Search results for: clinical laboratory persons
Commenced in January 2007
Frequency: Monthly
Edition: International
Paper Count: 6288

Search results for: clinical laboratory persons

468 A Model to Assess Sustainability Using Multi-Criteria Analysis and Geographic Information Systems: A Case Study

Authors: Antonio Boggia, Luisa Paolotti, Gianluca Massei, Lucia Rocchi, Elaine Pace, Maria Attard

Abstract:

The aim of this paper is to present a methodology and a computer model for sustainability assessment based on the integration of Multi-criteria Decision Analysis (MCDA) with a Geographic Information System (GIS). It presents the result of a study for the implementation of a model for measuring sustainability to address the policy actions for the improvement of sustainability at territory level. The aim is to rank areas in order to understand the specific technical and/or financial support that is required to develop sustainable growth. Assessing sustainable development is a multidimensional problem: economic, social and environmental aspects have to be taken into account at the same time. The tool for a multidimensional representation is a proper set of indicators. The set of indicators must be integrated into a model, that is an assessment methodology, to be used for measuring sustainability. The model, developed by the Environmental Laboratory of the University of Perugia, is called GeoUmbriaSUIT. It is a calculation procedure developed as a plugin working in the open-source GIS software QuantumGIS. The multi-criteria method used within GeoUmbriaSUIT is the algorithm TOPSIS (Technique for Order Preference by Similarity to Ideal Design), which defines a ranking based on the distance from the worst point and the closeness to an ideal point, for each of the criteria used. For the sustainability assessment procedure, GeoUmbriaSUIT uses a geographic vector file where the graphic data represent the study area and the single evaluation units within it (the alternatives, e.g. the regions of a country, or the municipalities of a region), while the alphanumeric data (attribute table), describe the environmental, economic and social aspects related to the evaluation units by means of a set of indicators (criteria). The use of the algorithm available in the plugin allows to treat individually the indicators representing the three dimensions of sustainability, and to compute three different indices: environmental index, economic index and social index. The graphic output of the model allows for an integrated assessment of the three dimensions, avoiding aggregation. The presence of separate indices and graphic output make GeoUmbriaSUIT a readable and transparent tool, since it doesn’t produce an aggregate index of sustainability as final result of the calculations, which is often cryptic and difficult to interpret. In addition, it is possible to develop a “back analysis”, able to explain the positions obtained by the alternatives in the ranking, based on the criteria used. The case study presented is an assessment of the level of sustainability in the six regions of Malta, an island state in the middle of the Mediterranean Sea and the southernmost member of the European Union. The results show that the integration of MCDA-GIS is an adequate approach for sustainability assessment. In particular, the implemented model is able to provide easy to understand results. This is a very important condition for a sound decision support tool, since most of the time decision makers are not experts and need understandable output. In addition, the evaluation path is traceable and transparent.

Keywords: GIS, multi-criteria analysis, sustainability assessment, sustainable development

Procedia PDF Downloads 264
467 The Role of High-Intensity Focused Ultrasound (HIFU) in the Treatment of Fibroadenomas: A Systematic Review

Authors: Ahmed Gonnah, Omar Masoud, Mohamed Abdel-Wahab, Ahmed ElMosalamy, Abdulrahman Al-Naseem

Abstract:

Introduction: Fibroadenomas are solid, mobile, and non-tender benign breast lumps, with the highest prevalence amongst young women aged between 15 and 35. Symptoms can include discomfort, and they can become problematic, particularly when they enlarge, resulting in many referrals for biopsies, with fibroadenomas accounting for 30-75% of the cases. Diagnosis is based on triple assessment that involves a clinical examination, ultrasound imaging and mammography, as well as core needle biopsies. Current management includes observation for 6-12 months, with the indication of definitive surgery, in cases that are older than 35 years or with fibroadenoma persistence. Serious adverse effects of surgery might include nipple-areolar distortion, scarring and damage to the breast tissue, as well as the risks associated with surgery and anesthesia, making it a non-feasible option. Methods: A literature search was performed on the databases EMBASE. MEDLINE/PubMed, Google scholar and Ovid, for English language papers published between 1st of January 2000 and 17th of March 2021. A structured protocol was employed to devise a comprehensive search strategy with keywords and Boolean operators defined by the research question. The keywords used for the search were ‘HIFU’, ‘High-Intensity Focused Ultrasound’, ‘Fibroadenoma’, ‘Breast’, ‘Lesion’. This review was carried out in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Results: Recently, a thermal ablative technique, High Intensity Focused Ultrasound (HIFU), was found to be a safe, non-invasive, and technically successful alternative, having displayed promising outcomes in reducing the volume of fibroadenomas, pain experienced by patients, and the length of hospitalization. Quality of life improvement was also evidenced, exhibited by the disappearance of symptoms, and enhanced physical activity post-intervention, in addition to patients’ satisfaction with the cosmetic results and future recommendation of the procedure to other patients. Conclusion: Overall, HIFU is a well-tolerated treatment associated with a low risk of complications that can potentially include erythema, skin discoloration and bruising, with the majority of this self-resolving shortly after the procedure.

Keywords: ultrasound, HIFU, breast, efficacy, side effects, fibroadenoma

Procedia PDF Downloads 194
466 A Dimensional Approach to Family Involvement in Forensic Mental Health Settings - Prevention of the Systemic Replication of Abuse, Need for Accepted Falsehoods and Family Guilt and Shame

Authors: Katie E. Jennings

Abstract:

The interactions between family dynamics and environmental factors with mental health vulnerability in individuals are well known and are a theme for on-going research and debate. The impact upon mental health issues and forensic issues on family dynamics, experience, and emotional wellbeing cannot be over-Emphasised. For forensic patients with diagnosed mental disorders, these relationships and environments may have also been functionally linked to the development and maintenance of those disorders; with significant adverse childhood experiences being a common feature of many Patient’s histories. Mental health hospitals remove the patient from their home environments and provide treatment outside of these relationships and often outside of the home area. There is, therefore, a major focus on Services ensuring that patients are able to build and maintain relationships with family and friends, requiring services to involve families in Patients' care and treatment wherever possible. There are standards set by Government and clinical bodies that require absolute demonstration of the inclusion of family and friends in all aspects of the care and treatment of forensic patients. For some patients and family members, this push to take on a “role” in care can be unhelpful, extremely stressful, and has constant implications for the potential delicate reparation of relationships. Based on work undertaken for over 20 years in forensic mental health settings, this paper explores the positive psychology approach to a dimensional model to family inclusion in mental health care that learns from family court work and allows for the maintenance of relationships to be at both proximal and Distil levels; to prevent the replication of abuse, decrease the need for falsehoods and assist the recovery of all. The model is based on allowing families to choose to not be involved or be involved in different ways if this is seen to be more helpful. It also allows patients to choose the level of potential involvement that they would find helpful, and for this to be reviewed at a timeframe agreed by all parties, rather than when the next survey is due or the patient has a significant care meeting. This paper is significant as there is a lack of research to support services to use a positive psychology approach to work in this area, the assumption that being asked to be involved must be positive for all seems naïve at best for this patient group. Work relating to the psychology of family can significantly contribute to the development of knowledge in this area. The development of a dimensional model will support choice within families and assist in the development of more honest and open relationships.

Keywords: family dynamics, forensic, mental disorder, positive psychology

Procedia PDF Downloads 130
465 Automatic Differentiation of Ultrasonic Images of Cystic and Solid Breast Lesions

Authors: Dmitry V. Pasynkov, Ivan A. Egoshin, Alexey A. Kolchev, Ivan V. Kliouchkin

Abstract:

In most cases, typical cysts are easily recognized at ultrasonography. The specificity of this method for typical cysts reaches 98%, and it is usually considered as gold standard for typical cyst diagnosis. However, it is necessary to have all the following features to conclude the typical cyst: clear margin, the absence of internal echoes and dorsal acoustic enhancement. At the same time, not every breast cyst is typical. It is especially characteristic for protein-contained cysts that may have significant internal echoes. On the other hand, some solid lesions (predominantly malignant) may have cystic appearance and may be falsely accepted as cysts. Therefore we tried to develop the automatic method of cystic and solid breast lesions differentiation. Materials and methods. The input data were the ultrasonography digital images with the 256-gradations of gray color (Medison SA8000SE, Siemens X150, Esaote MyLab C). Identification of the lesion on these images was performed in two steps. On the first one, the region of interest (or contour of lesion) was searched and selected. Selection of such region is carried out using the sigmoid filter where the threshold is calculated according to the empirical distribution function of the image brightness and, if necessary, it was corrected according to the average brightness of the image points which have the highest gradient of brightness. At the second step, the identification of the selected region to one of lesion groups by its statistical characteristics of brightness distribution was made. The following characteristics were used: entropy, coefficients of the linear and polynomial regression, quantiles of different orders, an average gradient of brightness, etc. For determination of decisive criterion of belonging to one of lesion groups (cystic or solid) the training set of these characteristics of brightness distribution separately for benign and malignant lesions were received. To test our approach we used a set of 217 ultrasonic images of 107 cystic (including 53 atypical, difficult for bare eye differentiation) and 110 solid lesions. All lesions were cytologically and/or histologically confirmed. Visual identification was performed by trained specialist in breast ultrasonography. Results. Our system correctly distinguished all (107, 100%) typical cysts, 107 of 110 (97.3%) solid lesions and 50 of 53 (94.3%) atypical cysts. On the contrary, with the bare eye it was possible to identify correctly all (107, 100%) typical cysts, 96 of 110 (87.3%) solid lesions and 32 of 53 (60.4%) atypical cysts. Conclusion. Automatic approach significantly surpasses the visual assessment performed by trained specialist. The difference is especially large for atypical cysts and hypoechoic solid lesions with the clear margin. This data may have a clinical significance.

Keywords: breast cyst, breast solid lesion, differentiation, ultrasonography

Procedia PDF Downloads 250
464 Nimart-trained Nurses' Perspectives Regarding Virally Unsuppressed Children HIV-positive on Antiretroviral Therapy and Missing Scheduled Clinic Visits: Mopani District, Limpopo Province

Authors: Linneth Nkateko Mabila, Patrick Hulisani Demana, Tebogo Maria Mothiba

Abstract:

Background: Sustaining adherence to antiretroviral therapy (ART) over the long term by people, especially children living with Human-Immunodeficiency Virus (HIV), requires accurate and consistent monitoring, and this is a particular challenge for countries in sub-Saharan Africa. However, the regularity and punctuality in monthly antiretroviral treatment collections indicate medication adherence to a certain extent since it has been revealed to be a significant determinant of the outcome of ART. Aim: This study assessed and described the pattern of monthly antiretroviral treatment collections among a cohort of virally unsuppressed HIV-positive children initiated and managed on ART in the rural public clinics of Mopani District, Limpopo, and explored the nurses' perceptions and views of the findings. Methods: A facility-based mixed-methods study was conducted to assess the honoring of scheduled monthly treatment collection practices by a cohort of HIV-positive children under 15 years initiated and managed on ART by Nurse Initiated Management of Antiretroviral Treatment (NIMART)-trained professional nurses (PNs) from 01 January 2015 to 31 December 2015 in public PHC clinics of Mopani District Municipality. This was followed by the exploration of the nurses' perceptions and views regarding this issue to share their experiences and knowledge acquired through managing these children on ART. Results: From a total of 7105 analysable visits, only 44% (3134) were honored as scheduled, with 40% (2828) of children presenting to the clinics after the scheduled appointment date – they missed their appointments, and 11% (768) of treatment collections that took place before the scheduled appointment date. This finding was further confirmed by 90% (97) of the nurses, who reported that they have children who miss scheduled appointments in their public clinics. The primary reasons for children missing appointments were related to caregivers' forgetfulness and conflict between the school schedule and the dates of clinic visits. Conclusion: We confirmed a high prevalence of non-adherence to scheduled monthly ART collections and the existence of health system, social, and caregiver-related factors that threaten treatment adherence and proper clinical outcomes. These findings suggest an urgent need for intervention since non-adherence to ARV therapy can be life-threatening to the child and poses the danger of reduced life expectancy.

Keywords: antiretroviral therapy (art), nimart, virally unsuppressed children, missed appointments

Procedia PDF Downloads 81
463 Cord Blood Hematopoietic Stem Cell Expansion Ability of Mesenchymal Stem Cells Isolated From Different Sources

Authors: Ana M. Lara, Manuela Llano, Felipe Gaitán, Rosa H. Bustos, Ana Maria Perdomo-Arciniegas, Ximena Bonilla

Abstract:

Umbilical cord blood is used as a source of progenitor and stem cells for the regeneration of the hematopoietic and immune system to treat patients with different hematological or non-hematological diseases. This stem cell source represents an advantage over the use of bone marrow or mobilized peripheral blood because it has a lower incidence rate of graft-versus-host disease, probably due to fewer immunological compatibility restrictions. However, its low cellular dose limits its use in pediatric patients. This work proposes the standardization of a cell expansion technique to compensate for the dose of infused cells through the ex-vivo manipulation of hematopoietic progenitor cells from umbilical cord blood before transplantation. The expansion model is carried out through co-cultures with mesenchymal stem cells (MSC) from bone marrow (BM) and less explored fetal tissues such as Wharton's jelly (WJ) and umbilical cord blood (UCB). Initially, a master cell bank of primary mesenchymal stem cells isolated from different sources was established and characterized following International Society of Cell Therapies (ISCT) indications. Additionally, we assessed the effect of a short 25 Gy cycle of gamma irradiation on cell cycle arrest of mesenchymal cells over the support capacity for the expansion of hematopoietic stem cells from umbilical cord blood was evaluated. The results show that co-cultures with MSC from WJ and UCB allow the cellular dose of HSPC to be maximized between 5 and 16 times having a similar support capacity as BM. In addition, was evaluated the hematopoietic stem progenitor cell's HSPC functionality through the evaluation of migration capacity, their differentiation capacity during culture time by flow cytometry to evaluate the expression of membrane markers associated with lineage-committed progenitors, their clonogenic potential, and the evaluation of secretome profile in the expansion process was evaluated. So far, the treatment with gamma irradiation maintains the hematopoietic support capacity of mesenchymal stem cells from the three sources studied compared to treatments without irradiation, favoring the use of fetal tissues that are generally waste to obtain mesenchymal cell lines for ex-vivo expansion systems. With the results obtained, a standardized protocol that will contribute to the development of ex-vivo expansion with MSC on a larger scale will be achieved, enabling its clinical use and expanding its application in adults.

Keywords: ex-vivo expansion, hematopoietic stem cells, hematopoietic stem cell transplantation, mesenchymal stem cells, umbilical cord blood

Procedia PDF Downloads 98
462 Process Improvement and Redesign of the Immuno Histology (IHC) Lab at MSKCC: A Lean and Ergonomic Study

Authors: Samantha Meyerholz

Abstract:

MSKCC offers patients cutting edge cancer care with the highest quality standards. However, many patients and industry members do not realize that the operations of the Immunology Histology Lab (IHC) are the backbone for carrying out this mission. The IHC lab manufactures blocks and slides containing critical tissue samples that will be read by a Pathologist to diagnose and dictate a patient’s treatment course. The lab processes 200 requests daily, leading to the generation of approximately 2,000 slides and 1,100 blocks each day. Lab material is transported through labeling, cutting, staining and sorting manufacturing stations, while being managed by multiple techs throughout the space. The quality of the stain as well as wait times associated with processing requests, is directly associated with patients receiving rapid treatments and having a wider range of care options. This project aims to improve slide request turnaround time for rush and non-rush cases, while increasing the quality of each request filled (no missing slides or poorly stained items). Rush cases are to be filled in less than 24 hours, while standard cases are allotted a 48 hour time period. Reducing turnaround times enable patients to communicate sooner with their clinical team regarding their diagnosis, ultimately leading faster treatments and potentially better outcomes. Additional project goals included streamlining tech and material workflow, while reducing waste and increasing efficiency. This project followed a DMAIC structure with emphasis on lean and ergonomic principles that could be integrated into an evolving lab culture. Load times and batching processes were analyzed using process mapping, FMEA analysis, waste analysis, engineering observation, 5S and spaghetti diagramming. Reduction of lab technician movement as well as their body position at each workstation was of top concern to pathology leadership. With new equipment being brought into the lab to carry out workflow improvements, screen and tool placement was discussed with the techs in focus groups, to reduce variation and increase comfort throughout the workspace. 5S analysis was completed in two phases in the IHC lab, helping to drive solutions that reduced rework and tech motion. The IHC lab plans to continue utilizing these techniques to further reduce the time gap between tissue analysis and cancer care.

Keywords: engineering, ergonomics, healthcare, lean

Procedia PDF Downloads 211
461 Promoting Patients' Adherence to Home-Based Rehabilitation: A Randomised Controlled Trial of a Theory-Driven Mobile Application

Authors: Derwin K. C. Chan, Alfred S. Y. Lee

Abstract:

The integrated model of self-determination theory and the theory of planned behaviour has been successfully applied to explain individuals’ adherence to health behaviours, including behavioural adherence toward rehabilitation. This study was a randomised controlled trial that examined the effectiveness of an mHealth intervention (i.e., mobile application) developed based on this integrated model in promoting treatment adherence of patients of anterior cruciate ligament rupture during their post-surgery home-based rehabilitation period. Subjects were 67 outpatients (aged between 18 and 60) who undertook anterior cruciate ligament (ACL) reconstruction surgery for less than 2 months for this study. Participants were randomly assigned either into the treatment group (who received the smartphone application; N = 32) and control group (who receive standard treatment only; N = 35), and completed psychological measures relating to the theories (e.g., motivations, social cognitive factors, and behavioural adherence) and clinical outcome measures (e.g., subjective knee function (IKDC), laxity (KT-1000), muscle strength (Biodex)) relating to ACL recovery at baseline, 2-month, and 4-month. Generalise estimating equation showed the interaction between group and time was significant on intention was only significant for intention (Wald x² = 5.23, p = .02), that of perceived behavioural control (Wald x² = 3.19, p = .07), behavioural adherence (Wald x² = 3.08, p = .08, and subjective knee evaluation (Wald x² = 2.97, p = .09) were marginally significant. Post-hoc between-subject analysis showed that control group had significant drop of perceived behavioural control (p < .01), subjective norm (p < .01) and intention (p < .01), behavioural adherence (p < .01) from baseline to 4-month, but such pattern was not observed in the treatment group. The treatment group had a significant decrease of behavioural adherence (p < .05) in the 2-month, but such a decrease was not observed in 4-month (p > .05). Although the subjective knee evaluation in both group significantly improved at 2-month and 4-month from the baseline (p < .05), and the improvements in the control group (mean improvement at 4-month = 40.18) were slightly stronger than the treatment group (mean improvement at 4-month = 34.52). In conclusion, the findings showed that the theory driven mobile application ameliorated the decline of treatment intention of home-based rehabilitation. Patients in the treatment group also reported better muscle strength than control group at 4-month follow-up. Overall, the mobile application has shown promises on tackling the problem of orthopaedics outpatients’ non-adherence to medical treatment.

Keywords: self-determination theory, theory of planned behaviour, mobile health, orthopaedic patients

Procedia PDF Downloads 182
460 Preceptor Program: A Way to Reduce Absconding Rate and Increase Patient Satisfaction

Authors: Akanksha Dicholkar, Celin Jacob, Omkar More

Abstract:

Work force instability, as demonstrated by high rates of staff turnover and lingering vacancy rates, continues to be a major challenge faced by health care organizations. The impact is manifested in workflow inefficiencies, delays in delivering patient care, and dissatisfaction among patients and staff, all of which can have significant negative effects on quality of care and patient safety. In addition, the staggering administrative costs created by a transient work force threaten health care organizations financial viability. One nurse retention strategy is to have newly hired nurses partake in Preceptorship. Precepting is a way to enculturate new employees into their role. Also good professional, collegial relationship between an experienced nurse and a newly hired nurse relations was evidenced. This study demonstrates impact of preceptor program on absconding rate, employee satisfaction & Patient satisfaction. Purpose of study: To decrease absconding rate. Objective: 1. To reduce the high absconding rate among nurses in Aster Medcity (AMC). 2. To facilitate the acclimatization of the newly hired nurse into their role, focusing on professional growth, inter-professional relationships and clinical skills required for the job. Methodology: Descriptive study by Convenience sampling method and collect data by direct observation, questionnaire, interviews. Sample size as per Sample size statistical table at 95 % CI. We conducted a pre and post intervention analysis to assess the impact of Preceptorship at AMC, with a daily occupancy of approx. 300 patients. Result: Preceptor program has had a significant improvement positive impact on all measured parameters. Absconding rate came down from 20% to 0% (P= 0.001). Patient satisfaction scores rose from 85% to 95%. Employee satisfaction rose form 65% to 85%. Conclusion: The project proved that Preceptor Development Programme and the steps taken in hand holding of the new joinees were effective in reducing the absconding rate among nurses and improved the overall satisfaction of new nurses. Preceptee satisfaction with the preceptorship experience was correlated with favorable evaluation of the relationship between the preceptee and preceptor. These findings indicate that when preceptors and preceptees have the benefit of formal preceptorship programs that are well supported, and when the preceptors’ efforts are rewarded, satisfaction is enhanced for both participants, preceptor commitment to the role is reinforced.

Keywords: absconding rate, preceptor, employee satisfaction index, satisfaction index

Procedia PDF Downloads 283
459 Relationship between Pushing Behavior and Subcortical White Matter Lesion in the Acute Phase after Stroke

Authors: Yuji Fujino, Kazu Amimoto, Kazuhiro Fukata, Masahide Inoue, Hidetoshi Takahashi, Shigeru Makita

Abstract:

Aim: Pusher behavior (PB) is a disorder in which stroke patients shift their body weight toward the affected side of the body (the hemiparetic side) and push away from the non-hemiparetic side. These patients often use further pushing to resist any attempts to correct their position to upright. It is known that the subcortical white matter lesion (SWML) usually correlates of gait or balance function in stroke patients. However, it is unclear whether the SWML influences PB. The purpose of this study was to investigate if the damage of SWML affects the severity of PB on acute stroke patients. Methods: Fourteen PB patients without thalamic or cortical lesions (mean age 73.4 years, 17.5 days from onset) participated in this study. Evaluation of PB was performed according to the Scale for Contraversive Pushing (SCP) for sitting and/or standing. We used modified criteria wherein the SCP subscale scores in each section of the scale were >0. As a clinical measurement, patients were evaluated by the Stroke Impairment Assessment Set (SIAS). For the depiction of SWML, we used T2-weighted fluid-attenuated inversion-recovery imaging. The degree of damage on SWML was assessed using the Fazekas scale. Patients were divided into two groups in the presence of SWML (SWML+ group; Fazekas scale grade 1-3, SWML- group; Fazekas scale grade 0). The independent t-test was used to compare the SCP and SIAS. This retrospective study was approved by the Ethics Committee. Results: In SWML+ group, the SCP was 3.7±1.0 points (mean±SD), the SIAS was 28.0 points (median). In SWML- group, the SCP was 2.0±0.2 points, and the SIAS was 31.5 points. The SCP was significantly higher in SWML+ group than in SWML- group (p<0.05). The SIAS was not significant in both groups (p>0.05). Discussion: It has been considered that the posterior thalamus is the neural structures that process the afferent sensory signals mediating graviceptive information about upright body orientation in humans. Therefore, many studies reported that PB was typically associated with unilateral lesions of the posterior thalamus. However, the result indicates that these extra-thalamic brain areas also contribute to the network controlling upright body posture. Therefore, SMWL might induce dysfunction through malperfusion in distant thalamic or other structurally intact neural structures. This study had a small sample size. Therefore, future studies should be performed with a large number of PB patients. Conclusion: The present study suggests that SWML can be definitely associated with PB. The patients with SWML may be severely incapacitating.

Keywords: pushing behavior, subcortical white matter lesion, acute phase, stroke

Procedia PDF Downloads 230
458 Quercetin and INT3 Inhibits Endocrine Therapy Resistance and Epithelial to Mesenchymal Transition in MCF7 Breast Cancer Cells

Authors: S. Pradhan, D. Pradhan, G. Tripathy

Abstract:

Anti-estrogen treatment resistant is a noteworthy reason for disease relapse and mortality in estrogen receptor alpha (ERα)- positive breast cancers. Tamoxifen or estrogen withdrawal increases the dependance of breast malignancy cells on INT3 signaling. Here, we researched the contribution of Quercetin and INT3 signaling in endocrine resistant breast cancer cells. Methods: We utilized two models of endocrine therapies resistant (ETR-) breast cancer: tamoxifen-resistant (TamR) and long term estrogen-deprived (LTED) MCF7 cells. We assessed the migratory and invasive limit of these cells by Transwell assay. Expression of epithelial to mesenchymal transition (EMT) controllers and in addition INT3 receptors and targets were assessed by real-time PCR and western blot analysis. Besides, we tried in vitro anti-Quercetin monoclonal antibodies (mAbs) and gamma secretase inhibitors (GSIs) as potential EMT reversal therapeutic agents. At last, we created stable Quercetin over expessing MCF7 cells and assessed their EMT features and response to tamoxifen. Results:We found that ETR cells acquired an epithelial to mesenchymal transition (EMT) phenotype and showed expanded levels of Quercetin and INT3 targets. Interestingly, we detected higher level of INT3 however lower levels of INT31 and INT32 proposing a switch to targeting through distinctive INT3 receptors after obtaining of resistance. Anti-Quercetin monoclonal antibodies and the GSI PF03084014 were effective in obstructing the Quercetin/INT3 axis and in part inhibiting the EMT process. As a consequence of this, cell migration and invasion were weakened and the stem cell like population was considerably decreased. Genetic hushing of Quercetin and INT3 prompted proportionate impacts. Finally, stable overexpression of Quercetin was adequate to make MCF7 lethargic to tamoxifen by INT3 activation. Conclusions: ETR cells express abnormal amounts of Quercetin and INT3, whose actuation eventually drives invasive conduct. Anti-Quercetin mAbs and GSI PF03084014 lessen expression of EMT molecules decreasing cellular invasiveness. Quercetin overexpression instigates tamoxifen resistance connected to obtaining of EMT phenotype. Our discovering propose that focusing on Quercetin and/or INT3 warrants further clinical assessment as substantial therapeutic methodologies in endocrine-resistant breast cancer.

Keywords: quercetin, INT3, mesenchymal transition, MCF7 breast cancer cells

Procedia PDF Downloads 299
457 The Efficacy of Lithium vs. Valporate on Bipolar Patients and Their Sexual Side Effect: A Meta-Analysis of 4159 Patients

Authors: Yasmeen Jamal Alabdallat, Almutazballlah Bassam Qablan, Obada Ahmad Al Jayyousi, Ihdaa Mahmoud Bani Khalaf, Eman E. Alshial

Abstract:

Background: Bipolar disorder, formerly known as manic depression, is a mental health status that leads to extreme mood swings that include emotional lows (depression) and highs (mania or hypomania). This systematic review and meta-analysis aimed to assess the safety and efficacy of lithium versus valproate among bipolar patients. Methods: A computer literature search of PubMed, Scopus, Web of Science, and Cochrane Central Register of Controlled Trials was conducted from inception until June 2022. Studies comparing lithium versus valproate among bipolar patients were selected for the analysis, and all relevant outcomes were pooled in the meta-analysis using Review Manager Software. Results: 11 Randomized Clinical Trials were included in this meta-analysis with a total of 4159 patients. Our meta showed that lithium was superior to valproate in terms of Young Mania Rating Scale (YMRS) (MD = 0.00 with 95% CI, (-0.55 – 0.55; I2 = 0%), P = 1.00). The results of the Hamilton Depression Rating Scale (HDRS) showed that the overall effect favored the valproate treated group (MD = 1.41 with 95% CI, (-0.15 – 2.67; I2 = 0%), P = 0.03). Concerning the results of the Montgomery-Asberg Depression Rating Scale (MADRS), the results showed that the lithium was superior to valproate (MD = 0.03 with 95% CI, (-0.80 to 0.87; I2 = 40%), P = 0.94). In terms of the sexual side effect, we found that the valproate was superior to lithium (RR 1.19 with 95% CI, (0.74 to 1.91; I2 = 0%), P = 0.47). The lithium-treated group was superior in comparison to valproate treated group in terms of Abnormal Involuntary Movement Scale (AIMS) (MD = -0.03 with 95% CI (-0.38 to 0.32; I2 = 0%), P = 0.87). The lithium was more favorable in terms of Simpson-Agnes scale (MD = -0.40 with 95% CI, (-0.86 to 0.06; I2 = 0%), P = 0.09). The results of the Barnes akathisia scale showed that the overall effect of the valproate was more favorable in comparison to lithium (MD = 0.05 with 95% CI, (-0.12 to 0.22; I2 = 0%), P = 0.57). Conclusion: Our study revealed that on the scales of efficacy Lithium treated group surpassed Valproate treated group in terms of Young Mania Rating Scale (YMRS), Abnormal Involuntary Movement Scale (AIMS) and Simpson-Agnes scale, but valproate surpassed it in Barnes Akathisia scale. Furthermore, on the scales of depression Hamilton Depression Rating Scale (HDRS) showed that the overall effect favored Valproate treated group, but Lithium surpassed valproate in terms of Montgomery-Asberg Depression Rating Scale (MADRS). Valproate surpassed Lithium in terms of sexual side effects.

Keywords: bipolar, mania, bipolar-depression, sexual dysfunction, sexual side effects, treatment

Procedia PDF Downloads 132
456 A Wasp Parasitoids of Genus Cotesia (Hymenoptera: Braconidae) Naturally Parasitizing Pectinophora gossypiella (Saunders) on Transgenic Cotton in Indian Punjab

Authors: Vijay Kumar, G. K. Grewal, Prasad S. Burange

Abstract:

India is one of the largest cultivators of cotton in the world. Among the various constraints, insect pests are posing a major hurdle to the success of cotton cultivation. Various bollworms, including the pink bollworm, Pectinophora gossypiella (Saunders), cause serious losses in India, China, Pakistan, Egypt, Brazil, tropical America, and Africa, etc. Bt cotton cultivars having Cry genes were introduced in India in 2002 (Cry1Ac) and 2006 (Cry1Ac+ Cry2Ab) for control of American, spotted, and pink bollworms. Pink bollworm (PBW) larvae infest flowers, squares, and bolls. Larva burrows into flowers and bolls to feed on pollen and seeds, respectively. It has a shorter lifecycle and more generations per year, so it develops resistance more quickly than other bollworms. Further, it has cryptic feeding sites, i.e., flowers and bolls/seeds, so it is not exposed to harsh environmental fluctuations and insecticidal applications. The cry toxin concentration is low in its feeding sites, i.e., seeds and flowers of cotton. The use of insecticide and Bt cotton is the primary control measure that has been successful in limiting the damage of PBW. But with the passage of time, it has developed resistance against insecticides and Bt cotton. However, the use of insecticides increases chemical control costs while causing secondary pest problems and environmental pollution. Extensive research has indicated that monitoring and control measures such as biological, cultural, chemical, and host plant resistance methods can be integrated for effective PBW management. The potential of various biological control organisms needs to be explored. The impact of transgenic cotton on non-target organisms, particularly natural enemies, which play an important role in pest control, is still being debated. According to some authors, Bt crops have a negative impact on natural enemies, particularly parasitoids. An experiment was carried out in the Integrated Pest Management Laboratory of the Department of Entomology, Punjab Agricultural University, Ludhiana, Punjab, India, to study the natural parasitization of PBW on Bt cotton in 2022. A large population of larvae of PBW were kept individually in plastic containers and fed with cotton bolls until the emergence of a parasitoid cocoon. The first cocoon of the parasitoid was observed on October 25, 2022. Symptoms of parasitization were never seen on larvae. Larvae stopped feeding and became inactive before the emergence of parasitoids for pupation. Grub makes its way out of larvae by making a hole in the integument, and immediately after coming out, it spins the cocoon. The adult parasitoid emerged from the cocoon after eight days. The parasitoids that emerged from the cocoon were identified as Cotesia (Braconidae: Hymenoptera) based on the features of the adult. Out of 475 larvae of PBW, 87 were parasitized, with 18.31% of parasitization. Out of these, 6.73% were first instar, 10.52% were second instar, and 1.05% were third instar larvae of PBW. No parasitization was observed in fourth instar larvae. Parasitoids were observed during the fag end of cropping season and mostly on the earlier instars. It is concluded that the potential of Cotesia may be explored as a biological control agent against PBW, which is safer to human beings, environment and non-taraltoget organisms.

Keywords: biocontrol, Bt cotton, Cotesia, Pectinophora gossypiella

Procedia PDF Downloads 63
455 Utilizing Artificial Intelligence to Predict Post Operative Atrial Fibrillation in Non-Cardiac Transplant

Authors: Alexander Heckman, Rohan Goswami, Zachi Attia, Paul Friedman, Peter Noseworthy, Demilade Adedinsewo, Pablo Moreno-Franco, Rickey Carter, Tathagat Narula

Abstract:

Background: Postoperative atrial fibrillation (POAF) is associated with adverse health consequences, higher costs, and longer hospital stays. Utilizing existing predictive models that rely on clinical variables and circulating biomarkers, multiple societies have published recommendations on the treatment and prevention of POAF. Although reasonably practical, there is room for improvement and automation to help individualize treatment strategies and reduce associated complications. Methods and Results: In this retrospective cohort study of solid organ transplant recipients, we evaluated the diagnostic utility of a previously developed AI-based ECG prediction for silent AF on the development of POAF within 30 days of transplant. A total of 2261 non-cardiac transplant patients without a preexisting diagnosis of AF were found to have a 5.8% (133/2261) incidence of POAF. While there were no apparent sex differences in POAF incidence (5.8% males vs. 6.0% females, p=.80), there were differences by race and ethnicity (p<0.001 and 0.035, respectively). The incidence in white transplanted patients was 7.2% (117/1628), whereas the incidence in black patients was 1.4% (6/430). Lung transplant recipients had the highest incidence of postoperative AF (17.4%, 37/213), followed by liver (5.6%, 56/1002) and kidney (3.6%, 32/895) recipients. The AUROC in the sample was 0.62 (95% CI: 0.58-0.67). The relatively low discrimination may result from undiagnosed AF in the sample. In particular, 1,177 patients had at least 1 AI-ECG screen for AF pre-transplant above .10, a value slightly higher than the published threshold of 0.08. The incidence of POAF in the 1104 patients without an elevated prediction pre-transplant was lower (3.7% vs. 8.0%; p<0.001). While this supported the hypothesis that potentially undiagnosed AF may have contributed to the diagnosis of POAF, the utility of the existing AI-ECG screening algorithm remained modest. When the prediction for POAF was made using the first postoperative ECG in the sample without an elevated screen pre-transplant (n=1084 on account of n=20 missing postoperative ECG), the AUROC was 0.66 (95% CI: 0.57-0.75). While this discrimination is relatively low, at a threshold of 0.08, the AI-ECG algorithm had a 98% (95% CI: 97 – 99%) negative predictive value at a sensitivity of 66% (95% CI: 49-80%). Conclusions: This study's principal finding is that the incidence of POAF is rare, and a considerable fraction of the POAF cases may be latent and undiagnosed. The high negative predictive value of AI-ECG screening suggests utility for prioritizing monitoring and evaluation on transplant patients with a positive AI-ECG screening. Further development and refinement of a post-transplant-specific algorithm may be warranted further to enhance the diagnostic yield of the ECG-based screening.

Keywords: artificial intelligence, atrial fibrillation, cardiology, transplant, medicine, ECG, machine learning

Procedia PDF Downloads 106
454 Chemopreventive Efficacy of Andrographolide in Rat Colon Carcinogenesis Model Using Aberrant Crypt Foci (ACF) as Endpoint Marker

Authors: Maryam Hajrezaie, Mahmood Ameen Abdulla, Nazia Abdul Majid, Hapipa Mohd Ali, Pouya Hassandarvish, Maryam Zahedi Fard

Abstract:

Background: Colon cancer is one of the most prevalent cancers in the world and is the third leading cause of death among cancers in both males and females. The incidence of colon cancer is ranked fourth among all cancers but varies in different parts of the world. Cancer chemoprevention is defined as the use of natural or synthetic compounds capable of inducing biological mechanisms necessary to preserve genomic fidelity. Andrographolide is the major labdane diterpenoidal constituent of the plant Andrographis paniculata (family Acanthaceae), used extensively in the traditional medicine. Extracts of the plant and their constituents are reported to exhibit a wide spectrum of biological activities of therapeutic importance. Laboratory animal model studies have provided evidence that Andrographolide play a role in inhibiting the risk of certain cancers. Objective: Our aim was to evaluate the chemopreventive efficacy of the Andrographolide in the AOM induced rat model. Methods: To evaluate inhibitory properties of andrographolide on colonic aberrant crypt foci (ACF), five groups of 7-week-old male rats were used. Group 1 (control group) were fed with 10% Tween 20 once a day, Group 2 (cancer control) rats were intra-peritoneally injected with 15 mg/kg Azoxymethan, Gropu 3 (drug control) rats were injected with 15 mg/kg azoxymethan and 5-Flourouracil, Group 4 and 5 (experimental groups) were fed with 10 and 20 mg/kg andrographolide each once a day. After 1 week, the treatment group rats received subcutaneous injections of azoxymethane, 15 mg/kg body weight, once weekly for 2 weeks. Control rats were continued on Tween 20 feeding once a day and experimental groups 10 and 20 mg/kg andrographolide feeding once a day for 8 weeks. All rats were sacrificed 8 weeks after the azoxymethane treatment. Colons were evaluated grossly and histopathologically for ACF. Results: Administration of 10 mg/kg and 20 mg/kg andrographolide were found to be effectively chemoprotective, as evidenced microscopily and biochemically. Andrographolide suppressed total colonic ACF formation up to 40% to 60%, respectively, when compared with control group. Pre-treatment with andrographolide, significantly reduced the impact of AOM toxicity on plasma protein and urea levels as well as on plasma aspartate aminotransferase (AST), alanine aminotransferase (ALT), lactate dehydrogenase (LDH) and gamma-glutamyl transpeptidase (GGT) activities. Grossly, colorectal specimens revealed that andrographolide treatments decreased the mean score of number of crypts in AOM-treated rats. Importantly, rats fed andrographolide showed 75% inhibition of foci containing four or more aberrant crypts. The results also showed a significant increase in glutathione (GSH), superoxide dismutase (SOD), nitric oxide (NO), and Prostaglandin E2 (PGE2) activities and a decrease in malondialdehyde (MDA) level. Histologically all treatment groups showed a significant decrease of dysplasia as compared to control group. Immunohistochemical staining showed up-regulation of Hsp70 and down-regulation of Bax proteins. Conclusion: The current study demonstrated that Andrographolide reduce the number of ACF. According to these data, Andrographolide might be a promising chemoprotective activity, in a model of AOM-induced in ACF.

Keywords: chemopreventive, andrographolide, colon cancer, aberrant crypt foci (ACF)

Procedia PDF Downloads 418
453 (Anti)Depressant Effects of Non-Steroidal Antiinflammatory Drugs in Mice

Authors: Horia Păunescu

Abstract:

Purpose: The study aimed to assess the depressant or antidepressant effects of several Nonsteroidal Anti-Inflammatory Drugs (NSAIDs) in mice: the selective cyclooxygenase-2 (COX-2) inhibitor meloxicam, and the non-selective COX-1 and COX-2 inhibitors lornoxicam, sodium metamizole, and ketorolac. The current literature data regarding such effects of these agents are scarce. Materials and methods: The study was carried out on NMRI mice weighing 20-35 g, kept in a standard laboratory environment. The study was approved by the Ethics Committee of the University of Medicine and Pharmacy „Carol Davila”, Bucharest. The study agents were injected intraperitoneally, 10 mL/kg body weight (bw) 1 hour before the assessment of the locomotor activity by cage testing (n=10 mice/ group) and 2 hours before the forced swimming tests (n=15). The study agents were dissolved in normal saline (meloxicam, sodium metamizole), ethanol 11.8% v/v in normal saline (ketorolac), or water (lornoxicam), respectively. Negative and positive control agents were also given (amitryptilline in the forced swimming test). The cage floor used in the locomotor activity assessment was divided into 20 equal 10 cm squares. The forced swimming test involved partial immersion of the mice in cylinders (15/9cm height/diameter) filled with water (10 cm depth at 28C), where they were left for 6 minutes. The cage endpoint used in the locomotor activity assessment was the number of treaded squares. Four endpoints were used in the forced swimming test (immobility latency for the entire 6 minutes, and immobility, swimming, and climbing scores for the final 4 minutes of the swimming session), recorded by an observer that was "blinded" to the experimental design. The statistical analysis used the Levene test for variance homogeneity, ANOVA and post-hoc analysis as appropriate, Tukey or Tamhane tests.Results: No statistically significant increase or decrease in the number of treaded squares was seen in the locomotor activity assessment of any mice group. In the forced swimming test, amitryptilline showed an antidepressant effect in each experiment, at the 10 mg/kg bw dosage. Sodium metamizole was depressant at 100 mg/kg bw (increased the immobility score, p=0.049, Tamhane test), but not in lower dosages as well (25 and 50 mg/kg bw). Ketorolac showed an antidepressant effect at the intermediate dosage of 5 mg/kg bw, but not so in the dosages of 2.5 and 10 mg/kg bw, respectively (increased the swimming score, p=0.012, Tamhane test). Meloxicam and lornoxicam did not alter the forced swimming endpoints at any dosage level. Discussion: 1) Certain NSAIDs caused changes in the forced swimming patterns without interfering with locomotion. 2) Sodium metamizole showed a depressant effect, whereas ketorolac proved antidepressant. Conclusion: NSAID-induced mood changes are not class effects of these agents and apparently are independent of the type of inhibited cyclooxygenase (COX-1 or COX-2). Disclosure: This paper was co-financed from the European Social Fund, through the Sectorial Operational Programme Human Resources Development 2007-2013, project number POSDRU /159 /1.5 /S /138907 "Excellence in scientific interdisciplinary research, doctoral and postdoctoral, in the economic, social and medical fields -EXCELIS", coordinator The Bucharest University of Economic Studies.

Keywords: antidepressant, depressant, forced swim, NSAIDs

Procedia PDF Downloads 218
452 National Digital Soil Mapping Initiatives in Europe: A Review and Some Examples

Authors: Dominique Arrouays, Songchao Chen, Anne C. Richer-De-Forges

Abstract:

Soils are at the crossing of many issues such as food and water security, sustainable energy, climate change mitigation and adaptation, biodiversity protection, human health and well-being. They deliver many ecosystem services that are essential to life on Earth. Therefore, there is a growing demand for soil information on a national and global scale. Unfortunately, many countries do not have detailed soil maps, and, when existing, these maps are generally based on more or less complex and often non-harmonized soil classifications. An estimate of their uncertainty is also often missing. Thus, there are not easy to understand and often not properly used by end-users. Therefore, there is an urgent need to provide end-users with spatially exhaustive grids of essential soil properties, together with an estimate of their uncertainty. One way to achieve this is digital soil mapping (DSM). The concept of DSM relies on the hypothesis that soils and their properties are not randomly distributed, but that they depend on the main soil-forming factors that are climate, organisms, relief, parent material, time (age), and position in space. All these forming factors can be approximated using several exhaustive spatial products such as climatic grids, remote sensing products or vegetation maps, digital elevation models, geological or lithological maps, spatial coordinates of soil information, etc. Thus, DSM generally relies on models calibrated with existing observed soil data (point observations or maps) and so-called “ancillary co-variates” that come from other available spatial products. Then the model is generalized on grids where soil parameters are unknown in order to predict them, and the prediction performances are validated using various methods. With the growing demand for soil information at a national and global scale and the increase of available spatial co-variates national and continental DSM initiatives are continuously increasing. This short review illustrates the main national and continental advances in Europe, the diversity of the approaches and the databases that are used, the validation techniques and the main scientific and other issues. Examples from several countries illustrate the variety of products that were delivered during the last ten years. The scientific production on this topic is continuously increasing and new models and approaches are developed at an incredible speed. Most of the digital soil mapping (DSM) products rely mainly on machine learning (ML) prediction models and/or the use or pedotransfer functions (PTF) in which calibration data come from soil analyses performed in labs or for existing conventional maps. However, some scientific issues remain to be solved and also political and legal ones related, for instance, to data sharing and to different laws in different countries. Other issues related to communication to end-users and education, especially on the use of uncertainty. Overall, the progress is very important and the willingness of institutes and countries to join their efforts is increasing. Harmonization issues are still remaining, mainly due to differences in classifications or in laboratory standards between countries. However numerous initiatives are ongoing at the EU level and also at the global level. All these progress are scientifically stimulating and also promissing to provide tools to improve and monitor soil quality in countries, EU and at the global level.

Keywords: digital soil mapping, global soil mapping, national and European initiatives, global soil mapping products, mini-review

Procedia PDF Downloads 168
451 Outcome of Dacryocystorhinostomy with Peroperative Local Use of Mitomycin-C

Authors: Chandra Shekhar Majumder, Orin Sultana Jamie

Abstract:

Background: Dacryocystorhinostomy (DCR) has been a widely accepted surgical intervention for nasolacrimal duct obstructions. Some previous studies demonstrated the potential benefits of the peroperative application of agents like Mitomycin-C (MMC) with DCR to improve surgical outcomes. Relevant studies are rare in Bangladesh, and there are controversies about the dose, duration of MMC, and outcome. Therefore, the present study aimed to investigate the comparative efficacy of DCR with and without MMC in a tertiary hospital in Bangladesh. Objective: The study aims to determine the outcome of a dacryocystorhinostomy with preoperative local use of mitomycin–C. Methods: An analytical study was conducted in the Department of Ophthalmology, Sir Salimullah Medical College & Mitford Hospital, Dhaka, from January 2023 to September 2023. Seventy patients who were admitted for DCR operation were included according to the inclusion and exclusion criteria. Patients were divided into two groups: those who underwent DCR with peroperative administration of 0.2 mg/ml Mitomycin-C for 5 minutes (Group I) and those who underwent DCR alone (Group II). All patients were subjected to detailed history taking, clinical examination, and relevant investigations. All patients underwent DCR according to standard guidelines and ensured the highest peroperative and postoperative care. Then, patients were followed up at 7th POD, 1-month POD, 3 months POD, and 6 months POD to observe the success rate between the two groups by assessing tearing condition, irrigation, height of tear meniscus, and FDDT- test. Data was recorded using a pre-structured questionnaire, and collected data were analyzed using SPSS 23. Results: The mean age of the study patients was 42.17±6.7 (SD) years and 42.29±7.1 (SD) years in Groups I and II, respectively, with no significant difference (p=0.945). At the 6th month’s follow-up, group I patients were observed with 94.3% frequency of symptom-free, 85.6% patency of lacrimal drainage system, 68.6% had tear meniscus <0.1mm and 88.6% had positive Fluorescence Dye Disappearance Test (FDDT test). In group II, 91.4% were symptom-free, 68.6% showed patency, 57.1% had a height of tear meniscus < 0.1 mm, and 85.6% had FDDT test positive. But no statistically significant difference was observed (p<.05). Conclusion: The use of Mitomycin-C preoperatively during DCR offers better postoperative outcomes, particularly in maintaining patency and achieving symptom resolution with more FDDT test positive and improvement of tear meniscus in the MMC group than the control group. However, this study didn’t demonstrate a statistically significant difference between the two groups. Further research with larger sample sizes and longer follow-up periods would be beneficial to corroborate these findings.

Keywords: dacryocystorhinostomy, mitomycin-c, dacryocystitis, nasolacrimal duct obstruction

Procedia PDF Downloads 31
450 Trends in Preoperative Self-Disclosure of Cannabis Use in Adult and Adolescent Orthopedic Surgical Patients: An Institutional Retrospective Study

Authors: Spencer Liu, William Chan, Marlena Komatz, Tommy Ramos, Mark Trentalange, Faye Rim, Dae Kim, Mary Kelly, Samuel Schuessler, Roberta Stack, Justas Lauzadis, Kathryn DelPizzo, Seth Waldman, Alexandra Sideris

Abstract:

Background & Significance: The increasing prevalence of cannabis use in the United States has important safety considerations in the perioperative setting, as chronic or heavy preoperative cannabis use may increase the risk of intraoperative complications, postoperative nausea and vomiting (PONV), increased postoperative pain levels, and acute side effects associated with cannabis use cessation. In this retrospective chart review study, we sought to determine the prevalence of self-reported cannabis use in the past 5-years at a single institution in New York City. We hypothesized that there is an increasing prevalence of preoperative self-reported cannabis use among adult and adolescent patients undergoing orthopedic surgery. Methods: After IRB approval for this retrospective study, surgical cases performed on patients 12 years of age and older at the hospital’s main campus and two ambulatory surgery centers between January 1st, 2018, and December 31st, 2023, with preoperatively self-disclosed cannabis use entered in the social history intake form were identified using the tool SlicerDicer in Epic. Case and patient characteristics were extracted, and trends in utilization over time were assessed by the Cochran-Armitage trend test. Results: Overall, the prevalence of self-reported cannabis use increased from 6.6% in 2018 to 10.6% in 2023. By age group, the prevalence of self-reported cannabis use among adolescents remained consistently low (2018: 2.6%, 2023: 2.6%) but increased with significant evidence for a linear trend (p < 0.05) within every adult age group. Among adults, patients who were 18-24 years old (2018: 18%, 2023: 20.5%) and 25-34 years old (2018: 15.9%, 2023: 24.2%) had the highest prevalences of disclosure, whereas patients who were 75 years of age or older had the lowest prevalence of disclosure (2018: 1.9%, 2023: 4.6%). Patients who were 25-34 years old had the highest percent difference in disclosure rates of 8.3%, which corresponded to a 52.2% increase from 2018 to 2023. The adult age group with the highest percent change was patients who were 75 years of age or older, with a difference of 2.7%, which corresponded to a 142.1% increase from 2018 to 2023. Conclusions: These trends in preoperative self-reported cannabis use among patients undergoing orthopedic surgery have important implications for perioperative care and clinical outcomes. Efforts are underway to refine and standardize cannabis use data capture at our institution.

Keywords: orthopedic surgery, cannabis, postoperative pain, postoperative nausea

Procedia PDF Downloads 17
449 Congenital Diaphragmatic Hernia Outcomes in a Low-Volume Center

Authors: Michael Vieth, Aric Schadler, Hubert Ballard, J. A. Bauer, Pratibha Thakkar

Abstract:

Introduction: Congenital diaphragmatic hernia (CDH) is a condition characterized by the herniation of abdominal contents into the thoracic cavity requiring postnatal surgical repair. Previous literature suggests improved CDH outcomes at high-volume regional referral centers compared to low-volume centers. The purpose of this study was to examine CDH outcomes at Kentucky Children’s Hospital (KCH), a low-volume center, compared to the Congenital Diaphragmatic Hernia Study Group (CDHSG). Methods: A retrospective chart review was performed at KCH from 2007-2019 for neonates with CDH, and then subdivided into two cohorts: those requiring ECMO therapy and those not requiring ECMO therapy. Basic demographic data and measures of mortality and morbidity including ventilator days and length of stay were compared to the CDHSG. Measures of morbidity for the ECMO cohort including duration of ECMO, clinical bleeding, intracranial hemorrhage, sepsis, need for continuous renal replacement therapy (CRRT), need for sildenafil at discharge, timing of surgical repair, and total ventilator days were collected. Statistical analysis was performed using IBM SPSS Statistics version 28. One-sample t-tests and one-sample Wilcoxon Signed Rank test were utilized as appropriate.Results: There were a total of 27 neonatal patients with CDH at KCH from 2007-2019; 9 of the 27 required ECMO therapy. The birth weight and gestational age were similar between KCH and the CDHSG (2.99 kg vs 2.92 kg, p =0.655; 37.0 weeks vs 37.4 weeks, p =0.51). About half of the patients were inborn in both cohorts (52% vs 56%, p =0.676). KCH cohort had significantly more Caucasian patients (96% vs 55%, p=<0.001). Unadjusted mortality was similar in both groups (KCH 70% vs CDHSG 72%, p =0.857). Using ECMO utilization (KCH 78% vs CDHSG 52%, p =0.118) and need for surgical repair (KCH 95% vs CDHSG 85%, p =0.060) as proxy for severity, both groups’ mortality were comparable. No significant difference was noted for pulmonary outcomes such as average ventilator days (KCH 43.2 vs. CDHSG 17.3, p =0.078) and home oxygen dependency (KCH 44% vs. CDHSG 24%, p =0.108). Average length of hospital stay for patients treated at KCH was similar to CDHSG (64.4 vs 49.2, p=1.000). Conclusion: Our study demonstrates that outcome in CDH patients is independent of center’s case volume status. Management of CDH with a standardized approach in a low-volume center can yield similar outcomes. This data supports the treatment of patients with CDH at low-volume centers as opposed to transferring to higher-volume centers.

Keywords: ECMO, case volume, congenital diaphragmatic hernia, congenital diaphragmatic hernia study group, neonate

Procedia PDF Downloads 75
448 Assessing Acceptability and Preference of Printed Posters on COVID-19 Related Stigma: A Post-Test Study Among HIV-Focused Health Workers in Greater Accra Region of Ghana

Authors: Jerry Fiave, Dacosta Aboagye, Stephen Ayisi-Addo, Mabel Kissiwah Asafo, Felix Osei-Sarpong, Ebenezer Kye-Mensah, Renee Opare-Otoo

Abstract:

Background: Acceptability and preference of social and behaviour change (SBC) materials by target audiences is an important determinant of effective health communication outcomes. In Ghana, however, pre-test and post-test studies on acceptability and preference of specific SBC materials for specific audiences are rare. The aim of this study was therefore to assess the acceptability and preference of printed posters on COVID-19 related stigma as suitable SBC materials for health workers to influence behaviours that promote uptake of HIV-focused services. Methods: A total of 218 health workers who provide HIV-focused services were purposively sampled in 16 polyclinics where the posters were distributed in the Greater Accra region of Ghana. Data was collected in March 2021 using an adapted self-administered questionnaire in Google forms deployed via WhatsApp to participants. The data were imported into SPSS version 27 where chi-square test and regression analyses were performed to establish association as well as strength of association between variables respectively. Results: A total of 142 participants (physicians, nurses, midwives, lab scientists, health promoters, diseases control officers) made up of 85(60%) females and 57(40%) males responded to the questionnaire, giving a response rate of 65.14%. Only 88 (61.97%) of the respondents were exposed to the posters. The majority of those exposed said the posters were informative [82(93.18%)], relevant [85(96.59%)] and attractive [83(94.32%)]. They [82(93.20%)] also rated the material as acceptable with no statistically significant association between category of health worker and acceptability of the posters (X =1.631, df=5, p=0.898). However, participants’ most preferred forms of material on COVID-19 related stigma were social media [38(26.76%)], television [33(23.24%)], SMS [19(13.38%)], and radio [18(12.70%)]. Clinical health workers were 4.88 times more likely to prefer online or electronic versions of SBC materials than nonclinical health workers [AOR= 4.88 (95% CI= 0.31-0.98), p=0.034]. Conclusions: Printed posters on COVID-19 related stigma are acceptable SBC materials in communicating behaviour change messages that target health workers in promoting uptake of HIV-focused services. Posters are however, not among the most preferred materials for health workers. It is therefore recommended that material assessment studies are conducted to inform the development of acceptable and preferred materials for target audiences.

Keywords: acceptability, AIDS, HIV, posters, preference, SBC, stigma, social and behaviour change communication

Procedia PDF Downloads 79
447 Clinical and Chemokine Profile in Leprosy Patients During Multidrug Therapy (MDT) and Their Healthy Contacts: A Randomized Control Trial

Authors: Rohit Kothari

Abstract:

Background: Leprosyis a chronic granulomatous diseasecaused by Mycobacterium leprae (M. Lepra). Reactions may interrupt its usual chronic course.Type-1 (T1R)and type-2 lepra reaction(T2R) are acute events and signifytype-IV and type-III hypersensitivity responses, respectively. Various chemokines like CCL3, 5, 11, and CCL24 may be increased during the course of leprosy or during reactions and may serve as markers of early diagnosis, response to therapy, and prognosis. Objective: To find correlation of CCL3, 5, 11, and CCL24 in leprosy patients on multidrug therapy and their family contacts after ruling out active disease during leprosy treatment and during periods of lepra reactions. Methodology: This randomized control trial was conducted in 50 clinico-histopathologically diagnosed cases of leprosy in a tertiary care hospital in Bengaluru, India. 50 of their family contacts were adequately examined and investigated should the need be to rule out active disease. The two study-groups comprised of leprosy cases, and the age, sex, and area of residence matched healthy contactswho were given single-dose rifampicin prophylaxis, respectively. Blood samples were taken at baseline, six months, and after one yearin both the groups (on completion of MDT in leprosy cases)and also during periods of reaction if occurred in leprosy cases. Results: Our study found that at baseline, CCL5, 11, and 24 were higher in leprosy cases as compared to the healthy contacts, and the difference was statistically significant.CCL3 was also found to be higherat baseline in leprosy cases, however, the difference was not statistically significant. At six months and one year, the levels of CCL 5, 11, and 24 reduced, and the difference was statistically significant in leprosy cases, whereas it remained almost static in all the healthy contacts. Twenty patients of leprosy developed lepra reaction during the course of one year, and during reaction, the increase in CCL11 and 24 was statistically significant from baseline, whereas CCL3 and 5 did not rise significantly. One of the healthy contacts developed signs of leprosy in the form of hypopigmented numb patch and was clinico-histopathologically, and CCL11 and 24 were found to be higher with a statistically significant difference from the baseline values. Conclusion: CCL5, 11, and 24 are sensitive markers of diagnosing leprosy, response to MDT, and prognosis and are not increased in healthy contacts. CCL11 and 24 are sensitive markers of lepra reactions and may serve as one of the early diagnostic modalities for identifying lepra reaction and also leprosy in healthy contacts. To the best of our knowledge, this is the first study to evaluate these biomarkers in leprosy cases and their healthy contacts with a follow-up of upto one year with one of them developing the disease, and the same was confirmed based on these biomarkers as well.

Keywords: chemokine profile, healthy contacts, leprosy, lepra reactions

Procedia PDF Downloads 125
446 Accessing Motional Quotient for All Round Development

Authors: Zongping Wang, Chengjun Cui, Jiacun Wang

Abstract:

The concept of intelligence has been widely used to access an individual's cognitive abilities to learn, form concepts, understand, apply logic, and reason. According to the multiple intelligence theory, there are eight distinguished types of intelligence. One of them is the bodily-kinaesthetic intelligence that links to the capacity of an individual controlling his body and working with objects. Motor intelligence, on the other hand, reflects the capacity to understand, perceive and solve functional problems by motor behavior. Both bodily-kinaesthetic intelligence and motor intelligence refer directly or indirectly to bodily capacity. Inspired by these two intelligence concepts, this paper introduces motional intelligence (MI). MI is two-fold. (1) Body strength, which is the capacity of various organ functions manifested by muscle activity under the control of the central nervous system during physical exercises. It can be measured by the magnitude of muscle contraction force, the frequency of repeating a movement, the time to finish a movement of body position, the duration to maintain muscles in a working status, etc. Body strength reflects the objective of MI. (2) Level of psychiatric willingness to physical events. It is a subjective thing and determined by an individual’s self-consciousness to physical events and resistance to fatigue. As such, we call it subjective MI. Subjective MI can be improved through education and proper social events. The improvement of subjective MI can lead to that of objective MI. A quantitative score of an individual’s MI is motional quotient (MQ). MQ is affected by several factors, including genetics, physical training, diet and lifestyle, family and social environment, and personal awareness of the importance of physical exercise. Genes determine one’s body strength potential. Physical training, in general, makes people stronger, faster and swifter. Diet and lifestyle have a direct impact on health. Family and social environment largely affect one’s passion for physical activities, so does personal awareness of the importance of physical exercise. The key to the success of the MQ study is developing an acceptable and efficient system that can be used to assess MQ objectively and quantitatively. We should apply different accessing systems to different groups of people according to their ages and genders. Field test, laboratory test and questionnaire are among essential components of MQ assessment. A scientific interpretation of MQ score is part of an MQ assessment system as it will help an individual to improve his MQ. IQ (intelligence quotient) and EQ (emotional quotient) and their test have been studied intensively. We argue that IQ and EQ study alone is not sufficient for an individual’s all round development. The significance of MQ study is that it offsets IQ and EQ study. MQ reflects an individual’s mental level as well as bodily level of intelligence in physical activities. It is well-known that the American Springfield College seal includes the Luther Gulick triangle with the words “spirit,” “mind,” and “body” written within it. MQ, together with IQ and EQ, echoes this education philosophy. Since its inception in 2012, the MQ research has spread rapidly in China. By now, six prestigious universities in China have established research centers on MQ and its assessment.

Keywords: motional Intelligence, motional quotient, multiple intelligence, motor intelligence, all round development

Procedia PDF Downloads 138
445 Geochemical Characterization of Geothermal Waters in Albania, Preliminary Results

Authors: Aurela Jahja, Katarzyna Wątor, Arjan Beqiraj, Piotr Rusiniak, Nevton Kodhelaj

Abstract:

Albanian geological terrains represent an important node of the Alpine – Mediterranean mountain belt and are divided into several predominantly NNW - SSE striking geotectonic units, which, based on the presence or lack of Cretaceous transgression and magmatic rocks, belong to Internal or External Albanides. The internal (Korabi, Mirdita and Gashi) units are characterized by the Lower Cretaceous discordance and the presence of abundant magmatic rocks whereas in the external (Alps, Krasta-Cukali, Kruja, Ionian, Sazani and Peri Adriatic Depression) units an almost continuous sedimentation from Triassic to Paleogene is evidenced. The internal and external units show relevant differences in both geothermal and heat flow density values. The gradient values vary from 15-21.3 to 36 mK/m, while the heat flow density ranges from 42 to 60 mW/m2, in the external (Preadriatic Depression) and internal (ophiolitic belt) units, respectively. The geothermal fluids, which are found in natural springs and deep oil wells of Albania, are located in four thermo-mineral provinces: a) Peshkopi (Korabi) province; b) Kruja province; c) Preadriatic basin province, and d) South Ionian province. Thirteen geothermal waters were sampled from 11 natural springs and 2 deep wells, of which 6 springs and 2 wells from Kruja, 1 spring from Peshkopia, 2 springs from Preadriatic basin and 2 springs South Ionian province. Temperature, pH and Electrical Conductivity were measured in situ, while in laboratory were analyzed by ICP method major anions and cations and several trace elements (B, Li, Sr, Rb, I, Br, etc.). The measured values of temperature, pH and electrical conductivity range within 17-63°C, 6.26-7.92 and 724- 26856µS/cm intervals, respectively. The chemical type of the Albania thermal waters is variable. In the Kruja province prevail the Cl-SO4-NaCa and Cl-Na-Ca water types; while SO4-Ca, HCO3-Ca and Cl-HCO3-Na-Ca, and Cl-Na are found in the provinces of Peshkopi, Ionian and Preadriatic basin, respectively. In the Cl-SO4-HCO3 triangular diagram most of the geothermal waters are close to the chloride corner that belong to “mature waters”, typical of geothermal deep and hot fluids. Only samples from the Ionian province are located within the region of high bicarbonate concentration and they can be classified as peripheral waters that may have mixed with cold groundwater. In the Na-Ca-Mg and Na-K-Mg triangular diagram the majority of waters fall in the corner of sodium, suggesting that their cation ratios are controlled by mineral-solution equilibrium. There is a linear relationship between Cl and B which indicates the mixing of geothermal water with cold water, where the low-chlorine thermal waters from Ionian basin and Preadriatic depression provinces are distinguished by high-chlorine thermal waters from Kruja province. The Cl/Br molar ration of the thermal waters from Kruja province ranges from 1000 to 2660 and separates them from the thermal waters of Ionian basin and Preadriatic depression provinces having Cl/Br molar ratio lower than 650. The apparent increase of Cl/Br molar ratio that correlates with the increasing of the chloride, is probably related with dissolution of the Halite.

Keywords: geothermal fluids, geotectonic units, natural springs, deep wells, mature waters, peripheral waters

Procedia PDF Downloads 203
444 Evaluating the Effectiveness of Plantar Sensory Insoles and Remote Patient Monitoring for Early Intervention in Diabetic Foot Ulcer Prevention in Patients with Peripheral Neuropathy

Authors: Brock Liden, Eric Janowitz

Abstract:

Introduction: Diabetic peripheral neuropathy (DPN) affects 70% of individuals with diabetes1. DPN causes a loss of protective sensation, which can lead to tissue damage and diabetic foot ulcer (DFU) formation2. These ulcers can result in infections and lower-extremity amputations of toes, the entire foot, and the lower leg. Even after a DFU is healed, recurrence is common, with 49% of DFU patients developing another ulcer within a year and 68% within 5 years3. This case series examines the use of sensory insoles and newly available plantar data (pressure, temperature, step count, adherence) and remote patient monitoring in patients at risk of DFU. Methods: Participants were provided with custom-made sensory insoles to monitor plantar pressure, temperature, step count, and daily use and were provided with real-time cues for pressure offloading as they went about their daily activities. The sensory insoles were used to track subject compliance, ulceration, and response to feedback from real-time alerts. Patients were remotely monitored by a qualified healthcare professional and were contacted when areas of concern were seen and provided coaching on reducing risk factors and overall support to improve foot health. Results: Of the 40 participants provided with the sensory insole system, 4 presented with a DFU. Based on flags generated from the available plantar data, patients were contacted by the remote monitor to address potential concerns. A standard clinical escalation protocol detailed when and how concerns should be escalated to the provider by the remote monitor. Upon escalation to the provider, patients were brought into the clinic as needed, allowing for any issues to be addressed before more serious complications might arise. Conclusion: This case series explores the use of innovative sensory technology to collect plantar data (pressure, temperature, step count, and adherence) for DFU detection and early intervention. The results from this case series suggest the importance of sensory technology and remote patient monitoring in providing proactive, preventative care for patients at risk of DFU. This robust plantar data, with the addition of remote patient monitoring, allow for patients to be seen in the clinic when concerns arise, giving providers the opportunity to intervene early and prevent more serious complications, such as wounds, from occurring.

Keywords: diabetic foot ulcer, DFU prevention, digital therapeutics, remote patient monitoring

Procedia PDF Downloads 61
443 Biosensor for Determination of Immunoglobulin A, E, G and M

Authors: Umut Kokbas, Mustafa Nisari

Abstract:

Immunoglobulins, also known as antibodies, are glycoprotein molecules produced by activated B cells that transform into plasma cells and result in them. Antibodies are critical molecules of the immune response to fight, which help the immune system specifically recognize and destroy antigens such as bacteria, viruses, and toxins. Immunoglobulin classes differ in their biological properties, structures, targets, functions, and distributions. Five major classes of antibodies have been identified in mammals: IgA, IgD, IgE, IgG, and IgM. Evaluation of the immunoglobulin isotype can provide a useful insight into the complex humoral immune response. Evaluation and knowledge of immunoglobulin structure and classes are also important for the selection and preparation of antibodies for immunoassays and other detection applications. The immunoglobulin test measures the level of certain immunoglobulins in the blood. IgA, IgG, and IgM are usually measured together. In this way, they can provide doctors with important information, especially regarding immune deficiency diseases. Hypogammaglobulinemia (HGG) is one of the main groups of primary immunodeficiency disorders. HGG is caused by various defects in B cell lineage or function that result in low levels of immunoglobulins in the bloodstream. This affects the body's immune response, causing a wide range of clinical features, from asymptomatic diseases to severe and recurrent infections, chronic inflammation and autoimmunity Transient infant hypogammaglobulinemia (THGI), IgM deficiency (IgMD), Bruton agammaglobulinemia, IgA deficiency (SIgAD) HGG samples are a few. Most patients can continue their normal lives by taking prophylactic antibiotics. However, patients with severe infections require intravenous immune serum globulin (IVIG) therapy. The IgE level may rise to fight off parasitic infections, as well as a sign that the body is overreacting to allergens. Also, since the immune response can vary with different antigens, measuring specific antibody levels also aids in the interpretation of the immune response after immunization or vaccination. Immune deficiencies usually occur in childhood. In Immunology and Allergy clinics, apart from the classical methods, it will be more useful in terms of diagnosis and follow-up of diseases, if it is fast, reliable and especially in childhood hypogammaglobulinemia, sampling from children with a method that is more convenient and uncomplicated. The antibodies were attached to the electrode surface via the poly hydroxyethyl methacrylamide cysteine nanopolymer. It was used to evaluate the anodic peak results obtained in the electrochemical study. According to the data obtained, immunoglobulin determination can be made with a biosensor. However, in further studies, it will be useful to develop a medical diagnostic kit with biomedical engineering and to increase its sensitivity.

Keywords: biosensor, immunosensor, immunoglobulin, infection

Procedia PDF Downloads 74
442 Design, Fabrication and Analysis of Molded and Direct 3D-Printed Soft Pneumatic Actuators

Authors: N. Naz, A. D. Domenico, M. N. Huda

Abstract:

Soft Robotics is a rapidly growing multidisciplinary field where robots are fabricated using highly deformable materials motivated by bioinspired designs. The high dexterity and adaptability to the external environments during contact make soft robots ideal for applications such as gripping delicate objects, locomotion, and biomedical devices. The actuation system of soft robots mainly includes fluidic, tendon-driven, and smart material actuation. Among them, Soft Pneumatic Actuator, also known as SPA, remains the most popular choice due to its flexibility, safety, easy implementation, and cost-effectiveness. However, at present, most of the fabrication of SPA is still based on traditional molding and casting techniques where the mold is 3d printed into which silicone rubber is cast and consolidated. This conventional method is time-consuming and involves intensive manual labour with the limitation of repeatability and accuracy in design. Recent advancements in direct 3d printing of different soft materials can significantly reduce the repetitive manual task with an ability to fabricate complex geometries and multicomponent designs in a single manufacturing step. The aim of this research work is to design and analyse the Soft Pneumatic Actuator (SPA) utilizing both conventional casting and modern direct 3d printing technologies. The mold of the SPA for traditional casting is 3d printed using fused deposition modeling (FDM) with the polylactic acid (PLA) thermoplastic wire. Hyperelastic soft materials such as Ecoflex-0030/0050 are cast into the mold and consolidated using a lab oven. The bending behaviour is observed experimentally with different pressures of air compressor to ensure uniform bending without any failure. For direct 3D-printing of SPA fused deposition modeling (FDM) with thermoplastic polyurethane (TPU) and stereolithography (SLA) with an elastic resin are used. The actuator is modeled using the finite element method (FEM) to analyse the nonlinear bending behaviour, stress concentration and strain distribution of different hyperelastic materials after pressurization. FEM analysis is carried out using Ansys Workbench software with a Yeon-2nd order hyperelastic material model. FEM includes long-shape deformation, contact between surfaces, and gravity influences. For mesh generation, quadratic tetrahedron, hybrid, and constant pressure mesh are used. SPA is connected to a baseplate that is in connection with the air compressor. A fixed boundary is applied on the baseplate, and static pressure is applied orthogonally to all surfaces of the internal chambers and channels with a closed continuum model. The simulated results from FEM are compared with the experimental results. The experiments are performed in a laboratory set-up where the developed SPA is connected to a compressed air source with a pressure gauge. A comparison study based on performance analysis is done between FDM and SLA printed SPA with the molded counterparts. Furthermore, the molded and 3d printed SPA has been used to develop a three-finger soft pneumatic gripper and has been tested for handling delicate objects.

Keywords: finite element method, fused deposition modeling, hyperelastic, soft pneumatic actuator

Procedia PDF Downloads 74
441 Comprehensive Analysis of Electrohysterography Signal Features in Term and Preterm Labor

Authors: Zhihui Liu, Dongmei Hao, Qian Qiu, Yang An, Lin Yang, Song Zhang, Yimin Yang, Xuwen Li, Dingchang Zheng

Abstract:

Premature birth, defined as birth before 37 completed weeks of gestation is a leading cause of neonatal morbidity and mortality and has long-term adverse consequences for health. It has recently been reported that the worldwide preterm birth rate is around 10%. The existing measurement techniques for diagnosing preterm delivery include tocodynamometer, ultrasound and fetal fibronectin. However, they are subjective, or suffer from high measurement variability and inaccurate diagnosis and prediction of preterm labor. Electrohysterography (EHG) method based on recording of uterine electrical activity by electrodes attached to maternal abdomen, is a promising method to assess uterine activity and diagnose preterm labor. The purpose of this study is to analyze the difference of EHG signal features between term labor and preterm labor. Free access database was used with 300 signals acquired in two groups of pregnant women who delivered at term (262 cases) and preterm (38 cases). Among them, EHG signals from 38 term labor and 38 preterm labor were preprocessed with band-pass Butterworth filters of 0.08–4Hz. Then, EHG signal features were extracted, which comprised classical time domain description including root mean square and zero-crossing number, spectral parameters including peak frequency, mean frequency and median frequency, wavelet packet coefficients, autoregression (AR) model coefficients, and nonlinear measures including maximal Lyapunov exponent, sample entropy and correlation dimension. Their statistical significance for recognition of two groups of recordings was provided. The results showed that mean frequency of preterm labor was significantly smaller than term labor (p < 0.05). 5 coefficients of AR model showed significant difference between term labor and preterm labor. The maximal Lyapunov exponent of early preterm (time of recording < the 26th week of gestation) was significantly smaller than early term. The sample entropy of late preterm (time of recording > the 26th week of gestation) was significantly smaller than late term. There was no significant difference for other features between the term labor and preterm labor groups. Any future work regarding classification should therefore focus on using multiple techniques, with the mean frequency, AR coefficients, maximal Lyapunov exponent and the sample entropy being among the prime candidates. Even if these methods are not yet useful for clinical practice, they do bring the most promising indicators for the preterm labor.

Keywords: electrohysterogram, feature, preterm labor, term labor

Procedia PDF Downloads 547
440 Leveraging the HDAC Inhibitory Pharmacophore to Construct Deoxyvasicinone Based Tractable Anti-Lung Cancer Agent and pH-Responsive Nanocarrier

Authors: Ram Sharma, Esha Chatterjee, Santosh Kumar Guru, Kunal Nepali

Abstract:

A tractable anti-lung cancer agent was identified via the installation of a Ring C expanded synthetic analogue of the alkaloid vasicinone [7,8,9,10-tetrahydroazepino[2,1-b] quinazolin-12(6H)-one (TAZQ)] as a surface recognition part in the HDAC inhibitory three-component model. Noteworthy to mention that the candidature of TAZQ was deemed suitable for accommodation in HDAC inhibitory pharmacophore as per the results of the fragment recruitment process conducted by our laboratory. TAZQ was pinpointed through the fragment screening program as a synthetically flexible fragment endowed with some moderate cell growth inhibitory activity against the lung cancer cell lines, and it was anticipated that the use of the aforementioned fragment to generate hydroxamic acid functionality (zinc-binding motif) bearing HDAC inhibitors would boost the antitumor efficacy of TAZQ. Consistent with our aim of applying epigenetic targets to the treatment of lung cancer, a strikingly potent anti-lung cancer scaffold (compound 6) was pinpointed through a series of in-vitro experiments. Notably, the compounds manifested a magnificent activity profile against KRAS and EGFR mutant lung cancer cell lines (IC50 = 0.80 - 0.96 µM), and the effects were found to be mediated through preferential HDAC6 inhibition (IC50 = 12.9 nM). In addition to HDAC6 inhibition, the compounds also elicited HDAC1 and HDAC3 inhibitory activity with an IC50 value of 49.9 nM and 68.5 nM, respectively. The HDAC inhibitory ability of compound 6 was also confirmed from the results of the western blot experiment that revealed its potential to decrease the expression levels of HDAC isoforms (HDAC1, HDAC3, and HDAC6). Noteworthy to mention that complete downregulation of the HDAC6 isoform was exerted by compound 6 at 0.5 and 1 µM. Moreover, in another western blot experiment, treatment with hydroxamic acid 6 led to upregulation of H3 acK9 and α-Tubulin acK40 levels, ascertaining its inhibitory activity toward both the class I HDACs and Class II B HDACs. The results of other assays were also encouraging as treatment with compound 6 led to the suppression of the colony formation ability of A549 cells, induction of apoptosis, and increase in autophagic flux. In silico studies led us to rationalize the results of the experimental assay, and some key interactions of compound 6 with the amino acid residues of HDAC isoforms were identified. In light of the impressive activity spectrum of compound 6, a pH-responsive nanocarrier (hyaluronic acid-compound 6 nanoparticles) was prepared. The dialysis bag approach was used for the assessment of the nanoparticles under both normal and acidic circumstances, and the pH-sensitive nature of hyaluronic acid-compound 6 nanoparticles was confirmed. Delightfully, the nanoformulation was devoid of cytotoxicity against the L929 mouse fibroblast cells (normal settings) and exhibited selective cytotoxicity towards the A549 lung cancer cell lines. In a nutshell, compound 6 appears to be a promising adduct, and a detailed investigation of this compound might yield a therapeutic for the treatment of lung cancer.

Keywords: HDAC inhibitors, lung cancer, scaffold, hyaluronic acid, nanoparticles

Procedia PDF Downloads 81
439 Sickle Cell Disease: Review of Managements in Pregnancy and the Outcome in Ampang Hospital, Selangor

Authors: Z. Nurzaireena, K. Azalea, T. Azirawaty, S. Jameela, G. Muralitharan

Abstract:

The aim of this study is the review of the management practices of sickle cell disease patients during pregnancy, as well as the maternal and neonatal outcome at Ampang Hospital, Selangor. The study consisted of a review of pregnant patients with sickle cell disease under follow up at the Hematology Clinic, Ampang Hospital over the last seven years to assess their management and maternal-fetal outcome. The results of the review show that Ampang Hospital is considered the public hematology centre for sickle cell disease and had successfully managed three pregnancies throughout the last seven years. Patients’ presentations, managements and maternal-fetal outcome were compared and reviewed for academic improvements. All three patients were seen very early in their pregnancy and had been given a regime of folic acid, antibiotics and thrombo-prophylactic drugs. Close monitoring of maternal and fetal well being was done by the hematologists and obstetricians. Among the patients, there were multiple admissions during the pregnancy for either a painful sickle cell bone crisis, haemolysis following an infection and anemia requiring phenotype- matched blood and exchange transfusions. Broad spectrum antibiotics coverage during and infection, hydration, pain management and venous-thrombolism prophylaxis were mandatory. The pregnancies managed to reach near term in the third trimester but all required emergency caesarean section for obstetric indications. All pregnancies resulted in live births with good fetal outcome. During post partum all were nursed closely in the high dependency units for further complications and were discharged well. Post partum follow up and contraception counseling was comprehensively given for future pregnancies. Sickle cell disease is uncommonly seen in the East, especially in the South East Asian region, yet more cases are seen in the current decade due to improved medical expertise and advance medical laboratory technologies. Pregnancy itself is a risk factor for sickle cell patients as increased thrombosis event and risk of infections can lead to multiple crisis, haemolysis, anemia and vaso-occlusive complications including eclampsia, cerebrovasular accidents and acute bone pain. Patients mostly require multiple blood product transfusions thus phenotype-matched blood is required to reduce the risk of alloimmunozation. Emphasizing the risks and complications in preconception counseling and establishing an ultimate pregnancy plan would probably reduce the risk of morbidity and mortality to the mother and unborn child. Early management for risk of infection, thromboembolic events and adequate hydration is mandatory. A holistic approach involving multidisciplinary team care between the hematologist, obstetricians, anesthetist, neonatologist and close nursing care for both mother and baby would ensure the best outcome. In conclusion, sickle cell disease by itself is a high risk medical condition and pregnancy would further amplify the risk. Thus, close monitoring with combine multidisciplinary care, counseling and educating the patients are crucial in achieving the safe outcome.

Keywords: anaemia, haemoglobinopathies, pregnancy, sickle cell disease

Procedia PDF Downloads 238