Search results for: Antiretroviral therapy

Authors: Rebekah Volgin, Jane Shakespeare-Finch, Ian Shochet

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Commercial sexual exploitation (CSE) and sex trafficking affect between 5000-7000 girls and women in Nepal each year and can have devastating physical and psychological consequences. Much research has documented these effects, however, there is no published longitudinal research that focuses on whether healing and growth outcomes are possible for survivors of CSE and sex trafficking. The narratives of 27 girls and women (13-22 years) were taken at two-time points during participation in a six-week group psychoeducation and art therapy program which was delivered across three NGO’s in Kathmandu, Nepal. These narratives form part of a larger ethnographic project. Thematic analysis of the data was undertaken. Themes emerging from time point 1 were: psychological distress in the form of anxiety and grief over loss of family, psychosomatic symptoms, empathy and compassion, and posttraumatic growth (PTG) in the form of new possibilities, relating to others and personal strength. Posttraumatic growth refers to positive changes in the aftermath of trauma. The themes emerging from time point 2, were: empathy and compassion and PTG (cognitive restructuring, new possibilities, relating to others and personal strength). Alongside the distress that these participants experienced, they also experienced positive outcomes such as empathy and compassion and psychological growth. Future research would advance knowledge by further examining the process of PTG in this population, if the changes observed were lasting, and if so, ways in which PTG can be facilitated or promoted.

Keywords: commercial sexual exploitation, human trafficking, posttraumatic growth, sexual trauma

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Authors: Seyed Fakhreddin Hejazi, Leili Iranirad, Mohammad Sadeghi, Mohsen Talebizadeh

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Background: Contrast-induced nephropathy (CIN) remains to be a potentially serious complication of radiographic procedures. We performed this clinical trial to assess the preventive effect of allopurinol against CIN in high-risk patients undergoing coronary angiography. Methods: In this prospective randomized controlled trial, 140 patients with at least two risk factors for CIN undergoing coronary angiography were randomly assigned to either the allopurinol group or the control group. Patients in the allopurinol group received 300 mg allopurinol 24 hours before a procedure and intravenous hydration for 12 hours before and after coronary angiography, whereas patients in the control group received intravenous hydration. Serum creatinine (SCr), blood urea nitrogen (BUN) and uric acid were measured before contrast exposure and at 48 hours. CIN was defined as an increase of 25% in serum creatinine (SCr) or >0.5 mg/dl 48 hours after contrast administration. Results: CIN occurred in 11 out of 70 (7.9%) patients in the control group and in 8 out of 70 (5.7%) patients in the allopurinol group. There was no significant difference in the incidence of CIN between the two groups at 48 hours after administering the radiocontrast agent (p = 0.459). However, there were significant differences between the two groups in SCr, BUN, uric acid, and eGFR 48 hours after radiocontrast administration (p < 0.05). Conclusion: Our findings revealed that allopurinol had no substantial efficacy over hydration protocol in high-risk patients for the development of CIN.

Keywords: contrast-induced nephropathy, allopurinol, coronary angiography, contrast agent

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Authors: Kazem Shakouri, Alireza Pishgahi, Homayoun Sadeghi-bBazargani, Shahla Dareshiri

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Introduction: Carpal Tunnel Syndrome has numerous nonsurgical treatments including splint, physical therapy and corticosteroid injections. Aim: The purpose of this study was to evaluate the effectiveness of an ultrasound guided treatment procedure, for individuals with severe carpal tunnel syndrome. Materials and Method: 20 patients with an electrodiagnostic evidence of severe carpal tunnel syndrome were treated by an office-based ultrasound guided procedure (combination of percutaneous needle release of carpal tunnel and corticosteroid injection). Electrodiagnostic (nerve conduction study), clinical (Boston Carpal Tunnel Questionnaire, grip strength) and ultrasonic (median nerve and carpal tunnel cross-sectional area) measurements were recorded at baseline and one month after intervention. Results: Our preliminary data analysis showed that in one month follow up, patients had a significantly smaller cross-sectional area of the median nerve compared to pretreatment values (mean difference 0.06; 95%CI: 0.02-0.1; p < 0.001). In addition, patients had significantly less functional impairment (mean difference 35; 95% CI:28.7-43.4 ; p < 0.001), and an improved hand grip strength in one month follow up (mean difference 5.4; 95%CI: 3.1-7.8; p < 0.001;). There were no significant complications. Conclusion: Patients with severe carpal tunnel syndrome, who are candidates for surgical intervention, can consider office-based ultrasound guided needle release of carpal tunnel as an alternative safe treatment.

Keywords: Carpal Tunnel Syndrome, needle release, pain, ultrasound

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Authors: Juan Antonio Mondragon Sanchez, Ruben Santamaria

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The DNA G-quadruplex is a four-stranded DNA structure conformed by stacked planes of four base paired guanines (G-quartet). The guanine rich DNA sequences are present in many sites of genomic DNA and can potentially lead to the formation of G-quadruplexes, especially at the 3'-terminus of the human telomeric DNA with many TTAGGG repeats. The formation and stabilization of a G-quadruplex by small ligands at the telomeric region can inhibit the telomerase activity. In turn, the ligands can be used to regulate oncogene expression making the G-quadruplex an attractive target for anticancer therapy. Clearly, the G-quadruplex structured in the telomeric DNA is of fundamental importance for rational drug design. In this context, we investigate two G-quadruplex structures, the first follows from the sequence TTAGGG(TTAGGG)3TT (HUT1), and the second from AAAGGG(TTAGGG)3AA (HUT2), both in a K+ solution. We determine the free energy surfaces of the HUT1 and HUT2 structures and investigate their conformations using replica-exchange metadynamics simulations. The carbonyl-carbonyl distances belonging to different guanines residues are selected as the main collective variables to determine the free energy surfaces. The surfaces exhibit two main local minima, compatible with experiments on the conformational transformations of HUT1 and HUT2 under substitution of the K+ ions by the Na+ ions. The conformational transitions are not observed in short MD simulations without the use of the metadynamics approach. The results of this work should be of help to understand the formation and stability of human telomeric G-quadruplex in environments including the presence of K+ and Na+ ions.

Keywords: g-quadruplex, metadynamics, molecular dynamics, replica-exchange

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Authors: P. Akbartehrani, M. Khaledi Pour, M. Amini, M. Khani, M. Mohajeri Tehrani, E. Ghasemi, P. Charipoor, B. Shokri

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A common problem between diabetic patients is foot ulcers which are chronic and require specialized treatment. Previous studies illustrate that Cold atmospheric plasma (CAP) has beneficial effects on wound healing and infection. Nevertheless, the comparison of different cap exposure protocols in diabetic ulcer wound healing remained to be studied. This study aims to determine the effect of two different exposure protocols on wound healing in diabetic ulcers. A prospective, randomized clinical trial was conducted at two clinics. Diabetic patients with G1 and G2 wanger classification diabetic foot ulcers were divided into two groups of study. One group was treated by the first protocol, which was treating wounds by argon-generated cold atmospheric plasma jet once a week for five weeks in a row. The other group was treated by the second protocol, which was treating wounds every three days for five weeks in a row. The wounds were treated for 40 seconds/cubic centimeter, while the nozzle tip was moved nonlocalized 1 cm above the wounds. A patient with one or more wounds could participate in different groups as wounds were separately randomized, which allow a participant to be treated several times during the study. The study's significant findings were two different reductions rate in wound size, microbial load, and two different healing speeds. This study concludes that CAP therapy by the second protocol yields more effective healing speeds, reduction in wound sizes, and microbial loads of foot ulcers in diabetic patients.

Keywords: wound healing, diabetic ulcers, cold atmospheric plasma, cold argon jet

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Authors: Alexander Hendricks, Sean Nevin, Clayton Wikoff, Melissa Dougherty, Jacob Orlita, Rafiqul Noorani

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Knee orthotics play an important role in aiding in the recovery of those with knee injuries, especially athletes. However, structural knee orthotics is often very expensive, ranging between $300 and $800. The primary reason for this project was to answer the question: can 3D printed orthotics represent a viable and cost-effective alternative to present structural knee orthotics? The primary objective for this research project was to design a knee orthotic for athletes with knee injuries for a low-cost under $100 and evaluate its effectiveness. The initial design for the orthotic was done in SolidWorks, a computer-aided design (CAD) software available at Loyola Marymount University. After this design was completed, finite element analysis (FEA) was utilized to understand how normal stresses placed upon the knee affected the orthotic. The knee orthotic was then adjusted and redesigned to meet a specified factor-of-safety of 3.25 based on the data gathered during FEA and literature sources. Once the FEA was completed and the orthotic was redesigned based from the data gathered, the next step was to move on to 3D-printing the first design of the knee brace. Subsequently, physical therapy movement trials were used to evaluate physical performance. Using the data from these movement trials, the CAD design of the brace was refined to accommodate the design requirements. The final goal of this research means to explore the possibility of replacing high-cost, outsourced knee orthotics with a readily available low-cost alternative.

Keywords: 3D printing, knee orthotics, finite element analysis, design for additive manufacturing

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Authors: Murtada Ahmed Oshi, Jin-Wook Yoo

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Layer-by-layer (LBL) coating has gained popularity for drug delivery of therapeutic drugs. Herein we described a novel approach for enhancing the therapeutic efficiency of the locally administered dexamethasone (Dex) for inflammatory bowel disease (IBD). We utilized a LBL-coating technique on Dex microcrystals (DexMCs) with multiple layers of polyelectrolytes composed of poly (allylamine hydrochloride) (PAH), poly (sodium 4-styrene sulfonate) (PSS) and Eudragit® S100 (ES). The successful deposition of the layers onto DexMCs surfaces were confirmed through zeta potential measurement and confocal laser scanning microscopy. The surface morphology was investigated through scanning electron microscopy. The drug encapsulation efficiency was 95% with a mean particle size of 2 µm and negative surface charge (-40 mV). Moreover, in vitro drug release study showed a minimum release of the drug ( 15%) at an acidic condition during initial first 5 h, followed by sustained-release at an alkaline condition. For in vivo study, LBL-DxMCs were administered orally to ICR mice suffering from dextran sulfate sodium-induced colitis. LBL-DxMCs substantially enhanced anti-IBD activities as compared to DxMCs. Macroscopic, histological and biochemical (tumor necrosis factor-α, interleukin-6 and myeloperoxidase) examinations revealed marked improvements of colitis signs in the mice treated with LBL-DxMCs compared with those treated with DxMCs. Overall, LBL-DxMCs could be a suitable candidate for the treatment of IBD.

Keywords: dexamethasone, inflammatory bowel disease, LBL-coating, polyelectrolytes

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Authors: Sadia Suri Kashif, Raheeda Fatima, Maqsood Ahmed Khan

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Purpose of the study: The objective of this research was to determine the perception of Pakistani physicians (whether primary care, specialists or residents) in Karachi, being one of the largest and highly populated cities of Pakistan, regarding clinical approaches towards diet, exercise, and therapy in obese patients. This research determines their understanding of obesity and employability of obesity management in their daily practices. Research methodology: This is a questionnaire-based survey. A minimum of 300 questionnaires (N=300) were distributed and filled by practicing physicians in a random selection of medical setups in Karachi. Randomly 246 physicians responded to the survey. The survey tested their views regarding weight management, importance of general awareness and their strategies to control weight. Results: In the first part of survey the physicians responded to almost 66% regarding the seriousness of obesity management with advising diet modification, physical exercise and decreasing calorie intake; 57% failed to employ Body Mass Index and Waist Hip Ratio as weight measurement tools in their daily practice; 50% disagreed on using pharmacotherapy as an option; 67% were not sure about the proper dosage and indication of anti-obesity medication while almost same disagreed on using surgical options for management of obesity; 83.3% physicians agreed on the increased obesity pandemic in Pakistan. Conclusion: The findings indicate that there is a gap between awareness and knowledge among Pakistani practicing physicians regarding pharmacotherapy for obesity. There is a need to frequently update latest guidelines to help manage this condition, which is becoming more prevalent in our country day by day. Physicians should be obligated to use updated knowledge for managing obesity.

Keywords: obesity, physicians, BMI, weight management, obesity awareness

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Authors: Efi Koutantou

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The foundation of successful therapy is the bond between the psychotherapist and the patient, Psychoanalysis would argue. The present study explores lived experiences of a psychotherapeutic relationship in different moments, initial and final with special reference to the transference love developed through the process. The fight between moments of ‘leaving a self’ behind and following ‘lines of flight’ in the process of creating a new subjectivity and ‘becoming-other’ will be explored. Moments between de-territorialisation – surpassing given constraints such as gender, family and religion, kinship bonds - freeing the space in favor of re-territorialisation – creation of oneself creation of oneself will also be analyzed. The generation of new possibilities of being, new ways of self-actualization for this patient will be discussed. The second part of this study will explore the extent to which this ‘transference love’ results for this specific patient to become ‘the discourse of the other’; it is a desideratum whether the patient finally becomes a subject of his/her own through his/her own self-exploration of new possibilities of existence or becomes alienated within the thought of the therapist. The way in which the patient uses or is (ab)used by the transference love in order to experience and undergo alienation from an ‘authority’ which may or may not sacrifice his/her own thought in favor of satisfying the therapist will be investigated. Finally, from an observer’s perspective and from the analysis of the results of this therapeutic relationship, the counter-transference will also be analyzed, in terms of an attempt of the analyst to relive and satisfy his/her own desires through the life of the analysand. The accession and fall of an idealized self will be analyzed, the turn of the transference love into ‘hate’ will conclude this case study through a lived experience in the therapeutic procedure; a relationship which can be called to be a mixture of a real relationship and remnants from a past object relationship.

Keywords: alienation, authority, counter-transference, hate, transference love

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Authors: Arash M. Shahidi, Tilak Dias, Gayani K. Nandasiri

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While graduated compression is the foundation of treatment and management of many medical complications such as leg ulcer, varicose veins, and lymphedema, monitoring the interface pressure has been conducted using different sensors that operate based on diverse approaches. The variations existed from the pressure readings collected using different interface pressure measurement systems would cause difficulties in taking a decision regarding the compression therapy. It is crucial to acknowledge the differences existing between direct and indirect pressure measurement systems while considering the commercially available systems such as AMI, Picopress and OPM which are under direct measurements systems, and HATRA (BSI), HOSY (RAL-GZ) and FlexiForce which comes under the indirect measurement system. Furthermore, Piezo-resistive sensors (Flexiforce) can measure the changes in resistance corresponding to the applied force on the sensing area. Direct pressure measuring systems are capable of measuring interface pressure on the three-dimensional states, while the indirect pressure measuring systems stretch the fabric in the two-dimensional direction and extrapolate pressure from surface tension measured on the device and neglect the vital factor which is the radius of curvature. In this study, a leg mannequin of known dimensions is selected with a knitted class 3 compression stocking. It has been decided to evaluate the data collected from different available systems (AMI, PicoPress, FlexiForce, and HATRA) and compare the results. The results showed a discrepancy between Hatra, AMI, Picopress, and Flexiforce against the pressure standard used to generate class 3 compression stocking. As predicted a higher pressure value with direct interface measuring systems were monitored against HATRA due to the effect of the radius of curvature.

Keywords: AMI, FlexiForce, graduated compression, HATRA, interface pressure, PicoPress

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Authors: Cheng-Chih Tsai, Yu-Hsuan Liu, Cheng-Ying Ho, Chun-Chin Huang

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The aim of this study evaluated the in vitro and in vivo antimicrobial activity of selected lactic acid bacteria (LAB) against Uropathogenic Escherichia coli (UPEC) for prevention and amelioration of UTIs. We screened LAB strains with antimicrobial effects on UPEC using a well-diffusion assay, bacterial adherence to the uroepithelium cell line SV-HUC-1 (BCRC 60358), and a coculture inhibition assay. The results showed that the 7 LAB strains (Lactobacillus paracasei, L. salivarius, two Pediococcus pentosaceus strains, two L. plantarum strains, and L. crispatus) and the fermented probiotic products produced by these multi-LAB strains exhibited potent zones of inhibition against UPEC. Moreover, the LAB strains and probiotic products adhered strongly to the uroepithelium SV-HUC-1 cell line. The growth of UPEC strains was also markedly inhibited after co-culture with the LAB strains and probiotic products in human urine. In addition, the enhanced levels of IL-6, IL-8 and lactic acid dehydrogenase were significantly decreased by treatments with the LAB strains and probiotic products in UPEC-induced SV-HUC-1 cells. Furthermore, oral administration of probiotic products reduced the number of viable UPEC in the urine of UPEC-challenged BALB/c mice. Taken together, this study demonstrates that probiotic supplementation may be useful as an adjuvant therapy for the treatment of bacterial-induced urinary tract infections.

Keywords: lactic acid bacterium, SV-HUC-1 uroepithelium, urinary tract infection, uropathogenic Escherichia coli, BALB/c mice

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Authors: Shohreh Ghasemi

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Introduction: Melanoma is a complex disease with various clinical and histopathological features that impact prognosis and treatment decisions. Traditional methods of melanoma prognosis involve manual examination and interpretation of clinical and histopathological data by dermatologists and pathologists. However, the subjective nature of these assessments can lead to inter-observer variability and suboptimal prognostic accuracy. AI, with its ability to analyze vast amounts of data and identify patterns, has emerged as a promising tool for improving melanoma prognosis. Methods: A comprehensive literature search was conducted to identify studies that employed AI techniques for melanoma prognosis. The search included databases such as PubMed and Google Scholar, using keywords such as "artificial intelligence," "melanoma," and "prognosis." Studies published between 2010 and 2022 were considered. The selected articles were critically reviewed, and relevant information was extracted. Results: The review identified various AI methodologies utilized in melanoma prognosis, including machine learning algorithms, deep learning techniques, and computer vision. These techniques have been applied to diverse data sources, such as clinical images, dermoscopy images, histopathological slides, and genetic data. Studies have demonstrated the potential of AI in accurately predicting melanoma prognosis, including survival outcomes, recurrence risk, and response to therapy. AI-based prognostic models have shown comparable or even superior performance compared to traditional methods.

Keywords: artificial intelligence, melanoma, accuracy, prognosis prediction, image analysis, personalized medicine

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Authors: Senthil Rajan Dharmalingam, Shamala Nadaraju, Srinivasan Ramamurthy

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Doxorubicin is the most widely used anticancer drugs in chemotherapy treatment. However, problems related to the development of multidrug resistance (MDR) and acute cardiotoxicity have led researchers to investigate alternative forms of administering doxorubicin for cancer therapy. Several methods have been attempted to overcome MDR, including the co-administration of a chemosensitizer inhibiting the efflux caused by ATP binding cassette transporters with anticancer drugs, and the bypass of the efflux mechanism. Co encapsulation of doxorubicin (Dox) and cyclosporine A (CSA) into poly (DL-lactide-co-glycolide) nanoparticles was emulsification-solvent evaporation method using polyvinyl alcohol as emulsion stabilizers. The Dox-CSA loaded nanoparticles were evaluated for particle size, zeta potential and PDI by light scattering analysis and thermal characterizations by differential scanning calorimetry (DSC). Loading efficiency (LE %) and in-vitro dissolution samples were evaluated by developed and validated HPLC method. The optimum particle size obtained is 298.6.8±39.4 nm and polydispersity index (PDI) is 0.098±0.092. Zeta potential is found to be -29.9±4.23. Optimum pH to increase Dox LE% was found 7.1 which gave 42.5% and 58.9% increase of LE% for pH 6.6 and pH 8.6 compared respectively. LE% achieved for Dox is 0.07±0.01 % and CSA is 0.09±0.03%. Increased volume of PVA and weight of PLGA shows increase in size of nanoparticles. DSC thermograms showed shift in the melting peak for the nanoparticles compared to Dox and CSA indicating encapsulation of drugs. In conclusion, these preliminary studies showed the feasibility of PLGA nanoparticles to entrap Dox and CSA and require future in-vivo studies to be performed to establish its potential.

Keywords: doxorubicin, cyclosporine, PLGA, nanoparticles

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Authors: Ammar Aljabri, Alhussain Halawani, Alaa Ashqar, Omar Alageely

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Objective: mild Traumatic Brain Injury (mTBI) or concussion is a common yet undermanaged and underreported condition. This systematic review and meta-analysis aim to determine the efficacy of VRT as a treatment option for mTBI. Method: This review and meta-analysis was performed following the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines and included RCTs and pre-VRT/post-VRT retrospective chart reviews. Records meeting the inclusion criteria were extracted from the following databases: Medline, Embase, and Cochrane Register of Controlled Trials (CENTRAL). Results: Eight articles met the inclusion criteria, and six RCTs were included in the meta-analysis. VRT demonstrated significant improvement in decreasing perceived dizziness at the end of the intervention program, as shown by DHI scores (SMD= -0.33, 95% CI -0.62 to -0.03, p=0.03, I2= 0%). However, no significant reduction in DHI was evident after two months of follow-up (SMD= 0.15, 95% CI -0.23 to 0.52, p=0.44, I2=0%). Quantitative analysis also depicts significant reduction in both VOMS (SMD=-0.40, 95% CI -0.60 to -0.20, p<0.0001, I2=0%) and PCSS (SMD= -0.39, 95% CI -0.71 to -0.07, p=0.02, I2=0%) following the intervention. Lastly, there was no significant difference between intervention groups on BESS scores (SMD= -31, 95% CI -0.71 to 0.10, p=0.14, I2=0%) and return to sport/function (95% CI 0.32 to 30.80, p=0.32, I2=82%). Conclusions: Current evidence on the efficacy of VRT for mTBI is limited. This review and analysis provide evidence that supports the role of VRT in improving perceived symptoms following concussion. There is still a need for high-quality trials evaluating the benefit of VRT using a standardized approach.

Keywords: concussion, traumatic brain injury, vestibular rehabilitation, neurorehabilitation

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Authors: Felicia Segeth, Florian G. Klein, Lea Berger, Andreas Kolk, Per S. Holm

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The entry of oncolytic viruses (OVs) into clinical application opens groundbreaking changes in current and future treatment regimens. However, despite their potent anti-cancer activity in vitro, clinical studies revealed limitations of OVs as monotherapy. The same applies to CDK 4/6 inhibitors (CDK4/6i) targeting cell cycle as well as bromodomain and extra-terminal domain inhibitors (BETi) targeting gene expression. In this study, the anti-tumoral effect of XVir-N-31, an YB-1 dependent oncolytic adenovirus, was evaluated in combination with Ribociclib, a CDK4/6i, and JQ1, a BETi. The head and neck squamous cell carcinoma (HNSCC) cell lines Fadu, SAS, and Cal-33 were used. DNA replication and gene expression of XVir-N-31 was measured by RT-qPCR, protein expression by western blotting, and cell lysis by SRB assays. Treatment with CDK4/6i and BETi increased viral gene expression, viral DNA replication, and viral particle formation. The data show that the combination of oncolytic adenovirus XVir-N-31 with CDK4/6i & BETi acts highly synergistic in cancer cell lysis. Furthermore, additional molecular analyses on this subject demonstrate that the positive transcription elongation factor P-TEFb plays a decisive role in this regard, indicating an influence of the combinational therapy on gene transcription control. The combination of CDK4/6i & BETi and XVir-N-31 is an attractive strategy to achieve substantial cancer cell killing and is highly suitable for clinical testing.

Keywords: adenovirus, BET, CDK4/6, HNSCC, P-TEFb, YB-1

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Authors: Betul Taspinar, Eda O. Okur, Ismail Saracoglu, Ismail Okur, Ferruh Taspinar

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Thoracic hyperkyphosis, is a well-known spinal phenomenon, refers to an excessive curvature (> 40 degrees) of the thoracic spine. The aim of this study was to explore the effectiveness of thrust manipulation on thoracic spine alignment. 31 young adults with hyperkyphosis diagnosed with Spinal Mouse® device were randomly assigned either thrust manipulation group (n=16, 11 female, 5 male) or sham manipulation group (n=15, 8 female, 7 male). Thrust and sham manipulations were performed by a blinded physiotherapist who is a certificated expert in musculoskeletal physiotherapy. Thoracic kyphosis degree was measured after the interventions via Spinal Mouse®. Wilcoxon test was used to analyse the data obtained before and after the manipulation for each group, whereas Mann-Whitney U test was used to compare the groups. The mean of baseline thoracic kyphosis degrees in thrust and sham groups were 50.69 o ± 7.73 and 48.27o ± 6.43, respectively. There was no statistically significant difference between groups in terms of initial thoracic kyphosis degrees (p=0.51). After the interventions, the mean of thoracic kyphosis degree in thrust and sham groups were measured as 44.06o ± 6.99 and 48.93o ± 6.57 respectively (p=0.03). There was no statistically significant difference between before and after interventions in sham group (p=0.33), while the mean of thoracic kyphosis degree in thrust group decreased significantly (p=0.00). Thrust manipulation can attenuate thoracic hyperkyphosis immediately in young adults by not using placebo effect. Manipulation might provide accurate proprioceptive (sensory) input to the spine joints and reduce kyphosis by restoring normal segment mobility. Therefore thoracic manipulation might be included in the physiotherapy programs to treat hyperkyphosis.

Keywords: hyperkyphosis, manual therapy, spinal mouse, physiotherapy

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Authors: Jamie R. Chua, Christina Irene D. Mejia, Regina P. Berba

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Disseminated tuberculosis is an infectious disease caused by Mycobacterium tuberculosis involving two or more non-contiguous sites identified through bacteriologic confirmation or clinical diagnosis. Over the five year period included in the study, the UP-PGH TB DOTS clinic had total of 3,967 referrals, and the prevalence of disseminated tuberculosis is 1% (68/3967). The mean age was 33.9 years (range 19-64 years) with a male: female ratio of 1:1. 67% (52 patients) had no predisposing comorbid illness or immune disorder. The most common presenting symptoms were abdominal pain (19%), back pain (13%), abdominal enlargement (11%) and mass (10.2%). Anemia, leukocytosis, hypoalbuminemia, and high-normal serum calcium were common biochemical and hematologic findings. Around 36% (25) of patients were diagnosed clinically with disseminated tuberculosis despite lacking bacteriologic evidence of multi-organ involvement. The lungs (86%) is still the most commonly involved site, followed by intestinal (22%), vertebral/Pott’s (27%), and pelvic/genital (19%). The mean time from presentation to initiation of therapy was 22 days (SD 32.7). Only 18 patients (29.3%) were properly recorded to have been referred to local TB DOTs facilities. Of the 68 patients, only 16% (11 patients) continued follow-up at PGH, and all had documented treatment completion. Treatment outcomes of the remaining were unknown. Due to the variety of involved sites, a high index of suspicion is required. Knowledge on clinical features, common radiographic findings, and histopathologic characteristics of disseminated TB is important as bacteriologic evidence of infection is not always apparent.

Keywords: disseminated tuberculosis, Mycobacterium tuberculosis, miliary tuberculosis, tuberculosis

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Authors: Michaela Dušková, Kateřina Šimůnková, Martin Hill, Hana Hruškovičová, Hana Pospíšilová, Eva Králíková, Luboslav Stárka

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Smoking represents the most widespread substance dependence in the world. Several studies show the nicotine's ability to alter women hormonal homeostasis. Women smokers have higher testosterone and lower estradiol levels throughout life compared to non-smoker women. We monitored the effect of smoking discontinuation on steroid spectrum with 40 premenopausal and 60 postmenopausal women smokers. These women had been examined before they discontinued smoking and also after 6, 12, 24, and 48 weeks of abstinence. At each examination, blood was collected to determine steroid spectrum (measured by GC-MS), LH, FSH, and SHBG (measured by IRMA). Repeated measures ANOVA model was used for evaluation of the data. The study has been approved by the local Ethics Committee. Given the small number of premenopausal women who endured not to smoke, only the first 6 week period data could be analyzed. A slight increase in androgens after the smoking discontinuation occurred. In postmenopausal women, an increase in testosterone, dihydrotestosterone, dehydroepiandrosterone, and other androgens occurred, too. Nicotine replacement therapy, weight changes, and age does not play any role in the androgen level increase. The higher androgens levels correlated with failure in smoking cessation. Women smokers have higher androgen levels, which might play a role in smoking dependence development. Women successful in smoking cessation, compared to the non-successful ones, have lower androgen levels initially and also after smoking discontinuation. The question is what androgen levels women have before they start smoking.

Keywords: addiction, smoking, cessation, androgens

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Authors: Mario Isaza-Ruget, Claudia C. Colmenares-Mejia, Nancy Yomayusa, Camilo A. González, Andres Cely, Jossie Murcia

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Quantification of risks associated with complications development from chronic kidney disease (CKD) through accurate survival models can help with patient management. A retrospective cohort that included patients diagnosed with CKD from a primary care program and followed up between 2013 and 2018 was carried out. Time-dependent and static covariates associated with demographic, clinical, and laboratory factors were included. Deep Learning (DL) survival analyzes were developed for three CKD outcomes: CKD stage progression, >25% decrease in Estimated Glomerular Filtration Rate (eGFR), and Renal Replacement Therapy (RRT). Models were evaluated and compared with Random Survival Forest (RSF) based on concordance index (C-index) metric. 2.143 patients were included. Two models were developed for each outcome, Deep Neural Network (DNN) model reported C-index=0.9867 for CKD stage progression; C-index=0.9905 for reduction in eGFR; C-index=0.9867 for RRT. Regarding the RSF model, C-index=0.6650 was reached for CKD stage progression; decreased eGFR C-index=0.6759; RRT C-index=0.8926. DNN models applied in survival analysis context with considerations of longitudinal covariates at the start of follow-up can predict renal stage progression, a significant decrease in eGFR and RRT. The success of these survival models lies in the appropriate definition of survival times and the analysis of covariates, especially those that vary over time.

Keywords: artificial intelligence, chronic kidney disease, deep neural networks, survival analysis

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Authors: M. Klimova, O. Semyachkina-Glushkovskaya, J. Kurts, E. Zinchenko, N. Navolokin, A. Shirokov, A. Dubrovsky, A. Abdurashitov, A. Terskov, A. Mamedova, I. Agranovich, T. Antonova, I. Blokhina

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The direction for research of Alzheimer's disease is to find an effective non-invasive and non-pharmacological way of treatment. Here we tested our hypothesis that the opening of the blood-brain barrier (BBB) induces activation of lymphatic drainage and clearing functions that can be used as a method for non-invasive stimulation of clearance of beta-amyloid and therapy of Alzheimer’s disease (AD). To test our hypothesis, in this study on healthy male mice we analyzed the interaction between BBB opening by repeated loud music (100-10000 Hz, 100 dB, duration 2 h: 60 sec – sound; 60 sec - pause) and functional changes in the meningeal lymphatic vessels (MLVs). We demonstrate clearance of dextran 70 kDa (i.v. injection), fluorescent beta-amyloid (intrahippocampal injection) and gold nanorods (intracortical injection) via MLV that significantly increased after the opening of BBB. Our studies also demonstrate that the BBB opening was associated with the improvement of neurocognitive status in mice with AD. Thus, we uncover therapeutic effects of BBB opening by loud music, such as non-invasive stimulation of lymphatic clearance of beta-amyloid in mice with AD, accompanied by improvement of their neurocognitive status. Our data are consistent with other results suggesting the therapeutic effect of BBB opening by focused ultrasound without drugs for patients with AD. This research was supported by a grant from RSF 18-75-10033

Keywords: Alzheimer's disease, beta-amyloid, blood-brain barrier, meningeal lymphatic vessels, repeated loud music

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Authors: Ryuji Yamazaki, Masahiro Kochi, Weiran Zhu, Hiroko Kase

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In care for older adults, behavioral and psychological symptoms of dementia (BPSD) like agitation and aggression are distressing for patients and their caretakers, often resulting in premature institutionalization with increased costs of care. To improve mood and mitigate symptoms, as a non-pharmaceutical approach, emotion-oriented therapy like reminiscence work is adopted in face-to-face communication. Telecommunication support is expected to be provided by robotic media as a bridge for digital divide for those with dementia and facilitate social interaction both verbally and nonverbally. The purpose of this case study is to explore the conditions in which robotic media can effectively attract attention from older adults with dementia and promote their well-being. As a pilot study, we introduced the pillow-phone Hugvie^®, a huggable humanly shaped communication medium to five residents with dementia at a care facility, to investigate how the following conditions work for the elderly when they use the medium; 1) no sound, 2) radio, non-interactive, 3) daily conversation, and 4) reminiscence work. As a result, under condition 4, reminiscence work, the five participants kept concentration in interacting with the medium for a longer duration than other conditions. In condition 4, they also showed larger amount of utterances than under other conditions. These results indicate that providing topics related to personal histories through robotic media could affect communication positively and should, therefore, be further investigated. In addition, the issue of ethical implications by using persuasive technology that affects emotions and behaviors of older adults is also discussed.

Keywords: BPSD, reminiscence, tactile telecommunication, utterances

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Authors: H. M. Imam, H. M. Rezk, A. F. Tohamy

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Background: Human umbilical cord blood (HUCB) is considered as a unique source for stem cells. HUCB contain different types of progenitor cells which could differentiate into hepatocytes. Aims: To investigate the potential of rat's liver damage repair using human umbilical cord mesenchymal stem cells (hUCMSCs). We investigated the feasibility for hUCMSCs in recovery from liver damage. Moreover, investigating fibrotic liver repair and using the CCl4-induced model for liver damage in the rat. Methods: Rats were injected with 0.5 ml/kg CCl4 to induce liver damage and progressive liver fibrosis. hUCMSCs were injected into the rats through the tail vein; Stem cells were transplanted at a dose of 1×106 cells/rat after 72 hours of CCl4 injection without receiving any immunosuppressant. After (6 and 8 weeks) of transplantation, blood samples were collected to assess liver functions (ALT, AST, GGT and ALB) and level of Procollagen III as a liver fibrosis marker. In addition, hepatic tissue regeneration was assessed histopathologically and immunohistochemically using antihuman monoclonal antibodies against CD34, CK19 and albumin. Results: Biochemical and histopathological analysis showed significantly increased recovery from liver damage in the transplanted group. In addition, HUCB stem cells transdifferentiated into functional hepatocytes in rats with hepatic injury which results in improving liver structure and function. Conclusion: Our findings suggest that transplantation of hUCMSCs may be a novel therapeutic approach for treating liver fibrosis. Therefore, hUCMSCs are a potential option for treatment of liver cirrhosis.

Keywords: carbon tetra chloride, liver fibrosis, mesenchymal stem cells, rat

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Authors: M. S. M. Anjalee Umesha Bandara

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Hela Veda Shastra is a science that is an endowment from generation to generation. There is also an individualistic science and indigenous practice of traditional herbs. There are many effective cures for snakes, fractures, head cancer, cuts, lunatics, reflexology, etc. Hela physicians who rescued them from infections caused by snakes have recognized poems to remember the medicines they used to cure the patients. Due to the harmony of the Hela Osu and Hela Knowledge poetry collection, it has become easy for the juniors of the Hela Veda generation to gain medical knowledge. It is a research problem whether it is possible to arrive at a correct conclusion about the patient form of the snake information thread through the existing Dhuta characteristics of Hela Serpa Vedakam. This research was done with the assumption that snake venom can be successfully treated according to its characteristics. In this research, two generations related to the Ratmalavatiya Vedaparamparava and the Vannihatpattu of the Kalla Veda generation have been identified as Veda Paramparas who treat and created Dutha Kavya, including the form of the Serpent Dasthana. They have collected ancient books, documents and interviews related to qualitative research on snake disease treatment. In addition, collecting data by referring to books related to Hela medicine. The ancient indigenous lineage methods that are superior to modern Western science's snake therapy should save the Hela's amazing wealth of wisdom for the future, leaving aside the selfishness of keeping the teaching to themselves.

Keywords: snake venom medicine, vedic genealogy, Dhuta characteristic, snake

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Authors: Małgorzata Drzewiecka, Tomasz Śliwiński, Maciej Radek

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The inhibition of histone deacetyles (HDACs) holds promise as a potential anti-cancer therapy because histone and non-histone protein acetylation is frequently disrupted in cancer, leading to cancer initiation and progression. Additionally, histone deacetylase inhibitors (HDACi) such as class I HDAC inhibitor - valproic acid (VPA) have been shown to enhance the effectiveness of DNA-damaging factors, such as cisplatin or radiation. In this study, we found that, using of VPA in combination with talazoparib (BMN-637 – PARP1 inhibitor – PARPi) and/or Dacarabazine (DTIC - alkylating agent) resulted in increased DNA double strand break (DSB) and reduced survival (while not affecting primary melanocytes )and proliferation of melanoma cells. Furthermore, pharmacologic inhibition of class I HDACs sensitizes melanoma cells to apoptosis following exposure to DTIC and BMN-637. In addition, inhibition of HDAC caused sensitization of melanoma cells to dacarbazine and BMN-637 in melanoma xenografts in vivo. At the mRNA and protein level histone deacetylase inhibitor downregulated RAD51 and FANCD2. This study provides that combining HDACi, alkylating agent and PARPi could potentially enhance the treatment of melanoma, which is known for being one of the most aggressive malignant tumors. The findings presented here point to a scenario in which HDAC via enhancing the HR-dependent repair of DSBs created during the processing of DNA lesions, are essential nodes in the resistance of malignant melanoma cells to methylating agent-based therapies.

Keywords: melanoma, hdac, parp inhibitor, valproic acid

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Authors: Y. V. S. Annapurna, V. V. Lakshmi

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Urinary tract infection (UTI) is one of the most common infectious diseases at the community level with a high rate of morbidity . This is further augmented by increase in the number of resistant and multi resistant strains of bacteria particularly by those producing Extended spectrum of beta lactamases. The present study was aimed at analysis of antibiograms of E.coli and Klebsiella sp causing urinary tract infections. Between November 2011 and April 2013, a total of 1120 urine samples were analyzed,. Antibiotic sensitivity testing was done with 542(48%) isolates of E.coli and 446(39%) of Klebsiella sp using the standard disc diffusion method against eleven commonly used antibiotics .Organisms showed high susceptibility to Amikacin and Netilimicin and low susceptibility to Cephalosporins. MAR index was calculated for the multidrug resistant strains. Maximum MAR index detected among the isolates was 0.9. Phenotypic identification for ESBL production was confirmed by double disk synergy test (DDST) according to CLSI guidelines. Plasmid profile of the isolates was carried out using alkaline hydrolysis method. Agarose-gel electrophoresis showed presence of high-molecular weight plasmid DNA among the ESBL strains. This study emphasizes the importance of indiscriminate use of antibiotics which if discontinued, in turn would prevent further development of bacterial drug resistance. For this, a proper knowledge of susceptibility pattern of uropathogens is necessary before prescribing empirical antibiotic therapy and it should be made mandatory.

Keywords: escherichia coli, extended spectrum of beta lactamase, Klebsiella spp, Uropathogens

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Authors: Nishu Atrey, Priyanka Singh, G. P. Talwar, Jagdish Gupta, Alka Kriplani, Rohini Sehgal, Indrani Ganguli, Soni Sinha

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Background: Vaginosis is a widely prevalent syndrome in India and elsewhere. Recurrence is frequent in women treated with antibiotics, whose vagina pH remains above 5.0 indicative of the loss of resident lactobacilli. The objective of the present trial was to determine whether a Polyherbal microbicide BASANT can regress Vaginosis. Another objective was to determine whether the three selected strains of Probiotics endowed with making high amounts of lactic acid can colonise and restore the pH of the vagina to the acidic healthy range. Materials and Procedure: BASANT, was employed in powder form in veg (cellulose) capsules. TRF#36 strain of Lactobacillus fermentum, TRF#8 strain of L.gasseri, and TRF#30 strain of L.salivarius (combination termed as Pro-vag-Health) were employed at 3x109 bacilli lyophilized, packaged in capsules. The trials were conducted in women suffering from vaginosis with vaginal pH above 5.0. Women were given intravaginally either BASANT, Pro-vag-Health or a combination of the two intravaginally for seven days and thereafter once weekly as a maintenance dose. Results: BASANT cleared vaginosis in 14/20 women and Pro-vag-Health in 13/20 women. Interestingly, the combination of BASANT plus Pro-vag-Health was effective in 19/20 women, in contrast to Placebo capsules effective only in 1/20 women. Interpretation and Conclusion: The combination of BASANT and Pro-veg-Health Probiotics taken together intravaginally for seven days relieves 19 out of 20 women from vaginosis to restore acidic pH and healthy vagina. Extension of trial with this combination in larger number is indicated.

Keywords: microbicide, probiotics, vaginal pH, vaginosis

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Authors: Elin Julianti, Marlia Singgih, Masayoshi Arai, Jianyu Lin, Masteria Yunovilsa Putra, Muhammad Azhari, Agnia S. Muharam

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The search for a source of new medicinal compounds with anticancer activity from natural products has become important to resolve the ineffectiveness problem of pancreatic cancer therapy. Fungal marine microorganisms are prolific sources of bioactive natural products. In this present study, the ethyl acetate extract of cultured broth of Trichoderma longibrachiatum marine sponge-derived fungi exhibited selective cytotoxicity against human pancreatic carcinoma PANC-1 cells cultured under glucose-deficient conditions (IC50 = 98,4 µg/mL). The T. longibrachiatum was fermented by the static method at room temperature for 60 days. The culture broth was extracted using ethyl acetate by liquid-liquid extraction method. The liquid-liquid extraction was conducted toward the ethyl extract by using 90% MeOH-H₂O and n-|Hexane as a solvent. The extract of 90% MeOH-H₂O was fractionated by liquid extraction using by C₁₈ reversed-phase vacuum flash chromatography using mixtures of MeOH-H₂O, from 50:50 to 100:0, and 1% TFA MeOH as the eluents to yield six fractions. The fraction 2 (MeOH-H2O, 70:30) and fraction 3 (MeOH-H2O, 80:20) showed moderate cytotoxicity with IC50 value of 119.3 and 274.7 µg/mL, respectively. Fraction 4 (MeOH-H₂O, 90:10) showed the highest cytotoxicity activity with IC₅₀value of < 10 µg/mL. The chemical compounds of the fractions that are responsible for cytotoxic activity are potent for further investigation.

Keywords: cytotoxic activity, trichoderma longibrachiatum, marine-derived fungi, PANC-1 cell line

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Authors: Stephanie Cheng, Benjamin Poh, Vivyan Tay, Sachin Mathur

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Aim: Diabetes mellitus (DM) is a worldwide pandemic affecting 500 million people. It is known to be associated with increased susceptibility to soft tissue infections (STI). Despite being a major public health burden, the literature relating the effects of DM and the presentation, severity and healing of STIs in general surgical patients remain limited. Methods: We conducted a retrospective review of all patients admitted with STI in a tertiary teaching hospital over a 12-month period. Patient demographics and surgical outcomes were collected and analyzed. Results: During the study period, 1059 patients were admitted for STIs, of which 936 (88%) required surgical intervention. Diabetic patients were presented with a higher body-mass index (BMI) (28 vs 26), larger abscess size (24 vs 14 cm²) and a longer length of stay (LOS)(4.4 days vs 2.9 days). They also underwent a higher proportion of wide debridement as well as application of negative pressure wound therapy (NPWT) (42% vs 35%). More diabetic patients underwent subsequent re-operation within the same sitting (8 vs 4). There were no differences in re-admission rates within 30 days nor subsequent abscess formation in those followed for 6 months. Conclusion: The incidence of STIs among DM patients represents a significant disease burden; surgeons should consider intensive patient counseling and partnering with primary care providers in order to help reduce the incidence of future STI admissions based on lifestyle modification and glucose control.

Keywords: general surgery, emergency general surgery, acute care surgery, soft tissue infections, diabetes mellitus

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Authors: Sara Mohammad Atef Sabaika

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Background: The development of factor VIII (FVIII) inhibitor and hemophilic arthropathy in patients with hemophilia A (PWHA) are a great challenge for hemophilia care. Both genetic and environmental factors led to complications in PWHA. The development of inhibitory antibodies is usually induced by the immune response. Tumor necrosis factor α (TNF-α), one of the cytokines, might contribute to its polymorphism. Aim: Study the association between tumor necrosis alpha level and genotypes in pediatric patients with hemophilia A and its relation to inhibitor development and joint status. Methods: A cross-sectional study was conducted among a sufficient number of PWHA attending the Pediatric Hematology and Oncology Unit, Pediatric department in Menoufia University hospital. The clinical parameters, FVIII, FVIII inhibitor, and serum TNF-α level were assessed. The genotyping of −380G > A TNF-α gene polymorphism was performed using real time polymerase chain reaction. Results: Among the 50 PWHA, 28 (56%) were identified as severe PWHA. The FVIII inhibitor was identified in 6/28 (21.5%) of severe PWHA. There was a significant correlation between serum TNF-α level and the development of inhibitor (p = 0:043). There was significant correlation between polymorphisms of −380G > A TNF-α gene and hemophilic arthropathy development (p = 0:645). Conclusion: The prevalence of FVIII inhibitor in severe PWHA in Menoufia was 21.5%. The frequency of replacement therapy is a risk factor for inhibitor development. Serum TNF-α level and its gene polymorphism might be used to predict inhibitor development and joint status in pediatric patients with hemophilia A.

Keywords: hemophilic arthropathy, TNF alpha., patients witb hemophilia A PWHA, inhibitor

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Authors: Murali Munisamy, Gauthaman Karunakaran, Mubarak Al-Gahtany, Vivekanandhan Subbiah, M. Manjari Tripati

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Background: Sodium valproate is a widely prescribed broad-spectrum anti-epileptic drug. It shows high inter-individual variability in pharmacokinetics and pharmacodynamics and has a narrow therapeutic range. We evaluated the effects of polymorphic uridine diphosphate glucuronosyltransferase (UGT1A9) metabolizing enzyme on the pharmacokinetics of sodium valproate in the patients with epilepsy who showed toxicity to therapy. Methods: Genotype analysis of the patients was made with polymerase chain–restriction fragment length polymorphism (RFLP) with sequencing. Plasma drug concentrations were measured with reversed phase high-performance liquid chromatography (HPLC) and concentration–time data were analyzed by using a non-compartmental approach. Results: The results of this study suggested a significant genotypic as well as allelic association with valproic acid toxicity for UGT1A9 polymorphic enzymes. The elimination half-life (t 1/2=40.2 h) of valproic acid was longer and the clearance rate (CL=937 ml/h) was lower in the poor metabolizers group of UGT1A9 polymorphism who showed toxicity than in the intermediate metabolizers group (t1/2=35.5 h, CL=1042 ml/h) or the extensive metabolizers group (t1/2=26. h, CL=1,302 ml/h). Conclusion: Our findings suggest that the UGT1A9 genetic polymorphism plays a significant role in the steady state concentration of sodium valproate, and it thereby has an impact on the toxicity of the sodium valproate used in the patients with epilepsy.

Keywords: UGT1A9, sodium valporate, pharmacogenetics, polymorphism

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