Fricke and ethanol chlorobenzene (ECB) dosimeters have been suggested. Dose measurement is usually calculated and calibrated in the Zmax. Ksat calculated by comparison of ion chamber response and ECB dosimeter at each applicator degree, size, and dose. The relative output factors for IORT applicators have been calculated and compared with experimentally determined values and the results simulated by Monte Carlo software. The absorbed doses have been calculated and measured with statistical uncertainties less than 0.7% and 2.5% consecutively. The relative differences between calculated and measured OF’s were up to 2.5%, for major OF’s the agreement was better. In these conditions, together with the relative absorbed dose calculations, the OF’s could be considered as an indication that the IORT electron beams have been well simulated. These investigations demonstrate the utility of the full Monte Carlo simulation of accelerator head with ECB dosimeter allow us to obtain detailed information of clinical IORT beams.

Keywords: intra operative radiotherapy, ethanol chlorobenzene, ksat, output factor, monte carlo simulation

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Authors: Sarah Crawford, Gerry Lesley

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This research is a pre-clinical assessment of anti-cancer effects of novel non-steroidal diethyl stilbestrol-like estrogen analogs in estrogen-receptor positive/ progesterone-receptor positive human breast cancer microtumors of MCF 7 cell line. Tamoxifen analog formulation (Tam A1) was used as a single agent or in combination with therapeutic concentrations of 4-hydroxytamoxifen, currently used as a long-term treatment for the prevention of breast cancer recurrence in women with estrogen receptor positive/ progesterone receptor positive malignancies. At concentrations ranging from 30-50 microM, Tam A1 induced microtumor disaggregation and cell death. Incremental cytotoxic effects correlated with increasing concentrations of Tam A1. Live tumor microscopy showed that microtumos displayed diffuse borders and substrate-attached cells were rounded-up and poorly adherent. A complete cytotoxic effect was observed using 40-50 microM Tam A1 with time course kinetics similar to 4-hydroxytamoxifen. Combined treatment with TamA1 (30-50 microM) and 4-hydroxytamoxifen (10-15 microM) induced a highly cytotoxic, synergistic combined treatment response that was more rapid and complete than using 4-hydroxytamoxifen as a single agent therapeutic. Microtumors completely dispersed or formed necrotic foci indicating a highly cytotoxic combined treatment response. Moreover, breast cancer microtumors treated with both 4-hydroxytamoxifen and Tam A1 displayed lower levels of long-term post-treatment regrowth, a critical parameter of primary drug resistance, than observed for 4-hydroxytamoxifen when used as a single agent therapeutic. Tumor regrowth at 6 weeks post-treatment with either single agent 4-hydroxy tamoxifen, Tam A1 or a combined treatment was assessed for the development of drug resistance. Breast cancer cells treated with both 4-hydroxytamoxifen and Tam A1 displayed significantly lower levels of post-treatment regrowth, indicative of decreased drug resistance, than observed for either single treatment modality. The preclinical data suggest that combined treatment involving the use of tamoxifen analogs may be a novel clinical approach for long-term maintenance therapy in patients with estrogen-receptor positive/progesterone-receptor positive breast cancer receiving hormonal therapy to prevent disease recurrence. Detailed data on time-course, IC50 and tumor regrowth assays post- treatment as well as a proposed mechanism of action to account for observed synergistic drug effects will be presented.

Keywords: 4-hydroxytamoxifen, tamoxifen analog, drug-resistance, microtumors

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Authors: Mathula Thangarajh

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Duchenne muscular dystrophy (DMD) is a severe form of X-linked muscular dystrophy caused by mutations in the dystrophin gene resulting in progressive skeletal muscle weakness. Boys with DMD also have significant cognitive disabilities. The intelligence quotient of boys with DMD, compared to peers, is approximately one standard deviation below average. Detailed neuropsychological testing has demonstrated that boys with DMD have a global developmental impairment, with verbal memory and visuospatial skills most significantly affected. Furthermore, the total brain volume and gray matter volume are lower in children with DMD compared to age-matched controls. These results are suggestive of a significant structural and functional compromise to the developing brain as a result of absent dystrophin protein expression. There is also some genetic evidence to suggest that mutations in the 3’ end of the DMD gene are associated with more severe neurocognitive problems. Our working hypothesis is that (i) boys with DMD do not make gains in neurodevelopmental skills compared to typically developing children and (ii) women carriers of DMD mutations may have subclinical cognitive deficits. We also hypothesize that there may be an intergenerational vulnerability of cognition, with boys of DMD-carrier mothers being more affected cognitively than boys of non-DMD-carrier mothers. The objectives of this study are: 1. Assess the neurodevelopment in boys with DMD at 4-time points and perform baseline neuroradiological assessment, 2. Assess cognition in biological mothers of DMD participants at baseline, 3. Assess possible correlation between DMD mutation and cognitive measures. This study also explores functional brain abnormalities in people with DMD by exploring how regional and global connectivity of the brain underlies executive function deficits in DMD. Such research can contribute to a better holistic understanding of the cognition alterations due to DMD and could potentially allow clinicians to create better-tailored treatment plans for the DMD population. There are four study visits for each participant (baseline, 2-4 weeks, 1 year, 18 months). At each visit, the participant completes the NIH Toolbox Cognition Battery, a validated psychometric measure that is recommended by NIH Common Data Elements for use in DMD. Visits 1, 3, and 4 also involve the administration of the BRIEF-2, ABAS-3, PROMIS/NeuroQoL, PedsQL Neuromuscular module 3.0, Draw a Clock Test, and an optional fMRI scan with the N-back matching task. We expect to enroll 52 children with DMD, 52 mothers of children with DMD, and 30 healthy control boys. This study began in 2020 during the height of the COVID-19 pandemic. Due to this, there were subsequent delays in recruitment because of travel restrictions. However, we have persevered and continued to recruit new participants for the study. We partnered with the Muscular Dystrophy Association (MDA) and helped advertise the study to interested families. Since then, we have had families from across the country contact us about their interest in the study. We plan to continue to enroll a diverse population of DMD participants to contribute toward a better understanding of Duchenne Muscular Dystrophy.

Keywords: neurology, Duchenne muscular dystrophy, muscular dystrophy, cognition, neurodevelopment, x-linked disorder, DMD, DMD gene

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Authors: Yuko Ishiwaka, Tomohiro Yoshida, Tadateru Itoh

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Human makes preparation called readiness potential unconsciously (RP) before awareness of their own decision. For example, when recognizing a button and pressing the button, the RP peaks are observed 200 ms before the initiation of the movement. It has been known that the preparatory movements are acquired before actual movements, but it has not been still well understood how humans can obtain the RP during their growth. On the proposition of why the brain must respond earlier, we assume that humans have to adopt the dangerous environment to survive and then obtain the behavior to cover the various time lags distributed in the body. Without RP, humans cannot take action quickly to avoid dangerous situations. In taking action, the brain makes decisions, and signals are transmitted through the Spinal Cord to the muscles to the body moves according to the laws of physics. Our research focuses on the time lag of the neuron signal transmitting from a brain to muscle via a spinal cord. This time lag is one of the essential factors for readiness potential. We propose a firing pattern controller model of a motor nerve system considered innervation and jitter, which produces time lag. In our simulation, we adopt innervation and jitter in our proposed muscle-skeleton model, because these two factors can create infinitesimal time lag. Q10 Hodgkin Huxley model to calculate action potentials is also adopted because the refractory period produces a more significant time lag for continuous firing. Keeping constant power of muscle requires cooperation firing of motor neurons because a refractory period stifles the continuous firing of a neuron. One more factor in producing time lag is slow or fast-twitch. The Expanded Hill Type model is adopted to calculate power and time lag. We will simulate our model of muscle skeleton model by controlling the firing pattern and discuss the relationship between the time lag of physics and neurons. For our discussion, we analyze the time lag with our simulation for knee bending. The law of inertia caused the most influential time lag. The next most crucial time lag was the time to generate the action potential induced by innervation and jitter. In our simulation, the time lag at the beginning of the knee movement is 202ms to 203.5ms. It means that readiness potential should be prepared more than 200ms before decision making.

Keywords: firing patterns, innervation, jitter, motor nerve system, readiness potential

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Authors: Nitin Dwivedi, Jigna Shah

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Aim and objective of study: This article indicates a comparison among various generations of dendrimers, a dendrimer is a bioactive material has repetitively branched molecule and used for delivery of various therapeutic active agents. This debut report compares the effect various generations of PPI dendrimers for brain targeting and management of neurodegenerative disorders potential on single platform. This report involves the study of the various mechanism of synthesis ligand anchored various generations PPI dendrimers deliver the drug directly to the CNS, prove their effectiveness in the management of the various neurodegenerative disease. Material and Methods: The Memantine an anti-Alzheimer drug loaded in different generations (3.0G, 4.0G, and 5.0G) of PPI dendrimers which were synthesized were synthesized. The various studies investigate the effect of PPI dendrimers generation on different characteristic parameters i.e. synthesis procedure, drug loading, release behavior, hemolysis profile at different concentration, MRI study for determine the route drug from olfactory transfer, animal model study in vitro, as well as in vivo performance. The outcomes of the investigation indicate drug delivery benefit as well as superior biocompatibility of 4.0G PPI dendrimer over 3.0G and 5.0G dendrimer, respectively. Results and Conclusion: The above study indicate the superiority of in drug delivery system with maximum drug utilization and minimize the drug dose for neurodegenerative disorder over 5.0G PPI dendrimers. So, 4.0G PPI dendrimers are the safe formulations for the symptomatic treatment of the neurodegenerative disorder. The fifth-generation poly(propyleneimine) (PPI) dendrimers, inherent toxicity due to the presence of many peripheral cationic groups is the major issue that limits their applicability.

Keywords: Alzheimer disease, generation, memantine, PPI

Procedia PDF Downloads 649

Authors: Vitor M. Vilas Boas, Cleison D. Silva, Gustavo S. Mafra, Alexandre Trofino Neto

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Motor imagery (MI) based brain-computer interfaces (BCI) uses event-related (de)synchronization (ERS/ ERD), typically recorded using electroencephalography (EEG), to translate brain electrical activity into control commands. To mitigate undesirable artifacts and noise measurements on EEG signals, methods based on band-pass filters defined by a specific frequency band (i.e., 8 – 30Hz), such as the Infinity Impulse Response (IIR) filters, are typically used. Spatial techniques, such as Common Spatial Patterns (CSP), are also used to estimate the variations of the filtered signal and extract features that define the imagined motion. The CSP effectiveness depends on the subject's discriminative frequency, and approaches based on the decomposition of the band of interest into sub-bands with smaller frequency ranges (SBCSP) have been suggested to EEG signals classification. However, despite providing good results, the SBCSP approach generally increases the computational cost of the filtering step in IM-based BCI systems. This paper proposes the use of the Fast Fourier Transform (FFT) algorithm in the IM-based BCI filtering stage that implements SBCSP. The goal is to apply the FFT algorithm to reduce the computational cost of the processing step of these systems and to make them more efficient without compromising classification accuracy. The proposal is based on the representation of EEG signals in a matrix of coefficients resulting from the frequency decomposition performed by the FFT, which is then submitted to the SBCSP process. The structure of the SBCSP contemplates dividing the band of interest, initially defined between 0 and 40Hz, into a set of 33 sub-bands spanning specific frequency bands which are processed in parallel each by a CSP filter and an LDA classifier. A Bayesian meta-classifier is then used to represent the LDA outputs of each sub-band as scores and organize them into a single vector, and then used as a training vector of an SVM global classifier. Initially, the public EEG data set IIa of the BCI Competition IV is used to validate the approach. The first contribution of the proposed method is that, in addition to being more compact, because it has a 68% smaller dimension than the original signal, the resulting FFT matrix maintains the signal information relevant to class discrimination. In addition, the results showed an average reduction of 31.6% in the computational cost in relation to the application of filtering methods based on IIR filters, suggesting FFT efficiency when applied in the filtering step. Finally, the frequency decomposition approach improves the overall system classification rate significantly compared to the commonly used filtering, going from 73.7% using IIR to 84.2% using FFT. The accuracy improvement above 10% and the computational cost reduction denote the potential of FFT in EEG signal filtering applied to the context of IM-based BCI implementing SBCSP. Tests with other data sets are currently being performed to reinforce such conclusions.

Keywords: brain-computer interfaces, fast Fourier transform algorithm, motor imagery, sub-band common spatial patterns

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Authors: Anjali N. Shete, G. D. Mahajan, Nanda Somwanshi

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Context: Smartphones are the new generation of mobile phones; they have emerged over the last few years. Technology has developed so much that it has become part of our life and mobile phones are one of them. These smartphones are equipped with the capabilities to display photos, play games, watch videos and navigation, etc. The advances have a huge impact on many walks of life. The adoption of new technology has been challenging for the elderly. But, the elder population is also moving towards digitally connected lives. As age advances, there is a decline in the motor and cognitive functions of the brain, and hence the reaction time is affected. The study was undertaken to assess the usefulness of smartphones in improving cognitive functions. Aims and Objectives: The aim of the study was to observe the effects of smartphone addiction on reaction time in elderly population Material and Methods: This is an experimental study. 100 elderly subjects were enrolled in this study randomly from urban areas. They all were using smartphones for several hours a day. They were divided into two groups according to the scores of the mobile phone addiction scale (MPAS). Simple reaction time was estimated by the Ruler drop method. The reaction time was then calculated for each subject in both groups. The data were analyzed using mean, standard deviation, and Pearson correlation test. Results: The mean reaction time in Group A is 0.27+ 0.040 and in Group B is 0.20 + 0.032. The values show a statistically significant change in reaction time. Conclusion: Group A with a high MPAS score has a low reaction time compared to Group B with a low MPAS score. Hence, it can be concluded that the use of smartphones in the elderly is useful, delaying the neurological decline, and smarten the brain.

Keywords: smartphones, MPAS, reaction time, elderly population

Procedia PDF Downloads 160

Authors: Franklin Chu Buh, Irene Ule Ngole Sumbele, Andrew I. R. Maas, Mathieu Motah, Jogi V. Pattisapu, Eric Youm, Basil Kum Meh, Firas H. Kobeissy, Kevin W. Wang, Peter J. A. Hutchinson, Germain Sotoing Taiwe

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Introduction: Studying TBI characteristics and their relation to outcomes can identify initiatives to improve TBI prevention and care. The objective of this study was to define the features and outcomes of TBI patients seen over a 1-year period in a level-I trauma center in Cameroon. Methods: Data on demographics, causes, injury mechanisms, clinical aspects, and discharge status were prospectively collected over a period of 12 months. The Glasgow Outcome Scale-Extended (GOSE) and the Quality of Life Questionnaire after Brain Injury (QoLIBRI) were used to evaluate outcomes 6-months after TBI. Categorical variables were described as frequencies and percentages. Comparisons between 2 categorical variables were done using Pearson's Chi-square test or Fisher's exact test. Results: A total of 160 TBI patients participated in the study. The age group 15-45 years (78%; 125) was most represented. Males were more affected (90%; 144). Low educational level was recorded in 122 (76%) cases. Road traffic incidents (RTI) were the main cause of TBI (85%), with professional bike riders being frequently involved (27%, 43/160). Assaults (7.5%) and falls (2.5%) represent the second and third most common causes of TBI in Cameroon, respectively. Only 15 patients were transported to the hospital by ambulance, and 14 of these were from a referring hospital. CT-imaging was performed in 78% (125/160) of cases intracranial traumatic abnormality was identified in 77/125 (64%) cases. Financial constraints were the main reason for not performing a CT scan on 35 patients. A total of 46 (33%) patients were discharged against medical advice (DAMA) due to financial constraints. Mortality was 14% (22/160) but disproportionately high in patients with severe TBI (46%). DAMA had poor outcomes with QoLIBRI. Only 4 patients received post-injury physiotherapy services. Conclusion: TBI in Cameroon mainly results from RTIs and commonly affects young adult males, and low educational or socioeconomic status and commercial bike riding appear to be predisposing factors. Lack of pre-hospital care, financial constraints limiting both CT-scanning and medical care, and lack of acute physiotherapy services likely influenced care and outcomes adversely.

Keywords: characteristics, traumatic brain injury, outcome, disparities in care, prospective study

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Authors: Abdoulie K. Ceesay

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Within the sequence of the whole genome, it is known that 99.9% of the human genome is similar, whilst our difference lies in just 0.1%. Among these minor dissimilarities, the most common type of genetic variations that occurs in a population is SNP, which arises due to nucleotide substitution in a protein sequence that leads to protein destabilization, alteration in dynamics, and other physio-chemical properties’ distortions. While causing variations, they are equally responsible for our difference in the way we respond to a treatment or a disease, including various cancer types. There are two types of SNPs; synonymous single nucleotide polymorphism (sSNP) and non-synonymous single nucleotide polymorphism (nsSNP). sSNP occur in the gene coding region without causing a change in the encoded amino acid, while nsSNP is deleterious due to its replacement of a nucleotide residue in the gene sequence that results in a change in the encoded amino acid. Predicting the effects of cancer related nsSNPs on protein stability, function, and dynamics is important due to the significance of phenotype-genotype association of cancer. In this thesis, Data of 5 oncogenes (ONGs) (AKT1, ALK, ERBB2, KRAS, BRAF) and 5 tumor suppressor genes (TSGs) (ESR1, CASP8, TET2, PALB2, PTEN) were retrieved from ClinVar. Five common in silico tools; Polyphen, Provean, Mutation Assessor, Suspect, and FATHMM, were used to predict and categorize nsSNPs as deleterious, benign, or neutral. To understand the impact of each variation on the phenotype, Maestro, PremPS, Cupsat, and mCSM-NA in silico structural prediction tools were used. This study comprises of in-depth analysis of 10 cancer gene variants downloaded from Clinvar. Various analysis of the genes was conducted to derive a meaningful conclusion from the data. Research done indicated that pathogenic variants are more common among ONGs. Our research also shows that pathogenic and destabilizing variants are more common among ONGs than TSGs. Moreover, our data indicated that ALK(409) and BRAF(86) has higher benign count among ONGs; whilst among TSGs, PALB2(1308) and PTEN(318) genes have higher benign counts. Looking at the individual cancer genes predisposition or frequencies of causing cancer according to our research data, KRAS(76%), BRAF(55%), and ERBB2(36%) among ONGs; and PTEN(29%) and ESR1(17%) among TSGs have higher tendencies of causing cancer. Obtained results can shed light to the future research in order to pave new frontiers in cancer therapies.

Keywords: tumor suppressor genes (TSGs), oncogenes (ONGs), non synonymous single nucleotide polymorphism (nsSNP), single nucleotide polymorphism (SNP)

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Authors: Himanshu Rohela

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BACKGROUND: Ewing sarcoma can arise in either bone or soft tissue. Extraskeletal Ewing sarcoma (EES) is an uncommon primary tumor of the soft tissues, accounting for 20 30% of all reported cases of ES. AIM: Was to investigate demographic distribution, survival analysis and factors affecting the survival and recurrence in patients of EES. METHODS: Retrospective study of 19 biopsy-proven EES was performed. Overall survival (OS) using log-rank test and factors affecting OS and local recurrence (LR) were evaluated for the entire cohort. RESULTS: Patients with EES had a mean age of 19.5 and it was more commonly seen in males (63%). Axial location (58%) and solitary presentation (84%) were more common. The average size was 11 cm, 3 of 19 were metastatic at presentation, with the lung beings the most common site for metastasis. 17 received NACT, 16 with VAC-IE regimen and 1 underwent a second line with GEM/DOCE regimen. Unplanned surgery was done in 2 of 19. 3 patients received definitive RT and 13 underwent surgical-wide local excision. 2 of 13 showed good response to NACT. 10 patients required readmission out of which 6 patients had chemotherapy-related complications, 2 had surgical site complications and one patient developed secondary AML post-completion of treatment. A total of 4 patients had a recurrence. One had local recurrence alone, one had distant recurrence alone and 2 patients had a distant and local recurrence both. Tumor size >10 cm, axial location, and previous unplanned surgery was associated with higher LR rate. The mean overall survival was 32 months (2.66 years), with higher rates seen in non-metastatic and non-recurrent settings. CONCLUSIONS: Early and accurate diagnosis is the key to the management of EES, with promising results seen via NACT and RO resection regimens. But further studies with larger study groups are needed to standardize the treatment protocol and evaluate its efficacy.

Keywords: Ewings, sarcoma, extraskeletal, chemotherapy

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Authors: Jaspreet Kaur, Parminder Nain, Vipin Saini, Sumitra Dahiya

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Elaeocarpus sphaericus has been traditionally used in the Indian traditional medicine system for the treatment of stress, anxiety, depression, palpitation, epilepsy, migraine and lack of concentration. The study was investigated to evaluate the neurological potential such as anxiolytic, muscle relaxant and sedative activity of methanolic extract of Elaeocarpus sphaericus stem bark (MEESSB) in mice. Preliminary phytochemical screening and acute oral toxicity of MEESSB was carried out by using standard methods. The anxiety was induced by employing Elevated Plus-Maze (EPM), Light and Dark Test (LDT), Open Field Test (OFT) and Social Interaction test (SIT). The motor coordination and sedative effect was also observed by using actophotometer, rota-rod apparatus and ketamine-induced sleeping time, respectively. Animals were treated with different doses of MEESSB (i.e.100, 200, 400 and 800 mg/kg orally) and diazepam (2 mg/kg i.p) for 21 days. Brain neurotransmitters like dopamine, serotonin and nor-epinephrine level were estimated by validated methods. Preliminary phytochemical analysis of the extract revealed the presence of tannins, phytosterols, steroids and alkaloids. In the acute toxicity studies, MEESSB was found to be non-toxic and with no mortality. In anxiolytic studies, the different doses of MEESSB showed a significant (p<0.05) effect on EPM and LDT. In OFT and SIT, a significant (p<0.05) increase in ambulation, rearing and social interaction time was observed. In the case of motor coordination activity, the MEESSB does not cause any significant effect on the latency to fall off from the rotarod bar as compared to the control group. Moreover, no significant effects on ketamine-induced sleep latency and total sleeping time induced by ketamine were observed. Results of neurotransmitter estimation revealed the increased concentration of dopamine, whereas the level of serotonin and nor-epinephrine was found to be decreased in the mice brain, with MEESSB at dose 800 mg/kg only. The study has validated the folkloric use of the plant as an anxiolytic in Indian traditional medicine while also suggesting potential usefulness in the treatment of stress and anxiety without causing sedation.

Keywords: anxiolytic, behavior experiments, brain neurotransmitters, elaeocarpus sphaericus

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Authors: E. Locatelli, I. Monaco, R. C. Martin, Y. Li, R. Pini, M. Chiariello, M. Comes Franchini

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Despite the many advantages of application of nanomaterials in the field of nanomedicine, increasing concerns have been expressed on their potential adverse effects on human health. There is urgency for novel green strategies toward novel materials with enhanced biocompatibility using safe reagents. Photothermal ablation therapy, which exploits localized heat increase of a few degrees to kill cancer cells, has appeared recently as a non-invasive and highly efficient therapy against various cancer types; anyway new agents able to generate hyperthermia when irradiated are needed and must have precise biocompatibility in order to avoid damage to healthy tissues and prevent toxicity. Recently, there has been increasing interest in magnesium as a biomaterial: it is the fourth most abundant cation in the human body, and it is essential for human metabolism. However magnesium nanoparticles (Mg NPs) have had limited diffusion due to the high reduction potential of magnesium cations, which makes NPs synthesis challenging. Herein, we report the synthesis of Mg NPs and their surface functionalization for the obtainment of a stable and biocompatible nanomaterial suitable for photothermal ablation therapy against cancer. We synthesized the Mg crystals by reducing MgCl2 with metallic lithium and exploiting naphthalene as an electron carrier: the lithium–naphthalene complex acts as the real reducing agent. Firstly, the nanocrystal particles were coated with the ligand 12-ethoxy ester dodecanehydroxamic acid, and then entrapped into water-dispersible polymeric micelles (PMs) made of the FDA-approved PLGA-b-PEG-COOH copolymer using the oil-in-water emulsion technique. Lately, we developed a more straightforward methodology by introducing chitosan, a highly biocompatible natural product, at the beginning of the process, simultaneously using lithium–naphthalene complex, thus having a one-pot procedure for the formation and surface modification of MgNPs. The obtained MgNPs were purified and fully characterized, showing diameters in the range of 50-300 nm. Notably, when coated with chitosan the particles remained stable as dry powder for more than 10 months. We proved the possibility of generating a temperature rise of a few to several degrees once MgNPs were illuminated using a 810 nm diode laser operating in continuous wave mode: the temperature rise resulted significant (0-15 °C) and concentration dependent. We then investigated potential cytotoxicity of the MgNPs: we used HN13 epithelial cells, derived from a head and neck squamous cell carcinoma and the hepa1-6 cell line, derived from hepatocellular carcinoma and very low toxicity was observed for both nanosystems. Finally, in vivo photothermal therapy was performed on xenograft hepa1-6 tumor bearing mice: the animals were treated with MgNPs coated with chitosan and showed no sign of suffering after the injection. After 12 hours the tumor was exposed to near-infrared laser light. The results clearly showed an extensive damage to tumor tissue after only 2 minutes of laser irradiation at 3Wcm-1, while no damage was reported when the tumor was treated with the laser and saline alone in control group. Despite the lower photothermal efficiency of Mg with respect to Au NPs, we consider MgNPs a promising, safe and green candidate for future clinical translations.

Keywords: chitosan, magnesium nanoparticles, nanomedicine, photothermal therapy

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Authors: Marta E. Hernandez-Caballero, Veronica Borgonio-Cuadra, Antonio Miranda-Duarte, Xochitl Rojas-Toledo, Normand Garcia-Hernandez, Maura Cardenas-Garcia, Teresa Abad-Camacho

Abstract:

Breast cancer (BC) is the most common tumor in women over the world. DNA methylation is an epigenetic modification critical in CpG sites, aberrant methylation of CpG islands in promoters is a hallmark of cancer. So, gene expression can be regulated by alterations in DNA methylation. In cell lines DACT2 gene reduces the growth and migration of tumor cells by its participation in the suppression of TGFb/SMAD2/3. PHF20L1 is involved in histone acetylation therefore, it regulates transcription. Our aim was to analyze the methylation status of the DACT2 and PHF20L1 promoter regions in tumoral and healthy mammary tissue from women with BC in different progression states. The study included 77 patients from Centro Medico Nacional La Raza in Mexico City. After identifying a CpG island in DACT2 and PHF20L1 promoters, DNA methylation status was analyzed through sodium bisulfite with subsequent amplification using methylation-specific PCR. Results revealed no changes in methylation status of PHF20L1 and cancer stages (II y III) or in comparison to healthy tissues, it was demethylated. DACT2 promoter methylation was no significant between tumoral stages (II, P = 0.37; III, P = 0.17) or with healthy tissue. Previous data reported DACT2 methylated in nasopharyngeal carcinoma but in this study promoter methylation was not observed. PHF20L1 protein contains N-terminal Tudor and C-terminal plant homeodomain domains, it has been suggested that can stabilize DNMT1 regulating DNA methylation, therefore, was associated with poor prognostic in BC. We found no evidence of methylation in patients and controls in PHF20L1 promoter, so its association with BC may have no direct relation with promoter methylation. More studies including other methylation sites in these genes in BC are necessary.

Keywords: bisulfite conversion, breast cancer, DACT2, DNA methylation, PHF20L1, tumoral status

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Authors: Keyvan Kashkouli Nejad, Motoaki Sugiura, Atsushi Sato, Takayuki Nozawa, Hyeonjeong Jeong, Sugiko Hanawa , Yuka Kotozaki, Ryuta Kawashima

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The perception of agency/control is altered with presence of discrepancies in the environment or mismatch of predictions (of possible results) and actual results the sense of agency might become altered. Synofzik et al. proposed a two layer model of agency: In the first layer, the Feeling of Agency (FoA) is not directly available to awareness; a slight mismatch in the environment/outcome might cause alterations in FoA, while the agent still feels in control. If the discrepancy passes a threshold, it becomes available to consciousness and alters Judgment of Agency (JoA), which is directly available in the person’s awareness. Most experiments so far only investigate subjects rather conscious JoA, while FoA has been neglected. In this experiment we target FoA by using subliminal discrepancies that can not be consciously detectable by the subjects. Here, we explore whether we can detect this two level model in the subjects behavior and then try to map this in their brain activity. To do this, in a fMRI study, we incorporated both consciously detectable mismatching between action and result and also subliminal discrepancies in the environment. Also, unlike previous experiments where subjective questions from the participants mainly trigger the rather conscious JoA, we also tried to measure the rather implicit FoA by asking participants to rate their performance. We compared behavioral results and also brain activation when there were conscious discrepancies and when there were subliminal discrepancies against trials with no discrepancies and against each other. In line with our expectations, conditions with consciously detectable incongruencies triggered lower JoA ratings than conditions without. Also, conditions with any type of discrepancies had lower FoA ratings compared to conditions without. Additionally, we found out that TPJ and angular gyrus in particular to have a role in coding of JoA and also FoA.

Keywords: agency, fMRI, TPJ, two layer model

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Authors: Tamar Bikashvili, Tamar Lordkipanidze, Ilia Lazrishvili

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Heavy metals remain one of serious environmental problems due to their toxic effects. The effect of arsenic and manganese compounds on rat behavior and neuromorphology was studied. Wistar rats were assigned to four groups: rats in control group were given regular water, while rats in other groups drank water with final manganese concentration of 10 mg/L (group A), 20 mg/L (group B) and final arsenic concentration 68 mg/L (group C), respectively, for a month. To study exploratory and anxiety behavior and also to evaluate aggressive performance in “home cage” rats were tested in “Open Field” and to estimate learning and memory status multi-branched maze was used. Statistically significant increase of motor and oriental-searching activity in experimental groups was revealed by an open field test, which was expressed in increase of number of lines crossed, rearing and hole reflexes. Obtained results indicated the suppression of fear in rats exposed to manganese. Specifically, this was estimated by the frequency of getting to the central part of the open field. Experiments revealed that 30-day exposure to 10 mg/ml manganese did not stimulate aggressive behavior in rats, while exposure to the higher dose (20 mg/ml), 37% of initially non-aggressive animals manifested aggressive behavior. Furthermore, 25% of rats were extremely aggressive. Obtained data support the hypothesis that excess manganese in the body is one of the immediate causes of enhancement of interspecific predatory aggressive and violent behavior in rats. It was also discovered that manganese intoxication produces non-reversible severe learning disability and insignificant, reversible memory disturbances. Studies of rodents exposed to arsenic also revealed changes in the learning process. As it is known, the distribution of metal ions differs in various brain regions. The principle manganese accumulation was observed in the hippocampus and in the neocortex, while arsenic was predominantly accumulated in nucleus accumbens, striatum, and cortex. These brain regions play an important role in the regulation of emotional state and motor activity. Histopathological analyzes of brain sections illustrated two morphologically distinct altered phenotypes of neurons: (1) shrunk cells with indications of apoptosis - nucleus and cytoplasm were very difficult to be distinguished, the integrity of neuronal cytoplasm was not disturbed; and (2) swollen cells - with indications of necrosis. Pyknotic nucleus, plasma membrane disruption and cytoplasmic vacuoles were observed in swollen neurons and they were surrounded by activated gliocytes. It’s worth to mention that in the cortex the majority of damaged neurons were apoptotic while in subcortical nuclei –neurons were mainly necrotic. Ultrastructural analyses demonstrated that all cell types in the cortex and the nucleus caudatus represent destructed mitochondria, widened neurons’ vacuolar system profiles, increased number of lysosomes and degeneration of axonal endings.

Keywords: arsenic, manganese, behavior, learning, neuron

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Authors: M. Saard, A. Kolk, K. Sepp, L. Pertens, L. Reinart, C. Kööp

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Introduction: Social competence is often impaired in children with acquired brain injury (ABI), but evidence-based rehabilitation for social skills has remained undeveloped. Modern technology-based methods create effective and safe learning environments for pediatric social skills remediation. The aim of the study was to implement our structured model of neuro rehab for socio-cognitive deficit using multitouch-multiuser tabletop (MMT) computer-based platforms and virtual reality (VR) technology. Methods: 40 children aged 8-13 years (yrs) have participated in the pilot study: 30 with ABI -epilepsy, traumatic brain injury and/or tic disorder- and 10 healthy age-matched controls. From the patients, 12 have completed the training (M = 11.10 yrs, SD = 1.543) and 20 are still in training or in the waiting-list group (M = 10.69 yrs, SD = 1.704). All children performed the first individual and paired assessments. For patients, second evaluations were performed after the intervention period. Two interactive applications were implemented into rehabilitation design: Snowflake software on MMT tabletop and NoProblem on DiamondTouch Table (DTT), which allowed paired training (2 children at once). Also, in individual training sessions, HTC Vive VR device was used with VR metaphors of difficult social situations to treat social anxiety and train social skills. Results: At baseline (B) evaluations, patients had higher deficits in executive functions on the BRIEF parents’ questionnaire (M = 117, SD = 23.594) compared to healthy controls (M = 22, SD = 18.385). The most impaired components of social competence were emotion recognition, Theory of Mind skills (ToM), cooperation, verbal/non-verbal communication, and pragmatics (Friendship Observation Scale scores only 25-50% out of 100% for patients). In Sentence Completion Task and Spence Anxiety Scale, the patients reported a lack of friends, behavioral problems, bullying in school, and social anxiety. Outcome evaluations: Snowflake on MMT improved executive and cooperation skills and DTT developed communication skills, metacognitive skills, and coping. VR, video modelling and role-plays improved social attention, emotional attitude, gestural behaviors, and decreased social anxiety. NEPSY-II showed improvement in Affect Recognition [B = 7, SD = 5.01 vs outcome (O) = 10, SD = 5.85], Verbal ToM (B = 8, SD = 3.06 vs O = 10, SD = 4.08), Contextual ToM (B = 8, SD = 3.15 vs O = 11, SD = 2.87). ToM Stories test showed an improved understanding of Intentional Lying (B = 7, SD = 2.20 vs O = 10, SD = 0.50), and Sarcasm (B=6, SD = 2.20 vs O = 7, SD = 2.50). Conclusion: Neurorehabilitation based on the Structured Model of Neurorehab for Socio-Cognitive Deficit in children with ABI were effective in social skills remediation. The model helps to understand theoretical connections between components of social competence and modern interactive computerized platforms. We encourage therapists to implement these next-generation devices into the rehabilitation process as MMT and VR interfaces are motivating for children, thus ensuring good compliance. Improving children’s social skills is important for their and their families’ quality of life and social capital.

Keywords: acquired brain injury, children, social skills deficit, technology-based neurorehabilitation

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Authors: Hasan Frookh Jamal

Abstract:

This is a case of a 36-year-old Bahraini gentleman diagnosed to have Cushing's Syndrome with a large anterior mediastinal mass. He was sent abroad to the Speciality hospital in Jordan, where he underwent diagnostic video-assisted thoracoscopy, partial thymectomy and pericardial fat excision. Histopathology of the mass was reported to be an Atypical carcinoid tumor with a low Ki67 proliferation index of 5%, the mitotic activity of 4 MF/10HPF and pathological stage classification(pTNM): pT1aN1. MRI of the pituitary gland showed an ill-defined non-enhancing focus of about 3mm on the Rt side of the pituitary on coronal images, with a similar but smaller one on the left side, which could be due to enhancing pattern rather than a real lesion as reported. The patient underwent Ga68 Dotate PET/CT scan post-operatively, which showed multiple somatostatin receptor-positive lesions seen within the tail, body and head of the pancreas and positive somatostatin receptor lymph nodes located between the pancreatic head and IVC. There was no uptake detected at the anterior mediastinum nor at the site of thymic mass resection. There was no evidence of any positive somatostatin uptake at the soft tissue or lymph nodes. The patient underwent IPSS, which proved that the source is, in fact, an ectopic source of ACTH secretion. Unfortunately, the patient's serum cortisol remained elevated after surgery and failed to be suppressed by 1 mg ODST and by 2 days LLDST with a high ACTH value. The patient was started on Osilodrostat for treatment of hypercortisolism for the time being and his future treatment plan with Lutetium-177 Dotate therapy vs. bilateral adrenalectomy is to be considered in an MDT meeting.

Keywords: cushing syndrome, neuroendocrine tumur, carcinoid tumor, Thymoma

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Authors: Salina Budin, Shaira Ismail

Abstract:

Students learn effectively in a learning environment with a suitable teaching approach that matches their learning preferences. The main objective of the study is to examine the learning preferences amongst the students in the Science and Technology (S&T), and Social Science (SS) fields of study at the Universiti Teknologi Mara (UiTM), Pulau Pinang. The measurement instrument is based on the Dunn and Dunn Learning Styles which measure five elements of learning styles; environmental, sociological, emotional, physiological and psychological. Questionnaires are distributed amongst undergraduates in the Faculty of Mechanical Engineering and Faculty of Business Management. The respondents comprise of 131 diploma students of the Faculty of Mechanical Engineering and 111 degree students of the Faculty of Business Management. The results indicate that, both S&T and SS students share a similar learning preferences on the environmental aspect, emotional preferences, motivational level, learning responsibility, persistent level in learning and learning structure. Most of the S&T students are concluded as analytical learners and the majority of SS students are global learners. Both S&T and SS students are concluded as visual learners, preferred to be in an active mobility in a relaxing and enjoying mode with some light of refreshments during the learning process and exhibited reflective characteristics in learning. Obviously, the S&T students are considered as left brain dominant, whereas the SS students are right brain dominant. The findings highlighted that both categories of students exhibited similar learning preferences except on psychological preferences.

Keywords: learning preferences, Dunn and Dunn learning style, teaching approach, science and technology, social science

Procedia PDF Downloads 226

Authors: Sadeem Aljamaan, Reem Hariri, Rahaf Alghamdi, Batool Alotaibi, Batool Alsenan, Lama Althunayyan, Areej Alnemer

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The aim of this study is to correlate between radiological findings and histopathological results in regard to the breast imaging-reporting and data system scores, size of breast masses, molecular subtypes and suspicious radiological features, as well as to assess the concordance rate in histological grade between core biopsy and surgical excision among breast cancer patients, followed by analyzing the change of concordance rate in relation to neoadjuvant chemotherapy in a Saudi population. A retrospective review was conducted over 6-year period (2017-2022) on all breast core biopsies of women preceded by radiological investigation. Chi-squared test (χ2) was performed on qualitative data, the Mann-Whitney test for quantitative non-parametric variables, and the Kappa test for grade agreement. A total of 641 cases were included. Ultrasound, mammography, and magnetic resonance imaging demonstrated diagnostic accuracies of 85%, 77.9% and 86.9%; respectively. magnetic resonance imaging manifested the highest sensitivity (72.2%), and the lowest was for ultrasound (61%). Concordance in tumor size with final excisions was best in magnetic resonance imaging, while mammography demonstrated a higher tendency of overestimation (41.9%), and ultrasound showed the highest underestimation (67.7%). The association between basal-like molecular subtypes and the breast imaging-reporting and data system score 5 classifications was statistically significant only for magnetic resonance imaging (p=0.04). Luminal subtypes demonstrated a significantly higher percentage of speculation in mammography. Breast imaging-reporting and data system score 4 manifested a substantial number of benign pathologies in all the 3 modalities. A fair concordance rate (k= 0.212 & 0.379) was demonstrated between excision and the preceding core biopsy grading with and without neoadjuvant therapy, respectively. The results demonstrated a down-grading in cases post-neoadjuvant therapy. In cases who did not receive neoadjuvant therapy, underestimation of tumor grade in biopsy was evident. In summary, magnetic resonance imaging had the highest sensitivity, specificity, positive predictive value and accuracy of both diagnosis and estimation of tumor size. Mammography demonstrated better sensitivity than ultrasound and had the highest negative predictive value, but ultrasound had better specificity, positive predictive value and accuracy. Therefore, the combination of different modalities is advantageous. The concordance rate of core biopsy grading with excision was not impacted by neoadjuvant therapy.

Keywords: breast cancer, mammography, MRI, neoadjuvant, pathology, US

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Authors: M. R. Akbari, M. Sadeghi, R. Faghihi, M. A. Mosleh-Shirazi, A. R. Khorrami-Moghadam

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Proton radiotherapy (PRT) is becoming an established treatment modality for cancer. The localized tumors, the same as undifferentiated thyroid tumors are insufficiently handled by conventional radiotherapy, while protons would propose the prospect of increasing the tumor dose without exceeding the tolerance of the surrounding healthy tissues. In spite of relatively high advantages in giving localized radiation dose to the tumor region, in proton therapy, secondary neutron production can have significant contribution on integral dose and lessen advantages of this modality contrast to conventional radiotherapy techniques. Furthermore, neutrons have high quality factor, therefore, even a small physical dose can cause considerable biological effects. Measuring of this neutron dose is a very critical step in prediction of secondary cancer incidence. It has been found that FLUKA Monte Carlo code simulations have been used to evaluate dose due to secondaries in proton therapy. In this study, first, by validating simulated proton beam range in water phantom with CSDA range from NIST for the studied proton energy range (34-54 MeV), a proton therapy in thyroid gland cancer was simulated using FLUKA code. Secondary neutron dose equivalent of some organs and tissues after the target volume caused by 34 and 54 MeV proton interactions were calculated in order to evaluate secondary cancer incidence. A multilayer cylindrical neck phantom considering all the layers of neck tissues and a proton beam impinging normally on the phantom were also simulated. Trachea (accompanied by Larynx) had the greatest dose equivalent (1.24×10-1 and 1.45 pSv per primary 34 and 54 MeV protons, respectively) among the simulated tissues after the target volume in the neck region.

Keywords: FLUKA code, neutron dose equivalent, proton therapy, thyroid gland

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Authors: M. G. Talasbayen, N. N. Dyussenbayev, Y. D. Kali, R. A. Zholbarysov, Y. N. Duissenbayev, I. Z. Mammadinova, S. M. Nuradilov

Abstract:

Background. Hemorrhagic stroke is an acute cerebrovascular accident resulting from rupture of a cerebral vessel or increased permeability of the wall and imbibition of blood into the brain parenchyma. Arterial hypertension is a common cause of hemorrhagic stroke. Male gender and age over 55 years is a risk factor for intracerebral hemorrhage. Treatment of intracerebral hemorrhage is aimed at the primary pathophysiological link: the relief of coagulopathy and the control of arterial hypertension. Early surgical treatment can limit cerebral compression; prevent toxic effects of blood to the brain parenchyma. Despite progress in the development of neuroimaging data, the use of minimally invasive techniques, and navigation system, mortality from intracerebral hemorrhage remains high. Materials and methods. The study included 78 patients (62.82% male and 37.18% female) with a verified diagnosis of hemorrhagic stroke in the period from 2019 to 2021. The age of patients ranged from 25 to 80 years, the average age was 54.66±11.9 years. Demographic, brain CT data (localization, volume of hematomas), methods of treatment, and disease outcome were analyzed. Results. The retrospective analyze demonstrate that 78.2% of all patients underwent surgical treatment: decompressive craniectomy in 37.7%, craniotomy with hematoma evacuation in 29.5%, and hematoma draining in 24.59% cases. The study of the proportion of deaths, depending on the volume of intracerebral hemorrhage, shows that the number of deaths was higher in the group with a hematoma volume of more than 60 ml. Evaluation of the relationship between the time before surgery and mortality demonstrates that the most favorable outcome is observed during surgical treatment in the interval from 3 to 24 hours. Mortality depending on age did not reveal a significant difference between age groups. An analysis of the impact of the surgery type on mortality reveals that decompressive craniectomy with or without hematoma evacuation led to an unfavorable outcome in 73.9% of cases, while craniotomy with hematoma evacuation and drainage led to mortality only in 28.82% cases. Conclusion. Even though the multimodal approaches, the development of surgical techniques and equipment, and the selection of optimal conservative therapy, the question of determining the tactics of managing and treating hemorrhagic strokes is still controversial. Nevertheless, our experience shows that surgical intervention within 24 hours from the moment of admission and craniotomy with hematoma evacuation improves the prognosis of treatment outcomes.

Keywords: hemorragic stroke, Intracerebral hemorrhage, surgical treatment, stroke mortality

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Authors: V. Veeraprathap, G. S. Harish, G. Narendra Kumar

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Uncontrolled growth of abnormal cells in the lung in the form of tumor can be either benign (non-cancerous) or malignant (cancerous). Patients with Lung Cancer (LC) have an average of five years life span expectancy provided diagnosis, detection and prediction, which reduces many treatment options to risk of invasive surgery increasing survival rate. Computed Tomography (CT), Positron Emission Tomography (PET), and Magnetic Resonance Imaging (MRI) for earlier detection of cancer are common. Gaussian filter along with median filter used for smoothing and noise removal, Histogram Equalization (HE) for image enhancement gives the best results without inviting further opinions. Lung cavities are extracted and the background portion other than two lung cavities is completely removed with right and left lungs segmented separately. Region properties measurements area, perimeter, diameter, centroid and eccentricity measured for the tumor segmented image, while texture is characterized by Gray-Level Co-occurrence Matrix (GLCM) functions, feature extraction provides Region of Interest (ROI) given as input to classifier. Two levels of classifications, K-Nearest Neighbor (KNN) is used for determining patient condition as normal or abnormal, while Artificial Neural Networks (ANN) is used for identifying the cancer stage is employed. Discrete Wavelet Transform (DWT) algorithm is used for the main feature extraction leading to best efficiency. The developed technology finds encouraging results for real time information and on line detection for future research.

Keywords: artificial neural networks, ANN, discrete wavelet transform, DWT, gray-level co-occurrence matrix, GLCM, k-nearest neighbor, KNN, region of interest, ROI

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Authors: Rawan Al-Nemari, Abdulrahman Al-Senaidy, Abdelhabib Semlali

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Background and objectives: The most common cause of death in women worldwide is breast cancer. Regarding all chemotherapy disadvantages and side effects, it’s becoming necessary to identify natural products that target cancer cells with lesser harmful side effects on non-targeted cells and biological environment. Different parts of A. squamosa L., commonly known as custard apple, show varied therapeutic effects. The objective of this study is to investigate in vitro and in vivo, the anti-cancer activity of A. squamosa leaves extract. Methods: The physiological responses using MTT, nucleus staining, and LDH assays were used to evaluate cell survival and proliferation in both ER+ and ER- cells when they were exposed to extract. Monolayer wound repair assay was used to investigate the effect of extracts on cell migration. Apoptotic gene’s expression was investigated by real-time polymerase chain reaction. To study the effect of the extract on the size of tumor, breast cancer induced rats were used. Results: A. squamosa leaves extract showed high anti-proliferative and cytotoxicity effects against different breast cancer cell lines with high concentration, 100 ug/ml. The extracts have reduced the cells wound closure. Polymerase chain reaction revealed downregulation of Bcl-2 and upregulation of Bax. In breast cancer model animal developed in our laboratory, after 4 weeks treatment, treated groups have shown smaller tumor size in comparison with control group (n=4). Conclusion: These results suggest that A. squamosa leaves extract has anti-cancer activity against breast cancer in both in vitro and in vivo, and it may be developed as a potential novel agent to treat breast cancer.

Keywords: apoptosis, breast cancer, migration, proliferation

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Authors: Olusola Olalekan Elekofehinti, Isaac Gbadura Adanlawo, Joao Batista Teixeira Rocha

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We evaluated the potential neuroprotective effect of Phyllantus nuriri against Fe2+ and SNP induced oxidative stress in mitochondria of rats brain. Cellular viability was assessed by MTT reduction, reactive oxygen species (ROS) generation was measured using the probe 2,7-dichlorofluorescein diacetate (DCFH-DA). Glutathione content was measured using dithionitrobenzoic acid (DTNB). Fe2+ (10µM) and SNP (5µM) significantly decreased mitochondrial activity, assessed by MTT reduction assay, in a dose-dependent manner, this occurred in parallel with increased glutathione oxidation, ROS production and lipid peroxidation end-products (thiobarbituric acid reactive substances, TBARS). The co-incubation with methanolic extract of Phyllantus nuriri (10-100 µg/ml) reduced the disruption of mitochondrial activity, gluthathione oxidation, ROS production as well as the increase in TBARS levels caused by both Fe2+ and SNP in a dose dependent manner. HPLC analysis of the extract revealed the presence of gallic acid (20.54±0.01), caffeic acid (7.93±0.02), rutin (25.31±0.05), quercetin (31.28±0.03) and kaemferol (14.36±0.01). This result suggests that these phytochemicals account for the protective actions of Phyllantus nuriri against Fe2+ and SNP -induced oxidative stress. Our results show that Phyllantus nuriri consist important bioactive molecules in the search for an improved therapy against the deleterious effects of Fe2+, an intrinsic producer of reactive oxygen species (ROS), that leads to neuronal oxidative stress and neurodegeneration.

Keywords: Phyllantus niruri, neuroprotection, oxidative stress, mitochondria, synaptosome

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Authors: Evangelos Koumparoudis

Abstract:

The definition of death is a deep philosophical question, and no single meaning can be ascribed to it. This essay focuses on the ontological, epistemological, and ethical aspects of death and dying in view of technological progress in information technology and biomedicine. It starts with the ad hoc 1968 Harvard committee that proposed that the criterion for the definition of death be irreversible coma and then refers to the debate over the whole brain death formula, emphasizing the integrated function of the organism and higher brain formula, taking consciousness and personality as essential human characteristics. It follows with the contribution of information technology in personalized and precision medicine and anti-aging measures aimed at life prolongation. It also touches on the possibility of the creation of human-machine hybrids and how this raises ontological and ethical issues that concern the “cyborgization” of human beings and the conception of the organism and personhood based on a post/transhumanist essence, and, furthermore, if sentient AI capable of autonomous decision-making that might even surpass human intelligence (singularity, superintelligence) deserves moral or legal personhood. Finally, there is the question as to whether death and dying should be redefined at a transcendent level, which is reinforced by already-existing technologies of “virtual after-” life and the possibility of uploading human minds. In the last section, I refer to the current (and future) applications of nanomedicine in diagnostics, therapeutics, implants, and tissue engineering as well as the aspiration to “immortality” by cryonics. The definition of death is reformulated since age and disease elimination may be realized, and the criterion of irreversibility may be challenged.

Keywords: death, posthumanism, infomedicine, nanomedicine, cryonics

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Authors: Takashi Kaburagi, Masashi Takenaka, Yosuke Kurihara, Takashi Matsumoto

Abstract:

Major depressive disorder (MDD) is one of the most common mental illnesses today. It is believed to be caused by a combination of several factors, including stress. Stress can be quantitatively evaluated using the State-Trait Anxiety Inventory (STAI), one of the best indices to evaluate anxiety. Although STAI scores are widely used in applications ranging from clinical diagnosis to basic research, the scores are calculated based on a self-reported questionnaire. An objective evaluation is required because the subject may intentionally change his/her answers if multiple tests are carried out. In this article, we present a modified index called the “multi-channel Laterality Index at Rest (mc-LIR)” by recording the brain activity from a wider area of the frontal lobe using multi-channel functional near-infrared spectroscopy (fNIRS). The presented index aims to measure multiple positions near the F_pz defined by the international 10-20 system positioning. Using 24 subjects, the dependencies on the number of measuring points used to calculate the mc-LIR and its correlation coefficients with the STAI scores are reported. Furthermore, a simple linear regression was performed to estimate the STAI scores from mc-LIR. The cross-validation error is also reported. The experimental results show that using multiple positions near the Fpz will improve the correlation coefficients and estimation than those using only two positions.

Keywords: frontal lobe, functional near-infrared spectroscopy, state-trait anxiety inventory score, stress

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