Search results for: clinical trial optimization

Authors: Fares A. Mayia, Mahmoud A. Yamany, Mushabbab A. Asiri

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In recent years, non-invasive Focused Ultrasound (FU) has been utilized for generating bubbles (cavities) to ablate target tissue by mechanical fractionation. Intensities >10 kW/cm² are required to generate the inertial cavities. The generation, rapid growth, and collapse of these inertial cavities cause tissue fractionation and the process is called Histotripsy. The ability to fractionate tissue from outside the body has many clinical applications including the destruction of the tumor mass. The process of tissue fractionation leaves a void at the treated site, where all the affected tissue is liquefied to particles at sub-micron size. The liquefied tissue will eventually be absorbed by the body. Histotripsy is a promising non-invasive treatment modality. This paper presents a technique for generating inertial cavities at lower intensities (< 1 kW/cm²). The technique (patent pending) is based on amplitude modulation (AM), whereby a low frequency signal modulates the amplitude of a higher frequency FU wave. Cavitation threshold is lower at low frequencies; the intensity required to generate cavitation in water at 10 kHz is two orders of magnitude lower than the intensity at 1 MHz. The Amplitude Modulation technique can operate in both continuous wave (CW) and pulse wave (PW) modes, and the percentage modulation (modulation index) can be varied from 0 % (thermal effect) to 100 % (cavitation effect), thus allowing a range of ablating effects from Hyperthermia to Histotripsy. Furthermore, changing the frequency of the modulating signal allows controlling the size of the generated cavities. Results from in vitro work demonstrate the efficacy of the new technique in fractionating soft tissue and solid calcium carbonate (Chalk) material. The technique, when combined with MR or Ultrasound imaging, will present a precise treatment modality for ablating diseased tissue without affecting the surrounding healthy tissue.

Keywords: focused ultrasound therapy, histotripsy, inertial cavitation, mechanical tissue ablation

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Authors: Catherine P. Bradshaw, Elise T. Pas, Katrina J. Debnam, Jessika H. Bottiani, Michael Rosenberg

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Worldwide, ethnically and culturally diverse students are at increased risk for school failure, discipline problems, and dropout. Despite decades of concern about this issue of disparities in education and other fields (e.g., 'school to prison pipeline'), there has been limited empirical examination of models that can actually reduce these gaps in schools. Moreover, few studies have examined the effectiveness of in-service teacher interventions and supports specifically designed to reduce discipline disparities and improve student engagement. This session provides an overview of the evidence-based Double Check model which serves as a framework for teachers to use culturally-responsive strategies to engage ethnically and culturally diverse students in the classroom and reduce discipline problems. Specifically, Double Check is a school-based prevention program which includes three core components: (a) enhancements to the school-wide Positive Behavioral Interventions and Supports (PBIS) tier-1 level of support; (b) five one-hour professional development training sessions, each of which addresses five domains of cultural competence (i.e., connection to the curriculum, authentic relationships, reflective thinking, effective communication, and sensitivity to students’ culture); and (c) coaching of classroom teachers using an adapted version of the Classroom Check-Up, which intends to increase teachers’ use of effective classroom management and culturally-responsive strategies using research-based motivational interviewing and data-informed problem-solving approaches. This paper presents findings from a randomized controlled trial (RCT) testing the impact of Double Check, on office discipline referrals (disaggregated by race) and independently observed and self-reported culturally-responsive practices and classroom behavior management. The RCT included 12 elementary and middle schools; 159 classroom teachers were randomized either to receive coaching or serve as comparisons. Specifically, multilevel analyses indicated that teacher self-reported culturally responsive behavior management improved over the course of the school year for teachers who received the coaching and professional development. However, the average annual office discipline referrals issued to black students were reduced among teachers who were randomly assigned to receive coaching relative to comparison teachers. Similarly, observations conducted by trained external raters indicated significantly more teacher proactive behavior management and anticipation of student problems, higher student compliance, less student non-compliance, and less socially disruptive behaviors in classrooms led by coached teachers than classrooms led teachers randomly assigned to the non-coached condition. These findings indicated promising effects of the Double Check model on a range of teacher and student outcomes, including disproportionality in office discipline referrals among Black students. These results also suggest that the Double Check model is one of only a few systematic approaches to promoting culturally-responsive behavior management which has been rigorously tested and shown to be associated with improvements in either student or staff outcomes indicated significant reductions in discipline problems and improvements in behavior management. Implications of these findings are considered within the broader context of globalization and demographic shifts, and their impacts on schools. These issues are particularly timely, given growing concerns about immigration policies in the U.S. and abroad.

Keywords: ethnically and culturally diverse students, student engagement, school-based prevention, academic achievement

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Authors: Ajay Gogia, Svs Deo, Dn Sharma, Atul Batra, Ashutash Mishra

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Background and Aims: Breast cancer in women aged less than 25 years (defined as very young breast cancer, VYBC) is rare and accounts for 0.25% of all breast cancer in the West. There is no data available on VYBC from developing countries. The aim of this study was to analyze the clinical, pathological, and prognostic factors and outcomes in VYBC. Methods: This retrospective analysis was performed on 80 patients aged 25 years or less (screened 8000 files of female BC) who were registered at All India Institute of Medical Sciences (AIIMS), New Delhi, India, over a 15-year period between 2011 and 2023. Results: The median age was 21.5 years (range 16-25). A positive family history (siblings and parents) was elicited in 30% of cases, and breast cancer gene (BRCA1/2) mutation was found in 33% of cases patients. Ten patients (12.5%) patients have pregnancy-associated breast cancer (BC detected during pregnancy or 1 year after postpartum period). The TNM stage distribution was Stage I was 0, stage II -30%, stage III –60% and Stage IV -10 %patients. Seventy percent of tumors were high grade, and 90% had pathological node-positive disease. Estrogen, Progesterone, and human epidermal growth factor receptor 2 (HER2)/neu positivity were 25%,25% and 35%, respectively. Triple-negative breast cancer constituted 40% of patients. With a median follow-up of 42 months, 3 years, relapse-free survival (nonmetastatic disease), progression-free survival (metastatic disease) and overall survival were 30%, 15% and 50%, respectively. Conclusions: Very young women constituted 1% of all breast cancer cases. Advanced disease at presentation and high-risk pathological features result in poor outcomes. One-third of VYBCs are associated with BRCA mutation, which requires genetic counseling and risk reduction surgery if required. Due to the aggressive behavior of BC in this age group, need early diagnosis and prompt treatment

Keywords: very young, breast cancer, outcome, developing country, India

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Authors: Nikhil A. Gavhane, Sachin Shah, Ishant S. Mahajan, Pawan D. Bahekar

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Introduction: Millions of people are affected with dengue fever every year, which drives up healthcare expenses in many low-income countries. Organ failure and other serious symptoms may result. Another worldwide public health problem is sickle cell anaemia, which is most prevalent in Africa, the Caribbean, and Europe. Dengue epidemics have reportedly occurred in locations with a high frequency of sickle cell disease, compounding the health problems in these areas. Aims and Objectives: This study examines dengue infection in sickle cell disease-afflicted pre-schoolers. Method:This Retrospective cohort study examined paediatric patients. Young people with sickle cell disease (SCD), dengue infection, and a control group without SCD or dengue were studied. Data on demographics, SCD consequences, medical treatments, and laboratory findings were gathered to analyse the influence of SCD on dengue severity and clinical outcomes, classified as severe or non-severe by the 2009 WHO classification. Using fever or admission symptoms, the research estimated acute illness duration. Result: Table 1 compares haemoglobin genotype-based dengue episode features in SS, SC, and controls. Table 2 shows that severe dengue cases are older, have longer admission delays, and have particular symptoms. Table 3's multivariate analysis indicates SS genotype's high connection with severe dengue, multiorgan failure, and acute pulmonary problems. Table 4 relates severe dengue to greater white blood cell counts, anaemia, liver enzymes, and reduced lactate dehydrogenase. Conclusion: This study is valuable but confined to hospitalised dengue patients with sickle cell illness. Small cohorts limit comparisons. Further study is needed since findings contradict predictions.

Keywords: dengue, chills, headache, severe myalgia, vomiting, nausea, prostration

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Authors: Naum Simanovsky, Vladimir Goldman, Michael Zaidman

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Background: The optimal algorithm for the management of symptomatic tarsal coalition is still under discussion in pediatric literature. It's debatable what surgical steps are essential to achieve the best outcome. Method: The investigators retrospectively reviewed the records of twelve patients with symptomatic tarsal coalition that were treated operatively between 2017 and 2019. Only painful flat feet were operated. Two patients were excluded from the study due to lack of sufficient follow-up. Ten of eleven feet were treated with the combination of calcaneal lengthening osteotomy (CLO) and resection of coalition (RC). Only one foot was operated with CLO alone. In half of our patients, Achilles lengthening was performed. For two children, medial plication was added. Short leg cast was applied to all children for 6-8 weeks, and soft shoe insoles for medial arch support were prescribed after. Demographic, clinical, and radiographic records were reviewed. The outcome was evaluated using American Orthopedic Foot and Ankle Society (AOFAS) Ankle Hindfoot Score. Results: There were seven boys and three girls. The mean age at the time of surgery was 13.9 (range 12 to 17) years, and the mean follow-up was 18 (range 8 to 34) months. The early complications included one superficial wound infection and dehiscence. Late complication includes two children with residual forefoot supination. None of our patients required additional operations during the follow-up period. All feet achieved complete deformity correction or dramatic improvement. In the last follow-up, seven feet were painless, and four children had some mild pain after intensive activities. All feet achieved excellent and good scoring on AOFAS. Conclusions: Many patients with talocalcaneal coalition also have rigid or stiff, painful, flat feet. For these patients, the resection of coalition with concomitant CLO can be safely recommended.

Keywords: Tarsal coalition, calcaneal lengthening osteotomy., flat foot, coalition resection

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Authors: Ouassila Bekkal Brikci Benhabib, Zahia Boucherit Otmani, Kebir Boucherit, A. Seghir

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The establishment of intravenous catheters in hospitalized patient is an act common in many clinical situations. These therapeutic tools, from their insertion in the body, represent gateways including fungal germs prone. The latter can generate the growth of biofilms, which can be the cause of fungal infection. Faced with this problem, we conducted a study at the University Hospital of Tlemcen in the neurosurgery unit and aims to isolate and identify Candida yeasts from intravenous catheters. Then test their ability to form biofilms. Materials and methods: 256 patient hospitalized in surgery of the hospital in west Algeria were submitted to this study. All samples were taken from peripheral venous catheters implanted for 72 hours or more days. A total of 31 isolates of Candida species were isolated. MIC and SMIC are determined at 80% inhibition by the test XTT tetrazolium measured at 490 nm. The final concentrations of antifungal agent being between 0.03 and 16 mg / ml for amphotericin B and from 0.015 to 8 mg / mL caspofungin. Results: 31 Candida species isolates from catheters including 14 Candida albicans and 17 Candida non albicans . 21 strains of all the isolates were able to form biofilms. In their form of Planktonic cells, all isolates are 100% susceptible to antifungal agents tested. However, in their state of biofilms, more isolates have become tolerant to the tested antifungals. Conclusion: Candida yeasts isolated from intravascular catheters are considered an important virulence factor in the pathogenesis of infections. Their involvement in catheter-related infections can be disastrous for their potential to generate biofilms. They survive high concentrations of antifungal where treatment failure. Pending the development of a therapeutic approach antibiofilm related to catheters, their mastery is going through: -The risk of infection prevention based on the training and awareness of medical staff, -Strict hygiene and maximum asepsis, and -The choice of material limiting microbial colonization.

Keywords: candida, biofilm, hospital, infection, amphotericin B, caspofungin

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Authors: Dewi Retno Sari Saputro, Purnami Widyaningsih, Hendrika Handayani

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Extreme data on an observation can occur due to unusual circumstances in the observation. The data can provide important information that can’t be provided by other data so that its existence needs to be further investigated. The method for obtaining extreme data is one of them using maxima block method. The distribution of extreme data sets taken with the maxima block method is called the distribution of extreme values. Distribution of extreme values is Gumbel distribution with two parameters. The parameter estimation of Gumbel distribution with maximum likelihood method (ML) is difficult to determine its exact value so that it is necessary to solve the approach. The purpose of this study was to determine the parameter estimation of Gumbel distribution with quasi-Newton BFGS method. The quasi-Newton BFGS method is a numerical method used for nonlinear function optimization without constraint so that the method can be used for parameter estimation from Gumbel distribution whose distribution function is in the form of exponential doubel function. The quasi-New BFGS method is a development of the Newton method. The Newton method uses the second derivative to calculate the parameter value changes on each iteration. Newton's method is then modified with the addition of a step length to provide a guarantee of convergence when the second derivative requires complex calculations. In the quasi-Newton BFGS method, Newton's method is modified by updating both derivatives on each iteration. The parameter estimation of the Gumbel distribution by a numerical approach using the quasi-Newton BFGS method is done by calculating the parameter values that make the distribution function maximum. In this method, we need gradient vector and hessian matrix. This research is a theory research and application by studying several journals and textbooks. The results of this study obtained the quasi-Newton BFGS algorithm and estimation of Gumbel distribution parameters. The estimation method is then applied to daily rainfall data in Purworejo District to estimate the distribution parameters. This indicates that the high rainfall that occurred in Purworejo District decreased its intensity and the range of rainfall that occurred decreased.

Keywords: parameter estimation, Gumbel distribution, maximum likelihood, broyden fletcher goldfarb shanno (BFGS)quasi newton

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Authors: Öznur Saribaş, Si̇bel Kahraman Çeti̇ntaş

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It is aimed to compare target volume and critical organ doses by using CyberKnife (CK) in accelerated partial breast irradiation (APBI) in patients with early stage breast cancer. Three different virtual plans were made for Iris, fixed and multi-leaf collimator (MLC) for 5 patients who received radiotherapy in the CyberKnife system. CyberKnife virtual plans were created, with 6 Gy per day totaling 30 Gy. Dosimetric parameters for the three collimators were analyzed according to the restrictions in the NSABP-39/RTOG 0413 protocol. The plans ensured critical organs were protected and GTV received 95 % of the prescribed dose. The prescribed dose was defined by the isodose curve of a minimum of 80. Homogeneity index (HI), conformity index (CI), treatment time (min), monitor unit (MU) and doses taken by critical organs were compared. As a result of the comparison of the plans, a significant difference was found for the duration of treatment, MU. However, no significant difference was found for HI, CI. V30 and V15 values of the ipsi-lateral breast were found in the lowest MLC. There was no significant difference between Dmax values for lung and heart. However, the mean MU and duration of treatment were found in the lowest MLC. As a result, the target volume received the desired dose in each collimator. The contralateral breast and contralateral lung doses were the lowest in the Iris. Fixed collimator was found to be more suitable for cardiac doses. But these values did not make a significant difference. The use of fixed collimators may cause difficulties in clinical applications due to the long treatment time. The choice of collimator in breast SBRT applications with CyberKnife may vary depending on tumor size, proximity to critical organs and tumor localization.

Keywords: APBI, CyberKnife, early stage breast cancer, radiotherapy.

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Authors: Shahindokht Bassiri-Jahromi, Mohammad Reza Pourshafie, Farzad Katiraee, Mannan Hajimahmoodi, Ehsan Mostafavi, Malihe Talebi

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Objective: Resistance of Candida species to antifungal agents has potentially serious implications for management of infections. Candida species are now fourth common organisms isolated from hospitalized patients. It is important to increase effective therapy. In the past decade, numerous reports of treatment failures were reported. Prevention and control of these infections will require new antimicrobial agents. Plant-derived antifungal have always been a source of novel therapeutics. The aim of this study was to investigate the antifungal effect of methanolic extract of pomegranate peel and pulp against Candida species. Material and Methods: Eight cultivars of Punica granatum L. were collected from Saveh Agricultural Investigation Center in Iran. Both pomegranate pulp and peel were dried and powdered separately. The dried powders were extracted by using a soxhlet extractor. The antifungal effect of methanolic extract of pomegranate peel and pulp were determined in vitro by minimum inhibitory concentration (MIC) against five standard species of (ATCC 10231), C. parapsilosis (ATCC 22019), C. tropicalis (ATCC 750), C. glabrata (PTCC 5297), and C. kroseii (PTCC 5295). Results: Maximum inhibitions of antifungal effect were attributed to peel extract pomegranate cultivar and Candida species. The most potential antifungal inhibition among 8 different cultivars observed by sour malas, sour white peel, and sour summer extracts respectively, against five Candida strains. The antifungal activity of pulp extracts against Candida species was approximately negative. Conclusion: The use of Punica granatum peel extract has been shown to possess antifungal activities. The phytochemistry and pharmacological actions of Punica granatum peel components suggest a wide range of clinical applications for the treatment and prevention of candidiasis.

Keywords: antifungal activity, Candida species, Punica granatum L., pharmacognosy

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Authors: Julie Connelly, Tanvi Toprani, Xin Xie, Dhinoth Kumar Bangarusamy, Kris C. Gunsalus

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The overuse of antibiotics worldwide has contributed to the development of multi-drug resistant (MDR) pathogenic bacterial strains. There is an increasing urgency to discover antibiotics to combat MDR pathogens. The microbiome of the Arabian Gulf is a largely unexplored and potentially rich source of novel bioactive compounds. Microbes that inhabit the Abu Dhabi coastal regions adapt to extreme environments with high salinity, hot temperatures, large temperature fluctuations, and acute exposure to solar energy. The microbes native to this region may produce unique metabolites with therapeutic potential as antibiotics and antifungals. We have isolated 200 pure bacterial strains from mangrove sediments, cyanobacterial mats, and coral reefs of the Abu Dhabi region. In this project, we aim to screen the marine bacterial strains to identify antibiotics, in particular undocumented compounds that show activity against existing antibiotic-resistant strains. We have acquired the ESKAPE pathogen panel, which consists of six antibiotic-resistant gram-positive and gram-negative bacterial pathogens that collectively cause most clinical infections. Our initial efforts of the primary screen using colony-picking co-culture assay have identified several candidate marine strains producing potential antibiotic compounds. We will next apply different assays, including disk-diffusion and broth turbidity growth assay, to confirm the results. This will be followed by bioactivity-guided purification and characterization of target compounds from the scaled-up volume of candidate strains, including SPE fraction, HPLC fraction, LC-MS, and NMR. For antimicrobial compounds with unknown structures, our final goal is to investigate their mode of action by identifying the molecular target.

Keywords: marine bacteria, natural products, drug discovery, ESKAPE panel

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Authors: Arben Murtezani, Shefqet Mrasori, Vančo Spirov, Bukurije Rama, Oliver Dimitrovski, Visar Bunjaku

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Overview: Temporomandibular disorders (TMDs) are chronic musculoskeletal pain conditions. Clinical indicators of discomfort are related to the use of the joint stiffness during first motions after extended rest and restricted joint range of motion can cause substantial pain and disability. There is little evidence that physical therapy methods of management cause long-lasting reduction in signs and symptoms. Exercise programs premeditated to improve physical fitness have beneficial effects on chronic pain and disability of the musculoskeletal system. Objective: The aim of this study was to assess the effectiveness of physical therapy interventions in the management of temporomandibular disorders. Materials and Methods: A prospective comparative study with a 2-month follow-up period was conducted between April 2016 and June 2016 at the Physical Medicine and Rehabilitation Clinic in Prishtina. Forty six patients with TMDs, (more than three months duration of symptoms) were randomized into two groups: the TENS therapy group (n=24) and combination of active exercise and manual therapy group (n=22). The TENS therapy group patients were treated with twelve sessions of TENS. The treatment period of both groups was 3 weeks at an outpatient clinic. Following main outcome measures were evaluated: (1) pain at rest (2) pain at stress (3) impairment (4) mouth opening at base-line, before and after treatment and at 3 month follow-up. Results: Significant reduction in pain was observed in both treatment groups. In the TENS group 73% (16/22) achieved at least 80% improvement from baseline in TMJ pain at 2 months compared with 54% (13/24) in the exercise group (difference of 19%; 95% confidence interval 220 to 30%). Active and passive maximum mouth opening has been greater in the TENS group (p < 0.05). Conclusion: Exercise therapy in combination with TENS seems to be useful in the treatment of temporomandibular disorders.

Keywords: temporomandibular joint disorders, TENS, manual therapy, exercise

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Authors: Ergün Şakalar, Şeyma Özçirak Ergün, Emrah Yalazi̇, Emine Altinkaya, Cengiz Ataşoğlu

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In recent years, food allergies which cause serious health problems affect to public health around the world. Foodstuffs which contain allergens are either intentionally used as ingredients or are encased as contaminant in food products. The prevalence of clinical allergy to peanuts and nuts is estimated at about 0.4%-1.1% of the adult population, representing the allergy to pistachio the 7% of the cases of tree nut causing allergic reactions. In order to protect public health and enforce the legislation, methods for sensitive analysis of pistachio and peanut contents in food are required. Pea, pistachio and peanut are used together, to reduce the cost in food production such as baklava, snack foods.DNA technology-based methods in food analysis are well-established and well-roundedtools for species differentiation, allergen detection. Especially, the probe-based TaqMan real-time PCR assay can amplify target DNA with efficiency, specificity, and sensitivity.In this study, pistachio, peanut and pea were finely ground and three separate series of triplet mixtures containing 0.1, 1, 10, 100, 1000, 10,000 and 100,000 mg kg-1 of each sample were prepared for each series, to a final weight of 100 g. DNA from reference samples and industrial products was successfully extracted with the GIDAGEN® Multi-Fast DNA Isolation Kit. TaqMan probes were designed for triplex determination of ITS, Ara h 3 and pea lectin genes which are specific regions for identification pistachio, peanut and pea, respectively.The real-time PCR as quantitative detected pistachio, peanut and pea in these mixtures down to the lowest investigated level of 0.1, 0.1 and 1 mg kg-1, respectively. Also, the methods reported here are capable of detecting of as little as 0.001% level of peanut DNA, 0,000001% level of pistachio DNA and 0.000001% level of pea DNA. We accomplish that the quantitative triplex real-time PCR method developed in this study canbe applied to detect pistachio, peanut and peatraces for three allergens at once in commercial food products.

Keywords: allergens, DNA, real-time PCR, TaqMan probe

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Authors: Yenny Paola Morales Cortés, Fabián Rico Rodríguez, Juan Carlos Serrato Bermúdez, Carlos Arturo Martínez Riascos

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Numerous benefits of galactooligosaccharides (GOS) as prebiotics have motivated the study of enzymatic processes for their production. These processes have special complexities due to several factors that make difficult high productivity, such as enzyme type, reaction medium pH, substrate concentrations and presence of inhibitors, among others. In the present work the production of galactooligosaccharides (with different degrees of polymerization: two, three and four) from lactose was studied. The study considers the formulation of a mathematical model that predicts the production of GOS from lactose using the enzyme β-galactosidase. The effect of pH in the reaction was studied. For that, phosphate buffer was used and with this was evaluated three pH values (6.0.6.5 and 7.0). Thus it was observed that at pH 6.0 the enzymatic activity insignificant. On the other hand, at pH 7.0 the enzymatic activity was approximately 27 times greater than at 6.5. The last result differs from previously reported results. Therefore, pH 7.0 was chosen as working pH. Additionally, the enzyme concentration was analyzed, which allowed observing that the effect of the concentration depends on the pH and the concentration was set for the following studies in 0.272 mM. Afterwards, experiments were performed varying the lactose concentration to evaluate its effects on the process and to generate the data for the adjustment of the mathematical model parameters. The mathematical model considers the reactions of lactose hydrolysis and transgalactosylation for the production of disaccharides and trisaccharides, with their inverse reactions. The production of tetrasaccharides was negligible and, because of that, it was not included in the model. The reaction was monitored by HPLC and for the quantitative analysis of the experimental data the Matlab programming language was used, including solvers for differential equations systems integration (ode15s) and nonlinear problems optimization (fminunc). The results confirm that the transgalactosylation and hydrolysis reactions are reversible, additionally inhibition by glucose and galactose is observed on the production of GOS. In relation to the production process of galactooligosaccharides, the results show that it is necessary to have high initial concentrations of lactose considering that favors the transgalactosylation reaction, while low concentrations favor hydrolysis reactions.

Keywords: β-galactosidase, galactooligosaccharides, inhibition, lactose, Matlab, modeling

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Authors: Mohamed Abdelmongy

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Autologous Blood for Conjunctival Autograft Fixation in Primary Pterygium Surgery: A Systematic Review and Meta-analysis Hossam Zein1,2, Ammar Ismail1,3, Mohamed Abdelmongy1,4, Sherif Elsherif1,5,6, Ahmad Hassanen1,4, Basma Muhammad2, Fathy Assaf1,3, Ahmed Elsehili1,7, Ahmed Negida1,7, Shin Yamane9, Mohamed M. Abdel-Daim8,9 and Kazuaki Kadonosono9 https://www.ncbi.nlm.nih.gov/pubmed/30277146 BACKGROUND: Pterygium is a benign ocular lesion characterized by triangular fibrovascular growth of conjunctival tissue over the cornea. Patients complain of the bad cosmetic appearance, ocular surface irritation and decreased visual acuity if the pterygium is large enough to cause astigmatism or encroach on the pupil. The definitive treatment of pterygium is surgical removal. However, outcomes are compromised by recurrence . The aim of the current study is to systematically review the current literature to explore the efficacy and safety of fibrin glue, suture and autologous blood coagulum for conjunctivalautograft fixation in primary pterygium surgery. OBJECTIVES: To assess the effectiveness of fibrin glue compared to sutures and autologous blood coagulum in conjunctival autografting for the surgical treatment of pterygium. METHODS: During preparing this manuscript, we followed the steps adequately illustrated in the Cochrane Handbook for Systematic Reviews of Interventions version 5.3, and reported it according to the preferred reporting of systematic review and meta-analysis (PRISMA) statement guidelines. We searched PubMed, Ovid (both through Medline), ISI Web of Science, and Cochrane Central Register of Controlled Trials (Central) through January 2017, using the following keywords “Pterygium AND (blood OR glue OR suture)” SELECTION CRITERIA: We included all randomized controlled trials (RCTs) that met the following criteria: 1) comparing autologous blood vs fibrin glue for conjunctivalautograft fixation in primary pterygium surgery 2) comparing autologous blood vs sutures for conjunctivalautograft fixation in primary pterygium surgery DATA COLLECTION AND ANALYSIS: Two review authors independently screened the search results, assessed trial quality, and extracted data using standard methodological procedures expected by Cochrane. The extracted data included A) study design, sample size, and main findings, B) Baseline characteristics of patients included in this review including their age, sex, pterygium site and grade, and graft size. C) Study outcomes comprising 1) primary outcomes: recurrence rate 2) secondary outcomes: graft stability outcomes (graft retraction, graft displacement), operation time (min) and postoperative symptoms (pain, discomfort, foreign body sensation, tearing) MAIN RESULTS: We included 7 RCTs and The review included662eyes (Blood: 293; Glue: 198; Suture: 171). we assess the 1) primary outcomes: recurrence rate 2) secondary outcomes: graft stability outcomes (graft retraction, graft displacement), operation time (min) and postoperative symptoms (pain, discomfort, foreign body sensation, tearing) CONCLUSIONS: Autologous blood for conjunctivalautograft fixation in pterygium surgery is associated with lower graft stability than fibrin glue or sutures. It was not inferior to fibrin glue or sutures regarding recurrence rate. The overall quality of evidence is low. Further well designed RCTs are needed to fully explore the efficacy of this new technique.

Keywords: pterygium, autograft, ophthalmology, cornea

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Authors: Donna Erika E. De Jesus

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Introduction: Cardiac arrest occurs when abrupt cessation of cardiac function results in loss of effective circulation and complete cardiovascular collapse. For every minute of cardiac arrest without early intervention (cardiopulmonary resuscitation [CPR], defibrillation), chances of survival drop by 7-10%. It is crucial that CPR be initiated within 4-6 minutes to avoid brain death. Most out-of-hospital cardiac arrests (OHCA) occur in a residential setting where access to trained personnel and equipment is not readily available, resulting in poor victim outcomes. Methods: This is a descriptive study done from August to November 2021 using a prospective cohort design. Participants of the study include adult patients aged 18 years and above brought to the emergency room who suffered from out-of-hospital cardiac arrest. Out of the total 102 cases of OHCA, 63 participants were included in the study. Descriptive statistics were used to summarize the demographic and clinical characteristics of the patients. Results: 43 were male patients, comprising the majority at 73.02%. Hypertension was identified as the top co-morbidity, followed by diabetes mellitus, heart failure, and chronic kidney disease (CKD). Medical causes of arrest were identified in 96.83% of the cases. 90.48% of cardiac arrests occurred at home. Only 26 patients (41.27%) received pre-hospital intervention prior to ER arrival, which comprised only hands-only CPR. Twenty-three of which were performed by individuals with background knowledge of CPR. 60.32% were brought via self-conduction, the remainder by ambulances, which were noted to have no available equipment necessary to provide proper resuscitation. The average travel time from dispatch to ER arrival is 20 minutes. Conclusion: Overall survival of OHCA in our local setting remains dismal, as a return of spontaneous circulation was not achieved in any of the patients. The small number of patients having pre-hospital CPR indicates the need for emphasis on training and community education.

Keywords: out-of-hospital cardiac arrest, cardiopulmonary resuscitation, basic life support, emergency medical services

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Authors: Zhenzhen Xu, Chunfu Shao, Shengyou Wang, Chunjiao Dong

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To improve the satisfaction of residents' travel, this paper analyzes the characteristics and influencing factors of urban residents' travel behavior. First, a Multinominal Logit Model (MNL) model is built to analyze the characteristics of residents' travel behavior, reveal the influence of individual attributes, family attributes and travel characteristics on the choice of travel mode, and identify the significant factors. Then put forward suggestions for policy improvement. Finally, Support Vector Machine (SVM) and Multi-Layer Perceptron (MLP) models are introduced to evaluate the policy effect. This paper selects Futian Street in Futian District, Shenzhen City for investigation and research. The results show that gender, age, education, income, number of cars owned, travel purpose, departure time, journey time, travel distance and times all have a significant influence on residents' choice of travel mode. Based on the above results, two policy improvement suggestions are put forward from reducing public transportation and non-motor vehicle travel time, and the policy effect is evaluated. Before the evaluation, the prediction effect of MNL, SVM and MLP models was evaluated. After parameter optimization, it was found that the prediction accuracy of the three models was 72.80%, 71.42%, and 76.42%, respectively. The MLP model with the highest prediction accuracy was selected to evaluate the effect of policy improvement. The results showed that after the implementation of the policy, the proportion of public transportation in plan 1 and plan 2 increased by 14.04% and 9.86%, respectively, while the proportion of private cars decreased by 3.47% and 2.54%, respectively. The proportion of car trips decreased obviously, while the proportion of public transport trips increased. It can be considered that the measures have a positive effect on promoting green trips and improving the satisfaction of urban residents, and can provide a reference for relevant departments to formulate transportation policies.

Keywords: neural network, travel characteristics analysis, transportation choice, travel sharing rate, traffic resource allocation

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Authors: Inayat Ur Rahman Arshad

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Stevia rebaudiana B. is a shrubby perennial herb of Asteraceae family that possesses the unique ability of accumulative non caloric sweet Steviol Glycosides (SGs). The purpose of the study is to optimize sugar concentration, pH level and inoculum size for inducing the callus with optimum growth and efficient antibacterial potential. Three different experiments were conducted in which Callus explant from three-months-old already established callus of Stevia reabudiana of four different sizes were inoculated on Murashige and Skoog (MS) basal medium supplemented with five different sucrose concentration and pH adjusted at four different levels. Maximum callus induction 100, 87.5 and 85.33% was resulted in the medium supplemented with 30g/l sucrose, pH maintained at 5.5 and inoculated with 1.25g inoculum respectively. Similarly, the highest fresh weight 65.00, 75.50 and 50.53g/l were noted in medium fortified with 40g/l sucrose, inoculated 1.25g inoculum and 6.0 pH level respectively. However, the callus developed in medium containing 50g/l sucrose found highly antibacterial potent with 27.3 and 26.5mm inhibition zone against P. vulgaris and B. subtilize respectively. Similarly, the callus grown on medium inoculated with 1.00g inoculum resulted in maximum antibacterial potential against S. aureus and P. vulgaris with 25 and 23.72mm inhibition zones respectively. However, in the case of pH levels the medium maintained at 6.5pH showed maximum antibacterial activity against P. vulgaris, B.subtilis and E.coli with 27.9, 25 and 23.72mm respectively. The ethyl acetate extract of Stevia callus and leaves did not show antibacterial potential against Xanthomonas campestris and Clavebactor michiganensis. In the entire experiment the standard antibacterial agent Streptomycin showed the highest inhibition zones from the rest of the callus extract, however the pure DMSO (Dimethyl Sulfoxide) caused no inhibitory zone against any bacteria. From these findings it is concluded that among various levels sucrose at the rate of 40g L-1, pH 6.0 and inoculums 0.75g was found best for most of the growth and quality attributes including fresh weight, dry weight and antibacterial activities and therefore can be recommended for callus proliferation and antibacterial potential of Stevia rebaudiana

Keywords: Steviol Glycosides, Skoog, Murashige, Clavebactor michiganensis

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Authors: Pooja Kumari, Anandkumar Tengli

Abstract:

Aurora kinase enzyme, a protein on overexpression, leads to metastasis and is extremely important for women’s health in terms of prevention or treatment. While creating a targeted technique, the aim of the work is to design purine molecules that inhibit in aurora kinase enzyme and helps to suppress breast cancer. Purine molecules attached to an amino acid in DNA block protein synthesis or halt the replication and metastasis caused by the aurora kinase enzyme. Various protein related to the overexpression of aurora protein was docked with purine molecule using Biovia Drug Discovery, the perpetual software. Various parameters like X-ray crystallographic structure, presence of ligand, Ramachandran plot, resolution, etc., were taken into consideration for selecting the target protein. A higher negative binding scored molecule has been taken for simulation studies. According to the available research and computational analyses, purine compounds may be powerful enough to demonstrate a greater affinity for the aurora target. Despite being clinically effective now, purines were originally meant to fight breast cancer by inhibiting the aurora kinase enzyme. In in-silico studies, it is observed that purine compounds have a moderate to high potency compared to other molecules, and our research into the literature revealed that purine molecules have a lower risk of side effects. The research involves the design, synthesis, and identification of active purine molecules against breast cancer. Purines are structurally similar to the normal metabolites of adenine and guanine; hence interfere/compete with protein synthesis and suppress the abnormal proliferation of cells/tissues. As a result, purine target metastasis cells and stop the growth of kinase; purine derivatives bind with DNA and aurora protein which may stop the growth of protein or inhibits replication and stop metastasis of overexpressed aurora kinase enzyme.

Keywords: aurora kinases, in silico studies, medicinal chemistry, combination therapies, chronic cancer, clinical translation

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Authors: Inayat Ur Rahman Arshad

Abstract:

Background: Stevia rebaudiana B. is a shrubby perennial herb of Asteraceae family that possesses the unique ability of accumulative non-caloric sweet steviol glycosides (SGs). Purpose: The purpose of the study is to optimize sugar concentration, pH level, and inoculum size for inducing the callus with optimum growth and efficient antibacterial potential. Method: Three different experiments were conducted in which Callus explant from three-months-old already established callus of Stevia reabudiana of four different sizes was inoculated on Murashige and Skoog (MS) basal medium supplemented with five different sucrose concentration and pH adjusted at four different levels. Results: Maximum callus induction 100, 87.5, and 85.33% resulted in the medium supplemented with 30 g/l sucrose, pH maintained at 5.5, and inoculated with 1.25g inoculum, respectively. Similarly, the highest fresh weights 65.00, 75.50, and 50.53 g/l were noted in a medium fortified with 40 g/l sucrose, inoculated 1.25g inoculum, and 6.0 pH level, respectively. However, the callus developed in a medium containing 50 g/l sucrose was found to be highly antibacterial potent with 27.3 and 26.5 mm inhibition zone against P. vulgaris and B. subtilis, respectively. Similarly, the callus grown on a medium inoculated with 1.00 g inoculum resulted in maximum antibacterial potential against S. aureus and P. vulgaris with 25 and 23.72 mm inhibition zone, respectively. However, in the case of pH levels, the medium maintained at 6.5 pH showed maximum antibacterial activity against P. vulgaris, B.subtilis, and E.coli with 27.9, 25, and 23.72 mm, respectively. The ethyl acetate extract of Stevia callus and leaves did not show antibacterial potential against Xanthomonas campestris and Clavebactor michiganensis. In the entire experiment, the standard antibacterial agent Streptomycin showed the highest inhibition zones among the rest of the callus extract; however, the pure dimethyl sulfoxide (DMSO) caused no inhibitory zone against any bacteria. Conclusion: From these findings, it is concluded that among various levels, sucrose @ 40 g L⁻¹, pH 6.0, and inoculums at 0.75 g were found best for most of the growth and quality attributes, including fresh weight, dry weight, and antibacterial activities and therefore can be recommended for callus proliferation and antibacterial potential of Stevia rebaudiana.

Keywords: Stevia rebaudiana, Steviol Glycosides, callus, Xanthomonas campestris

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Authors: P. V. Pramila , V. Mahesh

Abstract:

Pulmonary Function Tests are important non-invasive diagnostic tests to assess respiratory impairments and provides quantifiable measures of lung function. Spirometry is the most frequently used measure of lung function and plays an essential role in the diagnosis and management of pulmonary diseases. However, the test requires considerable patient effort and cooperation, markedly related to the age of patients esulting in incomplete data sets. This paper presents, a nonlinear model built using Multivariate adaptive regression splines and Random forest regression model to predict the missing spirometric features. Random forest based feature selection is used to enhance both the generalization capability and the model interpretability. In the present study, flow-volume data are recorded for N= 198 subjects. The ranked order of feature importance index calculated by the random forests model shows that the spirometric features FVC, FEF 25, PEF,FEF 25-75, FEF50, and the demographic parameter height are the important descriptors. A comparison of performance assessment of both models prove that, the prediction ability of MARS with the `top two ranked features namely the FVC and FEF 25 is higher, yielding a model fit of R2= 0.96 and R2= 0.99 for normal and abnormal subjects. The Root Mean Square Error analysis of the RF model and the MARS model also shows that the latter is capable of predicting the missing values of FEV1 with a notably lower error value of 0.0191 (normal subjects) and 0.0106 (abnormal subjects). It is concluded that combining feature selection with a prediction model provides a minimum subset of predominant features to train the model, yielding better prediction performance. This analysis can assist clinicians with a intelligence support system in the medical diagnosis and improvement of clinical care.

Keywords: FEV, multivariate adaptive regression splines pulmonary function test, random forest

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Authors: David Nieto Simavilla, Wilco M. H. Verbeeten

Abstract:

The viscoelastic behavior of polymeric flows under isothermal conditions has been extensively researched. However, most of the processing of polymeric materials occurs under non-isothermal conditions and understanding the linkage between the thermo-physical properties and the process state variables remains a challenge. Furthermore, the cost and energy required to manufacture, recycle and dispose polymers is strongly affected by the thermo-physical properties and their dependence on state variables such as temperature and stress. Experiments show that thermal conductivity in flowing polymers is anisotropic (i.e. direction dependent). This phenomenon has been previously omitted in the study and simulation of industrially relevant flows. Our work combines experimental evidence of a universal relationship between thermal conductivity and stress tensors (i.e. the stress-thermal rule) with differential constitutive equations for the viscoelastic behavior of polymers to provide predictions for the anisotropy in thermal conductivity in uniaxial, planar, equibiaxial and shear flow in commercial polymers. A particular focus is placed on the eXtended Pom-Pom model which is able to capture the non-linear behavior in both shear and elongation flows. The predictions provided by this approach are amenable to implementation in finite elements packages, since viscoelastic and thermal behavior can be described by a single equation. Our results include predictions for flow-induced anisotropy in thermal conductivity for low and high density polyethylene as well as confirmation of our method through comparison with a number of thermoplastic systems for which measurements of anisotropy in thermal conductivity are available. Remarkably, this approach allows for universal predictions of anisotropy in thermal conductivity that can be used in simulations of complex flows in which only the most fundamental rheological behavior of the material has been previously characterized (i.e. there is no need for additional adjusting parameters other than those in the constitutive model). Accounting for polymers anisotropy in thermal conductivity in industrially relevant flows benefits the optimization of manufacturing processes as well as the mechanical and thermal performance of finalized plastic products during use.

Keywords: anisotropy, differential constitutive models, flow simulations in polymers, thermal conductivity

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Authors: Aurora Gitto, Philipp Proksch

Abstract:

The presence of various microorganisms (bacteria, fungi) in surface water and groundwater represents an important issue for human health worldwide. The matrix-assisted laser desorption/ionization-time of flight mass spectrometry (MALDI-TOF-MS) has emerged as a promising and reliable tool for bacteria identification in clinical diagnostic microbiology and environmental strains thanks to an ionization technique that uses a laser energy absorbing matrix to create ions from large molecules with minimal fragmentation. The study aims first to conceptualise and set up library information and create a comprehensive database of MALDI-TOF-MS spectra from environmental water samples. The samples were analysed over a year (2021-2022) using membrane filtration methodology (0.45 μm and 0.22 μm) and then isolated on R2A agar for a period of 5 days and Yeast extract agar growing at 22 °C up to 4 days and 37 °C for 48 hours. The undetected organisms by MALDI-TOF-MS were analysed by PCR and then sequenced. The information obtained by the sequencing was further implemented in the MALDI-TOF-MS library. Among the culturable bacteria, the results show how the incubator temperature affects the growth of some genera instead of others, as demonstrated by Pseudomonas sp., which grows at 22 °C, compared to Bacillus sp., which is abundant at 37 °C. The bacteria community shows a variation in composition also between the media used, as demonstrated with R2A agar which has been defined by a higher presence of organisms not detected compared to YEA. Interesting is the variability of the Genus over one year of sampling and how the seasonality impacts the bacteria community; in fact, in some sampling locations, we observed how the composition changed, moving from winter to spring and summer. In conclusion, the bacteria community in groundwater and river bank filtration represents important information that needs to be added to the library to simplify future water quality analysis but mainly to prevent potential risks to human health.

Keywords: water quality, MALDI-TOF-MS, sequencing, library

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Authors: Fiona Bei Na Tan, Glen Wen Kiat Ho, Ee Leen Liow, Li Yin Tan, Sean Wei Loong Ho

Abstract:

Background: Shoulder arthroscopy is an increasingly common procedure. Pneumothorax post-shoulder arthroscopy is a rare complication. Objectives: Our aim is to highlight a case report of pneumothorax post shoulder arthroscopy and to conduct a literature review to evaluate the possible risk factors associated with developing a pneumothorax during or after shoulder arthroscopy. Case Report: We report the case of a 75-year-old male non-smoker who underwent left shoulder arthroscopy without regional anaesthesia and in the left lateral position. The general anaesthesia and surgery were uncomplicated. The patient was desaturated postoperatively and was found to have a pneumothorax on examination and chest X-ray. A chest tube drain was inserted promptly into the right chest. He had an uncomplicated postoperative course. Methods: PubMed Medline and Cochrane database search was carried out using the terms shoulder arthroplasty, pneumothorax, pneumomediastinum, and subcutaneous emphysema. We selected full-text articles written in English. Results: Thirty-two articles were identified and thoroughly reviewed. Based on our inclusion and exclusion criteria, 14 articles, which included 20 cases of pneumothorax during or after shoulder arthroscopy, were included. Eighty percent (16/20) of pneumothoraxes occurred postoperatively. In the articles that specify the side of pneumothorax, 91% (10/11) occur on the ipsilateral side of the arthroscopy. Eighty-eight percent (7/8) of pneumothoraxes occurred when subacromial decompression was performed. Fifty-six percent (9/16) occurred in patients placed in the lateral decubitus position. Only 30% (6/20) occurred in current or ex-smokers, and only 25% (5/20) had a pre-existing lung condition. Overall, of the articles that posit a mechanism, 75% (9/12) deem the pathogenesis to be multifactorial. Conclusion: The exact mechanism of pneumothorax is currently unknown. Awareness of this complication and timely recognition are important to prevent life-threatening sequelae. Surgeons should have a low threshold to obtain diagnostic plain radiographs in the event of clinical suspicion.

Keywords: rotator cuff repair, decompression, pressure, complication

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Authors: Syed Beenish Rufai, Sarman Singh

Abstract:

Background: Performance of Genotype MTBDRsl (Hain Life science GmbH Germany) for detection of mutations associated with second-line drug resistance is well known. However, less evidence regarding the association of mutations and genetic background of strains is known which, in the future, is essential for clinical management of anti-tuberculosis drugs in those settings where the probability of particular genotype is predominant. Material and Methods: During this retrospective study, a total of 259 MDR-TB isolates obtained from pulmonary TB patients were tested for second-line drug susceptibility testing (DST) using Genotype MTBDRsl VER 1.0 and compared with BACTEC MGIT-960 as a reference standard. All isolates were further characterized using spoligotyping. The spoligo patterns obtained were compared and analyzed using SITVIT_WEB. Results: Of total 259 MDR-TB isolates which were screened for second-line DST by Genotype MTBDRsl, mutations were found to be associated with gyrA, rrs and emb genes in 82 (31.6%), 2 (0.8%) and 90 (34.7%) isolates respectively. 16 (6.1%) isolates detected mutations associated with both FQ as well as to AG/CP drugs (XDR-TB). No mutations were detected in 159 (61.4%) isolates for corresponding gyrA and rrs genes. Genotype MTBDRsl showed a concordance of 96.4% for detection of sensitive isolates in comparison with second-line DST by BACTEC MGIT-960 and 94.1%, 93.5%, 60.5% and 50% for detection of XDR-TB, FQ, EMB, and AMK/CAP respectively. D94G was the most prevalent mutation found among (38 (46.4%)) OFXR isolates (37 FQ mono-resistant and 1 XDR-TB) followed by A90V (23 (28.1%)) (17 FQ mono-resistant and 6 XDR-TB). Among AG/CP resistant isolates A1401G was the most frequent mutation observed among (11 (61.1%)) isolates (2 AG/CP mono-resistant isolates and 9 XDR-TB isolates) followed by WT+A1401G (6 (33.3%)) and G1484T (1 (5.5%)) respectively. On spoligotyping analysis, Beijing strain (46%) was found to be the most predominant strain among pre-XDR and XDR TB isolates followed by CAS (30%), X (6%), Unique (5%), EAI and T each of 4%, Manu (3%) and Ural (2%) respectively. Beijing strain was found to be strongly associated with D94G (47.3%) and A90V mutations by (47.3%) and 34.8% followed by CAS strain by (31.6%) and 30.4% respectively. However, among AG/CP resistant isolates, only Beijing strain was found to be strongly associated with A1401G and WT+A1401G mutations by 54.5% and 50% respectively. Conclusion: Beijing strain was found to be strongly associated with the most prevalent mutations among pre-XDR and XDR TB isolates. Acknowledgments: Study was supported with Grant by All India Institute of Medical Sciences, New Delhi reference No. P-2012/12452.

Keywords: tuberculosis, line probe assay, XDR TB, drug susceptibility

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Authors: Adel Dalilottojari, Bahman Delalat, Frances J. Harding, Michaelia P. Cockshell, Claudine S. Bonder, Nicolas H. Voelcker

Abstract:

Endothelial Progenitor Cell (EPC) based therapies continue to be of interest to treat ischemic events based on their proven role to promote blood vessel formation and thus tissue re-vascularisation. Current strategies for the production of clinical-grade EPCs requires the in vitro isolation of EPCs from peripheral blood followed by cell expansion to provide sufficient quantities EPCs for cell therapy. This study aims to examine the use of different biomolecules to significantly improve the current strategy of EPC capture and expansion on collagen type I (Col I). In this study, four different biomolecules were immobilised on a surface and then investigated for their capacity to support EPC capture and proliferation. First, a cell microarray platform was fabricated by coating a glass surface with epoxy functional allyl glycidyl ether plasma polymer (AGEpp) to mediate biomolecule binding. The four candidate biomolecules tested were Col I, collagen type II (Col II), collagen type IV (Col IV) and vascular endothelial growth factor A (VEGF-A), which were arrayed on the epoxy-functionalised surface using a non-contact printer. The surrounding area between the printed biomolecules was passivated with polyethylene glycol-bisamine (A-PEG) to prevent non-specific cell attachment. EPCs were seeded onto the microarray platform and cell numbers quantified after 1 h (to determine capture) and 72 h (to determine proliferation). All of the extracellular matrix (ECM) biomolecules printed demonstrated an ability to capture EPCs within 1 h of cell seeding with Col II exhibiting the highest level of attachment when compared to the other biomolecules. Interestingly, Col IV exhibited the highest increase in EPC expansion after 72 h when compared to Col I, Col II and VEGF-A. These results provide information for significant improvement in the capture and expansion of human EPC for further application.

Keywords: biomolecules, cell microarray platform, cell therapy, endothelial progenitor cells, high throughput screening

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Authors: Sutapa Som Chaudhury, Chitrangada Das Mukhopadhyay

Abstract:

Alzheimer’s disease is a well-known form of dementia since its discovery in 1906. Current Food and Drug Administration approved medications e.g. cholinesterase inhibitors, memantine offer modest symptomatic relief but do not play any role in disease modification or recovery. In last three decades many small molecules, chaperons, synthetic peptides, partial β-secretase enzyme blocker have been tested for the development of a drug against Alzheimer though did not pass the 3rd clinical phase trials. Here in this study, we designed a PEGylated, aminogenic, tripeptidic polymer with two different molecular weights based on the aggregation prone amino acid sequence 17-20 in amyloid beta (Aβ) 1-42. Being conjugated with poly-ethylene glycol (PEG) which self-assembles into hydrophilic nanoparticles, these PEGylated tripeptides constitute a very good drug delivery system crossing the blood brain barrier while the peptide remains protected from proteolytic degradation and non-specific protein interactions. Moreover, being completely aminogenic they would not raise any side effects. These peptide inhibitors were evaluated for their effectiveness against Aβ42 fibrillation at an early stage of oligomer to fibril formation as well as preformed fibril clearance via Thioflavin T (ThT) assay, dynamic light scattering analyses, atomic force microscopy and scanning electron microscopy. The inhibitors were proved to be safe at a higher concentration of 20µM by the reduction assay of 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) dye. Moreover, SHSY5Y neuroblastoma cells have shown a greater survivability when treated with the inhibitors following Aβ42 fibril and oligomer treatment as compared with the control Aβ42 fibril and/or oligomer treated neuroblastoma cells. These make the peptidic inhibitors a promising compound in the aspect of the discovery of alternative medication for Alzheimer’s disease.

Keywords: Alzheimer’s disease, alternative medication, amyloid beta, PEGylated peptide

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Authors: Daria Zabolotnaya, Svetlana Degtyareva, Veronika Kanestri, Danila Konnov

Abstract:

An adequate choice of the initial antiretroviral treatment determines the treatment efficacy. In the clinical guidelines in Russia non-nucleoside reverse transcriptase inhibitors (NNRTIs) are still considered to be an option for first-line treatment while pretreatment drug resistance (PDR) testing is not routinely performed. We conducted a cohort retrospective study in HIV-positive treatment naïve patients of the H-clinic (Moscow, Russia) who performed PDR testing from July 2017 to November 2021. All the information was obtained from the medical records anonymously. We analyzed the mutations in reverse transcriptase and protease genes. RT-sequences were obtained by AmpliSens HIV-Resist-Seq kit. Drug resistance was defined using the HIVdb Program v. 8.9-1. PDR was estimated using the Stanford algorithm. Descriptive statistics were performed in Excel (Microsoft Office, 2019). A total of 261 HIV-1 infected patients were enrolled in the study including 197 (75.5%) male and 64 (24.5%) female. The mean age was 34.6±8.3 years. The median CD4 count – 521 cells/µl (IQR 367-687 cells/µl). Data on risk factors of HIV-infection were scarce. The total quantity of strains containing mutations in the reverse transcriptase gene was 75 (28.7%). From these 5 (1.9%) mutations were associated with PDR to nucleoside reverse transcriptase inhibitors (NRTIs) and 30 (11.5%) – with PDR to NNRTIs. The number of strains with mutations in protease gene was 43 (16.5%), from these only 3 (1.1%) mutations were associated with resistance to protease inhibitors. For NNRTIs the most prevalent PDR mutations were E138A, V106I. Most of the HIV variants exhibited a single PDR mutation, 2 were found in 3 samples. Most of HIV variants with PDR mutation displayed a single drug class resistance mutation. 2/37 (5.4%) strains had both NRTIs and NNRTIs mutations. There were no strains identified with PDR mutations to all three drug classes. Though earlier data demonstrated a lower level of PDR in HIV treatment naïve population in Russia and our cohort can be not fully representative as it is taken from the private clinic, it reflects the trend of increasing PDR especially to NNRTIs. Therefore, we consider either pretreatment testing or giving the priority to other drugs as first-line treatment necessary.

Keywords: HIV, resistance, mutations, treatment

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Authors: Rhodine Hickman, Craig Wylie, Michael G. McCaul

Abstract:

Introduction: The World Health Organisation has called on governments around the world to recognise emergency conditions as a global public health problem and respond with appropriate steps for effective preventative strategies. However, to understand the magnitude of the problem, good quality epidemiological data is required. This is especially challenging in low and middle-income countries, where routine data is scarce, specifically within the prehospital setting. Methods: We conducted a retrospective cross-sectional study of a national prehospital private sector EMS database. The database being the property of ER24 (private Emergency Medical Services (EMS) company in South Africa) contains claims submitted by the majority of ambulance services in South Africa during the period between 1 January 2008 to 28 March 2017. We used descriptive statistics and control charts to describe the data using STATA 14. Results: 299,257 calls were included in the analysis. The top clinical conditions requiring ambulance transport were transport accidents (10% of total call volume) and ischaemic heart disease (4.4%). The number of transport accidents consistently increased between 2009 and 2014 and reached beyond the limit for normal variation in 2015. Victims of transport accidents required basic life support services 60% of the time with 80% of injuries being minor to moderate. The frequency of ischaemic heart disease had a steady incline from 2011 to 2016. Advanced life support services were required about 50% of the time, with 60% of patients needing urgent care. Conclusion: Transport accidents, followed by ischaemic heart disease, are the most prevalent conditions in South African private EMS. There is a potential to address these conditions by developing the capacity of low and mid-level providers in trauma and advanced EMS providers in ischaemic heart disease.

Keywords: emergency care, emergency medicine, prehospital providers, South Africa

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Authors: Mahmoud A. Amin, Essam Taman, Ahmed Omran, Mahmoud Shawky, Ahmed Mekawy, Abdallah M. Kotkat, Saber Younes, Nehad N. Ghonemy, Amin Saad, Ezz-Aleslam, Abdullah M. Elosh

Abstract:

Introduction: TMJ is a one-of-a-kind, complicated synovial joint that helps with masticatory function by allowing the mandible to open and close the mouth. True ankylosis is a situation in which condylar movement is limited by a mechanical defect in the joint, whereas false ankylosis is a condition in which there is a restriction in mandibular movement due to muscular spasm myositis ossificans, and coronoid process hyperplasia. Ankylosis is characterized by the inability to open the mouth due to fusion of the TMJ condyle to the base of the skull as a result of trauma, infection, or systemic diseases such as rheumatoid arthritis (the most common) and psoraisis. Ankylosis causes facial asymmetry and affects the patient psychologically as well as speech, difficult mastication, poor oral hygiene, malocclusion, and other factors. TMJ is a technically challenging joint; hence TMJ ankylosis management is complicated. Case presentation: this case is a male patient 25 years old reported to our maxillofacial clinic in Damietta faculty of medicine, Al-Azhar University with the inability to open the mouth at all, with a history of difficulty of mouth breathing and eating foods, there was a history of falling from height at 2006, and the patient underwent corrective surgery before with no improvement because the ankylosis was relapsed short period after the previous operations with that done out of our hospital inter-incisor distant ZERO so, this condition need mandatory management. Clinical examination and radiological investigations were done after complete approval from the patient and his brother; tracheostomy was done for our patient before the operation. The patient entered the operation in our hospital and drastic improvement in mouth opening was noticed, helping to restore the physical psychological health of the patient.

Keywords: temporomandibular joint, TMJ, Ankylosis, mouth opening, physiotherapy, condylar plate

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Authors: Alma Ramić, Mirjana Skočibušić, Renata Odžak, Tomica Hrenar, Ines Primožič

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In an attempt to identify a new class of antimicrobial agents, the antimicrobial potential of Cinchona alkaloid derivatives was evaluated. The bark of the Cinchona trees is the source of a variety of alkaloids, among which the best known are quinine, quinidine, cinchonine and cinchonidine. They are very useful as organocatalysts in stereoselective synthesis. On the other hand, quinine is traditionally used in the treatment of malaria. Furthermore, Cinchona alkaloids possess various analgesic, anti-inflammatory and anti–arrhythmic properties as well. In this work we present the synthesis of twenty quaternary derivatives of pseudo−enantiomeric Cinchona alkaloid derivatives to evaluate their antibacterial activity. Quaternization of quinuclidine moiety was carried out with groups diverse in their size. The structures of compounds were systematically modified to obtain drug-like properties with proper physical and chemical properties and avoiding toxophore. All compounds were prepared in good yields and were characterized by standard analytical spectroscopy methods (1D and 2D NMR, IR, MS). The antibacterial activities of all compounds were evaluated against series of recent clinical isolates of antibiotic susceptible Gram-positive and resistant Gram-negative pathogens by determining their zone of inhibition and minimum inhibitory concentrations. All compounds showed good to strong broad-spectrum activity, equivalent or better in comparison with standard antibiotics used. Furthermore, seven compounds exhibited significant antibacterial efficiency against Gram-negative isolates. To visualize the results, principal component analysis was used as an additional classification tool. Cytotoxicity of compounds with different cell lines in human cell culture was determined. Based on these results, substituted quaternary Cinchona scaffold can be considered as promising new class of antimicrobials and further investigations should be performed. Supported by Croatian Science Foundation, Project No 3775 ADESIRE.

Keywords: antibacterial efficiency, cinchona alkaloids, cytotoxicity, pseudo‐enantiomers

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