Search results for: clinical markers
Commenced in January 2007
Frequency: Monthly
Edition: International
Paper Count: 4281

Search results for: clinical markers

2751 Anthocyanins as Markers of Enhanced Plant Defence in Maize (Zea Mays L.) Exposed to Copper Stress

Authors: Fadime Eryılmaz Pehlivan

Abstract:

Anthocyanins are important plant pigments having roles in many physiological and ecological functions; that are controlled by numerous regulatory factors. The accumulation of anthocyanins in Z. mays cause the plants stems to exhibit red coloration when encountering gradually increasing copper treatments (1, 5, and 10 mM of Cu in a period of 5 days) on maize seedlings. Stress injury was measured in terms of chlorophyll (a and b), carotenoid and anthocyanin contents, malondialdehyde (MDA), hydrogen peroxide (H2O2). Carotenoid and anthocyanin contents dramatically increased by increasing concentrations of Cu stress. MDA and H2O2 levels were found to significantly increase at high Cu treatments (5 and 10 mM of Cu). Chlorophyll content was observed to be highest at 1 mM Cu and then decreased at 5 and 10 mM of Cu. In addition, significant increases were determined in the activities of catalase (CAT), superoxide dismutase (SOD), glutathione reductase (GR) and ascorbate peroxidase (APX) under high Cu concentrations, while glutathione S-transferase (GST) and peroxidase (POX) activities showed no change. Treatments above 5 and 10 mM of Cu triggered copper stress in maize seedlings. The results of this study provide evidence that maize seedlings represent a high tolerance to gradually increasing copper treatments. Improved copper tolerance may relate to high anthocyanin, and carotenoid content besides antioxidant enzyme activity may improve the metal chelating ability of anthocyanin pigments. Data presented in this study may also contribute to a better understanding of phytoremediation studies in maize exposed to high copper contenting soils.

Keywords: anthocyanin, copper, maize , antioxidant

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2750 Effect of Visnagin on Altered Steroidogenesis and Spermatogenesis, and Testicular Injury Induced by the Heavy Metal Lead

Authors: Saleh N. Maodaa

Abstract:

Background: Lead (Pb) is an environmental pollutant causing serious health problems, including impairment of reproduction. Visnagin (VIS) is a furanochromone with promising antioxidant and anti-inflammatory effects; however, its protective efficacy against Pb toxicity has not been investigated. Objective: This study evaluated the protective effect of VIS on Pb reproductive toxicity, impaired steroidogenesis and spermatogenesis, oxidative stress and inflammation. Methods: Rats received VIS (30 or 60 mg/kg) and 50 mg/kg lead acetate for 3 weeks, and blood and testes samples were collected. Results: Pb intoxication impaired the pituitary-testicular axis (PTA), manifested by the decreased serum levels of gonadotropins and testosterone. Pb decreased sperm count, motility and viability, increased sperm abnormalities, and downregulated the steroidogenesis markers StAR, CYP17A1, 3β-HSD and 17β-HSD in the testis of rats. VIS significantly increased serum gonadotropins and testosterone, alleviated sperm parameters and upregulated steroidogenesis. In addition, VIS decreased pro-inflammatory cytokines, testicular lipid peroxidation and DNA fragmentation, downregulated Bax, and enhanced antioxidants and Bcl-2 Conclusion: These results demonstrate the protective effect of VIS against Pb reproductive toxicity in rats. VIS improved serum gonadotropins and testosterone, enhanced steroidogenesis and spermatogenesis, and attenuated oxidative injury, inflammation and apoptosis. Therefore, VIS is a promising candidate for the protection against Pb-induced reproduction impairment.

Keywords: pituitary-gonadal axis, cytokines, DNA damage, apoptosis

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2749 The Improvement in Clinical Outcomes with the Histological Presence of Nidus Following Radiofrequency Ablation (RFA) for Osteoid Osteoma (OO)

Authors: Amirul Adlan, Motaz AlAqeel, Scott Evans, Vaiyapuri sumathi, Mark Davies, Rajesh Botchu

Abstract:

Background & Objectives: Osteoid osteoma (OO) is a benign tumor of the bone commonly found in childhood and adolescence, causing bone pain, especially during the night. CT-guided radiofrequency ablation (RFA) is currently the mainstay treatment for OO. There is currently no literature reporting the outcomes of OO following RFA based on the histological presence of a nidus seen on a biopsy taken at the time of RFA. The primary aim of this study was to compare the clinical outcomes of OO between the group of patients with the presence of nidus on biopsy samples from RFA with those without nidus. Secondly, we aimed to examine other factors that may affect the outcomes of OO, reflecting our experience as a tertiary orthopedic oncology center. Methods: We retrospectively reviewed 88 consecutive patients diagnosed with osteoid osteoma treated with RFA between November 2005 and March 2015, consisting of 63 males (72%) and 25 females (28%). Sixty-six patients (75%) had nidus present in their biopsy samples. Patients’ mean age was 17.6 years (4-53). The median duration of follow-up was 12.5 months (6-20.8). Lesions were located in the appendicular skeleton in seventy-nine patients (90%), while nine patients (10%) had an OO in the axial skeleton. Outcomes assessed were based on patients’ pain alleviation (partial, complete, or no pain improvement) and the need for further interventions. Results: Pain improvement in the patient group with nidus in the histology sample was significantly better than in the group without nidus (OR 7.4, CI 1.35-41.4, p=0.021). The patient group with nidus on biopsy demonstrated less likelihood of having a repeat procedure compared to the group without nidus(OR 0.092, CI 0.016-0.542, p=0.008). Our study showed significantly better outcomes in pain improvement in appendicular lesions compared to the axially located lesions (p = 0.005). Patients with spinal lesions tend to have relatively poor pain relief than those with appendicular or pelvic lesions (p=0.007). Conclusions: Patients with nidus on histology had better pain alleviation compared to patients without nidus. The histological presence of nidus significantly reduces the chance of repeat interventions. The pain alleviation of osteoid osteoma following RFA is better in patients with appendicular lesions than spinal or axially located lesions.

Keywords: osteoid osteoma, benign tumour, radiofrequency ablation, oncology

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2748 Comparison of Methods for the Synthesis of Eu+++, Tb+++, and Tm+++ Doped Y2O3 Nanophosphors by Sol-Gel and Hydrothermal Methods for Bioconjugation

Authors: Ravindra P. Singh, Drupad Ram, Dinesh K. Gupta

Abstract:

Rare earth ions doped metal oxides are a class of luminescent materials which have been proved to be excellent for applications in field emission displays and cathode ray tubes, plasma display panels. Under UV irradiation Eu+++ doped Y2O3 is a red phosphor and Tb+++ doped Y 2O3 is a green phosphor. It is possible that, due to their high quantum efficiency, they might serve as improved luminescent markers for identification of biomolecules, as already reported for CdSe and CdSe/ZnS nanocrystals. However, for any biological applications these particle powders must be suspended in water while retaining their phosphorescence. We hereby report synthesis and characterization of Eu+++ and Tb+++ doped yttrium oxide nanoparticles by sol-gel and hydrothermal processes. Eu+++ and Tb+++ doped Y2O3 nanoparticles have been synthesized by hydrothermal process using yttrium oxo isopropoxide [Y5O(OPri)13] (crystallized twice) and it’s acetyl acetone modified product [Y(O)(acac)] as precursors. Generally the sol-gel derived metal oxides are required to be annealed to the temperature ranging from 400°C-800°C in order to develop crystalline phases. However, this annealing also results in the development of aggregates which are undesirable for bio-conjugation experiments. In the hydrothermal process, we have achieved crystallinity of the nanoparticles at 300°C and the development of crystalline phases has been found to be proportional to the time of heating of the reactor. The average particle sizes as calculated from XRD were found to be 28 nm, 32 nm, and 34 nm by hydrothermal process. The particles were successfully suspended in chloroform in the presence of trioctyl phosphene oxide and TEM investigations showed the presence of single particles along with agglomerates.

Keywords: nanophosphors, Y2O3:Eu+3, Y2O3:Tb+3, sol-gel, hydrothermal method, TEM, XRD

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2747 Polyphytopharmaca Improving Asthma Control Test Value, Biomarker (Eosinophils and Malondialdehyde): Quasi Experimental Test in Patients with Asthma

Authors: Andri Andri, Susanthy Djajalaksana, Iin Noor Chozin

Abstract:

Background: Despite advances in asthma therapies, a proportion of patients with asthma continue to have difficulty in gaining adequate asthma control. Complex immunological mechanisms and oxidative stress affect this condition, including the role of malondialdehyde (MDA) as a marker of inflammation. This research aimed to determine the effect of polyphytopharmaca administration on the value of asthma control test (ACT), blood eosinophils level and markers of MDA serum inflammation in patients with asthma. Method: Quasi experimental approach was conducted toward 15 stable asthma patients who were not fully controlled in outpatient pulmonary clinic, Public Hospital of Dr. Saiful Anwar Malang. Assessments of ACT values, eosinophil levels, and serum MDA levels were carried out before and after administration of polyphytopharmaca which contained a combination of 100 mg Nigella sativa extract, Kleinhovia hospita 100 mg, Curcuma xanthorrhiza 75 mg, and Ophiocephalus striatus 100 mg, three times daily with two capsules for 12 weeks. The ACT value was determined by the researcher by asking the patient directly, blood eosinophil levels were calculated by analyzing blood type counts, and serum MDA levels were detected by the qPCR method. Result: There was a significant enhancement of ACT value (18.07 ± 2.57 to 22.06 ± 1.83, p = 0.001) (from 60% uncontrolled ACT to 93.3% controlled ACT), a significant decrease in blood eosinophils levels (653.15 ± 276.15 pg/mL to 460.66 ± 202.04 pg/mL, p = 0.038), and decreased serum MDA levels (109.64 ± 53.77 ng / ml to 78.68 ± 64.92 ng/ml, p = 0.156). Conclusion: Administration of polyphytopharmaca can increase ACT value, decrease blood eosinophils levels and reduce MDA serum in stable asthma patients who are not fully controlled.

Keywords: asthma control test, eosinophils levels, malondialdehyde, polyphytopharmaca

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2746 Management of Femoral Neck Stress Fractures at a Specialist Centre and Predictive Factors to Return to Activity Time: An Audit

Authors: Charlotte K. Lee, Henrique R. N. Aguiar, Ralph Smith, James Baldock, Sam Botchey

Abstract:

Background: Femoral neck stress fractures (FNSF) are uncommon, making up 1 to 7.2% of stress fractures in healthy subjects. FNSFs are prevalent in young women, military recruits, endurance athletes, and individuals with energy deficiency syndrome or female athlete triad. Presentation is often non-specific and is often misdiagnosed following the initial examination. There is limited research addressing the return–to–activity time after FNSF. Previous studies have demonstrated prognostic time predictions based on various imaging techniques. Here, (1) OxSport clinic FNSF practice standards are retrospectively reviewed, (2) FNSF cohort demographics are examined, (3) Regression models were used to predict return–to–activity prognosis and consequently determine bone stress risk factors. Methods: Patients with a diagnosis of FNSF attending Oxsport clinic between 01/06/2020 and 01/01/2020 were selected from the Rheumatology Assessment Database Innovation in Oxford (RhADiOn) and OxSport Stress Fracture Database (n = 14). (1) Clinical practice was audited against five criteria based on local and National Institute for Health Care Excellence guidance, with a 100% standard. (2) Demographics of the FNSF cohort were examined with Student’s T-Test. (3) Lastly, linear regression and Random Forest regression models were used on this patient cohort to predict return–to–activity time. Consequently, an analysis of feature importance was conducted after fitting each model. Results: OxSport clinical practice met standard (100%) in 3/5 criteria. The criteria not met were patient waiting times and documentation of all bone stress risk factors. Importantly, analysis of patient demographics showed that of the population with complete bone stress risk factor assessments, 53% were positive for modifiable bone stress risk factors. Lastly, linear regression analysis was utilized to identify demographic factors that predicted return–to–activity time [R2 = 79.172%; average error 0.226]. This analysis identified four key variables that predicted return-to-activity time: vitamin D level, total hip DEXA T value, femoral neck DEXA T value, and history of an eating disorder/disordered eating. Furthermore, random forest regression models were employed for this task [R2 = 97.805%; average error 0.024]. Analysis of the importance of each feature again identified a set of 4 variables, 3 of which matched with the linear regression analysis (vitamin D level, total hip DEXA T value, and femoral neck DEXA T value) and the fourth: age. Conclusion: OxSport clinical practice could be improved by more comprehensively evaluating bone stress risk factors. The importance of this evaluation is demonstrated by the population found positive for these risk factors. Using this cohort, potential bone stress risk factors that significantly impacted return-to-activity prognosis were predicted using regression models.

Keywords: eating disorder, bone stress risk factor, femoral neck stress fracture, vitamin D

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2745 Importance of Detecting Malingering Patients in Clinical Setting

Authors: Sakshi Chopra, Harsimarpreet Kaur, Ashima Nehra

Abstract:

Objectives: Malingering is fabricating or exaggerating the symptoms of mental or physical disorders for a variety of secondary gains or motives, which may include financial compensation; avoiding work; getting lighter criminal sentences; or simply to attract attention or sympathy. Malingering is different from somatization disorder and factitious disorder. The prevalence of malingering is unknown and difficult to determine. In an estimated study in forensic population, it can reach up to 17% cases. But the accuracy of such estimates is questionable as successful malingerers are not detected and thus, not included. Methods: The case study of a 58 years old, right handed, graduate, pre-morbidly working in a national company with reported history of stroke leading to head injury; cerebral infarction/facial palsy and dementia. He was referred for disability certification so that his job position can be transferred to his son as he could not work anymore. A series of Neuropsychological tests were administered. Results: With a mental age of < 2.5 years; social adaptive functioning was overall < 20 showing profound Mental Retardation, less than 1 year social age in abilities of self-help, eating, dressing, locomotion, occupation, communication, self-direction, and socialization; severely impaired verbal and performance ability, 96% impairment in Activities of Daily Living, with an indication of very severe depression. With inconsistent and fluctuating medical findings and problem descriptions to different health professionals forming the board for his disability, it was concluded that this patient was malingering. Conclusions: Even though it can be easily defined, malingering can be very challenging to diagnosis. Cases of malingering impose a substantial economic burden on the health care system and false attribution of malingering imposes a substantial burden of suffering on a significant proportion of the patient population. Timely, tactful diagnosis and management can help ease this patient burden on the healthcare system. Malingering can be detected by only trained mental health professionals in the clinical setting.

Keywords: disability, India, malingering, neuropsychological assessment

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2744 Genotypic and Allelic Distribution of Polymorphic Variants of Gene SLC47A1 Leu125Phe (rs77474263) and Gly64Asp (rs77630697) and Their Association to the Clinical Response to Metformin in Adult Pakistani T2DM Patients

Authors: Sadaf Moeez, Madiha Khalid, Zoya Khalid, Sania Shaheen, Sumbul Khalid

Abstract:

Background: Inter-individual variation in response to metformin, which has been considered as a first line therapy for T2DM treatment is considerable. In the current study, it was aimed to investigate the impact of two genetic variants Leu125Phe (rs77474263) and Gly64Asp (rs77630697) in gene SLC47A1 on the clinical efficacy of metformin in T2DM Pakistani patients. Methods: The study included 800 T2DM patients (400 metformin responders and 400 metformin non-responders) along with 400 ethnically matched healthy individuals. The genotypes were determined by allele-specific polymerase chain reaction. In-silico analysis was done to confirm the effect of the two SNPs on the structure of genes. Association was statistically determined using SPSS software. Results: Minor allele frequency for rs77474263 and rs77630697 was 0.13 and 0.12. For SLC47A1 rs77474263 the homozygotes of one mutant allele ‘T’ (CT) of rs77474263 variant were fewer in metformin responders than metformin non-responders (29.2% vs. 35.5 %). Likewise, the efficacy was further reduced (7.2% vs. 4.0 %) in homozygotes of two copies of ‘T’ allele (TT). Remarkably, T2DM cases with two copies of allele ‘C’ (CC) had 2.11 times more probability to respond towards metformin monotherapy. For SLC47A1 rs77630697 the homozygotes of one mutant allele ‘A’ (GA) of rs77630697 variant were fewer in metformin responders than metformin non-responders (33.5% vs. 43.0 %). Likewise, the efficacy was further reduced (8.5% vs. 4.5%) in homozygotes of two copies of ‘A’ allele (AA). Remarkably, T2DM cases with two copies of allele ‘G’ (GG) had 2.41 times more probability to respond towards metformin monotherapy. In-silico analysis revealed that these two variants affect the structure and stability of their corresponding proteins. Conclusion: The present data suggest that SLC47A1 Leu125Phe (rs77474263) and Gly64Asp (rs77630697) polymorphisms were associated with the therapeutic response of metformin in T2DM patients of Pakistan.

Keywords: diabetes, T2DM, SLC47A1, Pakistan, polymorphism

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2743 The Effect of Kangaroo Mother Care and Swaddling Method on Venipuncture Pain in Premature Infant: Randomized Clinical Trials

Authors: Faezeh Jahanpour, Shahin Dezhdar, Saeedeh Firouz Bakht, Afshin Ostovar

Abstract:

Objective: The hospitalized premature babies often undergo various painful procedures such as venous sampling. The Kangaroo mother care (KMC) method is one of the pain reduction methods, but as mother’s presence is not always possible, this research was done to compare the effect of swaddling and KMC method on venous sampling pain on premature neonates. Methods: In this randomized clinical trial 90 premature infants selected and randomly alocated into three groups; Group A (swaddling), Group B (the kangaroo care), and group C (the control). From 10 minutes before blood sampling to 2 minutes after that in group A, the infant was wrapped in a thin sheet, and in group B, the infant was under Kangaroo care. In all three groups, the heart rate and arterial oxygen saturation in time intervals of 30 seconds before, during, 30-60-90, and 120 seconds after sampling were measured and recorded. The infant’s face was video recorded since sampling till 2 minutes and the videos were checked by a researcher who was unaware of the kind of intervention and the pain assessment tools for infants (PIPP) for time intervals of 30 seconds were completed. Data analyzed by t-test, Q square, Repeated Measure ANOVA, Kruskal-Wallis, Post-hoc and Bonferroni test. Results: Findings revealed that the pain was reduced to a great extent in swaddling and kangaroo method compared to that in control group. But there was not a significant difference between kangaroo and swaddling care method (P ≥ 0.05). In addition, the findings showed that the heart rate and arterial oxygen saturation was low and stable in swaddling and Kangaroo care method and returned to base status faster, whereas, the changes were severe in control group and did not return to base status even after 120 seconds. Discussion: The results of this study showed that there was not a meaningful difference between swaddling and kangaroo care method on physiological indexes and pain in infants. Therefore, swaddling method can be a good substitute for kangaroo care method in this regard.

Keywords: Kangaroo mother care, neonate, pain, premature, swaddling, venipuncture,

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2742 Urinary Volatile Organic Compound Testing in Fast-Track Patients with Suspected Colorectal Cancer

Authors: Godwin Dennison, C. E. Boulind, O. Gould, B. de Lacy Costello, J. Allison, P. White, P. Ewings, A. Wicaksono, N. J. Curtis, A. Pullyblank, D. Jayne, J. A. Covington, N. Ratcliffe, N. K. Francis

Abstract:

Background: Colorectal symptoms are common but only infrequently represent serious pathology, including colorectal cancer (CRC). A large number of invasive tests are presently performed for reassurance. We investigated the feasibility of urinary volatile organic compound (VOC) testing as a potential triage tool in patients fast-tracked for assessment for possible CRC. Methods: A prospective, multi-centre, observational feasibility study was performed across three sites. Patients referred on NHS fast-track pathways for potential CRC provided a urine sample which underwent Gas Chromatography Mass Spectrometry (GC-MS), Field Asymmetric Ion Mobility Spectrometry (FAIMS) and Selected Ion Flow Tube Mass Spectrometry (SIFT-MS) analysis. Patients underwent colonoscopy and/or CT colonography and were grouped as either CRC, adenomatous polyp(s), or controls to explore the diagnostic accuracy of VOC output data supported by an artificial neural network (ANN) model. Results: 558 patients participated with 23 (4.1%) CRC diagnosed. 59% of colonoscopies and 86% of CT colonographies showed no abnormalities. Urinary VOC testing was feasible, acceptable to patients, and applicable within the clinical fast track pathway. GC-MS showed the highest clinical utility for CRC and polyp detection vs. controls (sensitivity=0.878, specificity=0.882, AUROC=0.884). Conclusion: Urinary VOC testing and analysis are feasible within NHS fast-track CRC pathways. Clinically meaningful differences between patients with cancer, polyps, or no pathology were identified therefore suggesting VOC analysis may have future utility as a triage tool. Acknowledgment: Funding: NIHR Research for Patient Benefit grant (ref: PB-PG-0416-20022).

Keywords: colorectal cancer, volatile organic compound, gas chromatography mass spectrometry, field asymmetric ion mobility spectrometry, selected ion flow tube mass spectrometry

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2741 Anticancer Effect of Doxorubicin Using Injectable Hydrogel

Authors: Prasamsha Panta, Da Yeon Kim, Ja Yong Jang, Min Jae Kim, Jae Ho Kim, Moon Suk Kim

Abstract:

Introduction: Among the many anticancer drugs used clinically, doxorubicin (Dox), was one of widely used drugs to treat many types of solid tumors such as liver, colon, breast, or lung. Intratumoral injection of chemotherapeutic agents is a potentially more effective alternative to systemic administration because direct delivery of the anticancer drug to the target may improve both the stability and efficacy of anticancer drugs. Injectable in situ-forming gels have attracted considerable attention because they can achieve site specific drug delivery, long term action periods, and improved patient compliance. Objective: Objective of present study is to confirm clinical benefit of intratumoral chemotherapy using injectable in situ-forming poly(ethylene glycol)-b-polycaprolactone diblock copolymer (MP) and Dox with increase in efficacy and reducing the toxicity in patients with cancer diseases. Methods and methodology: We prepared biodegradable MP hydrogel and measured viscosity for the evaluation of thermo-sensitive property. In vivo antitumor activity was performed with normal saline, MP only, single free Dox, repeat free Dox, and Dox-loaded MP gel. The remaining amount of Dox drug was measured using HPLC after the mouse was sacrified. For cytotoxicity studies WST-1 assay was performed. Histological analysis was done with H&E and TUNEL processes respectively. Results: The works in this experiment showed that Dox-loaded MP have biodegradable drug depot property. Dox-loaded MP gels showed remarkable in vitro cytotoxicity activities against cancer cells. Finally, this work indicates that injection of Dox-loaded MP allowed Dox to act effectively in the tumor and induced long-lasting supression of tumor growth. Conclusion: This work has examined the potential clinical utility of intratumorally injected Dox-loaded MP gel, which shows significant effect of higher local Dox retention compared with systemically administered Dox.

Keywords: injectable in-situ forming hydrogel, anticancer, doxorubicin, intratumoral injection

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2740 Presence and Severity of Language Deficits in Comprehension, Production and Pragmatics in a Group of ALS Patients: Analysis with Demographic and Neuropsychological Data

Authors: M. Testa, L. Peotta, S. Giusiano, B. Lazzolino, U. Manera, A. Canosa, M. Grassano, F. Palumbo, A. Bombaci, S. Cabras, F. Di Pede, L. Solero, E. Matteoni, C. Moglia, A. Calvo, A. Chio

Abstract:

Amyotrophic Lateral Sclerosis (ALS) is a neurodegenerative disease of adulthood, which primarily affects the central nervous system and is characterized by progressive bilateral degeneration of motor neurons. The degeneration processes in ALS extend far beyond the neurons of the motor system, and affects cognition, behaviour and language. To outline the prevalence of language deficits in an ALS cohort and explore their profile along with demographic and neuropsychological data. A full neuropsychological battery and language assessment was administered to 56 ALS patients. Neuropsychological assessment included tests of executive functioning, verbal fluency, social cognition and memory. Language was assessed using tests for verbal comprehension, production and pragmatics. Patients were cognitively classified following the Revised Consensus Criteria and divided in three groups showing different levels of language deficits: group 1 - no language deficit; group 2 - one language deficit; group 3 - two or more language deficits. Chi-square for independence and non-parametric measures to compare groups were applied. Nearly half of ALS-CN patients (48%) reported one language test under the clinical cut-off, and only 13% of patents classified as ALS-CI showed no language deficits, while the rest 87% of ALS-CI reported two or more language deficits. ALS-BI and ALS-CBI cases all reported two or more language deficits. Deficits in production and in comprehension appeared more frequent in ALS-CI patients (p=0.011, p=0.003 respectively), with a higher percentage of comprehension deficits (83%). Nearly all ALS-CI reported at least one deficit in pragmatic abilities (96%) and all ALS-BI and ALS-CBI patients showed pragmatic deficits. Males showed higher percentage of pragmatic deficits (97%, p=0.007). No significant differences in language deficits have been found between bulbar and spinal onset. Months from onset and level of impairment at testing (ALS-FRS total score) were not significantly different between levels and type of language impairment. Age and education were significantly higher for cases showing no deficits in comprehension and pragmatics and in the group showing no language deficits. Comparing performances at neuropsychological tests among the three levels of language deficits, no significant differences in neuropsychological performances were found between group 1 and 2; compared to group 1, group 3 appeared to decay specifically on executive testing, verbal/visuospatial learning, and social cognition. Compared to group 2, group 3 showed worse performances specifically in tests of working memory and attention. Language deficits have found to be spread in our sample, encompassing verbal comprehension, production and pragmatics. Our study reveals that also cognitive intact patients (ALS-CN) showed at least one language deficit in 48% of cases. Pragmatic domain is the most compromised (84% of the total sample), present in nearly all ALS-CI (96%), likely due to the influence of executive impairment. Lower age and higher education seem to preserve comprehension, pragmatics and presence of language deficits. Finally, executive functions, verbal/visuospatial learning and social cognition differentiate the group with no language deficits from the group with a clinical language impairment (group 3), while attention and working memory differentiate the group with one language deficit from the clinical impaired group.

Keywords: amyotrophic lateral sclerosis, language assessment, neuropsychological assessment, language deficit

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2739 Developing Telehealth-Focused Advanced Practice Nurse Educational Partnerships

Authors: Shelley Y. Hawkins

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Introduction/Background: As technology has grown exponentially in healthcare, nurse educators must prepare Advanced Practice Registered Nurse (APRN) graduates with the knowledge and skills in information systems/technology to support and improve patient care and health care systems. APRN’s are expected to lead in caring for populations who lack accessibility and availability through the use of technology, specifically telehealth. The capacity to effectively and efficiently use technology in patient care delivery is clearly delineated in the American Association of Colleges of Nursing (AACN) Doctor of Nursing Practice (DNP) and Master of Science in Nursing (MSN) Essentials. However, APRN’s have minimal, or no, exposure to formalized telehealth education and lack necessary technical skills needed to incorporate telehealth into their patient care. APRN’s must successfully master the technology using telehealth/telemedicine, electronic health records, health information technology, and clinical decision support systems to advance health. Furthermore, APRN’s must be prepared to lead the coordination and collaboration with other healthcare providers in their use and application. Aim/Goal/Purpose: The purpose of this presentation is to establish and operationalize telehealth-focused educational partnerships between one University School of Nursing and two health care systems in order to enhance the preparation of APRN NP students for practice, teaching, and/or scholarly endeavors. Methods: The proposed project was initially presented by the project director to selected multidisciplinary stakeholders including leadership, home telehealth personnel, primary care providers, and decision support systems within two major health care systems to garner their support for acceptance and implementation. Concurrently, backing was obtained from key university-affiliated colleagues including the Director of Simulation and Innovative Learning Lab and Coordinator of the Health Care Informatics Program. Technology experts skilled in design and production in web applications and electronic modules were secured from two local based technology companies. Results: Two telehealth-focused APRN Program academic/practice partnerships have been established. Students have opportunities to engage in clinically based telehealth experiences focused on: (1) providing patient care while incorporating various technology with a specific emphasis on telehealth; (2) conducting research and/or evidence-based practice projects in order to further develop the scientific foundation regarding incorporation of telehealth with patient care; and (3) participating in the production of patient-level educational materials related to specific topical areas. Conclusions: Evidence-based APRN student telehealth clinical experiences will assist in preparing graduates who can effectively incorporate telehealth into their clinical practice. Greater access for diverse populations will be available as a result of the telehealth service model as well as better care and better outcomes at lower costs. Furthermore, APRN’s will provide the necessary leadership and coordination through interprofessional practice by transforming health care through new innovative care models using information systems and technology.

Keywords: academic/practice partnerships, advanced practice nursing, nursing education, telehealth

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2738 Clinical Empathy: The Opportunity to Offer Optimal Treatment to People with Serious Illness

Authors: Leonore Robieux, Franck Zenasni, Marc Pocard, Clarisse Eveno

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Empirical data in health psychology studies show the necessity to consider the doctor-patient communication and its positive impact on outcomes such as patients’ satisfaction, treatment adherence, physical and psychological wellbeing. In this line, the present research aims to define the role and determinants of an effective doctor–patient communication during the treatment of patients with serious illness (peritoneal carcinomatosis). We carried out a prospective longitudinal study including patients treated for peritoneal carcinomatosis of various origins. From November 2016, to date, data were collected using validated questionnaires at two times of evaluation: one month before the surgery (T0) and one month after (T1). Thus, patients reported their (a) anxiety and depression levels, (b) standardized and individualized quality of life and (c) how they perceived communication, attitude and empathy of the surgeon. 105 volunteer patients (Mean age = 58.18 years, SD = 10.24, 62.2% female) participated to the study. PC arose from rare diseases (14%), colorectal (38%), eso-gastric (24%) and ovarian (8%) cancer. Three groups are defined according to the severity of their pathology and the treatment offered to them: (1) important surgical treatment with the goal of healing (53%), (2) repeated palliative surgical treatment (17%), and (3) the patients recused for surgical treatment, only palliative approach (30%). Results are presented according to Baron and Kenny recommendations. The regressions analyses show that only depression and anxiety are sensitive to the communication and empathy of surgeon. The main results show that a good communication and high level of empathy at T0 and T1 limit depression and anxiety of the patients in T1. Results also indicate that the severity of the disease modulates this positive impact of communication: better is the communication the less are the level of depression and anxiety of the patients. This effect is higher for patients treated for the more severe disease. These results confirm that, even in the case severe disease a good communication between patient and physician remains a significant factor in promoting the well-being of patients. More specific training need to be developed to promote empathic care.

Keywords: clinical empathy, determinants, healthcare, psychological wellbeing

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2737 Relationships of Functional Status and Subjective Health Status among Stable Chronic Obstructive Pulmonary Disease Patients Residing in the Community

Authors: Hee-Young Song

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Background and objectives: In 2011, the Global Initiative for Chronic Obstructive Lung Disease (GOLD) recommendations proposed a multidimensional assessment of patients’ conditions that included both functional parameters and patient-reported outcomes, with the aim to provide a comprehensive assessment of the disease, thus meeting both the needs of the patient and the role of the physician. However, few studies have evaluated patient-reported outcomes as well as objective functional assessments among individuals with chronic obstructive pulmonary disease (COPD) in clinical practice in Korea. This study was undertaken to explore the relationship between functional status assessed by the 6-minute walking distance (MWD) test and subjective health status reported by stable patients with COPD residing in community. Methods: A cross-sectional descriptive study was conducted with 118 stable COPD patients aged 69.4 years old and selected by a convenient sampling from an outpatient department of pulmonology in a tertiaryhospitals. The 6-MWD test was conducted according to standardized instructions. Participants also completed a constructed questionnaire including general characteristics, smoking history, dyspnea by modified medical research council (mMRC) scale, and health status by COPD assessment test (CAT). Anthropometric measurements were performed for body mass index (BMI). Medical records were reviewed to obtain disease-related characteristics including duration of the disease and forced expiratory volume in 1 second (FEV1). Data were analyzed using PASW statistics 20.0. Results: Mean FEV1% of participants was 63.51% and mean 6-MWD and CAT scores were 297.54m and 17.7, respectively. The 6-MWD and CAT showed significant negative correlations (r= -.280, p=.002); FEV1 and CAT did as well correlations (r= -.347, p < .001). Conclusions: Findings suggest that the better functional status an individual with COPD has, the better subjective health status is, and provide the support for using patient-reported outcomes along with functional parameters to facilitate comprehensive assessment of COPD patients in real clinical practices.

Keywords: chronic obstructive pulmonary disease, COPD assessment test, functional status, patient-reported outcomes

Procedia PDF Downloads 365
2736 Enhancing Root Canal Therapy with MTA and Tetracycline-Loaded Nanochitosan: An Approach for Infected Root Canal Treatment in Dogs (in-vivo Animal Study)

Authors: Rania Hanafi Mahmoud Said, Rasha Mohamed Taha

Abstract:

Background: A recent study has explored the potential of an approach to treating infected root canals using a combination of Mineral Trioxide Aggregate (MTA) and Tetracycline-loaded Nanochitosan. Material and methods: Forty dogs were included in the study, with infected periapical areas induced by leaving access openings in their teeth for four months. Bacteriological samples from the infected root canals were collected and managed anaerobically to identify and count the different microorganisms present. The most common microorganisms detected were Prevotella oris, Fusobacterium nucleatum, Streptococcus viridans, Enterococcus faecalis, Clostridium subterminale, Porphyromonas gingivalis, and Peptostreptococcus anaerobius. The dogs were divided into four groups based on the sealant used to treat the infected periapical areas: Group I: Negative control (no treatment) Group II: Positive control (MTA only) Group III: MTA + tetracycline Group IV: MTA + tetracycline loaded on nanochitosan Results: Periapical areas in Group IV showed significantly more bone healing than those in Groups I, II, and III. The newly formed bone was evaluated radiographically, histologically, and immunohistochemically using Osteopontin (OSP) antibodies. Data collected was statistically analysed using SPSS software at a 0.05 significance level. Conclusion: The study concluded that the combined use of Tetracycline-loaded Nanochitosan and MTA presents a promising approach for the treatment of infected root canals. The potent antimicrobial activity of Tetracycline-loaded Nanochitosan, along with the biocompatibility and desirable properties of MTA, may synergistically contribute to improved clinical outcomes in endodontic therapy. This study has important implications for the clinical management of infected root canals. The combination of Tetracycline-loaded Nanochitosan and MTA could provide a more effective and efficient means of treating these challenging cases. Further research is needed to confirm these findings in humans and to optimize the treatment protocol.

Keywords: mineral trioxide aggregate, tetracycline-loaded nanochitosan, periapical infection, osteopontine

Procedia PDF Downloads 57
2735 Effect of Retained Posterior Horn of Medial Meniscus on Functional Outcome of ACL Reconstructed Knees

Authors: Kevin Syam, Devendra K. Chauhan, Mandeep Singh Dhillon

Abstract:

Background: The posterior horn of medial meniscus (PHMM) is a secondary stabilizer against anterior translation of tibia. Cadaveric studies have revealed increased strain on the ACL graft and greater instrumented laxity in Posterior horn deficient knees. Clinical studies have shown higher prevalence of radiological OA after ACL reconstruction combined with menisectomy. However, functional outcomes in ACL reconstructed knee in the absence of Posterior horn is less discussed, and specific role of posterior horn is ill-documented. This study evaluated functional and radiological outcomes in posterior horn preserved and posterior horn sacrificed ACL reconstructed knees. Materials: Of the 457 patients who had ACL reconstruction done over a 6 year period, 77 cases with minimum follow up of 18 months were included in the study after strict exclusion criteria (associated lateral meniscus injury, other ligamentous injuries, significant cartilage degeneration, repeat injury and contralateral knee injuries were excluded). 41 patients with intact menisci were compared with 36 patients with absent posterior horn of medial meniscus. Radiological and clinical tests for instability were conducted, and knees were evaluated using subjective International Knee Documentation Committee (IKDC) score and the Orthopadische Arbeitsgruppe Knie score (OAK). Results: We found a trend towards significantly better overall outcome (OAK) in cases with intact PHMM at average follow-up of 43.03 months (p value 0.082). Cases with intact PHMM had significantly better objective stability (p value 0.004). No significant differences were noted in the subjective IKDC score (p value 0.526) and the functional OAK outcome (category D) (p value 0.363). More cases with absent posterior horn had evidence of radiological OA (p value 0.022) even at mid-term follow-up. Conclusion: Even though the overall OAK and subjective IKDC scores did not show significant difference between the two subsets, the poorer outcomes in terms of objective stability and radiological OA noted in the absence of PHMM, indicates the importance of preserving this important part of the meniscus.

Keywords: ACL, functional outcome, knee, posterior of medial meniscus

Procedia PDF Downloads 358
2734 Ultrasensitive Detection and Discrimination of Cancer-Related Single Nucleotide Polymorphisms Using Poly-Enzyme Polymer Bead Amplification

Authors: Lorico D. S. Lapitan Jr., Yihan Xu, Yuan Guo, Dejian Zhou

Abstract:

The ability of ultrasensitive detection of specific genes and discrimination of single nucleotide polymorphisms is important for clinical diagnosis and biomedical research. Herein, we report the development of a new ultrasensitive approach for label-free DNA detection using magnetic nanoparticle (MNP) assisted rapid target capture/separation in combination with signal amplification using poly-enzyme tagged polymer nanobead. The sensor uses an MNP linked capture DNA and a biotin modified signal DNA to sandwich bind the target followed by ligation to provide high single-nucleotide polymorphism discrimination. Only the presence of a perfect match target DNA yields a covalent linkage between the capture and signal DNAs for subsequent conjugation of a neutravidin-modified horseradish peroxidase (HRP) enzyme through the strong biotin-nuetravidin interaction. This converts each captured DNA target into an HRP which can convert millions of copies of a non-fluorescent substrate (amplex red) to a highly fluorescent product (resorufin), for great signal amplification. The use of polymer nanobead each tagged with thousands of copies of HRPs as the signal amplifier greatly improves the signal amplification power, leading to greatly improved sensitivity. We show our biosensing approach can specifically detect an unlabeled DNA target down to 10 aM with a wide dynamic range of 5 orders of magnitude (from 0.001 fM to 100.0 fM). Furthermore, our approach has a high discrimination between a perfectly matched gene and its cancer-related single-base mismatch targets (SNPs): It can positively detect the perfect match DNA target even in the presence of 100 fold excess of co-existing SNPs. This sensing approach also works robustly in clinical relevant media (e.g. 10% human serum) and gives almost the same SNP discrimination ratio as that in clean buffers. Therefore, this ultrasensitive SNP biosensor appears to be well-suited for potential diagnostic applications of genetic diseases.

Keywords: DNA detection, polymer beads, signal amplification, single nucleotide polymorphisms

Procedia PDF Downloads 248
2733 Pharmacokinetics and Safety of Pacritinib in Patients with Hepatic Impairment and Healthy Volunteers

Authors: Suliman Al-Fayoumi, Sherri Amberg, Huafeng Zhou, Jack W. Singer, James P. Dean

Abstract:

Pacritinib is an oral kinase inhibitor with specificity for JAK2, FLT3, IRAK1, and CSF1R. In clinical studies, pacritinib was well tolerated with clinical activity in patients with myelofibrosis. The most frequent adverse events (AEs) observed with pacritinib are gastrointestinal (diarrhea, nausea, and vomiting; mostly grade 1-2 in severity) and typically resolve within 2 weeks. A human ADME mass balance study demonstrated that pacritinib is predominantly cleared via hepatic metabolism and biliary excretion (>85% of administered dose). The major hepatic metabolite identified, M1, is not thought to materially contribute to the pharmacological activity of pacritinib. Hepatic diseases are known to impair hepatic blood flow, drug-metabolizing enzymes, and biliary transport systems and may affect drug absorption, disposition, efficacy, and toxicity. This phase 1 study evaluated the pharmacokinetics (PK) and safety of pacritinib and the M1 metabolite in study subjects with mild, moderate, or severe hepatic impairment (HI) and matched healthy subjects with normal liver function to determine if pacritinib dosage adjustments are necessary for patients with varying degrees of hepatic insufficiency. Study participants (aged 18-85 y) were enrolled into 4 groups based on their degree of HI as defined by Child-Pugh Clinical Assessment Score: mild (n=8), moderate (n=8), severe (n=4), and healthy volunteers (n=8) matched for age, BMI, and sex. Individuals with concomitant renal dysfunction or progressive liver disease were excluded. A single 400 mg dose of pacritinib was administered to all participants. Blood samples were obtained for PK evaluation predose and at multiple time points postdose through 168 h. Key PK parameters evaluated included maximum plasma concentration (Cmax), time to Cmax (Tmax), area under the plasma concentration time curve (AUC) from hour zero to last measurable concentration (AUC0-t), AUC extrapolated to infinity (AUC0-∞), and apparent terminal elimination half-life (t1/2). Following treatment, pacritinib was quantifiable for all study participants at 1 h through 168 h postdose. Systemic pacritinib exposure was similar between healthy volunteers and individuals with mild HI. However, there was a significant difference between those with moderate and severe HI and healthy volunteers with respect to peak concentration (Cmax) and plasma exposure (AUC0-t, AUC0-∞). Mean Cmax decreased by 47% and 57% respectively in participants with moderate and severe HI vs matched healthy volunteers. Similarly, mean AUC0-t decreased by 36% and 45% and mean AUC0-∞ decreased by 46% and 48%, respectively in individuals with moderate and severe HI vs healthy volunteers. Mean t1/2 ranged from 51.5 to 74.9 h across all groups. The variability on exposure ranged from 17.8% to 51.8% across all groups. Systemic exposure of M1 was also significantly decreased in study participants with moderate or severe HI vs. healthy participants and individuals with mild HI. These changes were not significantly dissimilar from the inter-patient variability in these parameters observed in healthy volunteers. All AEs were grade 1-2 in severity. Diarrhea and headache were the only AEs reported in >1 participant (n=4 each). Based on these observations, it is unlikely that dosage adjustments would be warranted in patients with mild, moderate, or severe HI treated with pacritinib.

Keywords: pacritinib, myelofibrosis, hepatic impairment, pharmacokinetics

Procedia PDF Downloads 297
2732 A Next Generation Multi-Scale Modeling Theatre for in silico Oncology

Authors: Safee Chaudhary, Mahnoor Naseer Gondal, Hira Anees Awan, Abdul Rehman, Ammar Arif, Risham Hussain, Huma Khawar, Zainab Arshad, Muhammad Faizyab Ali Chaudhary, Waleed Ahmed, Muhammad Umer Sultan, Bibi Amina, Salaar Khan, Muhammad Moaz Ahmad, Osama Shiraz Shah, Hadia Hameed, Muhammad Farooq Ahmad Butt, Muhammad Ahmad, Sameer Ahmed, Fayyaz Ahmed, Omer Ishaq, Waqar Nabi, Wim Vanderbauwhede, Bilal Wajid, Huma Shehwana, Muhammad Tariq, Amir Faisal

Abstract:

Cancer is a manifestation of multifactorial deregulations in biomolecular pathways. These deregulations arise from the complex multi-scale interplay between cellular and extracellular factors. Such multifactorial aberrations at gene, protein, and extracellular scales need to be investigated systematically towards decoding the underlying mechanisms and orchestrating therapeutic interventions for patient treatment. In this work, we propose ‘TISON’, a next-generation web-based multiscale modeling platform for clinical systems oncology. TISON’s unique modeling abstraction allows a seamless coupling of information from biomolecular networks, cell decision circuits, extra-cellular environments, and tissue geometries. The platform can undertake multiscale sensitivity analysis towards in silico biomarker identification and drug evaluation on cellular phenotypes in user-defined tissue geometries. Furthermore, integration of cancer expression databases such as The Cancer Genome Atlas (TCGA) and Human Proteome Atlas (HPA) facilitates in the development of personalized therapeutics. TISON is the next-evolution of multiscale cancer modeling and simulation platforms and provides a ‘zero-code’ model development, simulation, and analysis environment for application in clinical settings.

Keywords: systems oncology, cancer systems biology, cancer therapeutics, personalized therapeutics, cancer modelling

Procedia PDF Downloads 221
2731 Co-Administration Effects of Conjugated Linoleic Acid and L-Carnitine on Weight Gain and Biochemical Profile in Diet Induced Obese Rats

Authors: Maryam Nazari, Majid Karandish, Alihossein Saberi

Abstract:

Obesity as a global health challenge motivates pharmaceutical industries to produce anti-obesity drugs. However, effectiveness of these agents is remained unclear. Because of popularity of dietary supplements, the aim of this study was tp investigate the effects of Conjugated Linoleic Acid (CLA) and L-carnitine (LC) on serum glucose, triglyceride, cholesterol and weight changes in diet induced obese rats. 48 male Wistar rats were randomly divided into two groups: Normal fat diet (n=8), and High fat diet (HFD) (n=32). After eight weeks, the second group which was maintained on HFD until the end of study, was subdivided into four categories: a) 500 mg Corn Oil (as control group), b) 500 mg CLA, c) 200 mg LC, d) 500 mg CLA+ 200 mg LC.All doses are planned per kg body weights, which were administered by oral gavage for four weeks. Body weights were measured and recorded weekly by means of a digital scale. At the end of the study, blood samples were collected for biochemical markers measurement. SPSS Version 16 was used for statistical analysis. At the end of 8th week, a significant difference in weight was observed between HFD and NFD group. After 12 weeks, LC significantly reduced weight gain by 4.2%. Trend of weight gain in CLA and CLA+LC groups was insignificantly decelerated. CLA+LC reduced triglyceride level significantly, but just CLA had significant influence on total cholesterol and insignificant decreasing effect on FBS. Our results showed that an obesogenic diet in a relative short time led to obesity and dyslipidemia which can be modified by LC and CLA to some extent.

Keywords: conjugated linoleic acid, high fat diet, L-Carnitine, obesity

Procedia PDF Downloads 156
2730 Clinical Profile of Oral Sensory Abilities in Developmental Dysarthria

Authors: Swapna N., Deepthy Ann Joy

Abstract:

One of the major causes of communication disorders in pediatric population is Motor speech disorders. These disorders which affect the motor aspects of speech articulators can have an adverse effect on the communication abilities of children in their developmental period. The motor aspects are dependent on the sensory abilities of children with motor speech disorders. Hence, oral sensorimotor evaluation is an important component in the assessment of children with motor speech disorders. To our knowledge, the importance of oral motor examination has been well established, yet the sensory assessment of the oral structures has received less focus. One of the most common motor speech disorders seen in children is developmental dysarthria. The present study aimed to assess the orosensory aspects in children with developmental dysarthria (CDD). The control group consisted of 240 children in the age range of four and eight years which was divided into four subgroups (4-4.11, 5-5.11, 6-6.11 and 7-7.11 years). The experimental group consisted of 15 children who were diagnosed with developmental dysarthria secondary to cerebral palsy who belonged in the age range of four and eight years. The oro-sensory aspects such as response to touch, temperature, taste, texture, and orofacial sensitivity were evaluated and profiled. For this purpose, the authors used the ‘Oral Sensorimotor Evaluation Protocol- Children’ which was developed by the authors. The oro-sensory section of the protocol was administered and the clinical profile of oro-sensory abilities of typically developing children and CDD was obtained for each of the sensory abilities. The oro-sensory abilities of speech articulators such as lips, tongue, palate, jaw, and cheeks were assessed in detail and scored. The results indicated that experimental group had poorer scores on oro-sensory aspects such as light static touch, kinetic touch, deep pressure, vibration and double simultaneous touch. However, it was also found that the experimental group performed similar to control group on few aspects like temperature, taste, texture and orofacial sensitivity. Apart from the oro-motor abilities which has received utmost interest, the variation in the oro-sensory abilities of experimental and control group is highlighted and discussed in the present study. This emphasizes the need for assessing the oro-sensory abilities in children with developmental dysarthria in addition to oro-motor abilities.

Keywords: cerebral palsy, developmental dysarthria, orosensory assessment, touch

Procedia PDF Downloads 161
2729 Caregiver Training Results in Accurate Reporting of Stool Frequency

Authors: Matthew Heidman, Susan Dallabrida, Analice Costa

Abstract:

Background:Accuracy of caregiver reported outcomes is essential for infant growth and tolerability study success. Crying/fussiness, stool consistencies, and other gastrointestinal characteristics are important parameters regarding tolerability, and inter-caregiver reporting can see a significant amount of subjectivity and vary greatly within a study, compromising data. This study sought to elucidate how caregiver reported questions related to stool frequency are answered before and after a short amount of training and how training impacts caregivers’ understanding, and how they would answer the question. Methods:A digital survey was issued for 90 daysin the US (n=121) and 30 days in Mexico (n=88), targeting respondents with children ≤4 years of age. Respondents were asked a question in two formats, first without a line of training text and second with a line of training text. The question set was as follows, “If your baby had stool in his/her diaper and you changed the diaper and 10 min later there was more stool in the diaper, how many stools would you report this as?” followed by the same question beginning with “If you were given the instruction that IF there are at least 5 minutes in between stools, then it counts as two (2) stools…”.Four response items were provided for both questions, 1) 2 stools, 2) 1stool, 3) it depends on how much stool was in the first versus the second diaper, 4) There is not enough information to be able to answer the question. Response frequencies between questions were compared. Results: Responses to the question without training saw some variability in the US, with 69% selecting “2 stools”,11% selecting “1 stool”, 14% selecting “it depends on how much stool was in the first versus the second diaper”, and 7% selecting “There is not enough information to be able to answer the question” and in Mexico respondents selected 9%, 78%, 13%, and 0% respectively. However, responses to the question after training saw more consolidation in the US, with 85% of respondents selecting“2 stools,” representing an increase in those selecting the correct answer. Additionally in Mexico, with 84% of respondents selecting “1 episode” representing an increase in the those selecting the correct response. Conclusions: Caregiver reported outcomes are critical for infant growth and tolerability studies, however, they can be highly subjective and see a high variability of responses without guidance. Training is critical to standardize all caregivers’ perspective regarding how to answer questions accurately in order to provide an accurate dataset.

Keywords: infant nutrition, clinical trial optimization, stool reporting, decentralized clinical trials

Procedia PDF Downloads 95
2728 Establishing Sequence Stratigraphic Framework and Hydrocarbon Potential of the Late Cretaceous Strata: A Case Study from Central Indus Basin, Pakistan

Authors: Bilal Wadood, Suleman Khan, Sajjad Ahmed

Abstract:

The Late Cretaceous strata (Mughal Kot Formation) exposed in Central Indus Basin, Pakistan is evaluated for establishing sequence stratigraphic framework and potential of hydrocarbon accumulation. The petrographic studies and SEM analysis were carried out to infer the hydrocarbon potential of the rock unit. The petrographic details disclosed 4 microfacies including Pelagic Mudstone, OrbitoidalWackestone, Quartz Arenite, and Quartz Wacke. The lowermost part of the rock unit consists of OrbitoidalWackestone which shows deposition in the middle shelf environment. The Quartz Arenite and Quartz Wacke suggest deposition on the deep slope settings while the Pelagic Mudstone microfacies point toward deposition in the distal deep marine settings. Based on the facies stacking patterns and cyclicity in the chronostratigraphic context, the strata is divided into two 3rd order cycles. One complete sequence i.e Transgressive system tract (TST), Highstand system tract (HST) and Lowstand system tract (LST) are again replaced by another Transgressive system tract and Highstant system tract with no markers of sequence boundary. The LST sands are sandwiched between TST and HST shales but no potential porosity/permeability values have been determined. Microfacies and SEM studies revealed very fewer chances for hydrocarbon accumulation and overall reservoir potential is characterized as low.

Keywords: cycle, deposition, microfacies, reservoir

Procedia PDF Downloads 149
2727 Genetic Diversity and Variation of Nigerian Pigeon (Columba livia domestica) Populations Based on the Mitochondrial Coi Gene

Authors: Foluke E. Sola-Ojo, Ibraheem A. Abubakar, Semiu F. Bello, Isiaka H. Fatima, Sule Bisola, Adesina M. Olusegun, Adeniyi C. Adeola

Abstract:

The domesticated pigeon, Columba livia domestica, has many valuable characteristics, including high nutritional value and fast growth rate. There is a lack of information on its genetic diversity in Nigeria; thus, the genetic variability in mitochondrial cytochrome oxidase subunit I (COI) sequences of 150 domestic pigeons from four different locations was examined. Three haplotypes (HT) were identified in Nigerian populations; the most common haplotype, HT1, was shared with wild and domestic pigeons from Europe, America, and Asia, while HT2 and HT3 were unique to Nigeria. The overall haplotype diversity was 0.052± 0.025, and nucleotide diversity was 0.026± 0.068 across the four investigated populations. The phylogenetic tree showed significant clustering and genetic relationship of Nigerian domestic pigeons with other global pigeons. The median-joining network showed a star-like pattern suggesting population expansion. AMOVA results indicated that genetic variations in Nigerian pigeons mainly occurred within populations (99.93%), while the Neutrality tests results suggested that the Nigerian domestic pigeons’ population experienced recent expansion. This study showed a low genetic diversity and population differentiation among Nigerian domestic pigeons consistent with a relatively conservative COI sequence with few polymorphic sites. Furthermore, the COI gene could serve as a candidate molecular marker to investigate the genetic diversity and origin of pigeon species. The current data is insufficient for further conclusions; therefore, more research evidence from multiple molecular markers is required.

Keywords: Nigeria pigeon, COI, genetic diversity, genetic variation, conservation

Procedia PDF Downloads 193
2726 A Precision Medicine Approach to Sickle Cell Disease by Targeting the Adhesion Interactome

Authors: Anthara Vivek, Manisha Shukla, Mahesh Narayan, Prakash Narayan

Abstract:

Sickle cell disease disproportionately affects sub-Saharan Africa and certain tribal populaces in India and has consequently drawn little intertest from Pharma. In sickle cell patients, adhesion of erythrocytes or reticulocytes to one another and the vessel wall results in painful ischemic episodes with few, if any, effective treatments for vaso-occlusive crises. Identification of disease-associated adhesion markers on erythrocytes or reticulocytes might inform the use of more effective therapies against vaso-occlusive crises. Increased expression of one or more of bcam, itga4, cd44, cd47, rap1a, vcam1, or icam4 has been reported in sickle cell subjects. Using the miRNet ontology knowledgebase, peripheral blood interactomes were generated by seeding various combinations of the afore-referenced mRNA. These interactomes yielded an array of miR targets. As examples, targeting hsa-miR-155-5p can potentially neutralize the rap1a-bcam-cd44-itga4-vcam1 erythrocyte/reticulocyte adhesion interactome whereas targeting hsa-miRs-103a-3p or 107 can potentially neutralize adhesion in cells overexpressing icam4-cd47-bcam-itga4-cd36. AM3380 (MIRacle™) is an off-the shelf hsa-miR-155-5p agomiR that can potentially neutralize the rap1a-bcam-cd44-itga4-vcam1 signaling axis. Phlebotomy coupled with transcriptomics represents a potentially feasible and effective precision medicine strategy to mitigate vaso-occlusive crises in sickle cell patients.

Keywords: adhesion, interactome, precision, medicine

Procedia PDF Downloads 73
2725 Enhanced Cytotoxic Effect of Expanded NK Cells with IL12 and IL15 from Leukoreduction Filter on K562 Cell Line Exhibits Comparable Cytotoxicity to Whole Blood

Authors: Abdulbaset Mazarzaei

Abstract:

Natural killer (NK) cells are innate immune effectors that play a pivotal role in combating tumors and infected cells. In recent years, the therapeutic potential of NK cells has gained significant attention due to their remarkable cytotoxic ability. This study focuses on investigating the cytotoxic effect of expanded NK cells enriched with interleukin 12 (IL12) and interleukin 15 (IL15), derived from the leukoreduction filter, on the K562 cell line. Firstly, NK cells were isolated from whole blood samples obtained from healthy volunteers. These cells were subsequently expanded ex vivo using a combination of feeder cells, IL12, and IL15. The expanded NK cells were then harvested and assessed for their cytotoxicity against K562, a well-established human chronic myelogenous leukemia cell line. The cytotoxicity was evaluated using flow cytometry assay. Results demonstrate that the expanded NK cells significantly exhibited enhanced cytotoxicity against K562 cells compared to non-expanded NK cells. Interestingly, the expanded NK cells derived specifically from IL12 and IL15-enriched leukoreduction filters showed a robust cytotoxic effect similar to the whole blood-derived NK cells. These findings suggest that IL12 and IL15 in the leukoreduction filter are crucial in promoting NK cell cytotoxicity. Furthermore, the expanded NK cells displayed relatively similar cytotoxicity profiles to whole blood-derived NK cells, indicating their comparable capability in targeting and eliminating tumor cells. This observation is of significant relevance as expanded NK cells from the leukoreduction filter could potentially serve as a readily accessible and efficient source for adoptive immunotherapy. In conclusion, this study highlights the significant cytotoxic effect of expanded NK cells enriched with IL12 and IL15 obtained from the leukoreduction filter on the K562 cell line. Moreover, it emphasizes that these expanded NK cells exhibit comparable cytotoxicity to whole blood-derived NK cells. These findings reinforce the potential clinical utility of using expanded NK cells from the leukoreduction filter as an effective strategy in adoptive immunotherapy for the treatment of cancer. Further studies are warranted to explore the broader implications of this approach in clinical settings.

Keywords: natural killer (NK) cells, Cytotoxicity, Leukoreduction filter, IL-12 and IL-15 Cytokines

Procedia PDF Downloads 62
2724 Update on Genetic Diversity for Lamotrigine Induced Stevens-Johnson Syndrome and Toxic Epidermal Necrolysis

Authors: Natida Thongsima, Patompong Satapornpong

Abstract:

Introduction: Lamotrigine is widely used in the treatment of epilepsy and bipolar disorder. However, lamotrigine leads to adverse drug reactions (ADRs) consist of severe cutaneous adverse reactions (SCARs) include Stevens–Johnson syndrome (SJS), toxic epidermal necrolysis (TEN) and drug rash with eosinophilia and systemic symptoms (DRESS). Moreover, lamotrigine-induced SCARs are usually manifested between 2 and 8 weeks after treatment initiation. According to a previous study, the association between HLA-B*15:02 and lamotrigine-induced cutaneous adverse drug reactions in the Thai population (odds ratio 4.89; 95% CI 1.28–18.66; p-value = 0.014) was found. Therefore, the distribution of pharmacogenetics markers a major role in predicting the culprit drugs for SCARs in many populations. Objective: In this study, we want to investigate the prevalence of HLA-B allele, which correlates with lamotrigine-induced SCARs in the healthy Thai population. Materials and Methods: We enrolled 350 healthy Thai individuals and were approved by the ethics committee of Rangsit University. HLA-B alleles were genotyped by the Lifecodes HLA SSO typing kits (Immucor, West Avenue, Stamford, USA). Results: The results presented HLA-B allele frequency in healthy Thai population were 14.71% (HLA-B*46:01), 8.57% (HLA-B*15:02), 6.71% (HLA-B*40:01), 5.86% (HLA-B*13:01), 5.71% (HLA-B*58:01), 5.14% (HLA-B*38:02), 4.86% (HLA-B*18:01), 4.86% (HLA-B*51:01), 3.86% (HLA-B*44:03) and 2.71% (HLA-B*07:05). Especially, HLA-B*15:02 allele was the high frequency in the Thais (8.57%), Han Chinese (7.30%), Vietnamese (13.50%), Malaysian (6.06%) and Indonesian (11.60%). Nevertheless, this allele was much lower in other populations, namely, Africans, Caucasians, and Japanese. Conclusions: Although the sample size of the healthy Thai population in this research was limited, there were found the frequency of the HLA-B*15:02 allele could predispose them toward to lamotrigine-induced SCARs in Thailand.

Keywords: lamotrigine, cutaneous adverse drug reactions, HLA-B, Thai population

Procedia PDF Downloads 189
2723 Endometrial Ablation and Resection Versus Hysterectomy for Heavy Menstrual Bleeding: A Systematic Review and Meta-Analysis of Effectiveness and Complications

Authors: Iliana Georganta, Clare Deehan, Marysia Thomson, Miriam McDonald, Kerrie McNulty, Anna Strachan, Elizabeth Anderson, Alyaa Mostafa

Abstract:

Context: A meta-analysis of randomized controlled trials (RCTs) comparing hysterectomy versus endometrial ablation and resection in the management of heavy menstrual bleeding. Objective: To evaluate the clinical efficacy, satisfaction rates and adverse events of hysterectomy compared to more minimally invasive techniques in the treatment of HMB. Evidence Acquisition: A literature search was performed for all RCTs and quasi-RCTs comparing hysterectomy with either endometrial ablation endometrial resection of both. The search had no language restrictions and was last updated in June 2020 using MEDLINE, EMBASE, Cochrane Central Register of Clinical Trials, PubMed, Google Scholar, PsycINFO, Clinicaltrials.gov and Clinical trials. EU. In addition, a manual search of the abstract databases of the European Haemophilia Conference on women's health was performed and further studies were identified from references of acquired papers. The primary outcomes were patient-reported and objective reduction in heavy menstrual bleeding up to 2 years and after 2 years. Secondary outcomes included satisfaction rates, pain, adverse events short and long term, quality of life and sexual function, further surgery, duration of surgery and hospital stay and time to return to work and normal activities. Data were analysed using RevMan software. Evidence synthesis: 12 studies and a total of 2028 women were included (hysterectomy: n = 977 women vs endometrial ablation or resection: n = 1051 women). Hysterectomy was compared with endometrial ablation only in five studies (Lin, Dickersin, Sesti, Jain, Cooper) and endometrial resection only in five studies (Gannon, Schulpher, O’Connor, Crosignani, Zupi) and a mixture of the Ablation and Resection in two studies (Elmantwe, Pinion). Of the 1² studies, 10 reported women’s perception of bleeding symptoms as improved. Meta-analysis showed that women in the hysterectomy group were more likely to show improvement in bleeding symptoms when compared with endometrial ablation or resection up to 2-year follow-up (RR 0.75, 95% CI 0.71 to 0.79, I² = 95%). Objective outcomes of improvement in bleeding also favored hysterectomy. Patient satisfaction was higher after hysterectomy within the 2 years follow-up (RR: 0.90, 95%CI: 0.86 to 0.94, I²:58%), however, there was no significant difference between the two groups at more than 2 years follow up. Sepsis (RR: 0.03, 95% CI 0.002 to 0.56; 1 study), wound infection (RR: 0.05, 95% CI: 0.01 to 0.28, I²: 0%, 3 studies) and Urinary tract infection (UTI) (RR: 0.20, 95% CI: 0.10 to 0.42, I²: 0%, 4 studies) all favoured hysteroscopic techniques. Fluid overload (RR: 7.80, 95% CI: 2.16 to 28.16, I² :0%, 4 studies) and perforation (RR: 5.42, 95% CI: 1.25 to 23.45, I²: 0%, 4 studies) however favoured hysterectomy in the short term. Conclusions: This meta-analysis has demonstrated that endometrial ablation and endometrial resection are both viable options when compared with hysterectomy for the treatment of heavy menstrual bleeding. Hysteroscopic procedures had better outcomes in the short term with fewer adverse events including wound infection, UTI and sepsis. The hysterectomy performed better when measuring more long-term impacts such as recurrence of symptoms, overall satisfaction at two years and the need for further treatment or surgery.

Keywords: menorrhagia, hysterectomy, ablation, resection

Procedia PDF Downloads 154
2722 Risk Factors for Severe Typhoid Fever in Children: A French Retrospective Study about 78 Cases from 2000-2017 in Six Parisian Hospitals

Authors: Jonathan Soliman, Thomas Cavasino, Virginie Pommelet, Lahouari Amor, Pierre Mornand, Simon Escoda, Nina Droz, Soraya Matczak, Julie Toubiana, François Angoulvant, Etienne Carbonnelle, Albert Faye, Loic de Pontual, Luu-Ly Pham

Abstract:

Background: Typhoid and paratyphoid fever are systemic infections caused by Salmonella enterica serovar Typhi or paratyphi (A, B, C). Children traveling to tropical areas are at risk to contract these diseases which can be complicated. Methods: Clinical, biological and bacteriological data were collected from 78 pediatric cases reported between 2000 and 2017 in six Parisian hospitals. Children aged 0 to 18 years old, with a diagnosis of typhoid or paratyphoid fever confirmed by bacteriological exams, were included. Epidemiologic, clinical, biological features and presence of multidrug-resistant (MDR) bacteria or intermediate susceptibility to ciprofloxacin (nalidixic acid resistant) were examined by univariate analysis and by logistic regression analysis to identify risk factors of severe typhoid in children. Results: 84,6% of the children were imported cases of typhoid fever (n=66/78) and 15,4% were autochthonous cases (n=12/78). 89,7% were caused by S.typhi (n=70/78) and 12,8% by S.paratyphi (n=10/78) including 2 co-infections. 19,2% were intrafamilial cases (n=15/78). Median age at diagnosis was 6,4 years-old [6 months-17,9 years]. 28,2% of the cases were complicated forms (n=22/78): digestive (n=8; 10,3%), neurological (n=7; 9%), pulmonary complications (n=4; 5,1%) and hemophagocytic syndrome (n=4; 5,1%). Only 5% of the children had prior immunization with typhoid non-conjugated vaccine (n=4/78). 28% of the cases (n=22/78) were caused by resistant bacteria. Thrombocytopenia and diagnosis delay was significantly associated with severe infection (p= 0.029 and p=0,01). Complicated forms were more common with MDR (p=0,1) and not statistically associated with a young age or sex in this study. Conclusions: Typhoid and paratyphoid fever are not rare in children back from tropical areas. This multicentric pediatric study seems to show that thrombocytopenia, diagnosis delay, and multidrug resistant bacteria are associated with severe typhoid fever and complicated forms in children.

Keywords: antimicrobial resistance, children, Salmonella enterica typhi and paratyphi, severe typhoid

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