Search results for: clinical markers

Authors: Nadia Arikat, Katharine Blain

Abstract:

During the worst of the COVID pandemic, only essential treatment was provided for patients needing urgent care. With the prolonged extent of the pandemic, there has been a return to more routine referrals for paediatric dentistry advice and treatment for specialist conditions. However, some of these patients and/or their carers may have significant medical issues meaning that attending in-person appointments carries additional risks. This poses an ethical dilemma for clinicians. This project looks at how a secure video conferencing platform (“Near Me”) has been used to assess the need and urgency for in-person new patient visits, particularly for patients and families with additional risks. “Near Me” is a secure online video consulting service used by NHS Scotland. In deciding whether to bring a new patient to the hospital for an appointment, the clinical condition of the teeth together with the urgency for treatment need to be assessed. This is not always apparent from the referral letter. In addition, it is important to judge the risks to the patients and carers of such visits, particularly if they have medical issues. The use and effectiveness of “Near Me” consultations to help decide whether vulnerable paediatric patients should have in-person appointments will be illustrated and discussed using two families: one where the child is medically compromised (Alagille syndrome with previous liver transplant), and the other where there is a medically compromised parent (undergoing chemotherapy and a bone marrow transplant). In both cases, it was necessary to take into consideration the risks and moral implications of requesting that they attend the dental hospital during a pandemic. The option of remote consultation allowed further clinical information to be evaluated and the families take part in the decision-making process about whether and when such visits should be scheduled. These cases will demonstrate how medically compromised patients (or patients with vulnerable carers), could have their dental needs assessed in a socially distanced manner by video consultation. Together, the clinician and the patient’s family can weigh up the risks, with regards to COVID-19, of attending for in-person appointments against the benefit of having treatment. This is particularly important for new paediatric patients who have not yet had a formal assessment. The limitations of this technology will also be discussed. It is limited by internet availability, the strength of the connection, the video quality and families owning a device which allows video calls. For those from a lower socio-economic background or living in some rural areas, this may not be possible or limit its usefulness. For the two patients discussed in this project, where the urgency of their dental condition was unclear, video consultation proved beneficial in deciding an appropriate outcome and preventing unnecessary exposure of vulnerable people to a hospital environment during a pandemic, demonstrating the usefulness of such technology when it is used appropriately.

Keywords: COVID-19, paediatrics, triage, video consultations

Procedia PDF Downloads 97

Authors: Li Wang, Dan Shu, Shiguang Pang, Lixiu Wang, Bing Xiang Yang, Qian Liu

Abstract:

Background: Cancer is one of the most severe diseases in childhood; long-term treatment and its side effects significantly impact the patient's physical, psychological, social functioning and quality of life while also placing substantial physical and psychological burdens on caregivers and families. Family resilience is crucial for children with cancer, helping them cope better with the disease and supporting the family in facing challenges together. As a family-level variable, family resilience requires information from multiple family members. However, to our best knowledge, there is currently no research investigating family resilience from both the perspectives of pediatric cancer patients and their caregivers. Therefore, this study aims to investigate the family resilience and quality of life of pediatric cancer patients from a patient–caregiver dyadic perspective. Methods: A total of 149 dyads of patients diagnosed with pediatric cancer patients and their principal caregivers were recruited from oncology departments of 4 tertiary hospitals in Wuhan and Taiyuan, China. All participants completed questionnaires that identified their demographic and clinical characteristics as well as assessed their family resilience and quality of life for both the patients and their caregivers. K-means cluster analysis was used to identify different clusters of family resilience based on the reports from patients and caregivers. Multivariate logistic regression and linear regression are used to analyze the factors influencing family resilience and quality of life, as well as the relationship between the two. Results: Three clusters of family resilience were identified: a cluster of high family resilience (HR), a cluster of low family resilience (LR), and a cluster of discrepant family resilience (DR). Most (67.1%) families fell into the cluster with low resilience. Characteristics such as the types of caregivers perceived social support of the patient were different among the three clusters. Compared to the LR group, families where the mother is the caregiver and where the patient has high social support are more likely to be assigned to the HR. The quality of life for caregivers was consistently highest in the HR cluster and lowest in the LR cluster. The patient's quality of life is not related to family resilience. In the linear regression analysis of the patient's quality of life, patients who are the first-born have higher quality of life, while those living with their parents have lower quality of life. The participants' characteristics were not associated with the quality of life for caregivers. Conclusions: In most families, family resilience was low. Families with maternal caregivers and patients receiving high levels of social support are more inclined to be higher levels of family resilience. Family resilience was linked to the quality of life of caregivers of pediatric cancer patients. The clinical implications of this findings suggest that healthcare and social support organizations should prioritize and support the participation of mothers in caregiving responsibilities. Furthermore, they should assist families in accessing social support to enhance family resilience. This study also emphasizes the importance of promoting family resilience for enhancing family health and happiness, as well as improving the quality of life for caregivers.

Keywords: pediatric cancer, cluster analysis, family resilience, quality of life

Procedia PDF Downloads 36

Authors: Neerja Meena, Paresh Sukhani

Abstract:

Dandy walker malformation is a generalised disorder of mesenchymal development that affect both the cerebellum and overlying meninges. Classically dandy-walker malformation consists of a triad of- 1:vermian and hemispheric cerebellar hypoplasia 2:cystic dilatation of 4th ventricle 3: enlarged posterior fossa with the upward migration of tentorium(lambdoid- torcular inversion). Clinical presentation: four months old female child with hydrocephalus and neurological symptoms. Generally- early death is common in classic dandy walker malformation. However, if it is relatively mild and uncomplicated by other CNS anomalies, intelligence can be normal and neurologic deficits minimal. Usually, VP shunting is the treatment of choice for this hydrocephalus. Conclusion: MRI is the modality of choice to diagnose posterior fossa malformation. However, it can be ruled out through using during the antenatal check as the prognosis of this malformation is not good; it's better to diagnose it inutero.

Keywords: Dandy Walker, Mri, Earlydaignosis, Treatment

Procedia PDF Downloads 73

Authors: Junior Akunzi

Abstract:

In the matter of patient treatment planning quality assurance in 3D conformational therapy (3D-CRT) and volumetric arc therapy (VMAT or RapidArc), the independent monitor unit verification calculation (MUVC) is an indispensable part of the process. Concerning 3D-CRT treatment planning, the MUVC can be performed manually applying the standard ESTRO formalism. However, due to the complex shape and the amount of beams in advanced treatment planning technic such as RapidArc, the manual independent MUVC is inadequate. Therefore, commercially available software such as RadCalc can be used to perform the MUVC in complex treatment planning been. Indeed, RadCalc (version 6.3 LifeLine Inc.) uses a simplified Clarkson algorithm to compute the dose contribution for individual RapidArc fields to the isocenter. The purpose of this project is the validation of RadCalc in 3D-CRT and RapidArc for treatment planning dosimetry quality assurance at Antoine Lacassagne center (Nice, France). Firstly, the interfaces between RadCalc and our treatment planning systems (TPS) Isogray (version 4.2) and Eclipse (version13.6) were checked for data transfer accuracy. Secondly, we created test plans in both Isogray and Eclipse featuring open fields, wedges fields, and irregular MLC fields. These test plans were transferred from TPSs according to the radiotherapy protocol of DICOM RT to RadCalc and the linac via Mosaiq (version 2.5). Measurements were performed in water phantom using a PTW cylindrical semiflex ionisation chamber (0.3 cm³, 31010) and compared with the TPSs and RadCalc calculation. Finally, 30 3D-CRT plans and 40 RapidArc plans created with patients CT scan were recalculated using the CT scan of a solid PMMA water equivalent phantom for 3D-CRT and the Octavius II phantom (PTW) CT scan for RapidArc. Next, we measure the doses delivered into these phantoms for each plan with a 0.3 cm³ PTW 31010 cylindrical semiflex ionisation chamber (3D-CRT) and 0.015 cm³ PTW PinPoint ionisation chamber (Rapidarc). For our test plans, good agreements were found between calculation (RadCalc and TPSs) and measurement (mean: 1.3%; standard deviation: ± 0.8%). Regarding the patient plans, the measured doses were compared to the calculation in RadCalc and in our TPSs. Moreover, RadCalc calculations were compared to Isogray and Eclispse ones. Agreements better than (2.8%; ± 1.2%) were found between RadCalc and TPSs. As for the comparison between calculation and measurement the agreement for all of our plans was better than (2.3%; ± 1.1%). The independent MU verification calculation software RadCal has been validated for clinical use and for both 3D-CRT and RapidArc techniques. The perspective of this project includes the validation of RadCal for the Tomotherapy machine installed at centre Antoine Lacassagne.

Keywords: 3D conformational radiotherapy, intensity modulated radiotherapy, monitor unit calculation, dosimetry quality assurance

Procedia PDF Downloads 214

Authors: Medha Basu, Kumardeb Banerjee, Dipak Ghosh

Abstract:

After the massive blow of the COVID-19 pandemic, several health hazards have been reported all over the world. Serious cases of Major Depressive Disorder (MDD) are seen to be common in about 15% of the global population, making depression one of the leading mental health diseases, as reported by the World Health Organization. Various psychological and pharmacological treatment techniques are regularly being reported. Music, a globally accepted mode of entertainment, is often used as a therapeutic measure to treat various health conditions. We have tried to understand how Indian Classical Music can affect the overall well-being of the human brain. A case study has been reported here, where a Flute-rendition has been chosen from a detailed audience response survey, and the effects of that clip on human brain conditions have been studied from both psychological and neural perspectives. Taking help from internationally-accepted depression-rating scales, two questionnaires have been designed to understand both the prolonged and immediate effect of music on various emotional states of human lives. Thereafter, from EEG experiments on 5 participants using the same clip, the parameter ‘ALAY’, alpha frontal asymmetry (alpha power difference of right and left frontal hemispheres), has been calculated. Works of Richard Davidson show that an increase in the ‘ALAY’ value indicates a decrease in depressive symptoms. Using the non-linear technique of MFDFA on EEG analysis, we have also calculated frontal asymmetry using the complexity values of alpha-waves in both hemispheres. The results show a positive correlation between both the psychological survey and the EEG findings, revealing the prominent role of music on the human brain, leading to a decrease in mental unrest and an increase in overall well-being. In this study, we plan to propose the scientific foundation of music therapy, especially from a neurocognition perspective, with appropriate neural bio-markers to understand the positive and remedial effects of music on the human brain.

Keywords: music therapy, EEG, psychological survey, frontal alpha asymmetry, wellbeing

Procedia PDF Downloads 40

Authors: Fathi Kallel, Saida Khachira, Mohamed Ben Slima, Ahmed Ben Hamida

Abstract:

Speckle noise is a main characteristic of cardiac ultrasound images, it corresponding to grainy appearance that degrades the image quality. For this reason, the ultrasound images are difficult to use automatically in clinical use, then treatments are required for this type of images. Then a filtering procedure of these images is necessary to eliminate the speckle noise and to improve the quality of ultrasound images which will be then segmented to extract the necessary forms that exist. In this paper, we present the importance of the pre-treatment step for segmentation. This work is applied to cardiac ultrasound images. In a first step, a comparative study of speckle filtering method will be presented and then we use a segmentation algorithm to locate and extract cardiac structures.

Keywords: medical image processing, ultrasound images, Speckle noise, image enhancement, speckle filtering, segmentation, snakes

Procedia PDF Downloads 524

Authors: J. F. Pollo Gaspary, F. Peron Gaspary, E. M. Simão, R. Concatto Beltrame, G. Orengo de Oliveira, M. S. Ristow Ferreira, J.C. Mairesse Siluk, I. F. Minello, F. dos Santos de Oliveira

Abstract:

Background: Although palliative care policies and services have been developed, research in this area continues to lag. An integrated model of palliative care is suggested, which includes complementary and alternative services aimed at improving the well-being of patients and their families. The palliative aquatics care multi-device (AuBento) uses several electromagnetic techniques to decrease pain and promote well-being through relaxation and interaction among patients, specialists, and family members. Aim: The scope of this paper is to present a preliminary design study of a device capable of exploring the various existing theories on the biomedical application of magnetic fields. This will be achieved by standardizing clinical data collection with sensory integration, and adding new therapeutic options to develop an advanced palliative aquatics care, innovating in symptom and pain management. Methods: The research methodology was based on the Work Package Methodology for the development of projects, separating the activities into seven different Work Packages. The theoretical basis was carried out through an integrative literature review according to the specific objectives of each Work Package and provided a broad analysis, which, together with the multiplicity of proposals and the interdisciplinarity of the research team involved, generated consistent and understandable complex concepts in the biomedical application of magnetic fields for palliative care. Results: Aubento ambience was idealized with restricted electromagnetic exposure (avoiding data collection bias) and sensory integration (allowing relaxation associated with hydrotherapy, music therapy, and chromotherapy or like floating tank). This device has a multipurpose configuration enabling classic or exploratory options on the use of the biomedical application of magnetic fields at the researcher's discretion. Conclusions: Several patients in diverse therapeutic contexts may benefit from the use of magnetic fields or fluids, thus validating the stimuli to clinical research in this area. A device in controlled and multipurpose environments may contribute to standardizing research and exploring new theories. Future research may demonstrate the possible benefits of the aquatics care multi-device AuBento to improve the well-being and symptom control in palliative care patients and their families.

Keywords: advanced palliative aquatics care, magnetic field therapy, medical device, research design

Procedia PDF Downloads 127

Authors: Mehrnaz Mostafavi

Abstract:

Recent advances in single-molecule protein identification (ID) and quantification techniques are poised to revolutionize proteomics, enabling researchers to delve into single-cell proteomics and identify low-abundance proteins crucial for biomedical and clinical research. This paper introduces a different approach to single-molecule protein ID and quantification using tri-color amino acid tags and a plasmonic nanopore device. A comprehensive simulator incorporating various physical phenomena was designed to predict and model the device's behavior under diverse experimental conditions, providing insights into its feasibility and limitations. The study employs a whole-proteome single-molecule identification algorithm based on convolutional neural networks, achieving high accuracies (>90%), particularly in challenging conditions (95–97%). To address potential challenges in clinical samples, where post-translational modifications affecting labeling efficiency, the paper evaluates protein identification accuracy under partial labeling conditions. Solid-state nanopores, capable of processing tens of individual proteins per second, are explored as a platform for this method. Unlike techniques relying solely on ion-current measurements, this approach enables parallel readout using high-density nanopore arrays and multi-pixel single-photon sensors. Convolutional neural networks contribute to the method's versatility and robustness, simplifying calibration procedures and potentially allowing protein ID based on partial reads. The study also discusses the efficacy of the approach in real experimental conditions, resolving functionally similar proteins. The theoretical analysis, protein labeler program, finite difference time domain calculation of plasmonic fields, and simulation of nanopore-based optical sensing are detailed in the methods section. The study anticipates further exploration of temporal distributions of protein translocation dwell-times and the impact on convolutional neural network identification accuracy. Overall, the research presents a promising avenue for advancing single-molecule protein identification and quantification with broad applications in proteomics research. The contributions made in methodology, accuracy, robustness, and technological exploration collectively position this work at the forefront of transformative developments in the field.

Keywords: nano proteomics, nanopore-based optical sensing, deep learning, artificial intelligence

Procedia PDF Downloads 93

Authors: Ehsan Ahmed Yahia

Abstract:

Introduction: The nursing role in nutrition screening and assessing hospitalized patients is important. Malnutrition is a common and costly problem, particularly among hospitalized patients, and can have an adverse effect on the healing process. The study's goal is to assess the prevalence of malnutrition among adult hospitalized orthopedic patients and to detect the barriers to the nutrition screening process. Aim of the study: This study aimed to (a) assess the prevalence of malnutrition in hospitalized orthopedic patients and (b) evaluate the relationship between malnutrition and selected clinical outcomes. Material and Methods: This prospective field study was conducted for three months between 03/2022 and 06/2022 in the selected orthopedic departments in a teaching hospital affiliated withCairo University, Egypt. with a total number of one hundred twenty (120) patients. Patients' assessment included checking for malnutrition using the Nutritional Risk Screening Questionnaire. Patients at risk for malnourishment were defined as NRS score ≥ 3. Clinical outcomes under consideration included 1) length of hospitalization, 2) mobilization after surgery and conservative treatment, and 3) rate of adverse events. Results: This study found that malnutrition is a significant problem among patients hospitalized in an orthopedic ward. The prevalence of malnutrition was the highest in patients with lumbar spine and pelvis fractures, followed by the proximal femur and proximal humerus fractures. Patients at risk for malnutrition had significantly prolonged hospitalization, delayed postoperative mobilization, and increased incidence of adverse events.27.8% of the study sample were at risk for malnutrition. The highest prevalence of malnourishment was found in Septic Surgery with 32%, followed by Traumatology with 19.6% and Arthroplasty with 15.3%. A higher prevalence of malnutrition was detected among patients with typical fractures, such as lumbar spine and pelvis (46.7%), proximal femur (34.4%), and proximal humeral (23.7%) fractures. Additionally, patients at risk for malnutrition showed prolonged hospitalization (14.7 ± 11.1 vs. 21.2 ± 11.7 days), delayed postoperative mobilization (2.3 ± 2.9 vs. 4.1 ± 4.9 days), and delayed to mobilize after conservative treatment (1.1 ± 2.7 vs. 1.8 ± 1.9 days). A significant statistical correlation of NRS with individual parameters (Spearman's rank correlation, p < 0.05) was observed. The rate of adverse incidents in patients at risk for malnutrition was significantly higher than that of patients with a regular nutritional status (37.2% vs. 21.1%, p < 0.001). Conclusions: Our results indicate that the prevalence of malnutrition in surgical patients is significant. The nutritional status of patients with typical fractures is especially at risk. Prolonged hospitalization, delayed postoperative mobilization, and delayed mobilization after conservative treatment is significantly associated with malnutrition. In addition, the incidence of adverse events in patients at risk for malnutrition is significantly higher.

Keywords: malnutrition, nutritional risk screening, surgery, nursing, orthopedic nurse

Procedia PDF Downloads 98

Authors: M. A. Sohaly, M. A. Elfouly

Abstract:

Parkinson's disease (PD) is a heterogeneous movement disorder that often appears in the elderly. PD is induced by a loss of dopamine secretion. Some drugs increase the secretion of dopamine. In this paper, we will simply study the stability of PD models as a nonlinear delay differential equation. After a period of taking drugs, these act as positive feedback and increase the tremors of patients, and then, the differential equation has positive coefficients and the system is unstable under these conditions. We will present a set of suggested modifications to make the system more compatible with the biodynamic system. When giving a set of numerical examples, this research paper is concerned with the mathematical analysis, and no clinical data have been used.

Keywords: Parkinson's disease, stability, simulation, two delay differential equation

Procedia PDF Downloads 128

Authors: Lise Alonso, Audrey Dubost, Patricia Luis, Thomas Pommier, Yvan Moënne-Loccoz

Abstract:

The Lascaux Cave in South-Est France is an archeological landmark renowned for its Paleolithic paintings dating back c.18.000 years. Extensive touristic frequenting and repeated chemical treatments have resulted in the development of microbial stains on cave walls, which is a major issue in terms of art conservation. Therefore, it is of prime importance to better understand the microbiology specific to the Lascaux Cave, in comparison to regional situations. To this end, we compared the microbial community (i.e. both prokaryotic and eukaryotic microbial populations) of Lascaux Cave with three other anthropized Périgord caves as well as three pristine caves from the same area. We used state-of-the-art metagenomic analyses of cave wall samples to obtain a global view of the composition of the microbial community colonizing cave walls. We measured the relative abundance and diversity of four DNA markers targeting different fractions of the ribosomal genes of bacteria (i.e. eubacteria), archaea (i.e. archeobacteria), fungi and other micro-eukaryotes. All groups were highly abundant and diverse in all Périgord caves, as several hundred genera of microorganisms were identified in each. However, Lascaux Cave displayed a specify microbial community, which differed from those of both pristine and anthropized caves. Comparison of stains versus non-stained samples from the Passage area of the Lascaux Cave indicated that a few taxa (e.g. the Sordiaromycetes amongst fungi) were more prevalent within than outside stains, yet the main difference was in the relative proportion of the different microbial taxonomic groups and genera, which supposedly supports the biological origin of the stains. Overall, metagenomic sequencing of cave wall samples was effective to evidence the large colonization of caves by a diversified range of microorganisms. It also showed that Lascaux Cave represented a very particular situation in comparison with neighboring caves, probably in relation to the extent of disturbance it had undergone. Our results provide key baseline information to guide conservation efforts in anthropized caves such as Lascaux and pave the way to modern monitoring of ornamented caves.

Keywords: cave conservation, Lascaux cave, microbes, paleolithic paintings

Procedia PDF Downloads 243

Authors: Nayera E. Hassan, Sahar A. El-Masry, Rokia El-Banna, Mohamed S. El Hussieny

Abstract:

There are several different modalities for treatment of obesity. Common intervention methods for obesity include low-calorie diet, exercise. Also acupuncture has shown good therapeutic results in the treatment of obesity. A recent clinical observation showed that laser acupuncture could reduce body weight and body mass index in obese persons. So, the aim of this research is focused on body composition changes as related to type of intervention, before and after intentional weight loss in overweight and obesity. 76 subjects were included in the study analysis. The present study recommended that every obese female must do lipid profile and fasting blood sugar analysis before weight-loss intervention to take the decision of which method should be used.

Keywords: obesity, weight-loss, body composition, modalities

Procedia PDF Downloads 486

Authors: Nancy Wilson

Abstract:

In utero, fetal drug exposure is prevalent amongst birthing facilities. Assessment tools for neonatal abstinence syndrome (NAS) are often cumbersome and ill-fitting, harboring immense subjectivity. This paradox often leads the clinical assessor to be hypervigilant when assessing the newborn for subtle symptoms of NAS, often mistaken for normal newborn behaviors. As a quality improvement initiative, this project led to a more adaptable NAS tool termed eat, sleep, console (ESC). This function-based NAS assessment scores the infant based on the ability to accomplish three basic newborn necessities- to sleep, to eat, and to be consoled. Literature supports that ESC methodology improves patient and family outcomes while providing more cost-effective care.

Keywords: neonatal abstinence syndrome, neonatal opioid withdrawal, maternal substance abuse, pregnancy, and addiction, Finnegan neonatal abstinence syndrome tool, eat, sleep, console

Procedia PDF Downloads 150

Authors: Subodh Kumar, Sanjeev Kumar Sharma, Gaurav Kaushik, Pramod Avti, Phulen Sarma, Bikash Medhi, Krishan Lal Khanduja

Abstract:

Background: It is well known that cigarette smoke is one of the causative factors in various lung diseases especially cancer. Carcinogens and oxidant molecules present in cigarette smoke not only damage the cellular constituents (lipids, proteins, DNA) but may also regulate the molecular pathways involved in inflammation and cancer. Continuous oxidative stress caused by the constituents of cigarette smoke leads to higher PhospholipaseA₂ (PLA₂) activity, resulting in elevated levels of secondary metabolites whose role is well defined in cancer. To reduce the burden of chronic inflammation as well as oxidative stress, and higher levels of secondary metabolites, we checked the curative potential of PLA₂ inhibitor Bromoenol Lactone (BEL) during continuous exposure of cigarette smoke condensate (CSC). Aim: To check the therapeutic potential of Bromoenol Lactone (BEL), an inhibitor of PhospholipaseA₂s, in pathways of CSC-induced changes in type I and type II alveolar epithelial cells. Methods: Effect of BEL on CSC-induced PLA2 activity were checked using colorimetric assay, cellular toxicity using cell viability assay, membrane integrity using fluorescein di-acetate (FDA) uptake assay, reactive oxygen species (ROS) levels and apoptosis markers through flow cytometry, and cellular regulation using MAPKinases levels, in lung epithelium. Results: BEL significantly mimicked CSC-induced PLA₂ activity, ROS levels, apoptosis, and kinases level whereas improved cellular viability and membrane integrity. Conclusions: Current observations revealed that BEL may be a potential therapeutic agent during Cigarette smoke-induced anomalies in lung epithelium.

Keywords: cigarette smoke condensate, phospholipase A₂, oxidative stress, alveolar epithelium, bromoenol lactone

Procedia PDF Downloads 187

Authors: Aliya Sekenova, Vyacheslav Ogay

Abstract:

The derivation of human induced pluripotent stem cells (iPSCs) from somatic cells by direct reprogramming opens wide perspectives in the regenerative medicine. It means the possibility to develop the personal and, consequently, any immunologically compatible cells for applications in cell-based therapy. The purpose of our study was to develop the technology for the production of NK cells from T cell-derived induced pluripotent stem cells (TiPSCs) for subsequent application in adoptive cancer immunotherapy. Methods: In this study iPSCs were derived from peripheral blood T cells using Sendai virus vectors expressing Oct4, Sox2, Klf4 and c-Myc. Pluripotent characteristics of TiPSCs were examined and confirmed with alkaline phosphatase staining, immunocytochemistry and RT-PCR analysis. For NK cell differentiation, embryoid bodies (EB) formed from (TiPSCs) were cultured in xenogeneic serum-free medium containing human serum, IL-3, IL-7, IL-15, SCF, FLT3L without using M210-B4 and AFT-024 stromal feeder cells. After differentiation, NK cells were characterized with immunofluorescence analysis, flow cytometry and cytotoxicity assay. Results: Here, we for the first time demonstrate that TiPSCs can effectively differentiate into functionally active NK cells without M210-B4 and AFT-024 xenogeneic stroma cells. Immunofluorescence and flow cytometry analysis showed that EB-derived cells can differentiate into a homogeneous population of NK cell expressing high levels of CD56, CD45 and CD16 specific markers. Moreover, these cells significantly express killing activation receptors such as NKp44 and NKp46. In the comparative analysis, we observed that NK cells derived using feeder-free culture system have more high killing activity against K-562 tumor cells, than NK cells derived by feeder-dependent method. Thus, we think that our obtained data will be useful for the development of large-scale production of NK cells for translation into cancer immunotherapy.

Keywords: induced pluripotent stem cells, NK cells, T cells, cell diffentiation, feeder cell-free culture system

Procedia PDF Downloads 324

Authors: Yusuf E. Mustapha, Inioluwa A Akindoyeni, Oluwatoyin G. Ezekiel, Ifeoluwa O. Awogbindin, Ebenezer O. Farombi

Abstract:

Background: Parkinson's disease (PD) is the most prevalent motor disorder. Available therapies are palliative with no effect on disease progression. Kolaviron (KV), a natural anti-inflammatory and antioxidant agent, has been reported to possess neuroprotective effects in Parkinsonian flies and rats. Objective: The present study investigates the neuroprotective effect of KV, focusing on the DJ1/Nrf2 signaling pathway. Methodology: All-trans retinoic acid (ATRA, 10 mg/kg, i.p.) was used to inhibit Nrf2. Murine model of PD was established with four doses of MPTP (20 mg/kg i.p.) at 2 hours interval. MPTP mice were pre-treated with either KV (200 mg/kg/day p.o), ATRA, or both conditions for seven days before PD induction. Motor behaviour was evaluated, and markers of oxidative stress/damage and its regulators were assessed with immunofluorescence and ELISA techniques. Results: MPTP-treated mice covered less distance with reduced numbers of anticlockwise rotations, heightened freezing, and prolonged immobility when compared to control. However, KV significantly attenuated these deficits. Pretreatment of MPTP mice with KV upregulated Nrf2 expression beyond MPTP level with a remarkable reduction in Keap1 expression and marked elevation of DJ-1 level, whereas co-administration with ATRA abrogated these effects. KV treatment restored MPTP-mediated depletion of endogenous antioxidant, striatal oxidative stress, oxidative damage, and inhibition of acetylcholinesterase activity. However, ATRA treatment potentiated acetylcholinesterase inhibition and attenuated the protective effect of KV on the level of nitric oxide and activities of catalase and superoxide dismutase. Conclusion: Kolaviron protects Parkinsonian mice by stabilizing and activating the Nrf2 signaling pathway. Thus, kolaviron can be explored as a pharmacological lead in PD management.

Keywords: Garcinia kola, Kolaviron, Parkinson Disease, Nrf2, behavioral incompetence, neurodegeneration

Procedia PDF Downloads 98

Authors: Mary Rose Eunice S. Gundayao, Manolo M. Fernandez

Abstract:

Metachromatic leukodystrophy (MLD) is a rare lysosomal storage disorder with an autosomal recessive inheritance pattern. Lysosomal storage disorders are often severe, follow a progressively neurodegenerative path, and may result in multi-organ failure, potentially leading to death within 5 to 6 years in cases of early-onset forms. There are limited data regarding cases of MLD in Filipino children. This is the case of a 2-year-old Filipino girl who presented with progressive neurological deterioration and was diagnosed with metachromatic leukodystrophy by molecular genetic testing. This case report aims to present this patient’s clinical history, neurological findings, diagnosis and novel genetic mutations causing MLD. A concise review of updated literature on MLD will be discussed.

Keywords: metachromatic leukodystrophy, ARSA gene, peripheral neuropathy, case report, demyelinating disease

Procedia PDF Downloads 17

Authors: Rajish Shil, Amal Alduhoori, Vipin Thomachan, Jamal Teir, Radhakrishnan Renganathan

Abstract:

Background: Antiphospholipid antibody syndrome (APS) has a broad spectrum of thrombotic and non-thrombotic clinical manifestations. We present a case of APS presenting with seizure, stroke, and atrial mass. Case Description: A 38-year-old male presented with headache of 10 days duration and tonic-clonic seizure. The neurological examination was normal. Magnetic resonance imaging of brain showed small acute right cerebellar infarct. Magnetic resonance angiography of brain and neck showed a focal narrowing in the origin of the internal carotid artery bilaterally. Electroencephalogram was normal. He was started on aspirin, atorvastatin, and carbamazepine. Transthoracic and trans-esophageal echocardiography showed a pedunculated and lobular atrial mass, measuring 1 X 1.5 cm, which was freely mobile across mitral valve opening across the left ventricular inflow. Autoimmune screening showed positive Antiphospholipid antibodies in high titer (Cardiolipin IgG > 120 units/ml, B2 glycoprotein IgG 90 units/mL). Anti-nuclear antibody was negative. Erythrocyte sedimentation rate and C-reactive protein levels were normal. Platelet count was low (111 x 109/L). The patient underwent successful surgical removal of the mass, which looked like a thrombotic clot, and Histopathological analysis confirmed it as a fibrinous clot, with no evidence of tumor cells. The patient was started on full anticoagulation treatment and was followed up regularly in the clinic, where our patient did not have any further complications from the disease. Discussion: Our patient was diagnosed to have APS based on the features of high positive anticardiolipin antibody IgG and B2 glycoprotein IgG levels, Stroke, thrombocytopenia, and abnormal echo findings. Thrombotic vegetation can mimic an atrial myxoma on echo. Conclusion: APS can present with neurological and cardiac manifestations, and therefore a high index of suspicion is necessary for a diagnosis of the disease as it can affect both short and long term treatment plans and prognosis. Therefore, in patients presenting with neurological symptoms like seizures, weakness and radiological diagnosis of stroke in a young patient, where atrial masses could be thought to be the cause of stroke, they should be screened for any concomitant findings of thrombocytopenia and/or activated partial thromboplastin time prolongation, which should raise the suspicion of vasculitis, specifically APS to be the primary cause of the clinical presentation.

Keywords: antiphospholipid syndrome, seizures, atrial mass, stroke

Procedia PDF Downloads 112

Authors: Leila Rashki Ghaleno, Mohamad Amin Hajari, Leila Montazeri, Abdolhossein Shahverdi, Mojtaba Rezazadeh Valojerdi

Abstract:

Background: Spermatogonia stem cells (SSCs) exhibit pluripotency, enabling them to undergo differentiation into many cell lineages, including neurons, glia, endothelial cells, and hepatocytes when cultured in vitro. Although the specific mechanisms are not yet fully understood, it has been observed that biopolymer agents, such as hyaluronic acid (HA) and alginate (Alg), have the potential to induce transdifferentiation of SSCs. The current work aimed to examine the process of in vitro spermatogenesis and the conversion of mouse testicular cells into hepatocytes and erythrocyte-like cells utilizing the HA-Alg hydrogel. Method: After being extracted from the testes of a 5-day postpartum mouse (5 DPP), the testicular cells were separated into two enzymatic stages and then put into a composite hydrogel containing 0.5% HA and 1% alginate. On days 14 and 28 of culture, the colonies' growth, the cells' viability, and their histology were assessed. Result: Despite observing significant cell proliferation on day 14 and the development of circular-shaped organoids on day 28, it was noted that the organoids generated in the HA-Alg medium tended to maintain their circular morphology on day 28. Notably, the testicular cells underwent transdifferentiation into cell types resembling erythrocytes and hepatocytes. The hepatocyte-like cells exhibited the presence of glycogen and lipid deposits, indicating their hepatocyte-like characteristics. Interestingly, immunostaining analysis revealed the secretion of albumin and the presence of VEGFR on day 14. However, on day 28, albumin expression was not detected, while the expression of Sox9 (a marker for hepatocytes), Vegf, CD34, and C-kit (markers for erythrocytes) showed increased levels in the gene expression evaluation. Conclusion: The present findings indicated that HA-Alg could be a potent and effective agent for the transdifferentiation of testis cells into erythrocyte and hepatocyte-like cells, as recent studies have confirmed the transformation of SSCs into hepatocyte cells during in vitro culture.

Keywords: 3D culture, mouse testicular cell, hyaluronic acid, liver organoids

Procedia PDF Downloads 68

Authors: Rajendra Kanojia

Abstract:

Femoral components with inbuilt rotation require thicker flexion resection of the lateral femoral condyle and could potential risk to damage the popliteus tendon especially in the smaller Asian knees. We prospectively evaluated 10 patients with bilateral varus osteoarthritis knee to size the cuts and their location in relation to the popliteus tendon. Two different types of implant were used on either side, one side requires resection in 3° external rotation (group A) and other side femoral component with inbuilt external roation (group B). We had popliteus tendon injury in 3 knees all from group B. Risk of damaging the popliteus tendon was found higher in group B.

Keywords: popliteaus tendon injury, TKA, orthopaedic surgery, biomechanics and clinical applications

Procedia PDF Downloads 333

Authors: Neha Bhattacharyya, Soumendra Singh, Amrita Banerjee, Ria Ghosh, Oindrila Sinha, Nairit Das, Rajkumar Gayen, Somya Subhra Pal, Sahely Ganguly, Tanmoy Dasgupta, Tanusree Dasgupta, Pulak Mondal, Aniruddha Adhikari, Sharmila Sarkar, Debasish Bhattacharyya, Asim Kumar Mallick, Om Prakash Singh, Samir Kumar Pal

Abstract:

Background: We aim to develop an integrated device comprised of single-probe EEG and CCD-based motion sensors for a more objective measure of Attention-deficit Hyperactivity Disorder (ADHD). While the integrated device (MAHD) relies on the EEG signal (spectral density of beta wave) for the assessment of attention during a given structured task (painting three segments of a circle using three different colors, namely red, green and blue), the CCD sensor depicts movement pattern of the subjects engaged in a continuous performance task (CPT). A statistical analysis of the attention and movement patterns was performed, and the accuracy of the completed tasks was analysed using indigenously developed software. The device with the embedded software, called MAHD, is intended to improve certainty with criterion E (i.e. whether symptoms are better explained by another condition). Methods: We have used the EEG signal from a single-channel dry sensor placed on the frontal lobe of the head of the subjects (3-5 years old pre-schoolers). During the painting of three segments of a circle using three distinct colors (red, green, and blue), absolute power for delta and beta EEG waves from the subjects are found to be correlated with relaxation and attention/cognitive load conditions. While the relaxation condition of the subject hints at hyperactivity, a more direct CCD-based motion sensor is used to track the physical movement of the subject engaged in a continuous performance task (CPT) i.e., separation of the various colored balls from one table to another. We have used our indigenously developed software for the statistical analysis to derive a scale for the objective assessment of ADHD. We have also compared our scale with clinical ADHD evaluation. Results: In a limited clinical trial with preliminary statistical analysis, we have found a significant correlation between the objective assessment of the ADHD subjects with that of the clinician’s conventional evaluation. Conclusion: MAHD, the integrated device, is supposed to be an auxiliary tool to improve the accuracy of ADHD diagnosis by supporting greater criterion E certainty.

Keywords: ADHD, CPT, EEG signal, motion sensor, psychometric test

Procedia PDF Downloads 97

Authors: Balazs Patczai, Katalin Gocze, Gabriella Kiss, Dorottya Szabo, Tibor Mintal

Abstract:

Introduction: Running has become increasingly popular on a global scale in the past decades. Amateur athletes are taking their sport to a new level in an attempt to surpass their performance goals. The aim of our study was to assess the musculoskeletal condition of amateur runners and the prevalence of injuries with a special focus on stress fracture risk. Methods: The cross sectional analysis included ankle mobility, hamstring and lower back flexibility, the use of Renne’s test for iliotibial band syndrome, functional tests for trunk and rotary stability, and measurements of bone density. Data was collected at 2 major half-marathon events in Hungary. Results: Participants (n=134) mean age was 41.76±8.57 years (males: 40.67±8.83, females: 42.08±8.56). Measures of hamstring and lower back flexibility fell into the category of good for both genders (males: 7.13±6.83cm, females: 10.17±6.67cm). No side asymmetry nor gender differences were characteristic in the case of ankle mobility. Trunk stability was significantly better for males than in females (p=0.004). Markers of bone health were in the low normal range for females and were significantly better for males (T-score: p=0.003, T-ratio: p=0.014, Z-score: p=0.034, Z-ratio: p=0.011). 5.2% of females had a previous stress fracture and 24.1% experienced irregular menstrual cycles during the past year. As for the knowledge on the possible association of energy deficiency, menstrual disturbances and their effect on bone health, Only 8.6% of females have heard of the female athlete triad either during their studies or from a health professional. Discussion: The overall musculoskeletal state was satisfactory for both genders both physically and functionally. More attention and effort should be placed on primary and secondary prevention of amateur runners. Very few active women are well informed about the effects of low energy availability and menstrual dysfunction and the negative impact these have on bone health.

Keywords: bone health, flexibility, running, stress fracture

Procedia PDF Downloads 124

Authors: J. Luché-Thayer, C. Perronne, C. Meseko

Abstract:

We reviewed how certain institutional policies and practices, as well as questionable research, are creating obstacles to care and informed consent for Lyme and relapsing fever Borreliosis patients. The interference is denying access to treatments that meet the internationally accepted standards as set by the Institute of Medicine. This obstruction to care contributes to significant human suffering, disability and negative economic effect across many nations and in many regions of the world. We note how evidence based medicine emphasizes the importance of clinical experience and patient-centered care and how these patients benefit significantly when their rights to choose among treatment options are upheld.  

Keywords: conflicts of interest, obstacles to healthcare accessibility, patient-centered care, the right to informed consent

Procedia PDF Downloads 206

Authors: Lucie Mrackova, Helena Kisvetrova

Abstract:

Spirituality is an integral part of human life. In a secular environment, spiritual needs are often overlooked, especially in acute nursing care. Spiritual needs assessment for patients (SNAP), which also exists in the Czech version (SNAP-CZ), can be used for objective evaluation. The aim of this study was to measure the psychometric properties of SNAP-CZ and to find correlations between SNAP-CZ and sociodemographic and clinical variables. A cross-sectional study with tools assessing spiritual needs (SNAP-CZ), anxiety (Beck Anxiety Inventory; BAI), depression (Beck Depression Inventory; BDI), pain (Visual Analogue Scale; VAS), self-sufficiency (Barthel Index; BI); cognitive function (Montreal Cognitive Test; MoCa) and selected socio-demographic data was performed. The psychometric properties of SNAP-CZ were tested using factor analysis, reliability and validity tests, and correlations between the questionnaire and sociodemographic data and clinical variables. Internal consistency was established with Cronbach’s alfa for the overall score, respective domains, and individual items. Reliability was assessed by test-retest by Interclass correlation coefficient (ICC). Data for correlation analysis were processed according to Pearson's correlation coefficient. The study included 172 trauma patients (the mean age = 40.6 ± 12.1 years) who experienced polytrauma or severe monotrauma. There were a total of 106 (61.6%) male subjects, 140 (81.4%) respondents identified themselves as non-believers. The full-scale Cronbach's alpha was 0.907. The test-retest showed the reliability of the individual domains in the range of 0.924 to 0.960 ICC. Factor analysis resulted in a three-factor solution (psychosocial needs (alfa = 0.788), spiritual needs (alfa = 0.886) and religious needs (alfa = 0.841)). Correlation analysis using Pearson's correlation coefficient showed that the domain of psychosocial needs significantly correlated only with gender (r = 0.178, p = 0.020). Males had a statistically significant lower average value in this domain (mean = 12.5) compared to females (mean = 13.8). The domain of spiritual needs significantly correlated with gender (r = 0.199, p = 0.009), social status (r = 0.156, p = 0.043), faith (r = -0.250, p = 0.001), anxiety (r = 0.194, p = 0.011) and depression (r = 0.155, p = 0.044). The domain of religious needs significantly correlated with age (r = 0,208, p = 0,007), education (r = -0,161, p = 0,035), faith (r = -0,575, p < 0,0001) and depression (r = 0,179, p = 0,019). Overall, the whole SNAP scale significantly correlated with gender (r = 0.219, p = 0.004), social status (r = 0.175, p = 0.023), faith (r = -0.334, p <0.0001), anxiety (r = 0.177, p = 0.022) and depression (r = 0.173, p = 0.025). The results of this study corroborate the reliability of the SNAP-CZ and support its future use in the nursing care of trauma patients in a secular society. Acknowledgment: The study was supported by grant nr. IGA_FZV_2020_003.

Keywords: acute nursing care, assessment of spiritual needs, patient, psychometric validation, spirituality

Procedia PDF Downloads 103

Authors: Virany Diana, Martono Tri Utomo, Risa Etika

Abstract:

Background: Shock is one severe condition that can be a major cause of morbidity and mortality in the Neonatal Intensive Care Unit. Preterm infants are very susceptible to shock caused by many complications such as asphyxia, patent ductus arteriosus, intra ventricle haemorrhage, necrotizing enterocolitis, persistent pulmonal hypertension of the newborn, and septicaemia. Limited hemodynamic monitoring for early detection of shock causes delayed intervention and comprises the outcomes. Clinical parameters still used in neonatal shock detection, such as Capillary Refill Time, heart rate, cold extremity, and urine production. Blood pressure is most frequently used to evaluate preterm's circulation, but hypotension indicates uncompensated shock. Near-infrared spectroscopy (NIRS) is known as a noninvasive tool for monitoring and detecting the state of inadequate tissue perfusion. Muscle oxygen saturation shows decreased cardiac output earlier than systemic parameters of tissue oxygenation when cerebral regional oxygen saturation is still stabilized by autoregulation. However, to our best knowledge, until now, no study has analyzed the decrease of muscle oxygen regional saturation (mRSO₂) and the ratio of muscle and cerebral oxygen regional saturation (mRSO₂/cRSO₂) by NIRS in preterm with shock. Purpose: The purpose of this study is to analyze the decrease of mRSO₂ and ratio of muscle to cerebral oxygen regional saturation (mRSO₂/cRSO₂) by NIRS in preterm with shock. Patients and Methods: This cross-sectional study was conducted on preterm infants with 28-34 weeks gestational age, admitted to the NICU of Dr. Soetomo Hospital from November to January 2022. Patients were classified into two groups: shock and non-shock. The diagnosis of shock is based on clinical criteria (tachycardia, prolonged CRT, cold extremity, decreased urine production, and MAP Blood Pressure less than GA in weeks). Measurement of mRSO₂ and cRSO₂ by NIRS was performed by the doctor in charge when the patient came to NICU. Results: We enrolled 40 preterm infants. The initial conventional hemodynamic parameter as the basic diagnosis of shock showed significant differences in all variables. Preterm with shock had higher mean HR (186.45±1.5), lower MAP (29.8±2.1), and lower SBP (45.1±4.28) than non-shock children, and most had a prolonged CRT. The patients’ outcome was not a significant difference between shock and non-shock patients. The mean mRSO₂ in the shock and non-shock groups were 33,65 ± 11,32 vs. 69,15 ± 3,96 (p=0.001), and the mean ratio mRSO₂/cRSO₂ 0,45 ± 0,12 vs. 0,84 ± 0,43 (p=0,001), were significantly different. The mean cRSO₂ in the shock and non-shock groups were 71,60 ± 4,90 vs. 81,85 ± 7,85 (p 0.082), not significantly different. Conclusion: The decrease of mRSO₂ and ratio of mRSO₂/cRSO₂ can differentiate between shock and non-shock in the preterm infant when cRSO₂ is still normal.

Keywords: preterm infant, regional muscle oxygen saturation, regional cerebral oxygen saturation, NIRS, shock

Procedia PDF Downloads 90

Authors: Akbar Nawaz Khan, Abdul Ghaffar, Muhammad Naeem Riaz

Abstract:

The study was conducted to investigate the phenotypic features, morphometry and production potentialities of indigenous naked neck chicken (NN) of Pakistan under intensive management condition. A total of 35 NN chicks were randomly selected, and the experiment was performed at Poultry and wildlife research section NARC Islamabad for a period of 22 weeks. The predominant plumage color was black and golden while skin color was observed white. The average shank length, leg length, thigh length, keel length, chest breadth, head width, wing space, wing length, body length, body girth, body height and pubic bone width in adult males and females were 69.19 ± 3.34mm, 117.93 ± 4.42mm, 117.93 ± 4.42mm, 90.87 ± 6.53mm, 95.03 ± 4.56mm, 49.77 ± 2.53mm, 30.63 ± 1.50cm, 27.24 ± 2.71cm, 18.88 ± 0.65cm, 17.77 ± 1.01cm, 25.96 ± 0.56cm, 47.81 ± 1.41cm and 35.69 ± 4.09mm respectively. The average age and live body weight of NN chicken at sexual maturity were recorded as 165.85 days and 1269.38 g. While hen-day egg production of NN was recorded as 45%. The present study was aimed to investigate the existence of polymorphism at IGF-I gene in indigenous naked neck chicken through PCR based Restriction Fragment Length Polymorphism. Based on restriction analysis using Hinf I restriction enzyme, three genotypes were detected designated as AA, AC, and CC. Restriction analysis of PCR amplified product showed the presence of DNA fragments of 622, 378, 244 and 191, (genotypes). The PCR-RFLP analysis is easy, cost effective method which permits the easy characterization of IGF-I gene. This showed the investigated IGF-I genes can serve as good molecular markers for marker assisted selection (MAS) concerning growth related traits in chicken.

Keywords: Desi chicken, naked neck, morphology, morphometry, production potential, egg traits, egg geometry, IGF-I, growth, PCR- RFLP, chicken

Procedia PDF Downloads 388

Authors: Melikulov A. A., Toshpulotov Sh. G., Akhmedova M. F., Beshimov A. S., Rakhimov M. K. Zokirov N. K.

Abstract:

Postinfarction ventricular septal defect (PVSD) is a rare but life-threatening complication of acute myocardial infarction. Currently, an alternative direction of minimally invasive treatment of postinfarction ventricular septal defect (PVSD) is being developed - transcatheter closure of the defect using an occluder, but surgical closure of the defect remains the <> correction of post-infarction VSD. Our article presents a case of successful surgical treatment of a patient with a large post-infarction rupture of the interventricular septum (IVS) and post-infarction LV aneurysm under cardiopulmonary bypass and parallel perfusion.

Keywords: echocardiography, myocardial infarction, ventricular septal defect, parallel perfusion

Procedia PDF Downloads 78

Authors: Tan Hui Ying Renee, Stella Rizalina Sasha, Farah Safdar Husain

Abstract:

Introduction: Menopause Hormone Therapy (MHT) is an effective drug indicated for the treatment of menopausal symptoms and as replacement therapy in women who undergo premature menopause. In 2020, less than 8.8% of perimenopausal Singaporean women are on hormonal therapy, as compared to the Western population, where up to 50% may be on MHT. Factors associated with MHT utilization have been studied from patient characteristics, but the impact of locally prescribing physicians resulting in low MHT utilization has yet to be evaluated. The aim of the study is to determine the level of knowledge physicians in the Obstetrics and Gynaecology specialty have and their attitudes toward MHT. We believe that knowledge of MHT is lacking and that negative attitudes towards MHT may influence its use and undermine the benefits MHT may have for women. This paper is a part of a larger study on Singaporean physicians’ knowledge and attitudes towards MHT. Methods: This is a cross-sectional study intended to assess the knowledge and attitudes of physicians toward Menopausal Hormone Therapy. An anonymous questionnaire was disseminated via institutional internal circulations to optimize reach to physicians who may prescribe MHT, particularly in the fields of Gynaecology, Family Medicine and Endocrinology. Responses were completed voluntarily. Physicians had the option for each question to declare that they were ‘unsure’ or that the question was ‘beyond their expertise’. 21 knowledge questions tested factual recall on indications, contraindications, and risks of MHT. The remaining 6 questions were clinical scenarios crafted with the intention of testing specific principles related to the use of MHT. These questions received face validation from experts in the field. 198 responses were collected, 79 of which were from physicians in the Obstetrics and Gynaecology specialty. The data will be statistically analyzed to investigate areas that can be improved to increase the overall benefits of MHT for the Singaporean population. Results: Preliminary results show that the prevailing factors that limit Singaporean gynecologists and obstetricians from prescribing MHT are a lack of knowledge of MHT and a lack of confidence in prescribing MHT. Risks and indications of MHT were not well known by many physicians, with the majority of the questions having more than 25% incorrect and ‘unsure’ as their reply. The clinical scenario questions revealed significant shortcomings in knowledge on how to navigate real-life challenges in MHT use, with 2 of 6 questions with more than 50% incorrect or ‘beyond their expertise’ as their reply. The portion of the questionnaire that investigated the attitudes of physicians showed that though a large majority believed MHT to be an effective drug, only 40.5% were confident in prescribing it. Conclusion: Physicians in the Obstetrics and Gynaecology specialty lack knowledge and confidence in MHT. Therefore, it is imperative to formulate solutions on both the individual and institutional levels to fill these gaps and ensure that MHT is used appropriately and prescribed to the patients who need it.

Keywords: menopause, menopause hormone therapy, physician factors, obstetrics and gynecology, menopausal symptoms, Singapore

Procedia PDF Downloads 39

Authors: Leixuri Aguirre, Iñaki Milton-Laskibar, Elizabeth Hijona, Luis Bujanda, Agnes M. Rimando, Maria P. Portillo

Abstract:

Introduction: In recent years great attention has been paid by scientific community to phenolic compounds as active biomolecules naturally present in foodstuffs due to their beneficial effects on health. Pterostilbene is a resveratrol dimethylether derivative which shows higher biodisponibility. Objective. To analyze the effects of two doses of pterostilbene on several markers of thermogenic capacity in a model of genetic obesity, which shows reduced thermogenesis. Methods: The experiment was conducted with thirty Zucker (fa/fa) rats that were distributed in 3 experimental groups, the control group and two groups orally administered with pterostilbene at 15 and 30 mg/kg body weight/day for 6 weeks. Gene expression of Ucp1, Pgc-1α, Cpt1b, Pparα, Nfr1, Tfam and Cox-2 were assessed by RT-PCR, protein expression of UCP1 and GLUT4 by western blot and enzyme activity of carnitine palmitoyl transferase 1b and citrate synthase by spectrophotometry in interscapular brown adipose tissue (iBAT). Statistical analysis was performed by using one way ANOVA and Newman-Keuls as post-hoc test. Results: Pterostilbene did not change gene expression of Pgc-1α. However, significant increases were found in the expression of Ucp1, Pparα, Nfr-1 and Cox-2. Protein expression of UCP1 and GLUT4 was increased in animals treated with pterostilbene, as well as the activities of CPT-1b and CS. These effects were observed with both doses of pterostilbene, without differences between them. Conclusions: These results show that pterostilbene increases thermogenic and oxidative capacity of brown adipose tissue in obese rats. Whether these effects effectively contribute to the anti-obesity properties of these compound needs further research. Acknowledgments: MINECO-FEDER (AGL2015-65719-R), Basque Government (IT-572-13), University of the Basque Country (ELDUNANOTEK UFI11/32), Institut of Health Carlos III (CIBERobn). Iñaki Milton is a fellowship from the Basque Government.

Keywords: brown adipose tissue, pterostilbene, thermogenesis, uncoupling protein 1

Procedia PDF Downloads 294

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

Procedia PDF Downloads 91