Search results for: family therapy
Commenced in January 2007
Frequency: Monthly
Edition: International
Paper Count: 4843

Search results for: family therapy

2983 Familial Exome Sequencing to Decipher the Complex Genetic Basis of Holoprosencephaly

Authors: Artem Kim, Clara Savary, Christele Dubourg, Wilfrid Carre, Houda Hamdi-Roze, Valerie Dupé, Sylvie Odent, Marie De Tayrac, Veronique David

Abstract:

Holoprosencephaly (HPE) is a rare congenital brain malformation resulting from the incomplete separation of the two cerebral hemispheres. It is characterized by a wide phenotypic spectrum and a high degree of locus heterogeneity. Genetic defects in 16 genes have already been implicated in HPE, but account for only 30% of cases, suggesting that a large part of genetic factors remains to be discovered. HPE has been recently redefined as a complex multigenic disorder, requiring the joint effect of multiple mutational events in genes belonging to one or several developmental pathways. The onset of HPE may result from accumulation of the effects of multiple rare variants in functionally-related genes, each conferring a moderate increase in the risk of HPE onset. In order to decipher the genetic basis of HPE, unconventional patterns of inheritance involving multiple genetic factors need to be considered. The primary objective of this study was to uncover possible disease causing combinations of multiple rare variants underlying HPE by performing trio-based Whole Exome Sequencing (WES) of familial cases where no molecular diagnosis could be established. 39 families were selected with no fully-penetrant causal mutation in known HPE gene, no chromosomic aberrations/copy number variants and without any implication of environmental factors. As the main challenge was to identify disease-related variants among a large number of nonpathogenic polymorphisms detected by WES classical scheme, a novel variant prioritization approach was established. It combined WES filtering with complementary gene-level approaches: transcriptome-driven (RNA-Seq data) and clinically-driven (public clinical data) strategies. Briefly, a filtering approach was performed to select variants compatible with disease segregation, population frequency and pathogenicity prediction to identify an exhaustive list of rare deleterious variants. The exome search space was then reduced by restricting the analysis to candidate genes identified by either transcriptome-driven strategy (genes sharing highly similar expression patterns with known HPE genes during cerebral development) or clinically-driven strategy (genes associated to phenotypes of interest overlapping with HPE). Deeper analyses of candidate variants were then performed on a family-by-family basis. These included the exploration of clinical information, expression studies, variant characteristics, recurrence of mutated genes and available biological knowledge. A novel bioinformatics pipeline was designed. Applied to the 39 families, this final integrated workflow identified an average of 11 candidate variants per family. Most of candidate variants were inherited from asymptomatic parents suggesting a multigenic inheritance pattern requiring the association of multiple mutational events. The manual analysis highlighted 5 new strong HPE candidate genes showing recurrences in distinct families. Functional validations of these genes are foreseen.

Keywords: complex genetic disorder, holoprosencephaly, multiple rare variants, whole exome sequencing

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2982 Hepatitis B, Hepatitis C and HIV Infections and Associated Risk Factors among Substance Abusers in Mekelle Substance Users Treatment and Rehabilitation Centers, Tigrai, Northern Ethiopia

Authors: Tadele Araya, Tsehaye Asmelash, Girmatsion Fiseha

Abstract:

Background: Hepatitis B virus (HBV), Hepatitis C virus (HCV) and Human Immunodeficiency Virus (HIV) constitute serious healthcare problems worldwide. Blood-borne pathogens HBV, HCV and HIV are commonly associated with infections among substance or Injection Drug Users (IDUs). The objective of this study was to determine the prevalence of HBV, HCV, and HIV infections among substance users in Mekelle Substance users Treatment and Rehabilitation Centers. Methods: A cross-sectional study design was used from Dec 2020 to Sep / 2021 to conduct the study. A total of 600 substance users were included. Data regarding the socio-demographic, clinical and sexual behaviors of the substance users were collected using a structured questionnaire. For laboratory analysis, 5-10 ml of venous blood was taken from the substance users. The laboratory analysis was performed by Enzyme-Linked Immunosorbent Assay (ELISA) at Mekelle University, Department of Medical Microbiology and Immunology Research Laboratory. The Data was analyzed using SPSS and Epi-data. The association of variables with HBV, HCV and HIV infections was determined using multivariate analysis and a P value < 0.05 was considered statistically significant. Result: The overall prevalence rate of HBV, HCV and HIV infections were 10%, 6.6%, and 7.5%, respectively. The mean age of the study participants was 28.12 ± 6.9. A higher prevalence of HBV infection was seen in participants who were users of drug injections and in those who were infected with HIV. HCV was comparatively higher in those who had a previous history of unsafe surgical procedures than their counterparts. Homeless participants were highly exposed to HCV and HIV infections than their counterparts. The HBV/HIV Co-infection prevalence was 3.5%. Those doing unprotected sexual practices [P= 0.03], Injection Drug users [P= 0.03], those who had an HBV-infected person in their family [P=0.02], infected with HIV [P= 0.025] were statistically associated with HBV infection. HCV was significantly associated with Substance users and previous history of unsafe surgical procedures [p=0.03, p=0.04), respectively. HIV was significantly associated with unprotected sexual practices and being homeless [p=0.045, p=0.05) respectively. Conclusion-The highly prevalent viral infection was HBV compared to others. There was a High prevalence of HBV/HIV co-infection. The presence of HBV-infected persons in a family, unprotected sexual practices and sharing of needles for drug injection were the risk factors associated with HBV, HIV, and HCV. Continuous health education and screening of the viral infection coupled with medical and psychological treatment is mandatory for the prevention and control of the infections.

Keywords: hepatitis b virus, hepatitis c virus, HIV, substance users

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2981 A Case of Postpartum Pulmonary Edema Induced by Oxytocin

Authors: May Zaw, Amber Latif, William Lim

Abstract:

Postpartum dyspnea can be due to many causes, such as pulmonary embolism, amniotic fluid embolism, and peripartum cardiomyopathy, but less frequently due to acute pulmonary edema. The incidence of acute pulmonary edema during pregnancy and in the postpartum period has been estimated to be around 0.08%. About half of the cases are attributed to tocolytic therapy. Herein, we present a case of a young woman presenting with acute hypoxia after induction of labor with oxytocin and found to have acute pulmonary edema. This case aims to illustrate and add to a growing body of literature regarding oxytocin-induced acute pulmonary edema and highlights the importance of recognizing the rare complication of oxytocin and necessary interventions to avoid complications. Oxytocin-induced pulmonary edema is a relatively uncommon condition, but physicians should have a high index of suspicion to initiate timely intervention and avoid fetal complications.

Keywords: pulmonary, pregnancy, oxytocin, postpartum

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2980 Men’s Attendance in Labour and Birth Room: A Choice and Coercion in Childbirth

Authors: A/Prof Marjan Khajehei

Abstract:

In the last century, the role of fathers in the birth has changed exponentially. Before the 1970s, the principal view was that birth was a female business and not a man’s place. Changing cultural and professional attitudes around the emotional bond between a man and a woman, family structure and the more proactive involved role of men in the family have encouraged fathers’ attendance at birth. There is evidence that fathers’ support can make birthing less traumatic for some women and can make couples closer. This has made some clinicians to believe the fathers should be more involved throughout the birth process. Some clinicians even go further and ask the fathers to watch the medical procedures, such as inserting vaginal speculum, forceps or vacuum, episiotomy and stitches. Although birth can unfold like a beautiful picture captured by birth photographers, with fathers massaging women’s backs by candle light and the miraculous moment of birth, it can be overshadowed by less attractive images of cervical mucous, emptying bowels and the invasive medical procedures. What happens in the birth room and the fathers’ reaction to the graphic experience of birthing can be unpredictable. Despite the fact that most men are absolutely thrilled to be in the delivery room, for some men, a very intimate body part can become completely desexualised, and they can experience psychological and sexual scarring. They see someone they cherish dramatically sliced open and can then associate their partners with a disturbing scene, and it can dramatically affect their relationships. While most women want the expectant fathers by their side for this life-changing event, not all of them may be happy for their partners to watch the perineum to be cut or stitched or when large blades of forceps are inserted inside the vagina. Anecdotal reports have shown that consent is not sought from the labouring women as to whether they want their partners to watch these procedures. The majority of research1, 2, 3 focuses on men’s and women’s retrospective attitudes towards their birth experience. However, the effect of witnessing invasive procedures during childbirth on a man's attraction to his partner, while she is most vulnerable, and also an increased risk of post-traumatic stress disorder in fathers have not been widely investigated. There is a lack of sufficient research investigating whether women need to be asked for their consent before inviting their partners to closely watch medical procedures during childbirth. Future research is required to provide a basis for better awareness and involve the consumers to understanding the men’s and women’s experience and their expectations for labour and birth.

Keywords: birth, childbirth, father, labour, men, women

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2979 Efficient Reuse of Exome Sequencing Data for Copy Number Variation Callings

Authors: Chen Wang, Jared Evans, Yan Asmann

Abstract:

With the quick evolvement of next-generation sequencing techniques, whole-exome or exome-panel data have become a cost-effective way for detection of small exonic mutations, but there has been a growing desire to accurately detect copy number variations (CNVs) as well. In order to address this research and clinical needs, we developed a sequencing coverage pattern-based method not only for copy number detections, data integrity checks, CNV calling, and visualization reports. The developed methodologies include complete automation to increase usability, genome content-coverage bias correction, CNV segmentation, data quality reports, and publication quality images. Automatic identification and removal of poor quality outlier samples were made automatically. Multiple experimental batches were routinely detected and further reduced for a clean subset of samples before analysis. Algorithm improvements were also made to improve somatic CNV detection as well as germline CNV detection in trio family. Additionally, a set of utilities was included to facilitate users for producing CNV plots in focused genes of interest. We demonstrate the somatic CNV enhancements by accurately detecting CNVs in whole exome-wide data from the cancer genome atlas cancer samples and a lymphoma case study with paired tumor and normal samples. We also showed our efficient reuses of existing exome sequencing data, for improved germline CNV calling in a family of the trio from the phase-III study of 1000 Genome to detect CNVs with various modes of inheritance. The performance of the developed method is evaluated by comparing CNV calling results with results from other orthogonal copy number platforms. Through our case studies, reuses of exome sequencing data for calling CNVs have several noticeable functionalities, including a better quality control for exome sequencing data, improved joint analysis with single nucleotide variant calls, and novel genomic discovery of under-utilized existing whole exome and custom exome panel data.

Keywords: bioinformatics, computational genetics, copy number variations, data reuse, exome sequencing, next generation sequencing

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2978 Video-Based System for Support of Robot-Enhanced Gait Rehabilitation of Stroke Patients

Authors: Matjaž Divjak, Simon Zelič, Aleš Holobar

Abstract:

We present a dedicated video-based monitoring system for quantification of patient’s attention to visual feedback during robot assisted gait rehabilitation. Two different approaches for eye gaze and head pose tracking are tested and compared. Several metrics for assessment of patient’s attention are also presented. Experimental results with healthy volunteers demonstrate that unobtrusive video-based gaze tracking during the robot-assisted gait rehabilitation is possible and is sufficiently robust for quantification of patient’s attention and assessment of compliance with the rehabilitation therapy.

Keywords: video-based attention monitoring, gaze estimation, stroke rehabilitation, user compliance

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2977 The Physiological Effect of Cold Atmospheric Pressure Plasma on Cancer Cells, Cancer Stem Cells, and Adult Stem Cells

Authors: Jeongyeon Park, Yeo Jun Yoon, Jiyoung Seo, In Seok Moon, Hae Jun Lee, Kiwon Song

Abstract:

Cold Atmospheric Pressure Plasma (CAPP) is defined as a partially ionized gas with electrically charged particles at room temperature and atmospheric pressure. CAPP generates reactive oxygen species (ROS) and reactive nitrogen species (RNS), and has potential as a new apoptosis-promoting cancer therapy. With an annular type dielectric barrier discharge (DBD) CAPP-generating device combined with a helium (He) gas feeding system, we showed that CAPP selectively induced apoptosis in various cancer cells while it promoted proliferation of the adipose tissue-derived stem cell (ASC). The apoptotic effect of CAPP was highly selective toward p53-mutated cancer cells. The intracellular ROS was mainly responsible for apoptotic cell death in CAPP-treated cancer cells. CAPP induced apoptosis even in doxorubicin-resistant cancer cell lines, demonstrating the feasibility of CAPP as a potent cancer therapy. With the same device and exposure conditions to cancer cells, CAPP stimulated proliferation of the ASC, a kind of mesenchymal stem cell that is capable of self-renewing and differentiating into adipocytes, chondrocytes, osteoblasts and neurons. CAPP-treated ASCs expressed the stem cell markers and differentiated into adipocytes as untreated ASCs. The increase of proliferation by CAPP in ASCs was offset by a NO scavenger but was not affected by ROS scavengers, suggesting that NO generated by CAPP is responsible for the activated proliferation in ASCs. Usually, cancer stem cells are reported to be resistant to known cancer therapies. When we applied CAPP of the same device and exposure conditions to cancer cells to liver cancer stem cells (CSCs) that express CD133 and epithelial cell adhesion molecule (EpCAM) cancer stem cell markers, apoptotic cell death was not examined. Apoptotic cell death of liver CSCs was induced by the CAPP generated from a device with an air-based flatten type DBD. An exposure of liver CSCs to CAPP decreased the viability of liver CSCs to a great extent, suggesting plasma be used as a promising anti-cancer treatment. To validate whether CAPP can be a promising anti-cancer treatment or an adjuvant modality to eliminate remnant tumor in cancer surgery of vestibular schwannoma, we applied CAPP to mouse schwannoma cell line SC4 Nf2 ‑/‑ and human schwannoma cell line HEI-193. A CAPP treatment leads to anti-proliferative effect in both cell lines. We are currently studying the molecular mechanisms of differential physiological effect of CAPP; the proliferation of ASCs and apoptosis of various cancer cells and CSCs.

Keywords: cold atmospheric pressure plasma, apoptosis, proliferation, cancer cells, adult stem cells

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2976 Visual Impairment Through Contextualized Lived Experiences: The Story of James

Authors: Jentel Van Havermaet, Geert Van Hove, Elisabeth De Schauwer

Abstract:

This study re-conceptualizes visual impairment in the interdependent context of James, his family, and allies. Living with a visual impairment is understood as an entanglement of assemblages, dynamics, disablism, systems… We narrated this diffractively into two meaningful events: decisions and processes on (inclusive) education and hinderances in connecting with others. We entangled and (un)raveled lived experiences in assemblages in which the contextualized meaning of visual impairment became more clearly. The contextualized narrative of James interwove complex intra-actions; showed the complexity and contextualization of entangled relationalities.

Keywords: disability studies, contextualization, visual impairment, assemblage, entanglement, lived experiences

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2975 A Systematic Review on the Whole-Body Cryotherapy versus Control Interventions for Recovery of Muscle Function and Perceptions of Muscle Soreness Following Exercise-Induced Muscle Damage in Runners

Authors: Michael Nolte, Iwona Kasior, Kala Flagg, Spiro Karavatas

Abstract:

Background: Cryotherapy has been used as a post-exercise recovery modality for decades. Whole-body cryotherapy (WBC) is an intervention which involves brief exposures to extremely cold air in order to induce therapeutic effects. It is currently being investigated for its effectiveness in treating certain exercise-induced impairments. Purpose: The purpose of this systematic review was to determine whether WBC as a recovery intervention is more, less, or equally as effective as other interventions at reducing perceived levels of muscle soreness and promoting recovery of muscle function after exercise-induced muscle damage (EIMD) from running. Methods: A systematic review of the current literature was performed utilizing the following MeSH terms: cryotherapy, whole-body cryotherapy, exercise-induced muscle damage, muscle soreness, muscle recovery, and running. The databases utilized were PubMed, CINAHL, EBSCO Host, and Google Scholar. Articles were included if they were published within the last ten years, had a CEBM level of evidence of IIb or higher, had a PEDro scale score of 5 or higher, studied runners as primary subjects, and utilized both perceived levels of muscle soreness and recovery of muscle function as dependent variables. Articles were excluded if subjects did not include runners, if the interventions included PBC instead of WBC, and if both muscle performance and perceived muscle soreness were not assessed within the study. Results: Two of the four articles revealed that WBC was significantly more effective than treatment interventions such as far-infrared radiation and passive recovery at reducing perceived levels of muscle soreness and restoring muscle power and endurance following simulated trail runs and high-intensity interval running, respectively. One of the four articles revealed no significant difference between WBC and passive recovery in terms of reducing perceived muscle soreness and restoring muscle power following sprint intervals. One of the four articles revealed that WBC had a harmful effect compared to CWI and passive recovery on both perceived muscle soreness and recovery of muscle strength and power following a marathon. Discussion/Conclusion: Though there was no consensus in terms of WBC’s effectiveness at treating exercise-induced muscle damage following running compared to other interventions, it seems as though WBC may at least have a time-dependent positive effect on muscle soreness and recovery following high-intensity interval runs and endurance running, marathons excluded. More research needs to be conducted in order to determine the most effective way to implement WBC as a recovery method for exercise-induced muscle damage, including the optimal temperature, timing, duration, and frequency of treatment.

Keywords: cryotherapy, physical therapy intervention, physical therapy, whole body cryotherapy

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2974 Evaluation of Cooperative Hand Movement Capacity in Stroke Patients Using the Cooperative Activity Stroke Assessment

Authors: F. A. Thomas, M. Schrafl-Altermatt, R. Treier, S. Kaufmann

Abstract:

Stroke is the main cause of adult disability. Especially upper limb function is affected in most patients. Recently, cooperative hand movements have been shown to be a promising type of upper limb training in stroke rehabilitation. In these movements, which are frequently found in activities of daily living (e.g. opening a bottle, winding up a blind), the force of one upper limb has to be equally counteracted by the other limb to successfully accomplish a task. The use of standardized and reliable clinical assessments is essential to evaluate the efficacy of therapy and the functional outcome of a patient. Many assessments for upper limb function or impairment are available. However, the evaluation of cooperative hand movement tasks are rarely included in those. Thus, the aim of this study was (i) to develop a novel clinical assessment (CASA - Cooperative Activity Stroke Assessment) for the evaluation of patients’ capacity to perform cooperative hand movements and (ii) to test its inter- and interrater reliability. Furthermore, CASA scores were compared to current gold standard assessments for upper extremity in stroke patients (i.e. Fugl-Meyer Assessment, Box & Blocks Test). The CASA consists of five cooperative activities of daily living including (1) opening a jar, (2) opening a bottle, (3) open and closing of a zip, (4) unscrew a nut and (5) opening a clipbox. Here, the goal is to accomplish the tasks as fast as possible. In addition to the quantitative rating (i.e. time) which is converted to a 7-point scale, also the quality of the movement is rated in a 4-point scale. To test the reliability of CASA, fifteen stroke subjects were tested within a week twice by the same two raters. Intra-and interrater reliability was calculated using the intraclass correlation coefficient (ICC) for total CASA score and single items. Furthermore, Pearson-correlation was used to compare the CASA scores to the scores of Fugl-Meyer upper limb assessment and the box and blocks test, which were assessed in every patient additionally to the CASA. ICC scores of the total CASA score indicated an excellent- and single items established a good to excellent inter- and interrater reliability. Furthermore, the CASA score was significantly correlated to the Fugl-Meyer and Box & Blocks score. The CASA provides a reliable assessment for cooperative hand movements which are crucial for many activities of daily living. Due to its non-costly setup, easy and fast implementation, we suggest it to be well suitable for clinical application. In conclusion, the CASA is a useful tool in assessing the functional status and therapy related recovery in cooperative hand movement capacity in stroke patients.

Keywords: activitites of daily living, clinical assessment, cooperative hand movements, reliability, stroke

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2973 Burnout and Personality Characteristics of University Students

Authors: Tazvin Ijaz, Rabia Khan

Abstract:

The current study was conducted to identify the predictors of burnout among university students. The sample for the study was collected through simple random sampling. The tools to measure burnout and personality characteristics included Indigenous burnout scale and Eysenck personality inventory respectively. Results indicated that neurotic personality traits significantly predicts burnout among university students while extraversion does not lead to burnout. Results also indicated female students experience more burnout than male students. It was also found that family size and birth order did not affected the level of burnout. Results of the study are discussed to explain association between etiological factors and burnout with in Pakistani cultural context.

Keywords: burnout, students, neuroticism, extraversion

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2972 Management Problems in a Patient With Long-term Undiagnosed Permanent Hypoparathyroidism

Authors: Babarina Maria, Andropova Margarita

Abstract:

Introduction: Hypoparathyroidism (HypoPT) is a rare endocrine disorder with an estimated prevalence of 0.25 per 1000 individuals. The most common cause of HypoPT is the loss of active parathyroid tissue following thyroid or parathyroid surgery. Sometimes permanent postoperative HypoPT occures, manifested by hypocalcemia in combination with low levels of PTH during 6 months or more after surgery. Cognitive impairments in patients with hypocalcemia due to chronic HypoPT are observed, and this can lead to problems and challenges in everyday living: memory loss and impaired concentration, that may be the cause of poor compliance. Clinical case: Patient K., 66 years old, underwent thyroidectomy in 2013 (at the age of 55) because of papillary thyroid cancer T1NxMx, histopathology findings confirmed the diagnosis. 5 years after the surgery, she was followed up on an outpatient basis, TSH levelsonly were monitored, and the dose of levothyroxine was adjusted. In 2018 due to, increasing complaints include tingling and cramps in the arms and legs, memory loss, sleep disorder, fatigue, anxiety, hair loss, muscle pain, tachycardia, positive Chvostek, and Trousseau signs were diagnosed during examination, also in blood analyses: total Ca 1.86 mmol/l (2.15-2.55), Ca++ 0.96 mmol/l (1.12-1.3), P 1.55 mmol/l (0.74-1.52), Mg 0.79 mmol/l (0.66-1.07) - chronic postoperative HypoPT was diagnosed. Therapy was initiated: alfacalcidol 0.5 mcg per day, calcium carbonate 2000 mg per day, cholecalciferol 1000 IU per day, magnesium orotate 3000 mg per day. During the case follow-up, hypocalcemia, hyperphosphatemia persisted, hypercalciuria15.7 mmol/day (2.5-6.5) was diagnosed. Dietary recommendations were given because of the high content of phosphorus rich foods, and therapy was adjusted: the dose of alfacalcidol was increased to 2.5 mcg per day, and the dose of calcium carbonate was reduced to 1500 mg per day. As part of the screening for complications of hypoPT, data for cataracts, Fahr syndrome, nephrocalcinosis, and kidney stone disease were not obtained. However, HypoPT compensation was not achieved, and therefore hydrochlorothiazide 25 mg was initiated, the dose of alfacalcidol was increased to 3 mcg per day, calcium carbonate to 3000 mg per day, magnesium orotate and cholecalciferol were continued at the same doses. Therapeutic goals were achieved: calcium phosphate product <4.4 mmol2/l2, there were no episodes of hypercalcemia, twenty-four-hour urinary calcium excretion was significantly reduced. Conclusion: Timely prescription, careful explanation of drugs usage rules, and monitoring and maintaining blood and urine parameters within the target contribute to the prevention of HypoPT complications development and life-threatening events.

Keywords: hypoparathyroidism, hypocalcemia, hyperphosphatemia, hypercalciuria

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2971 The Relationship between Caregiver Burden and Life Satisfaction of Caregivers of Elderly Individuals

Authors: Guler Duru Asiret, Cemile Kutmec Yilmaz, Gulcan Bagcivan, Tugce Turten Kaymaz

Abstract:

This descriptive study was conducted to determine the relationship between caregiver burden and life satisfaction who give home care to elderly individuals. The sample was recruited from the internal medicine unit and palliative unit of a state hospital located in Turkey on June 2016-2017. The study sample consisted of 231 primary caregiver family member, who met the eligibility criteria and agreed to participate in the study. The inclusion criteria were as follows: inpatient’s caregiver, primary caregiver for at least 3 months, at least 18 years of age, no communication problem or mental disorder. Data were gathered using an Information Form prepared by the researchers based on previous literature, the Zarit Burden Interview (ZBI), and the Satisfaction with Life Scale (SWLS). The data were analyzed using IBM SPSS Statistics software version 20.0 (SPSS, Chicago, IL). The descriptive characteristics of the participant were analyzed using number, percentage, mean and standard deviation. The suitability of normal distribution of scale scores was analyzed using Kolmogorov-Smirnov and Shapiro-Wilk test. Relationships between scales were analyzed using Spearman’s rank-correlation coefficient. P values less than 0.05 were considered to be significant. The average age of the caregivers was 50.11±13.46 (mean±SD) years. Of the caregivers, 76.2% were women, 45% were primary school graduates, 89.2% were married, 38.1% were the daughters of their patients. Among these, 52.4% evaluated their income level to be good. Of them, 53.6% had been giving care less than 2 years. The patients’ average age was 77.1±8.0 years. Of the patients, 55.8% were women, 56.3% were illeterate, 70.6% were married, and 97.4% had at least one chronic disease. The mean Zarit Burden Interview score was 35.4±1.5 and the Satisfaction with Life Scale score was 20.6±6.8. A negative relationship was found between the patients’ score average on the ZBI, and on the SWLS (r= -0.438, p=0.000). The present study determined that the caregivers have a moderate caregiver burden and the life satisfaction. And the life satisfaction of caregivers decreased as their caregiver burden increase. In line with the results obtained from the research, it is recommended that to increase the effectiveness of discharge training, to arrange training and counseling programs for caregivers to cope with the problems they experienced, to monitor the caregivers at regular intervals and to provide necessary institutional support.

Keywords: caregiver burden, family caregivers, nurses, satisfaction

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2970 Novel EGFR Ectodomain Mutations and Resistance to Anti-EGFR and Radiation Therapy in H&N Cancer

Authors: Markus Bredel, Sindhu Nair, Hoa Q. Trummell, Rajani Rajbhandari, Christopher D. Willey, Lewis Z. Shi, Zhuo Zhang, William J. Placzek, James A. Bonner

Abstract:

Purpose: EGFR-targeted monoclonal antibodies (mAbs) provide clinical benefit in some patients with H&N squamous cell carcinoma (HNSCC), but others progress with minimal response. Missense mutations in the EGFR ectodomain (ECD) can be acquired under mAb therapy by mimicking the effect of large deletions on receptor untethering and activation. Little is known about the contribution of EGFR ECD mutations to EGFR activation and anti-EGFR response in HNSCC. Methods: We selected patient-derived HNSCC cells (UM-SCC-1) for resistance to mAb Cetuximab (CTX) by repeated, stepwise exposure to mimic what may occur clinically and identified two concurrent EGFR ECD mutations (UM-SCC-1R). We examined the competence of the mutants to bind EGF ligand or CTX. We assessed the potential impact of the mutations through visual analysis of space-filling models of the native sidechains in the original structures vs. their respective side-chain mutations. We performed CRISPR in combination with site-directed mutagenesis to test for the effect of the mutants on ligand-independent EGFR activation and sorting. We determined the effects on receptor internalization, endocytosis, downstream signaling, and radiation sensitivity. Results: UM-SCC-1R cells carried two non-synonymous missense mutations (G33S and N56K) mapping to domain I in or near the EGF binding pocket of the EGFR ECD. Structural modeling predicted that these mutants restrict the adoption of a tethered, inactive EGFR conformation while not permitting association of EGFR with the EGF ligand or CTX. Binding studies confirmed that the mutant, untethered receptor displayed a reduced affinity for both EGF and CTX but demonstrated sustained activation and presence at the cell surface with diminished internalization and sorting for endosomal degradation. Single and double-mutant models demonstrated that the G33S mutant is dominant over the N56K mutant in its effect on EGFR activation and EGF binding. CTX-resistant UM-SCC-1R cells demonstrated cross-resistance to mAb Panitumuab but, paradoxically, remained sensitive to the reversible receptor tyrosine kinase inhibitor Erlotinib. Conclusions: HNSCC cells can select for EGFR ECD mutations under EGFR mAb exposure that converge to trap the receptor in an open, constitutively activated state. These mutants impede the receptor’s competence to bind mAbs and EGF ligand and alter its endosomal trafficking, possibly explaining certain cases of clinical mAb and radiation resistance.

Keywords: head and neck cancer, EGFR mutation, resistance, cetuximab

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2969 Obstructive Bronchitis and Pneumonia by a Mixed Infection of HPIV- 3, S. pneumoniae in an Immunocompromised 10M Infant: Case Report

Authors: Olga Smilevska Spasova, Katerina Boshkovska, Gorica Popova, Mirjana Popovska

Abstract:

Introduction: Pneumonia is an infection of the pulmonary parenchyma. HPIV 3 is one of four viruses that is a member of the Paramyxoviridae family designated types 1-4 that have a nonsegmented, single-stranded RNA genome with a lipid-containing envelope. They are spread from the respiratory tract by aerosolized secretions or by direct contact with secretions. Type 3 is endemic and can cause serious illness in immunocompromised patients. Illness caused by parainfluenza occurs shortly after inoculation with the virus. The level of immunoglobulin A antibody in serum is the best predictor of susceptibility to infection. Streptococcus pneumonia or pneumococcus is a Gram-positive, spherical bacteria, usually found in pairs and it is a member of the genus Streptococcus. Streptococcus pneumonia resides asymptomatically in healthy carriers typically colonizing the respiratory tract, sinuses, and nasal cavity. In individuals with weaker immune systems like young infants, pneumococcal bacterium is the most common cause of community-acquired pneumonia in the world. Case Report: The aim is to present a case of lower respiratory tract infection in an infant caused by parainfluenza virus 3, S. pneumonia and undifferentiated gram-negative bacteria that was successfully treated. The infant is with a history of recurrent episodes of wheezing in the past 3mounts.Infant of 10months presents 2weeks before admittance with high fever, runny nose, and cough. The primary pediatrician prescribed oral cefpodoxime for 10days and inhaled salbutamol. Two days before admittance in hospital the infant with high fever, cough, and difficulty breathing. At admittance, infant is pale, anxious with rapid respirations, cough, wheezing and tachycardia. On auscultation: vesicular breathing sounds with high pitched wheezing and on the right coarse crackles. Investigations: Blood analysis: RBC: 4, 7 x1012L, WBC: 8,3x109L: Neut: 42.73% Lym: 41.57%, Hgb: 9.38 g/dl MCV: 62.7fl, MCH: 20.0pg MCHC: 31.8 g/dl RDW: 18.7% Plt-307.9 x109LCRP: 2,5mg/l, serum iron-7.92umol/l, O2sat-97% on blood gas analysis, puls-125/min.X-ray of chest with hyperinflationand right pericardial consolidation. Microbiological analysis of sputum sample is positive for undifferentiated gram-negative bacteria (colonizer)–resistant to cefotaxime, ampicillin, cefoxitin, sulfamet.+trimetoprim and sensitive to amikacin, gentamicin, and ciprofloxacin. Molecular multiplex RT-PCR for 19 viruses and multiplex PCR for 7 bacteria test for respiratory pathogens positive for Parainfluenza virus 3(Ct=22.73), Streptococcus pneumonia (Ct=26.75).IED: IgG-9.31g/l, IgA-0.351g/l, IgM-0.86g/l. Therapy: Treatment was started with inhaled salbutamol, intravenous antibiotic cefotaxime as well as systemic corticosteroids. On day 7 because of slow clinical resolution of chest auscultation findings and an etiologic clue with a positive sputum sample for resistant undifferentiated gram negative bacteria, a second intravenous antibiotic was administered amikacin. The infant is discharged on day 14 with resolution of clinical findings. Conclusion: Mixed co-infections with respiratory viruses and bacteria in immunocompromised infants are likely to lead to a more severe form of community acquired pneumonia that will need hospitalization.

Keywords: HPIV- 3, infant, pneumonia, S. pneumonia, x-ray chest

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2968 A Geometrical Perspective on the Insulin Evolution

Authors: Yuhei Kunihiro, Sorin V. Sabau, Kazuhiro Shibuya

Abstract:

We study the molecular evolution of insulin from the metric geometry point of view. In mathematics, and particularly in geometry, distances and metrics between objects are of fundamental importance. Using a weaker notion than the classical distance, namely the weighted quasi-metrics, one can study the geometry of biological sequences (DNA, mRNA, or proteins) space. We analyze from the geometrical point of view a family of 60 insulin homologous sequences ranging on a large variety of living organisms from human to the nematode C. elegans. We show that the distances between sequences provide important information about the evolution and function of insulin.

Keywords: metric geometry, evolution, insulin, C. elegans

Procedia PDF Downloads 321
2967 Modeling and Control of a 4DoF Robotic Assistive Device for Hand Rehabilitation

Authors: Christopher Spiewak, M. R. Islam, Mohammad Arifur Rahaman, Mohammad H. Rahman, Roger Smith, Maarouf Saad

Abstract:

For those who have lost the ability to move their hand, going through repetitious motions with the assistance of a therapist is the main method of recovery. We have been developed a robotic assistive device to rehabilitate the hand motions in place of the traditional therapy. The developed assistive device (RAD-HR) is comprised of four degrees of freedom enabling basic movements, hand function, and assists in supporting the hand during rehabilitation. We used a nonlinear computed torque control technique to control the RAD-HR. The accuracy of the controller was evaluated in simulations (MATLAB/Simulink environment). To see the robustness of the controller external disturbance as modelling uncertainty (±10% of joint torques) were added in each joints.

Keywords: biorobotics, rehabilitation, robotic assistive device, exoskeleton, nonlinear control

Procedia PDF Downloads 459
2966 Erythema Multiforme Exudativum Major Caused by Isoniazid Hypersensitivity in a Child

Authors: Azwin Lubis, Rika Hapsari, Zahrah Hikmah, Anang Endaryanto, Ariyanto Harsono

Abstract:

Erythema Multiforme Exudativum Major (EMEM) is one of the drug allergy diseases. Drug allergies caused by isoniazid rarely causes EMEM. Cutaneous reactions caused by isoniazid were obtained in 0.98% of patients, but the precise occurrence of Steven Johnson’s Syndrome (SJS) and Toxic Epidermolisis Necrolisis (TEN) due to isoniazid is not known for certain. We present this case to show hypersensitivity of isoniazid in a child. Based on the history of drug intake, physical diagnostic tests, drug elimination and provocation; we established the diagnosis of isoniazid hypersensitivity. The child showed improvement on skin manifestation after stopped isoniazid therapy.

Keywords: erythema multiforme exudativum major, hypersensitivity, elimination test, provocation test

Procedia PDF Downloads 242
2965 Low Density Lipoprotein: The Culprit in the Development of Obesity

Authors: Ojiegbe Ikenna Nathan

Abstract:

Obesity is a medical condition in which excess body fat has accumulated to the extent that it leads to reduced life expectancy and or increased health problems. Obesity as a worldwide problem is seen clustered in the families and it moves from generation to generation. It causes some disabilities, mortality and morbidity if left unattended to. The predisposing factors to obesity are either genetic or environment in origin. Nevertheless, the main predisposing factor to obesity is the excessive consumption of food rich in low-density lipoprotein (LDL) such as organ meats, saturated fats etc. This low-density lipoprotein causes an increase in adipose tissue and complicates to obesity. There are varieties of obesity which one needs to take appropriate measures to avoid; such as android, gynoid and morbid obesity. Nonetheless, studies have shown that there is hope for the obese individuals, despite the cause, type and degree of their obesity. This is through the use of the different available treatment measures which increase in physical activities, caloric restrictions, drug therapy and surgical intervention.

Keywords: low-density, lipoprotein, culprit, obesity

Procedia PDF Downloads 389
2964 Delivery of Contraceptive and Maternal Health Commodities with Drones in the Most Remote Areas of Madagascar

Authors: Josiane Yaguibou, Ngoy Kishimba, Issiaka V. Coulibaly, Sabrina Pestilli, Falinirina Razanalison, Hantanirina Andremanisa

Abstract:

Background: Madagascar has one of the least developed road networks in the world with a majority of its national and local roads being earth roads and in poor condition. In addition, the country is affected by frequent natural disasters that further affect the road conditions limiting the accessibility to some parts of the country. In 2021 and 2022, 2.21 million people were affected by drought in the Grand Sud region, and by cyclones and floods in the coastal regions, with disruptions of the health system including last mile distribution of lifesaving maternal health commodities and reproductive health commodities in the health facilities. Program intervention: The intervention uses drone technology to deliver maternal health and family planning commodities in hard-to-reach health facilities in the Grand Sud and Sud-Est of Madagascar, the regions more affected by natural disasters. Methodology The intervention was developed in two phases. A first phase, conducted in the Grand Sud, used drones leased from a private company to deliver commodities in isolated health facilities. Based on the lesson learnt and encouraging results of the first phase, in the second phase (2023) the intervention has been extended to the Sud Est regions with the purchase of drones and the recruitment of pilots to reduce costs and ensure sustainability. Key findings: The drones ensure deliveries of lifesaving commodities in the Grand Sud of Madagascar. In 2023, 297 deliveries in commodities in forty hard-to-reach health facilities have been carried out. Drone technology reduced delivery times from the usual 3 - 7 days necessary by road or boat to only a few hours. Program Implications: The use of innovative drone technology demonstrated to be successful in the Madagascar context to reduce dramatically the distribution time of commodities in hard-to-reach health facilities and avoid stockouts of life-saving medicines. When the intervention reaches full scale with the completion of the second phase and the extension in the Sud-Est, 150 hard-to-reach facilities will receive drone deliveries, avoiding stockouts and improving the quality of maternal health and family planning services offered to 1,4 million people in targeted areas.

Keywords: commodities, drones, last-mile distribution, lifesaving supplies

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2963 In vitro Susceptibility of Isolated Shigella flexneri and Shigella dysenteriae to the Ethanolic Extracts of Trachyspermum ammi and Peganum harmala

Authors: Ibrahim Siddig Hamid, Ikram Mohamed Eltayeb

Abstract:

Trachyspermum ammi belongs to the family Apiaceae, is used traditionally for the treatment of gastrointestinal ailments, lack of appetite and bronchial problems as well used as antiseptic, antimicrobial, antipyretic, febrifugal and in the treatment of typhoid fever. Peganum harmala belongs to the family Zygophyllaceae it has been reported to have an antibacterial activity and used to treat depression and recurring fevers. It also used to kill algae, bacteria, intestinal parasites and molds. In Sudan, the combination of two plants are traditionally used for the treatment of bacillary dysentery. Bacillary dysentery is caused by one or more types of Shigella species bacteria mainly Shigella dysenteri and shigella flexneri. Bacillary dysentery is mainly found in hot countries like Sudan with poor hygiene and sanitation. Bacillary dysentery causes sudden onset of high fever and chills, abdominal pain, cramps and bloating, urgency to pass stool, weight loss, and dehydration and if left untreated it can lead to serious complications including delirium, convulsions and coma. A serious infection like this can be fatal within 24 hours. The objective of this study is to investigate the in vitro susceptibility of Sh. flexneri and Sh. dysenteriae to the T. ammi and P. harmala. T. ammi and P. harmala were extracted by 96% ethanol using Soxhlet apparatus. The antimicrobial activity of the extracts was investigated according to the disc diffusion method. The discs were prepared by soaking sterilized filter paper discs in 20 microliter of serially diluted solutions of each plant extract with the concentrations (100, 50, 25, 12.5, 6.25mg/dl) then placing them on Muller Hinton Agar plates that were inoculated with bacterial suspension separately, the plates were incubated for 24 hours at 37c and the minimum inhibitory concentration of the extract which was the least concentration of the extract to inhibit fungal growth was determined. The results showed the high antimicrobial activity of T. ammi extract with an average diameter zone ranging from 18-20 mm and its minimum inhibitory concentration was found to be 25 mg/ml against the two shigella species. P. harmala extract was found to have slight antibacterial effect against the two bacteria. This result justified the Sudanese traditional use of Trachyspermum ammi plant for the treatment of bacillary dysentery.

Keywords: harmala, peganum, shigella, trachyspermum

Procedia PDF Downloads 229
2962 An Elbow Biomechanical Model and Its Coefficients Adjustment

Authors: Jie Bai, Yongsheng Gao, Shengxin Wang, Jie Zhao

Abstract:

Through the establishment of the elbow biomechanical model, it can provide theoretical guide for rehabilitation therapy on the upper limb of the human body. A biomechanical model of the elbow joint can be built by the connection of muscle force model and elbow dynamics. But there are many undetermined coefficients in the model like the optimal joint angle and optimal muscle force which are usually specified as the experimental parameters of other workers. Because of the individual differences, there is a certain deviation of the final result. To this end, the RMS value of the deviation between the actual angle and calculated angle is considered. A set of coefficients which lead to the minimum RMS value will be chosen to be the optimal parameters. The direct search method and the conjugacy search method are used to get the optimal parameters, thus the model can be more accurate and mode adaptability.

Keywords: elbow biomechanical model, RMS, direct search, conjugacy search

Procedia PDF Downloads 533
2961 The Role of Genetic Markers in Prostate Cancer Diagnosis and Treatment

Authors: Farman Ali, Asif Mahmood

Abstract:

The utilization of genetic markers in prostate cancer management represents a significant advance in personalized medicine, offering the potential for more precise diagnosis and tailored treatment strategies. This paper explores the pivotal role of genetic markers in the diagnosis and treatment of prostate cancer, emphasizing their contribution to the identification of individual risk profiles, tumor aggressiveness, and response to therapy. By integrating current research findings, we discuss the application of genetic markers in developing targeted therapies and the implications for patient outcomes. Despite the promising advancements, challenges such as accessibility, cost, and the need for further validation in diverse populations remain. The paper concludes with an outlook on future directions, underscoring the importance of genetic markers in revolutionizing prostate cancer care.

Keywords: prostate cancer, genetic markers, personalized medicine, BRCA1 and BRCA2

Procedia PDF Downloads 49
2960 The Writing Eight Exercise and Its Impact on Kindergartners

Authors: Karima Merchant

Abstract:

The aim of this study was to analyze the impact of the Writing Eight Exercise, an exercise from the Brain Integration Therapy, with Kindergartners who are struggling with writing tasks in school. With the help of this exercise, children were able to cross the midline, an invisible line running from our brain to our feet, which separates the body’s right from left. Crossing the midline integrates the brain hemispheres, thus encouraging bilateral movement. The study was spread over 15 weeks where the children were required to do the Writing Eight Exercise 4 times a week. The data collection methods included observations, student work samples and feedback from teachers and parents. Based on the results of this study, it can be concluded that the Writing Eight Exercise had a positive impact on students’ approach towards writing tasks, letter formation, and fine motor skills.

Keywords: crossing the midline, fine motor skills, letter formation, writing

Procedia PDF Downloads 447
2959 Prediction of Outcome after Endovascular Thrombectomy for Anterior and Posterior Ischemic Stroke: ASPECTS on CT

Authors: Angela T. H. Kwan, Wenjun Liang, Jack Wellington, Mohammad Mofatteh, Thanh N. Nguyen, Pingzhong Fu, Juanmei Chen, Zile Yan, Weijuan Wu, Yongting Zhou, Shuiquan Yang, Sijie Zhou, Yimin Chen

Abstract:

Background: Endovascular Therapy (EVT)—in the form of mechanical thrombectomy—following intravenous thrombolysis is the standard gold treatment for patients with acute ischemic stroke (AIS) due to large vessel occlusion (LVO). It is well established that an ASPECTS ≥ 7 is associated with an increased likelihood of positive post-EVT outcomes, as compared to an ASPECTS < 7. There is also prognostic utility in coupling posterior circulation ASPECTS (pc-ASPECTS) with magnetic resonance imaging for evaluating the post-EVT functional outcome. However, the value of pc-ASPECTS applied to CT must be explored further to determine its usefulness in predicting functional outcomes following EVT. Objective: In this study, we aimed to determine whether pc-ASPECTS on CT can predict post-EVT functional outcomes among patients with AIS due to LVO. Methods: A total of 247 consecutive patients aged 18 and over receiving EVT for LVO-related AIS were recruited into a prospective database. The data were retrospectively analyzed between March 2019 to February 2022 from two comprehensive tertiary care stroke centers: Foshan Sanshui District People’s Hospital and First People's Hospital of Foshan in China. Patient parameters included EVT within 24hrs of symptom onset, premorbid modified Rankin Scale (mRS) ≤ 2, presence of distal and terminal cerebral blood vessel occlusion, and subsequent 24–72-hour post-stroke onset CT scan. Univariate comparisons were performed using the Fisher exact test or χ2 test for categorical variables and the Mann–Whitney U test for continuous variables. A p-value of ≤ 0.05 was statistically significant. Results: A total of 247 patients met the inclusion criteria; however, 3 were excluded due to the absence of post-CTs and 8 for pre-EVT ASPECTS < 7. Overall, 236 individuals were examined: 196 anterior circulation ischemic strokes and 40 posterior strokes of basilar artery occlusion. We found that both baseline post- and pc-ASPECTS ≥ 7 serve as strong positive markers of favorable outcomes at 90 days post-EVT. Moreover, lower rates of inpatient mortality/hospice discharge, 90-day mortality, and 90-day poor outcome were observed. Moreover, patients in the post-ASPECTS ≥ 7 anterior circulation group had shorter door-to-recanalization time (DRT), puncture-to-recanalization time (PRT), and last known normal-to-puncture-time (LKNPT). Conclusion: Patients of anterior and posterior circulation ischemic strokes with baseline post- and pc-ASPECTS ≥ 7 may benefit from EVT.

Keywords: endovascular therapy, thrombectomy, large vessel occlusion, cerebral ischemic stroke, ASPECTS

Procedia PDF Downloads 98
2958 Using a Phenomenological Approach to Explore the Experiences of Nursing Students in Coping with Their Emotional Responses in Caring for End-Of-Life Patients

Authors: Yun Chan Lee

Abstract:

Background: End-of-life care is a large area of all nursing practice and student nurses are likely to meet dying patients in many placement areas. It is therefore important to understand the emotional responses and coping strategies of student nurses in order for nursing education systems to have some appreciation of how nursing students might be supported in the future. Methodology: This research used a qualitative phenomenological approach. Six student nurses understanding a degree-level adult nursing course were interviewed. Their responses to questions were analyzed using interpretative phenomenological analysis. Finding: The findings identified 3 main themes. First, the common experience of ‘unpreparedness’. A very small number of participants felt that this was unavoidable and that ‘no preparation is possible’, the majority felt that they were unprepared because of ‘insufficient input’ from the university and as a result of wider ‘social taboos’ around death and dying. The second theme showed that emotions were affected by ‘the personal connection to the patient’ and the important sub-themes of ‘the evoking of memories’, ‘involvement in care’ and ‘sense of responsibility’. The third theme, the coping strategies used by students, seemed to fall into two broad areas those ‘internal’ with the student and those ‘external’. In terms of the internal coping strategies, ‘detachment’, ‘faith’, ‘rationalization’ and ‘reflective skills’ are the important components of this part. Regarding the external coping strategies, ‘clinical staff’ and ‘the importance of family and friends’ are the importance of accessing external forms of support. Implication: It is clear that student nurses are affected emotionally by caring for dying patients and many of them have apprehension even before they begin on their placements but very often this is unspoken. Those anxieties before the placement become more pronounced during and continue after the placements. This has implications for when support is offered and possibly its duration. Another significant point of the study is that participants often highlighted their wish to speak to qualified nurses after their experiences of being involved in end-of-life care and especially when they had been present at the time of death. Many of the students spoke that qualified nurses were not available to them. This seemed to be due to a number of reasons. Because the qualified nurses were not available, students had to make use of family members and friends to talk to. Consequently, the implication of this study is not only to educate student nurses but also to educate the qualified mentors on the importance of providing emotional support to students.

Keywords: nursing students, coping strategies, end-of-life care, emotional responses

Procedia PDF Downloads 148
2957 [Keynote Speech]: Facilitating Familial Support of Saudi Arabians Living with HIV/AIDS

Authors: Noor Attar

Abstract:

The paper provides an overview of the current situation of HIV/AIDS patients in the Kingdom of Saudi Arabia (KSA) and a literature review of the concepts of stigma communication, communication of social support. These concepts provide the basis for the proposed methods, which will include conducting a textual analysis of materials that are currently distributed to family members of persons living with HIV/AIDS (PLWHIV/A) in KSA and creating an educational brochure. The brochure will aim to help families of PLWHIV/A in KSA (1) understand how stigma shapes the experience of PLWHIV/A, (2) realize the role of positive communication as a helpful social support, and (3) develop the ability to provide positive social support for their loved ones.

Keywords:

Procedia PDF Downloads 306
2956 How Geant4 Hadronic Models Handle Tracking of Pion Particles Resulting from Antiproton Annihilation

Authors: M. B. Tavakoli, R. Reiazi, M. M. Mohammadi, K. Jabbari

Abstract:

From 2003, AD4/ACE experiment in CERN tried to investigate different aspects of antiproton as a new modality in particle therapy. Because of lack of reliable absolute dose measurements attempts to find out the radiobiological characteristics of antiproton have not reached to a reasonable result yet. From the other side, application of Geant4 in medical approaches is increased followed by Geant4-DNA project which focuses on using this code to predict radiation effects in the cellular scale. This way we can exploit Geant4-DNA results for antiproton. Unfortunately, previous studies showed there are serious problem in simulating an antiproton beam using Geant4. Since most of the problem was in the Bragg peak region which antiproton annihilates there, in this work we tried to understand if the problem came from the way in which Geant4 handles annihilation products especially pion particles. This way, we can predict the source of the dose discrepancies between Geant4 simulations and dose measurements done in CERN.

Keywords: Geant4, antiproton, annihilation, pion plus, pion minus

Procedia PDF Downloads 645
2955 Combined Treatment of Estrogen-Receptor Positive Breast Microtumors with 4-Hydroxytamoxifen and Novel Non-Steroidal Diethyl Stilbestrol-Like Analog Produces Enhanced Preclinical Treatment Response and Decreased Drug Resistance

Authors: Sarah Crawford, Gerry Lesley

Abstract:

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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2954 New Evaluation of the Richness of Cactus (Opuntia) in Active Biomolecules and their Use in Agri-Food, Cosmetic, and Pharmaceutical

Authors: Lazhar Zourgui

Abstract:

Opuntia species are used as local medicinal interventions for chronic diseases and as food sources, mainly because they possess nutritional properties and biological activities. Opuntia ficus-indica (L.) Mill, commonly known as prickly pear or nopal cactus, is the most economically valuable plant in the Cactaceae family worldwide. It is a tropical or subtropical plant native to tropical and subtropical America, which can grow in arid and semi-arid climates. It belongs to the family of angiosperms dicotyledons Cactaceae of which about 1500 species of cacti are known. The Opuntia plant is distributed throughout the world and has great economic potential. There are differences in the phytochemical composition of Opuntia species between wild and domesticated species and within the same species. It is an interesting source of plant bioactive compounds. Bioactive compounds are compounds with nutritional benefits and are generally classified into phenolic and non-phenolic compounds and pigments. Opuntia species are able to grow in almost all climates, for example, arid, temperate, and tropical climates, and their bioactive compound profiles change depending on the species, cultivar, and climatic conditions. Therefore, there is an opportunity for the discovery of new compounds from different Opuntia cultivars. Health benefits of prickly pear are widely demonstrated: There is ample evidence of the health benefits of consuming prickly pear due to its source of nutrients and vitamins and its antioxidant properties due to its content of bioactive compounds. In addition, prickly pear is used in the treatment of hyperglycemia and high cholesterol levels, and its consumption is linked to a lower incidence of coronary heart disease and certain types of cancer. It may be effective in insulin-independent type 2 diabetes mellitus. Opuntia ficus-Indica seed oil has shown potent antioxidant and prophylactic effects. Industrial applications of these bioactive compounds are increasing. In addition to their application in the pharmaceutical industries, bioactive compounds are used in the food industry for the production of nutraceuticals and new food formulations (juices, drinks, jams, sweeteners). In my lecture, I will review in a comprehensive way the phytochemical, nutritional, and bioactive compound composition of the different aerial and underground parts of Opuntia species. The biological activities and applications of Opuntia compounds are also discussed.

Keywords: medicinal plants, cactus, Opuntia, actives biomolecules, biological activities

Procedia PDF Downloads 88