Search results for: clinical pharmacology (CPH)

Authors: Pitchaporn Purngpiputtrakul, Suttasinee Petsakul, Sunisa Chatmongkolchart

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Nasogastric tube (NGT) insertion in anaesthetized and intubated patients can be challenging even for experienced anesthesiologists. Various techniques have been proposed to facilitate NGT insertion in these patients. This study aimed to compare the success rate and time required for NGT insertion between the GlideScope visualization and neck flexion with lateral neck pressure techniques. This randomized clinical trial was performed at a teaching hospital on 86 adult patients undergoing abdominal surgery under relaxant general anaesthesia who required intraoperative NGT insertion. The patients were randomized into two groups, the GlideScope group (group G) and the neck flexion with lateral neck pressure group (group F). The success rate of first and second attempts, duration of insertion, and complications were recorded. The total success rate was 79.1% in Group G compared with 76.7% in Group F (P=1) The median time required for NGT insertion was significantly longer in Group G, for both first and second attempts (97 vs 42 seconds P<0.001) and (70 vs 48.5 seconds P=0.015), respectively. Complications were reported in 23 patients (53.5%) in group G and 13 patients (30.2%) in group F. Bleeding and kinking were the most common complications in both techniques. Using GlideScope visualization to facilitate NGT insertion was comparable to neck flexion with lateral neck pressure technique in degree of success rate of insertion, while neck flexion with lateral neck pressure technique had fewer complications and was less time-consuming.

Keywords: anaesthesia, nasogastric tube, GlideScope, intubation

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Authors: Dorsa Rahi, Arghavan Tonkanbonbi, Soheila Manifar, Behzad Jafvarnejad

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Background and Aim: Intraoral manipulation is performed during endotracheal intubation for general anesthesia, which can traumatize the soft and hard tissue in the oral cavity and cause postoperative pain and discomfort. Dental trauma is the most common complication of intubation. This study aimed to assess the prevalence of dental complications due to intubation in patients hospitalized in Imam Khomeini Hospital during 2018-2019. Materials and Methods: A total of 805 patients presenting to the Cancer Institute of Imam Khomeini Hospital for preoperative anesthesia consultation were randomly enrolled. A dentist interviewed the patients and performed a comprehensive clinical oral examination preoperatively. The patients underwent clinical oral examination by another dentist postoperatively. Results: No significant correlation was found between dental trauma (tooth fracture, tooth mobility, or soft tissue injury) after intubation with the age or gender of patients. According to the Wilcoxon test and McNemar-Bowker Test, the rate of mobility before the intubation was significantly different from that after the intubation (P=0.000). Maxillary central incisors, maxillary left canine and mandibular right and left central incisors had the highest rate of fracture. Conclusion: Mobile teeth before the intubation are at higher risk of avulsion and aspiration during the procedure. Patients with primary temporomandibular joint disorders are more susceptible to post-intubation trismus.

Keywords: oral trauma, dental trauma, intubation, anesthesia

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Authors: Kristen Erekson, Sarah Spendlove Caswell

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Nurse educators have the challenge of training future nurses that will provide compassionate care to an increasingly diverse population of patients in a culturally sensitive way. One approach to this challenge is an immersive public and global health experience as part of the nursing program curriculum. Undergraduate nursing students at our institution are required to participate in a Public and Global Health course. They participate in a didactic preparatory course followed by a 3-to-4-week program in one of the following locations: The Czech Republic, Ecuador, Finland/Poland, Ghana, India, Spain, Taiwan, Tonga, an Honor Flight to Washington D.C. with Veterans, or in local (Utah) communities working with marginalized populations (including incarcerated individuals, refugees, etc.). The students are required to complete 84 clinical hours and 84 culture hours (which involve exposure to local history, art, architecture, customs, etc.). As Faculty, we feel strongly that these public and global health experiences help cultivate cultural awareness in our students and prepare nurses who are better prepared to serve a diverse population of patients throughout their careers. This presentation will highlight our experiences and provide ideas for other nurse educators who have an interest in developing similar programs in their schools but do not know where to start. Suggestions about how to start building relationships that can lead to these opportunities, along with logistics for continuing the programs, will be highlighted.

Keywords: global health nursing, nursing education, clinical education, public health nursing

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Authors: Elena K. Schneider, Johnny X. Huang, Vincenzo Carbone, Mark Baker, Mohammad A. K. Azad, Matthew A. Cooper, Jian Li, Tony Velkov

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Ivacaftor is a novel CF trans-membrane conductance regulator (CFTR) potentiator that improves the pulmonary function for cystic fibrosis patients bearing a G551D CFTR-protein mutation. Because ivacaftor is highly bound (>97%) to plasma proteins, there is the strong possibility that co-administered CF drugs that compete for the same plasma protein binding sites and impact the free drug concentration. This in turn could lead to drastic changes in the in vivo efficacy of ivacaftor and therapeutic outcomes. This study compares the binding affinity of ivacaftor and co-administered CF drugs for human serum albumin (HSA) and α1-acid glycoprotein (AGP) using surface plasmon resonance and fluorimetric binding assays that measure the displacement of site selective probes. Due to their high plasma protein binding affinities, drug-drug interactions between ivacaftor are to be expected with ducosate, montelukast, ibuprofen, dicloxacillin, omeprazole and loratadine. The significance of these drug-drug interactions is interpreted in terms of the pharmacodynamic/pharmacokinetic parameters and molecular docking simulations. The translational outcomes of the data are presented as recommendations for a staggered treatment regimen for future clinical trials which aims to maximize the effective free drug concentration and clinical efficacy of ivacaftor.

Keywords: human α-1-acid glycoprotein, binding affinity, human serum albumin, ivacaftor, cystic fibrosis

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Authors: Hwang Kwon

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Objective: To assess the efficacy of embryo transfer (ET) of accumulated vitrified embryos and compare pregnancy outcomes between ET of thawed embryos following accumulation of vitrified embryos (frozen ET) and ET of fresh and thawed frozen embryos following accumulation of vitrified embryos (fresh ET + frozen ET). Study design: Patients were poor ovarian responders defined according to the Bologna criteria as well as a subgroup of women whose previous IVF-ET cycle through controlled ovarian stimulation (COS) yielded one or no embryos. Sixty-four frozen ETs were performed following accumulation of vitrified embryos (ACCE )(ACCE Frozen) and 51 fresh + frozen ETs were performed following accumulation of vitrified embryos (ACCE Fresh + Frozen). Positive βhCG rate, clinical pregnancy rate, ongoing pregnancy rate, and good quality embryos (%, ±SD) were compared between two groups. Results: There were more good quality embryos in the ACCE Fresh + Frozen group than in the ACCE Frozen group: 60±34.7 versus 42.9±28.9, respectively (p=0.03). Positive βhCG rate [18/64(28.2%) vs. 13/51(25.5%); p=0.75] and clinical pregnancy rate [12/64 (18.8%) vs. 11/51 (10.9%); p=0.71] were comparable between the two groups. Conclusion: Accumulation of vitrified embryos is an effective method in patients with poor ovarian response who fulfill the Bologna criteria. Pregnancy outcomes were comparable between the two groups.

Keywords: accumulation of embryos, frozen embryo transfer, poor responder, Bologna criteria

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Authors: Noor Ayuni Che Zakaria, Takashi Komeda, Cheng Yee Low, Kaoru Inoue, Fazah Akhtar Hanapiah

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Previous studies have shown that there are arguments regarding the reliability and validity of the Ashworth and Modified Ashworth Scale towards evaluating patients diagnosed with upper limb disorders. These evaluations depended on the raters’ experiences. This initiated us to develop an upper limb disorder part-task trainer that is able to simulate consistent upper limb disorders, such as spasticity and rigidity signs, based on the Modified Ashworth Scale to improve the variability occurring between raters and intra-raters themselves. By providing consistent signs, novice therapists would be able to increase training frequency and exposure towards various levels of signs. A total of 22 physiotherapists and occupational therapists participated in the study. The majority of the therapists agreed that with current therapy education, they still face problems with inter-raters and intra-raters variability (strongly agree 54%; n = 12/22, agree 27%; n = 6/22) in evaluating patients’ conditions. The therapists strongly agreed (72%; n = 16/22) that therapy trainees needed to increase their frequency of training; therefore believe that our initiative to develop an upper limb disorder training tool will help in improving the clinical education field (strongly agree and agree 63%; n = 14/22).

Keywords: upper limb disorder, clinical education tool, inter/intra-raters variability, spasticity, modified Ashworth scale

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Authors: Norimichi Nagano, Yoshio Hirano, Tsutomu Yasukawa

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Mesenchymal stem cells are thought to confer neuroprotection, facilitate tissue regeneration and exert their effects on retinal degenerative diseases, however, adverse events such as proliferative vitreoretinopathy and preretinal membrane disease associated with cell suspension transplantation have also been reported. We have recently developed human (allogeneic) adipose tissue-derived mesenchymal stem cell (adMSC) sheets through our proprietary sheet transformation technique, which could potentially mitigate these adverse events. To clarify the properties of our adMSC sheets named PAL-222, we performed in vitro studies such as viability testing, cytokine secretions by ELISA, immunohistochemical study, and migration assay. The viability of the cells exceeded 70%. Vascular Endothelial Growth Factor (VEGF) and Pigment Epithelium-Derived Factor (PEDF), which are quite important cytokines for the retinal area, were observed. PAL-222 expressed type I collagen, a strength marker, type IV collagen, a marker of the basement membrane, and elastin, an elasticity marker. Finally, the migration assay was performed and showed negative, which means that PAL-222 is stably kept in the topical area and does not come to pieces. Next, to evaluate the efficacy in vivo, we transplanted PAL-222 into the subretinal space of the eye of Royal College of Surgeons rats with congenital retinal degeneration and assessed it for three weeks after transplantation. We confirmed that PAL-222 suppressed the decrease in the thickness of the outer nuclear layer, which means that the photoreceptor protective effect treated with PAL-222 was significantly higher than that in the sham group. (p < 0.01). This finding demonstrates that PAL-222 showed their retinoprotective effect in a model of congenital retinal degeneration. As the study suggested the efficacy of PAL-222 in both in vitro and in vivo studies, we are presently engaged in clinical trials of PAL-222 for myopic chorioretinal atrophy, which is one of the retinal degenerative diseases, for the purpose of regenerative medicine.

Keywords: cell sheet, clinical trial, mesenchymal stem cell, myopic chorioretinal atrophy

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Authors: Jamuna Rajeswaran

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In the past two decades, with a population of more than a billion. India is passing through a major socio-demographic and epidemiological transition with consequent changes in health scenario. TBI constitute significant burden on health care resources in India The impact on a person and family can be devastating. Patients with TBI experience persistent cognitive deficits, emotional changes, which contribute to the disruption of life activities. The recovery of TBI would be maximized by appropriate rehabilitation. Neurofeedback is an emerging neuroscience-based clinical application. Sixty patients were recruited for this study after obtaining informed consent. Rivermead Head Injury Follow-up Questionnaire, Rivermead Post Concussion Symptoms Questionnaire and Visual Analog Scale were used to assess the behavioral and symptomotolgy associated with post TBI. Neuropsychological assessment was carried out using NIMHANS neuropsychological battery 2004. The Intervention group received neurofeedback training and the waitlist group did not receive any treatment during this phase. Patients were allocated to intervention and waitlist group at random. There were 30 patients in each group. Patients were given 20 sessions of NFT Patients were trained on the O1 and O2 channels for alpha theta training. Each session was of 40 minutes duration with 5-6 sessions per week. The post-training assessment was carried out for the intervention group after 20 sessions of NFT. The waitlist group underwent assessment after one month. Results showed neurofeedback training is effective in ameliorating deficits in cognitive functions and quality of life in patients with TBI. Improvements were corroborated by the clinical interview with patients and significant others post NFT.

Keywords: assessment, rehabilitation, cognition, EEG neurofeedback

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Authors: Susan K. Steele-Moses, Aimee Badeaux

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Background Literature: Nurse anesthesia education placed high demands on students both personally and professionally. High levels of anxiety affect student’s mental, emotional, and physical well-being, which impacts their student success. Whereas more research has focused on the health and well-being of graduate students, far less has focused specifically on nurse anesthesia students (SNRAs), who may experience higher levels of anxiety due to the rigor of their academic program. Current literature describes stressors experienced by SRNAs that cause anxiety and affect their performance, including personal, academic, clinical, interpersonal, emotional, and financial. Sample: DNP-NA 2025 and DNP-NA 2024 cohorts (N = 36). Eighteen (66.7%) students participated in the study. Instrumentation: The DASS-21 was used to measure stress (7 items; α = .87) and anxiety (7 items; α = .74) from the participants. Intervention: The mind-shift meditation app, based on cognitive behavioral therapy, is being used daily before clinical and exams to decrease nurse anesthesia students’ stress and anxiety over time. Results: At baseline, the students exhibited a moderate level of stress, but their anxiety levels were low. The range of scores was 4-21 (out of 28) for stress (M = 12.88; SD = 5.40) and 0-16 (out of 28) for anxiety (M = 6.81; SD = 5.04). Both stress and anxiety were normally distributed [SW = .242 (stress); SW = .210 (anxiety)] without any outliers. There was a significant difference between their stress and anxiety levels (t = 5.55; p < .001) at baseline. Stress and anxiety will be measured over time, with the change analyzed using repeated measures ANOVA. Implications for Practice: The use of purposeful mindfulness meditation has been shown to decrease stress and anxiety in nursing students.

Keywords: mindfulness, meditation, graduate nursing education, nursing education

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Authors: Elizabeth M. Annoni, Elena G. Tolkacheva

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Atrial fibrillation (AF) is the most common sustained cardiac arrhythmia that is a known prognostic marker for stroke, heart failure and death. Reentrant mechanisms of rotor formation, which are stable electrical sources of cardiac excitation, are believed to cause AF. No existing commercial mapping systems have been demonstrated to consistently and accurately predict rotor locations outside of the pulmonary veins in patients with persistent AF. There is a clear need for robust spatio-temporal techniques that can consistently identify rotors using unique characteristics of the electrical recordings at the pivot point that can be applied to clinical intracardiac mapping. Recently, we have developed four new signal analysis approaches – Shannon entropy (SE), Kurtosis (Kt), multi-scale frequency (MSF), and multi-scale entropy (MSE) – to identify the pivot points of rotors. These proposed techniques utilize different cardiac signal characteristics (other than local activation) to uncover the intrinsic complexity of the electrical activity in the rotors, which are not taken into account in current mapping methods. We validated these techniques using high-resolution optical mapping experiments in which direct visualization and identification of rotors in ex-vivo Langendorff-perfused hearts were possible. Episodes of ventricular tachycardia (VT) were induced using burst pacing, and two examples of rotors were used showing 3-sec episodes of a single stationary rotor and figure-8 reentry with one rotor being stationary and one meandering. Movies were captured at a rate of 600 frames per second for 3 sec. with 64x64 pixel resolution. These optical mapping movies were used to evaluate the performance and robustness of SE, Kt, MSF and MSE techniques with respect to the following clinical limitations: different time of recordings, different spatial resolution, and the presence of meandering rotors. To quantitatively compare the results, SE, Kt, MSF and MSE techniques were compared to the “true” rotor(s) identified using the phase map. Accuracy was calculated for each approach as the duration of the time series and spatial resolution were reduced. The time series duration was decreased from its original length of 3 sec, down to 2, 1, and 0.5 sec. The spatial resolution of the original VT episodes was decreased from 64x64 pixels to 32x32, 16x16, and 8x8 pixels by uniformly removing pixels from the optical mapping video.. Our results demonstrate that Kt, MSF and MSE were able to accurately identify the pivot point of the rotor under all three clinical limitations. The MSE approach demonstrated the best overall performance, but Kt was the best in identifying the pivot point of the meandering rotor. Artifacts mildly affect the performance of Kt, MSF and MSE techniques, but had a strong negative impact of the performance of SE. The results of our study motivate further validation of SE, Kt, MSF and MSE techniques using intra-atrial electrograms from paroxysmal and persistent AF patients to see if these approaches can identify pivot points in a clinical setting. More accurate rotor localization could significantly increase the efficacy of catheter ablation to treat AF, resulting in a higher success rate for single procedures.

Keywords: Atrial Fibrillation, Optical Mapping, Signal Processing, Rotors

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Authors: Patrícia Pires, Renata Vaz, Bárbara Teles, Marco Pato, Pedro Beckert

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Introduction: The management of lateral third clavicle fractures can be challenging due to difficulty in distinguishing subtle variations in the fracture pattern, which may be suggestive of potential fracture instability. They occur most often in men between 30 and 50 years of age, and in individuals over 70 years of age, its distribution is equal between both men and women. These fractures account for 10%–30% of all clavicle fractures and roughly 30%–45% of all clavicle nonunion fractures. Lateral third clavicle fractures may be treated conservatively or surgically, and there is no gold standard, although the risk of nonunion or pseudoarthrosis impacts the recommendation of surgical treatment when these fractures are unstable. There are many strategies for surgical treatment, including locking plates, hook plates fixation, coracoclavicular fixation using suture anchors, devices or screws, tension band fixation with suture or wire, transacromial Kirschner wire fixation and arthroscopically assisted techniques. Whenever taking the hardware into consideration, we must not disregard that obtaining adequate lateral fixation of small fragments is a difficult task, and plates are more associated to local irritation. The aim of the appropriate treatment is to ensure fracture healing and a rapid return to preinjury activities of daily living but, as explained, definitive treatment strategies have not been established and the variety of techniques avalilable add up to the discussion of this topic. Methods and Results: We present a clinical case of a 43-year-old man with the diagnosis of a lateral third clavicle fracture (Neer IIC) in the sequence of a fall on his right shoulder after a bicycle fall. He was operated three days after the injury, and through K-wire temporary fixation and indirect reduction using a ZipTight, he underwent osteosynthesis with an interfragmentary figure-of-eight tension band with polydioxanone suture (PDS). Two weeks later, there was a good aligment. He kept the sling until 6 weeks pos-op, avoiding efforts. At 7-weeks pos-op, there was still a good aligment, starting the physiotherapy exercises. After 10 months, he had no limitation in mobility or pain and returned to work with complete recovery in strength. Conclusion: Some distal clavicle fractures may be conservatively treated, but it is widely accepted that unstable fractures require surgical treatment to obtain superior clinical outcomes. In the clinical case presented, the authors chose an osteosuture technique due to the fracture pattern, its location. Since there isn´t a consensus on the prefered fixation method, it is important for surgeons to be skilled in various techniques and decide with their patient which approach is most appropriate for them, weighting the risk-benefit of each method. For instance, with the suture technique used, there is no wire migration or breakage, and it doesn´t require a reoperation for hardware removal; there is also less tissue exposure since it requires a smaller approach in comparison to the plate fixation and avoids cuff tears like the hook plate. The good clinical outcome on this case report serves the purpose of expanding the consideration of this method has a therapeutic option.

Keywords: lateral third, clavicle, suture, fixation

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Authors: David Oluwole Moses, Odeyemi Adebowale Toba, Olawale Adetunji Kola

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Candida auris, an emerging fungus, has been reported in more than 30 countries around the world since its first detection in 2009. Due to its several virulence factors, resistance to antifungals, and persistence in hospital settings, Candida auris has been reported to cause treatment-failure infections. This study was therefore carried out to determine the incidence of Candida auris in a tertiary hospital in Ekiti State, Nigeria. In this study, a total of 115 samples were screened for Candida species using cultural and molecular methods. The carriage of virulence factors and antifungal resistance among C. auris was detected using standard microbiological methods. Candida species isolated from the samples were 15 (30.0%) in clinical samples and 22 (33.85%) in hospital equipment screened. Non-albicans Candida accounted for 3 (20%) and 8 (36.36%) among the isolates from the clinical samples and equipment, respectively. Only five of the non-albicans Candida isolates were C. auris. All the isolates produced biofilm, gelatinase, and hemolysin, while none produced germ tubes. Two of the isolates were resistant to all the antifungals tested. Also, all the isolates were resistant to fluconazole and itraconazole. Nystatin appeared to be the most effective among the tested antifungals. The isolation of Candida auris is being reported for the second time in Nigeria, further confirming that the fungus has spread beyond Lagos and Ibadan, where it was first reported. The extent of the spread of the nosocomial fungus needed to be further investigated and curtailed in Nigeria before its outbreak in healthcare facilities.

Keywords: candida auris, virulence factors, antifungals, pathogen, hospital, infection

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Authors: Ashti Morovati, Hushyar Azari, Bahram Pourghassem Gargari

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Objectives and goals: The prevalence of metabolic syndrome (MetS), as a major health burden for societies, is increasing. This clinical trial was conducted to evaluate the effects of CuEO supplementation on anthropometric indices, systolic and diastolic blood pressure, blood glucose level, insulin resistance and serum lipid level in patients suffering from MetS. Methods: This was a randomized, triple‐blind, placebo‐controlled clinical trial in which 56 patients with MetS aged 18–60 years who fulfilled the eligibility criteria were randomly allocated to an intervention or a control group. Inclusion criteria for the study were comprised of diagnosis of MetS according to the new International Federation of Diabetes. The exclusion criteria were defined as: taking herbal supplements, use of drugs having evident interaction with cumin such as anti‐depressant drugs, vitamin D, omega 3, selenium, zinc, smoking, pregnancy, or breastfeeding, suffering from cancer, having any history of gastrointestinal and hepatic, cardiovascular, thyroid and kidney disorders, and menopause. 75 mg CuEO or placebo soft gels were administered three times daily to the participants for eight weeks. The soft gel consumption was checked by asking the participants to bring the medication containers in the follow‐up visits at the 4th and the 8th weeks of the study. Data pertaining to blood pressure, height, weight, waist circumference, hip circumference and BMI, as well as food consumption were collected at the beginning and end of the study. Fasting blood samples ( glucose, triglyceride, total cholesterol, HDL-cholesterol and LDL-cholesterol) were obtained and biochemical measurements were assessed at the beginning and end of the study. Results: At eight weeks, a total of 44 patients completed this study. Except for diastolic blood pressure (DBP), the other assessed variables were not significantly different between the two groups. In intra group analysis, placebo and CuEO groups both had insignificant decrements in DBP (mean difference [MD] with 95% CI: −3.31 [−7.11, 0.47] and −1.77 [−5.95, 2.40] mmHg, respectively). However, DBP was significantly lower in CuEO compared with the placebo group at the end of study (81.41 ± 5.88 vs. 84.09 ± 5.54 mmHg, MD with 95% CI: −3.98 [−7.60, −0.35] mmHg, p < .05). Conclusions: The results of this study indicated that CuEO does not have any effect on MetS components, except for DBP in patients with MetS.

Keywords: blood pressure, fasting blood glucose, lipid profile, waist circumference

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Authors: Philippe Dillien, Patrice Forget, Harald Engel, Olivier Cornu, Marc De Kock, Jean Cyr Yombi

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Introduction: Hip fracture precedes commonly death in elderly people. Identification of high-risk patients may contribute to target patients in whom optimal management, resource allocation and trials efficiency is needed. The aim of this study is to construct a predictive score of mortality after hip fracture on the basis of the objective prognostic factors available: Neutrophil-to-lymphocyte ratio (NLR), age, and sex. C-Reactive Protein (CRP), is also considered as an alternative to the NLR. Patients and methods: After the IRB approval, we analyzed our prospective database including 286 consecutive patients with hip fracture. A score was constructed combining age (1 point per decade above 74 years), sex (1 point for males), and NLR at postoperative day+5 (1 point if >5). A receiver-operating curve (ROC) curve analysis was performed. Results: From the 286 patients included, 235 were analyzed (72 males and 163 females, 30.6%/69.4%), with a median age of 84 (range: 65 to 102) years, mean NLR values of 6.47+/-6.07. At one year, 82/280 patients died (29.3%). Graphical analysis and log-rank test confirm a highly statistically significant difference (P<0.001). Performance analysis shows an AUC of 0.72 [95%CI 0.65-0.79]. CRP shows no advantage on NLR. Conclusion: We have developed a score based on age, sex and the NLR to predict the risk of mortality at one year in elderly patients after surgery for a hip fracture. After external validation, it may be included in clinical practice as in clinical research to stratify the risk of postoperative mortality.

Keywords: neutrophil-to-lymphocyte ratio, hip fracture, postoperative mortality, medical and health sciences

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Authors: Zakia Belhadj, Bing He, Hua Zhang, Xueqing Wang, Wenbing Dai, Qiang Zhang

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Mononuclear phagocyte system (MPS) forms an abominable obstacle hampering the tumor delivery efficiency of nanoparticles. Passively targeted nanocarriers have received clinical approval over the past 20 years. However, none of the actively targeted nanocarriers have entered clinical trials. Thus it is important to endue effective targeting ability to actively targeted approaches by overcoming biological barriers to nanoparticle drug delivery. Here, it presents that an Esomeprazole-based preconditioning strategy for regulating nanocarrier-MPS interaction to substantially prolong circulation time and enhance tumor targeting of nanoparticles. In vitro, the clinically approved proton pump inhibitor Esomeprazole “ESO” was demonstrated to reduce interactions between macrophages and subsequently injected targeted vesicles by interfering with their lysosomal trafficking. Of note, in vivo studies demonstrated that ESO pretreatment greatly decreased the liver and spleen uptake of c(RGDm7)-modified vesicles, highly enhanced their tumor accumulation, thereby provided superior therapeutic efficacy of c(RGDm7)-modified vesicles co-loaded with Doxorubicin (DOX) and Gefitinib (GE). This MPS-preconditioning strategy using ESO provides deeper insights into regulating nanoparticles interaction with the phagocytic system and enhancing their cancer cells' accessibility for anticancer therapy.

Keywords: esomeprazole (ESO), mononuclear phagocyte system (MPS), preconditioning strategy, targeted lipid vesicles

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Authors: K. Genise, S. Murthy

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Introductory Statement: The results of this retrospective chart review suggest the effects of bacterial colonization in critically ill children with viral bronchiolitis, currently unproven, are clinically insignificant. Background: Viral bronchiolitis is one of the most prevalent causes of illness requiring hospitalization among children worldwide and one of the most common reasons for admission to pediatric intensive care. It has been hypothesized that co-infection with bacteria results in more severe clinical outcomes. Conversely, the effects of bacterial colonization in critically ill patients with bronchiolitis are poorly defined. Current clinical management of colonized patients consists primarily of supportive therapies with the role of antibiotics remaining controversial. Methods: A retrospective review of all critically ill children admitted to the BC Children’s Hospital Pediatric Intensive Care Unit (PICU) from 2014-2017 with a diagnosis of bronchiolitis was performed. Routine testing in this time frame consisted of complete pathogen testing, including PCR for Streptococcus pneumoniae. Analyses were performed to determine the impact of bacterial colonization and antibiotic use on a primary outcome of PICU length-of-stay, with secondary outcomes of hospital length-of-stay and duration of ventilation. Results: There were 92 patients with complete pathogen testing performed during the assessed timeframe. A comparison between children with detected Streptococcus pneumoniae (n=22) and those without (n=70) revealed no significant (p=0.20) differences in severity of illness on presentation as per Pediatric Risk of Mortality III scores (mean=3.0). Patients colonized with S. pneumoniae had significantly shorter PICU stays (p=0.002), hospital stays (p=0.0001) and duration of non-invasive ventilation (p=0.002). Multivariate analyses revealed that these effects on length of PICU stay and duration of ventilation do not persist after controlling for antibiotic use, presence of radiographic consolidation, age, and severity of illness (p=0.15, p=0.32). The relationship between colonization and duration of hospital stay persists after controlling for these variables (p=0.008). Conclusions: Children with viral bronchiolitis colonized with S. pneumoniae do not appear to have significantly different PICU length-of-stays or duration of ventilation compared to children who are not colonized. Colonized children appear to have shorter hospital stays. The results of this study suggest bacterial colonization is not associated with increased severity of presenting illness or negative clinical outcomes.

Keywords: bronchiolitis, colonization, critical care, pediatrics, pneumococcal, infection

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Authors: Qi En Han, Si En Wai, Eugene Quek

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As one of the two Academic Medical Centres (AMCs) in Singapore, SingHealth Duke-NUS AMC strives to improve patients’ lives through excellent clinical care, research and education. These efforts are enhanced with the establishment of Academic Clinical Programmes (ACPs). Each ACP brings together specialists in a particular discipline from different institutions to maximize the power of shared knowledge and resources. Initiated by Surgery ACP, the student research mentorship programme is a programme designed to facilitate engagement between medical students and the surgical faculty. The programme offers mentors not only the opportunity to supervise research but also to nurture future clinician scientists. In turn, medical students acquire valuable research experience which may be useful in their future careers. The programme typically lasts one year, depending on the students’ commitment. Surgery ACP matches students’ research interests with the mentor's area of expertise whenever possible. Surgery ACP organizes informal tea sessions to bring students and prospective mentors together. Once a match is made, the pair is required to submit a project proposal which includes the title, proposed start and end dates, ethical and biosafety considerations and project details. The mentees either think of their own research question with guidance from the mentors or join an existing project. The mentees may participate in data collection, data analysis, manuscript writing and conference presentation. The progress of each research project is monitored through half-yearly progress report. The mentees report problems encountered or changes made to existing proposal on top of the progress made. A total of 18 mentors were successfully paired with 36 mentees since 2013. Currently, there are 23 on-going and 13 completed projects. The mentees are encouraged to present their projects at conferences and to publish in peer-reviewed journals. Six mentees have presented their completed projects at local or international conferences and one mentee has her work published. To further support student research, Surgery ACP organized a Research Day in 2015 to recognize their research efforts and to showcase their wide-range of research. Surgery ACP recognizes that early exposure of medical students to research is important in developing them into clinician scientists. As interest in research take time to develop and are usually realized during various research attachments, it is crucial that programmes such as the student research mentorship programme exist. Surgery ACP will continue to build on this programme.

Keywords: academic clinical programme, clinician scientist, medical student, mentoring

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Authors: Zerrin Orbak, Busra Demir

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Osteopetrosis is a rare genetic disease characterized by impaired bone resorption and increased bone sclerosis. Clinical presentation is very different in osteopetrosis. It can be asymptomatic or can be seen with typical symptoms. Here, a case of osteopetrosis was presented when evaluated for nystagmus. She was 10 months old. Parents were second-degree relatives. On physical examination, pigeon chest deformity and horizontal nystagmus were observed. There was a failure of thrive but no fracture. The cardiovascular examination was normal. Cranial, vertebral and long bone roentgenograms revealed characteristic deformities of osteopetrosis and diffuse sclerosis. The diagnosis was confirmed by genetic testing. A Homozygous mutation was detected in the TNFRSF11A gene (c.508A>G p.(Arg170Gly)). RANKL is encoded by the tumor necrosis factor ligand superfamily member 11 (TNFSF11) gene, and the binding to its receptor RANK, encoded by the TNFRSF11A gene, determines the activation of the downstream pathway that drives osteoclast differentiation and activation (51). The complete absence of osteoclasts is the key feature of the osteoclast-poor form of osteopetrosis (46). Patients are characterized by the absence of TRAP-positive osteoclasts in bone biopsies. The osteoclast-poor subtype of osteopetrosis caused by mutations in TNFSF11 gene is ultra-rare in humans. Clinical presentation is usually severe, with onset in early infancy or in fetal life. But here, a case was presented with horizontal nystagmus. A case presented with horizontal nystagmus, which was evaluated by neurology and diagnosed incidentally, was shared.

Keywords: osteopetrosis, nystagmus, bone, osteoclast-poor

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Authors: Laura O’Halloran, Zhipeng Cao, Clare M. Kelly, Hugh Garavan, Robert Whelan

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Reaction time (RT) variability on cognitive tasks provides the index of the efficiency of executive control processes (e.g. attention and inhibitory control) and is considered to be a hallmark of clinical disorders, such as attention-deficit disorder (ADHD). Increased RT variability is associated with structural and functional brain differences in children and adults with various clinical disorders, as well as poorer task performance accuracy. Furthermore, the strength of functional connectivity across various brain networks, such as the negative relationship between the task-negative default mode network and task-positive attentional networks, has been found to reflect differences in RT variability. Although RT variability may provide an index of attentional efficiency, as well as being a useful indicator of neurological impairment, the brain substrates associated with RT variability remain relatively poorly defined, particularly in a healthy sample. Method: Firstly, we used the intra-individual coefficient of variation (ICV) as an index of RT variability from “Go” responses on the Stop Signal Task. We then examined the functional and structural neural correlates of ICV in a large sample of 14-year old healthy adolescents (n=1719). Of these, a subset had elevated symptoms of ADHD (n=80) and was compared to a matched non-symptomatic control group (n=80). The relationship between brain activity during successful and unsuccessful inhibitions and gray matter volume were compared with the ICV. A mediation analysis was conducted to examine if specific brain regions mediated the relationship between ADHD symptoms and ICV. Lastly, we looked at functional connectivity across various brain networks and quantified both positive and negative correlations during “Go” responses on the Stop Signal Task. Results: The brain data revealed that higher ICV was associated with increased structural and functional brain activation in the precentral gyrus in the whole sample and in adolescents with ADHD symptoms. Lower ICV was associated with lower activation in the anterior cingulate cortex (ACC) and medial frontal gyrus in the whole sample and in the control group. Furthermore, our results indicated that activation in the precentral gyrus (Broadman Area 4) mediated the relationship between ADHD symptoms and behavioural ICV. Conclusion: This is the first study first to investigate the functional and structural correlates of ICV collectively in a large adolescent sample. Our findings demonstrate a concurrent increase in brain structure and function within task-active prefrontal networks as a function of increased RT variability. Furthermore, structural and functional brain activation patterns in the ACC, and medial frontal gyrus plays a role-optimizing top-down control in order to maintain task performance. Our results also evidenced clear differences in brain morphometry between adolescents with symptoms of ADHD but without clinical diagnosis and typically developing controls. Our findings shed light on specific functional and structural brain regions that are implicated in ICV and yield insights into effective cognitive control in healthy individuals and in clinical groups.

Keywords: ADHD, fMRI, reaction-time variability, default mode, functional connectivity

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Authors: Dylan Treger, Lujia Zhang, Xiaoxiao Jia, Jessica H. Hui, Munkh-Amgalan Gantumur, Mizhou Hui, Li Liu

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Hyaluronic acid (HA) is involved in wound healing via inflammation, granulation, and re-epithelialization mechanisms. The poor physical properties of natural high-molecular-weight polymers limit their direct use in the medical field. In this clinical study, we investigated whether the local injection of a tissue-permeable 35 kDa HA fragment (HA35) could favor the healing process in patients with chronic wounds accompanied by neuropathic pain. The HA35 fragments were freshly manufactured by degradation of high-molecular-weight HA with bovine testis-derived hyaluronidase PH20. Twenty patients in this study had nonhealing wounds and wound-related pain for more than 3 months. Freshly produced HA35 was locally injected into healthy skin immediately surrounding chronic wounds once a day for 10 days. Wound-associated pain and the degree of wound healing were evaluated. The injection of HA35 relieved the pain associated with chronic wounds in 24 hours. HA35 treatment significantly promoted the healing of chronic wounds, including expanded fresh granulation tissue on the wounds; reduced darkness or redness, dryness, and damaged areas on the surface of the skin surrounding the wounds; and decreased the size of the wound area. It can be concluded that the topical injection of tissue-permeable HA35 around chronic wounds has great potential to promote wound healing.

Keywords: 35 kDa hyaluronan fragment HA35, chronic wound, wound healing, tissue permeability

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Authors: Mehrnaz Mostafavi

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Nanoliposomes, minute lipid-based vesicles at the nano-scale, show promise in the realm of photothermal therapy (PTT). This study presents an extensive overview of nanoliposomes in PTT, exploring their distinct attributes and the significant progress in this therapeutic methodology. The research delves into the fundamental traits of nanoliposomes, emphasizing their adaptability, compatibility with biological systems, and their capacity to encapsulate diverse therapeutic substances. Specifically, it examines the integration of light-absorbing materials, like gold nanoparticles or organic dyes, into nanoliposomal formulations, enabling their efficacy as proficient agents for photothermal treatment Additionally, this paper elucidates the mechanisms involved in nanoliposome-mediated PTT, highlighting their capability to convert light energy into localized heat, facilitating the precise targeting of diseased cells or tissues. This precise regulation of light absorption and heat generation by nanoliposomes presents a non-invasive and precisely focused therapeutic approach, particularly in conditions like cancer. The study explores advancements in nanoliposomal formulations aimed at optimizing PTT outcomes. These advancements include strategies for improved stability, enhanced drug loading, and the targeted delivery of therapeutic agents to specific cells or tissues. Furthermore, the paper discusses multifunctional nanoliposomal systems, integrating imaging components or targeting elements for real-time monitoring and improved accuracy in PTT. Moreover, the review highlights recent preclinical and clinical trials showcasing the effectiveness and safety of nanoliposome-based PTT across various disease models. It also addresses challenges in clinical implementation, such as scalability, regulatory considerations, and long-term safety assessments. In conclusion, this paper underscores the substantial potential of nanoliposomes in advancing PTT as a promising therapeutic approach. Their distinctive characteristics, combined with their precise ability to convert light into heat, offer a tailored and efficient method for treating targeted diseases. The encouraging outcomes from preclinical studies pave the way for further exploration and potential clinical applications of nanoliposome-based PTT.

Keywords: nanoliposomes, photothermal therapy, light absorption, heat conversion, therapeutic agents, targeted delivery, cancer therapy

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Authors: Michael Dolgin, Oz Hamtzani, Talma Kushnir

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A literature review has shown that while parents of children with cancer experience increased levels of psychological distress associated with their child's medical condition, considerable variability in parental adjustment is evident. Of the factors that may account for this variability, little attention has been devoted to the simultaneous interaction of three coping constructs and their role in parental adjustment: (1) Coping techniques employed, (2) Repertoire of coping techniques, and (3) Flexibility in applying coping techniques. While these constructs have been studied individually in relation to adjustment in general, studies to date have not included them together within a single conceptual model and research design and evaluated them in a clinical population. The objective of the current study was to determine how these three coping technique constructs interact to impact parental adjustment to pediatric cancer. A cross-sectional sample of 145 parents of children in active cancer treatment completed standardized measures of coping techniques, repertoire, flexibility, and parental distress. A hierarchical multiple regression analysis demonstrated that 37% of the variance in parental distress was predicted by the use of avoidance-focused coping techniques [F(1,118)=69.843, p<.001], with an additional 3% predicted by coping repertoire [F(2,117)=7.63, p=.00] for a total of 40% variance explained. Coping flexibility was found to mediate the relationship between coping repertoire and parental distress. These findings suggest that coping techniques employed by parents (problem/emotion-focused vs. avoidance-focused), as well as coping repertoire, significantly impact parental adjustment. Flexibility in applying coping techniques within one’s coping repertoire further contributes to parental adjustment. Implications for further study and clinical intervention will be presented.

Keywords: coping techniques, repertoire, flexibility, adjustment

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Authors: Marta Fernández Batalla, José María Santamaría García, Maria Lourdes Jiménez Rodríguez, Roberto Barchino Plata, Adriana Cercas Duque, Enrique Monsalvo San Macario

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Background: Primary Care Nursing is taking more autonomy in clinical decisions. One of the most frequent therapies to solve is related to the problems of maintaining a sufficient supply of food. Nursing diagnoses related to food are addressed by the nurse-family and community as the first responsible. Objectives and interventions are set according to each patient. To improve the goal setting and the treatment of these care problems, a technological tool is developed to help nurses. Objective: To evaluate the computational tool developed to support the clinical decision in feeding problems. Material and methods: A cross-sectional descriptive study was carried out at the Meco Health Center, Madrid, Spain. The study population consisted of four specialist nurses in primary care. These nurses tested the tool on 30 people with ‘need for nutritional therapy’. Subsequently, the usability of the tool and the satisfaction of the professional were sought. Results: A simple and convenient computational tool is designed for use. It has 3 main entrance fields: age, size, sex. The tool returns the following information: BMI (Body Mass Index) and caloric consumed by the person. The next step is the caloric calculation depending on the activity. It is possible to propose a goal of BMI or weight to achieve. With this, the amount of calories to be consumed is proposed. After using the tool, it was determined that the tool calculated the BMI and calories correctly (in 100% of clinical cases). satisfaction on nutritional assessment was ‘satisfactory’ or ‘very satisfactory’, linked to the speed of operations. As a point of improvement, the options of ‘stress factor’ linked to weekly physical activity. Conclusion: Based on the results, it is clear that the computational tools of decision support are useful in the clinic. Nurses are not only consumers of computational tools, but can develop their own tools. These technological solutions improve the effectiveness of nutrition assessment and intervention. We are currently working on improvements such as the calculation of protein percentages as a function of protein percentages as a function of stress parameters.

Keywords: feeding behavior health, nutrition therapy, primary care nursing, technology assessment

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Authors: Samson F. Agberotimi, Rachel B. Asagba, Choja Oduaran

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Disturbing rate of use of different substances such as cannabis, alcohol, as well as pharmaceutical drugs among Nigerian youth in recent times has been affirmed in the literature. There is, however, a paucity of literature addressing the pattern of usage of such drugs, especially for clinical relevance and intervention planning. The present study investigated the prevalence and pattern of drug usage among youth in Ogbomoso, Nigeria. A cross-sectional survey involving 92 purposively selected participants comprising of 82 males and 10 females aged between 15 and 24 years was conducted. A measure of drug involvement and demographic characteristics was administered to the participants. Descriptive analysis was done using the SPSS v.21. Cannabis (79.4%), alcohol (77.2%), codeine (70.7%), tobacco (65.2%) and tramadol (47.8%) are the five most frequently used substances. However, the majority of the users of tobacco (68.3%) and alcohol (62.0%) are casual users indicating a mild level of use of the substances among the participants. On the other hand, 49.2% of the codeine users, 27.3% of the tramadol users, and 21.9% of the cannabis users reported harmful/intensive levels of use. Furthermore, the results revealed individuals at the pathological level of use as 28.8% for cannabis, 25.0% for tramadol, and 21.6% for codeine, and thus require clinical/therapeutic intervention. In conclusion, cannabis remains the most frequently used substance among youths. However, there appears to be a shift from the use of conventional psychoactive substances to pharmaceutical/prescription drugs such as codeine and tramadol. The findings of this study raised the need for both preventive and therapeutic interventions addressing the problem of substance use disorder among youth in contemporary society.

Keywords: Ogbomoso, pattern of drug use, prevalence of drug use, youth

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Authors: Nasreen Basoudan, Andrea Tales, Frederic Boy

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Non-clinical anxiety may be comprised of state anxiety - temporarily experienced anxiety related to a specific situation, and trait anxiety - a longer lasting response or a general disposition to anxiety. While temporary and occasional anxiety whether as a mood state or personality dimension is normal, nonclinical anxiety may influence many more components of information processing than previously recognized. In ageing and dementia-related research, disease characterization now involves attempts to understand a much wider range of brain function such as loss of inhibitory control, as against the more common focus on memory and cognition. However, in many studies, the tendency has been to include individuals with clinical anxiety disorders while excluding persons with lower levels of state or trait anxiety. Loss of inhibitory cognitive control can lead to behaviors such as aggression, reduced sensitivity to others, sociopathic thoughts and actions. Anxiety has also been linked to inhibitory control, with research suggesting that people with anxiety are less capable of inhibiting their emotions than the average person. This study investigates the relationship between anxiety and loss of inhibitory control in younger and older adults, using a variety of questionnaires and computers-based tests. Based on the premise that irrespective of classification, anxiety is associated with a wide range of physical, affective, and cognitive responses, this study explores evidence indicative of the potential influence anxiety per se on loss of inhibitory control, in order to contribute to discussion and appropriate consideration of anxiety-related factors in methodological practice.

Keywords: anxiety, ageing, dementia, inhibitory control

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Authors: Chul Hyun Park

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Background:Repair using the Achillon deviceis a representative mini-open repair technique;however, the limitations of this technique includethe need for special instruments and decreasedrepair strength.A modifiedmini-open repair using ring forcepsmight overcome these limitations. Purpose:This study was performed to compare the Achillon device with ring forceps in mini-open repairsof acute Achilles tendon rupture. Study Design:This was a retrospective cohort study, and the level of evidence was3. Methods:Fifty patients (41 men and 9 women), withacute Achilles tendon rupture on one foot, were consecutively treated using mini-open repair techniques. The first 20 patients were treated using the Achillon device (Achillon group) and the subsequent 30 patients were treated using a ring forceps (Forcep group). Clinical, functional, and isokinetic results,and postoperative complications were compared between the two groups at the last follow-up. Clinical evaluations wereperformed using the American Orthopedic Foot and Ankle Society (AOFAS) score, Achilles tendon Total Rupture Score (ATRS), length of incision, and operation time. Functional evaluationsincludedactive range of motion (ROM) of the ankle joint, maximum calf circumference (MCC), hopping test, and single limb heel-rise (SLHR) test. Isokinetic evaluations were performed using the isokinetic test for ankle plantar flexion. Results:The AOFAS score (p=0.669), ATRS (p=0.753), and length of incision (p=0.305) were not significantly different between the groups. Operative times in the Achillon group were significantly shorter than that in the Forcep group (p<0.001).The maximum height of SLHR (p=0.023) and number of SLHRs (p=0.045) in the Forcep group were significantly greater than that in the Achillon group. No significant differences in the mean peak torques for plantar flexion at angular speeds of 30°/s (p=0.219) and 120°/s (p=0.656) were detected between the groups. There was no significant difference in the occurrence of postoperative complications between the groups (p=0.093). Conclusion:The ring forceps technique is comparable with the Achillon technique with respect to clinical, functional, and isokinetic results and the postoperative complications. Given that no special instrument is required, the ring forceps technique could be a better option for acute Achilles tendon rupture repair.

Keywords: achilles tendon, acute rupture, repair, mini-open

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Authors: Rajesh Kumar G

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A challenging aspect of any clinical trial is to carefully plan the study design to meet the study objective in optimum way and to validate the assumptions made during protocol designing. And when it is a pediatric study, there is the added challenge of stringent guidelines and difficulty in recruiting the necessary subjects. Unlike adult trials, there is not much historical data available for pediatrics, which is required to validate assumptions for planning pediatric trials. Typically, pediatric studies are initiated as soon as approval is obtained for a drug to be marketed for adults, so with the adult study historical information and with the available pediatric pilot study data or simulated pediatric data, the pediatric study can be well planned. Generalizing the historical adult study for new pediatric study is a tedious task; however, it is possible by integrating various statistical techniques and utilizing the advantage of hybrid study design, which will help to achieve the study objective in a smoother way even with the presence of many constraints. This research paper will explain how well the hybrid study design can be planned along with integrated technique (SEV) to plan the pediatric study; In brief the SEV technique (Simulation, Estimation (using borrowed adult data and applying Bayesian methods)) incorporates the use of simulating the planned study data and getting the desired estimates to Validate the assumptions.This method of validation can be used to improve the accuracy of data analysis, ensuring that results are as valid and reliable as possible, which allow us to make informed decisions well ahead of study initiation. With professional precision, this technique based on the collected data allows to gain insight into best practices when using data from historical study and simulated data alike.

Keywords: adaptive design, simulation, borrowing data, bayesian model

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Authors: Mohamed Majrashi, Patricia Connolly, Terry Gourlay

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Cardiopulmonary bypass is known to cause inflammatory response during open heart surgery. It includes the initiation of different cascades such as coagulation, complement system and cytokines. Although the immune system is body’s key defense mechanism against external assault, when overexpressed, it can be injurious to the patient, particularly in a cohort of patients in which there is a heightened and uncontrolled response. The inflammatory response develops in these patients to an exaggerated level resulting in an autoimmune injury and may lead to poor postoperative outcomes (systemic inflammatory response syndrome and multi-organs failure). Previous studies by this group have suggested a correlation between the level of IL6 measured in patient’s blood before surgery and after polymeric activation and the observed inflammatory response during surgery. Based upon these findings, the present work is aimed at using this response to develop a test which can be used prior to the open heart surgery to identify the high-risk patients before their operation. The work will be accomplished via three main clinical phases including some pilot in-vitro studies, device development and clinical investigation. Current findings from studies using animal blood, employing DEHP and DEHP plasticized PVC materials as the activator, support the earlier results in patient samples. Having established this relationship, ongoing work will focus on developing an activated lateral flow strip technology as a screening device for heightened inflammatory propensity.

Keywords: cardiopulmonary bypass, cytokines, inflammatory response, overexpression

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Authors: Rihab Idoudi, Karim Saheb Ettabaa, Basel Solaiman, Kamel Hamrouni

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Medical association rules induction is used to discover useful correlations between pertinent concepts from large medical databases. Nevertheless, ARs algorithms produce huge amount of delivered rules and do not guarantee the usefulness and interestingness of the generated knowledge. To overcome this drawback, we propose an ontology based interestingness measure for ARs ranking. According to domain expert, the goal of the use of ARs is to discover implicit relationships between items of different categories such as ‘clinical features and disorders’, ‘clinical features and radiological observations’, etc. That’s to say, the itemsets which are composed of ‘similar’ items are uninteresting. Therefore, the dissimilarity between the rule’s items can be used to judge the interestingness of association rules; the more different are the items, the more interesting the rule is. In this paper, we design a distinct approach for ranking semantically interesting association rules involving the use of an ontology knowledge mining approach. The basic idea is to organize the ontology’s concepts into a hierarchical structure of conceptual clusters of targeted subjects, where each cluster encapsulates ‘similar’ concepts suggesting a specific category of the domain knowledge. The interestingness of association rules is, then, defined as the dissimilarity between corresponding clusters. That is to say, the further are the clusters of the items in the AR, the more interesting the rule is. We apply the method in our domain of interest – mammographic domain- using an existing mammographic ontology called Mammo with the goal of deriving interesting rules from past experiences, to discover implicit relationships between concepts modeling the domain.

Keywords: association rule, conceptual clusters, interestingness measures, ontology knowledge mining, ranking

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Authors: Polina Prokopovich

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Disease-modifying osteoarthritis drugs (DMOADs) are a new therapeutic class for OA, preventing or inhibiting OA development. Unfortunately, none of the DMOADs have been clinically approved due to their poor therapeutic effects in clinical trials. The joint environment has played a role in the poor clinical performance of these drugs by limiting the amount of drug effectively delivered as well as the time that the drug spends within the joint space. The current study aims to enhance the cartilage uptake and retention time of the DMOADs-model (licofelone), which showed a significant therapeutic effect against OA progression and is currently in phase III. Licofelone will be covalently conjugated to the hydrolysable, cytocompatible, and cationic poly beta-amino ester polymers (PBAE). The cationic polymers (A16 and A87) can be electrostatically attached to the negatively charged cartilage component (glycosaminoglycan), which will increase the drug penetration through the cartilage and extend the drug time within the cartilage. In the cartilage uptake and retention time studies, an increase of 18 to 37 times of the total conjugated licofelone to A87 and A16 was observed when compared to the free licofelone. Furthermore, the conjugated licofelone to A87 was detectable within the cartilage at 120 minutes, while the free licofelone was not detectable after 60 minutes. Additionally, the A87-licofelone conjugate showed no effect on the chondrocyte viability. In conclusion, the cationic A87 and A16 polymers increased the percentage of licofelone within the cartilage, which could potentially enhance the therapeutic effect and pharmacokinetic performance of licofelone or other DMOADs clinically.

Keywords: PBAE, cartilage., osteoarthritis, injectable biomaterials, drug delivery

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