Search results for: successful treatment

Authors: Ana Miguel

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Purpose: Glaucoma is the second cause of worldwide blindness and the first cause of irreversible blindness. Trabeculectomy, the standard glaucoma surgery, has a success rate between 36.0% and 98.0% at three years and a high complication rate, leading to the development of different surgeries, micro-invasive glaucoma surgeries (MIGS). MIGS devices are diverse and have various indications, risks, and effectiveness. We intended to review MIGS’ surgical techniques, indications, contra-indications, and IOP effect. Methods: We performed a literature review of MIGS to differentiate the devices and their reported effectiveness compared to traditional surgery (tubes and blebs). We also conducted a video review of the last 1000 glaucoma surgeries of the author (including MIGS, but also trabeculectomy, deep sclerectomy, and tubes of Ahmed and Baerveldt) performed at glaucoma and advanced anterior segment fellowship in Canada and France, to describe preferred surgical techniques for each. Results: We present the videos with surgical techniques and pearls for each surgery. Glaucoma surgeries included: 1- bleb surgery (namely trabeculectomy, with releasable sutures or with slip knots, deep sclerectomy, Ahmed valve, Baerveldt tube), 2- MIGS with bleb, also known as MIBS (including XEN 45, XEN 63, and Preserflo), 3- MIGS increasing supra-choroidal flow (iStar), 4-MIGS increasing trabecular flow (iStent, gonioscopy-assisted transluminal trabeculotomy - GATT, goniotomy, excimer laser trabeculostomy -ELT), and 5-MIGS decreasing aqueous humor production (endocyclophotocoagulation, ECP). There was also needling (ab interno and ab externo) performed at the operating room and irido-zonulo-hyaloïdectomy (IZHV). Each technique had different indications and contra-indications. Conclusion: MIGS are valuable in glaucoma surgery, such as traditional surgery with trabeculectomy and tubes. All glaucoma surgery can be combined with phacoemulsification (there may be a synergistic effect on MIGS + cataract surgery). In addition, some MIGS may be combined for further intraocular pressure lowering effect (for example, iStents with goniotomy and ECP). A good surgical technique and postoperative management are fundamental to increasing success and good practice in all glaucoma surgery.

Keywords: glaucoma, migs, surgery, video, review

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Authors: Moshe Wasserblat, Jonathan Mamou, Oren Pereg

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Natural Language Processing (NLP) has made a major leap in the last few years, in practical integration into medical solutions; for example, extracting clinical concepts from medical texts such as medical condition, medication, treatment, and symptoms. However, training and deploying those models in real environments still demands a large amount of annotated data and NLP/Machine Learning (ML) expertise, which makes this process costly and time-consuming. We present a practical and efficient method for clinical concept extraction that does not require costly labeled data nor ML expertise. The method includes three steps: Step 1- the user injects a large in-domain text corpus (e.g., PubMed). Then, the system builds a contextual model containing vector representations of concepts in the corpus, in an unsupervised manner (e.g., Phrase2Vec). Step 2- the user provides a seed set of terms representing a specific medical concept (e.g., for the concept of the symptoms, the user may provide: ‘dry mouth,’ ‘itchy skin,’ and ‘blurred vision’). Then, the system matches the seed set against the contextual model and extracts the most semantically similar terms (e.g., additional symptoms). The result is a complete set of terms related to the medical concept. Step 3 –in production, there is a need to extract medical concepts from the unseen medical text. The system extracts key-phrases from the new text, then matches them against the complete set of terms from step 2, and the most semantically similar will be annotated with the same medical concept category. As an example, the seed symptom concepts would result in the following annotation: “The patient complaints on fatigue [symptom], dry skin [symptom], and Weight loss [symptom], which can be an early sign for Diabetes.” Our evaluations show promising results for extracting concepts from medical corpora. The method allows medical analysts to easily and efficiently build taxonomies (in step 2) representing their domain-specific concepts, and automatically annotate a large number of texts (in step 3) for classification/summarization of medical reports.

Keywords: clinical concepts, concept expansion, medical records annotation, medical records summarization

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Authors: Navpreet Kaur, Himkusha Thakur, Nirmal Prabhakar

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The most controversial issue in crop production is the use of Organophosphate insecticides. This is evident in many reports that Organophosphate (OP) insecticides, among the broad range of pesticides are mainly involved in acute and chronic poisoning cases. OPs detection is of crucial importance for health protection, food and environmental safety. In our study, a nanocomposite of poly (3,4 ethylenedioxythiophene) (PEDOT) and multi-walled carbon nanotubes (MWCNTs) has been deposited electrochemically onto the surface of fluorine doped tin oxide sheets (FTO) for the analysis of malathion OP. The -COOH functionalization of MWCNTs has been done for the covalent binding with amino groups of AChE enzyme. The use of PEDOT-MWCNT films exhibited an excellent conductivity, enables fast transfer kinetics and provided a favourable biocompatible microenvironment for AChE, for the significant malathion OP detection. The prepared biosensors were characterized by Fourier transform infrared spectrometry (FTIR), Field emission-scanning electron microscopy (FE-SEM) and electrochemical studies. Various optimization studies were done for different parameters including pH (7.5), AChE concentration (50 mU), substrate concentration (0.3 mM) and inhibition time (10 min). Substrate kinetics has been performed and studied for the determination of Michaelis Menten constant. The detection limit for malathion OP was calculated to be 1 fM within the linear range 1 fM to 1 µM. The activity of inhibited AChE enzyme was restored to 98% of its original value by 2-pyridine aldoxime methiodide (2-PAM) (5 mM) treatment for 11 min. The oxime 2-PAM is able to remove malathion from the active site of AChE by means of trans-esterification reaction. The storage stability and reusability of the prepared biosensor is observed to be 30 days and seven times, respectively. The application of the developed biosensor has also been evaluated for spiked lettuce sample. Recoveries of malathion from the spiked lettuce sample ranged between 96-98%. The low detection limit obtained by the developed biosensor made them reliable, sensitive and a low cost process.

Keywords: PEDOT-MWCNT, malathion, organophosphates, acetylcholinesterase, biosensor, oxime (2-PAM)

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Authors: Hami Ashraf, Mohammad Heydarnejad

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Introduction: The landscape of cancer treatment has been revolutionized by immunotherapy, offering novel therapeutic avenues for diverse cancer types. Animal models play a pivotal role in the development and elucidation of these therapeutic modalities. Nevertheless, the manifestation of Graft-versus-Host Disease (GVHD) in such models poses significant challenges, muddling the interpretation of experimental data within the ambit of cancer immunotherapy. This study is dedicated to scrutinizing the role of GVHD as a confounding factor in animal models used for cancer immunotherapy, alongside proposing viable strategies to mitigate this complication. Method: Employing a systematic review framework, this study undertakes a comprehensive literature survey including academic journals in PubMed, Embase, and Web of Science databases and conference proceedings to collate pertinent research that delves into the impact of GVHD on animal models in cancer immunotherapy. The acquired studies undergo rigorous analysis and synthesis, aiming to assess the influence of GVHD on experimental results while identifying strategies to alleviate its confounding effects. Results: Findings indicate that GVHD incidence significantly skews the reliability and applicability of experimental outcomes, occasionally leading to erroneous interpretations. The literature surveyed also sheds light on various methodologies under exploration to counteract the GVHD dilemma, thereby bolstering the experimental integrity in this domain. Conclusion: GVHD's presence critically affects both the interpretation and validity of experimental findings, underscoring the imperative for strategies to curtail its confounding impacts. Current research endeavors are oriented towards devising solutions to this issue, aiming to augment the dependability and pertinence of experimental results. It is incumbent upon researchers to diligently consider and adjust for GVHD's effects, thereby enhancing the translational potential of animal model findings to clinical applications and propelling progress in the arena of cancer immunotherapy.

Keywords: graft-versus-host disease, cancer immunotherapy, animal models, preclinical model

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Authors: Manal M. Shehata, Kawther M. Abdel-Hamid, Nashwa A. Mohamed, Marwa H. Bakr, Maged S. Mahmoud, Hala M. Elbadre

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Introduction: The worldwide rapid increase in diabetes poses a significant challenge to current therapeutic approaches. Therapeutic utility of bone marrow transplantation in diabetes is an attractive approach. However, the oxidative stress generated by hyperglycemia may hinder β-cell regeneration. Curcumin, is a dietary spice with antioxidant activity. Aim of work: The present study was undertaken to investigate the therapeutic potential of curcumin, bone marrow transplantation, and their combined effects in the reversal of experimental diabetes. Material and Methods: Fifty adult male healthy albino rats were included in the present study.They were divided into two groups: Group І: (control group) included 10 rats. Group П: (diabetic group): included 40 rats. Diabetes was induced by single intraperitoneal injection of streptozotocin (STZ). Group II will be further subdivided into four groups (10 rats for each): Group II-a (diabetic control). Group II-b: rats were received single intraperitoneal injection of bone marrow suspension (un-fractionated bone marrow cells) prepared from rats of the same family. Group II-c: rats were treated with curcumin orally by gastric intubation for 6 weeks. Group II-d: rats were received a combination of single bone marrow transplantation and curcumin for 6 weeks. After 6 weeks, blood glucose, insulin levels were measured and the pancreas from all rats were processed for Histological, Immunohistochemical and morphometric examination. Results: Diabetic group, showed progressive histological changes in the pancreatic islets. Treatment with either curcumin or bone marrow transplantation improved the structure of the islets and reversed streptozotocin-induced hyperglycemia and hypoinsulinemia. Combination of curcumin and bone marrow transplantation elicited more profound alleviation of streptozotocin-induced changes including islet regeneration and insulin secretion. Conclusion: The use of natural antioxidants combined with bone marrow transplantation to induce pancreatic regeneration is a promising strategy in the management of diabetes.

Keywords: diabtes, panceatic islets, bone marrow transplantation, curcumin

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Authors: Renu Pattanshetty

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The aim of this narrative review is to highlight the impact of menopause on osteoporosis and weight gain. The review also aims to summarize physiotherapeutic strategies to combat the same.A thorough literature search was conducted using electronic databases like MEDline, PUBmed, Highwire Press, PUBmed Central for English language studies that included search terms like menopause, osteoporosis, obesity, weight gain, exercises, physical activity, physiotherapy strategies from the year 2000 till date. Out of 157 studies that included metanalyses, critical reviews and randomized clinical trials, a total of 84 were selected that met the inclusion criteria. Prevalence of obesity is increasing world - wide and is reaching epidemic proportions even in the menopausal women. Prevalence of abdominal obesity is almost double than that general obesity with rates in the US with 65.5% in women ages 40-59 years and 73.8 in women aged 60 years or more. Physical activities and exercises play a vital role in prevention and treatment of osteoporosis and weight gain related to menopause that aim to boost the general well-being and any symptoms brought about by natural body changes. Endurance exercises lasting about 30 minutes /day for 5 days/ week has shown to decrease weight and prevent weight gain. In addition, strength training with at least 8 exercises of 8-12 repetitions working for whole body and for large muscle groups has shown to result positive outcomes. Hot flashes can be combatted through yogic breathing and relaxation exercises. Prevention of fall strategies and resistance training are key to treat diagnosed cases of osteoporosis related to menopause. One to three sets with five to eight repetitions of four to six weight bearing exercises have shown positive results. Menopause marks an important time for women to evaluate their risk of obesity and osteoporosis. It is known fact that bone benefit from exercises are lost when training is stopped, hence, practicing bone smart habits and strict adherence to recommended physical activity programs are recommended which are enjoyable, safe and effective.

Keywords: menopause, osteoporosis, obesity, weight gain, exercises, physical activity, physiotherapy strategies

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Authors: Sophio Kobauri, Tengiz Kantaria, Temur Kantaria, David Tugushi, Nina Kulikova, Ramaz Katsarava

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Nanosized environmentally responsive materials are of special interest for various applications, including targeted drug to a considerable potential for treatment of many human diseases. The important technological advantages of nanoparticles (NPs) usage as drug carriers (nanocontainers) are their high stability, high carrier capacity, feasibility of encapsulation of both hydrophilic or hydrophobic substances, as well as a high variety of possible administration routes, including oral application and inhalation. NPs can also be designed to allow controlled (sustained) drug release from the matrix. These properties of NPs enable improvement of drug bioavailability and might allow drug dosage decrease. The targeted and controlled administration of drugs using NPs might also help to overcome drug resistance, which is one of the major obstacles in the control of epidemics. Various degradable and non-degradable polymers of both natural and synthetic origin have been used for NPs construction. One of the most promising for the design of NPs are amino acid-based biodegradable polymers (AABBPs) which can clear from the body after the fulfillment of their function. The AABBPs are composed of naturally occurring and non-toxic building blocks such as α-amino acids, fatty diols and dicarboxylic acids. The particles designed from these polymers are expected to have an improved bioavailability along with a high biocompatibility. The present work deals with a systematic study of the preparation of NPs by cost-effective polymer deposition/solvent displacement method using AABBPs. The influence of the nature and concentration of surfactants, concentration of organic phase (polymer solution), and the ratio organic phase/inorganic (water) phase, as well as of some other factors on the size of the fabricated NPs have been studied. It was established that depending on the used conditions the NPs size could be tuned within 40-330 nm. As the next step of this research an evaluation of biocompatibility and bioavailability of the synthesized NPs has been performed, using two stable human cell culture lines – HeLa and A549. This part of study is still in progress now.

Keywords: amino acids, biodegradable polymers, nanoparticles (NPs), non-toxic building blocks

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Authors: Faiz N. K. Yusufi, Aquil Ahmed, Jamal Ahmad

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Diabetes in India is growing at an alarming rate and the complications caused by it need to be controlled. Coronary heart disease (CHD) is one of the complications that will be discussed for prediction in this study. India has the second most number of diabetes patients in the world. To the best of our knowledge, there is no CHD risk score for Indian type 2 diabetes patients. Any form of CHD has been taken as the event of interest. A sample of 750 was determined and randomly collected from the Rajiv Gandhi Centre for Diabetes and Endocrinology, J.N.M.C., A.M.U., Aligarh, India. Collected variables include patients data such as sex, age, height, weight, body mass index (BMI), blood sugar fasting (BSF), post prandial sugar (PP), glycosylated haemoglobin (HbA1c), diastolic blood pressure (DBP), systolic blood pressure (SBP), smoking, alcohol habits, total cholesterol (TC), triglycerides (TG), high density lipoprotein (HDL), low density lipoprotein (LDL), very low density lipoprotein (VLDL), physical activity, duration of diabetes, diet control, history of antihypertensive drug treatment, family history of diabetes, waist circumference, hip circumference, medications, central obesity and history of CHD. Predictive risk scores of CHD events are designed by cox proportional hazard regression. Model calibration and discrimination is assessed from Hosmer Lemeshow and area under receiver operating characteristic (ROC) curve. Overfitting and underfitting of the model is checked by applying regularization techniques and best method is selected between ridge, lasso and elastic net regression. Youden’s index is used to choose the optimal cut off point from the scores. Five year probability of CHD is predicted by both survival function and Markov chain two state model and the better technique is concluded. The risk scores for CHD developed can be calculated by doctors and patients for self-control of diabetes. Furthermore, the five-year probabilities can be implemented as well to forecast and maintain the condition of patients.

Keywords: coronary heart disease, cox proportional hazard regression, ROC curve, type 2 diabetes Mellitus

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Authors: George Shaker, Maike Eylert

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Recurrent urinary tract infections (UTIs) in patients with mesh implants, particularly following pelvic or abdominal surgeries, pose significant clinical challenges. This paper investigates whether flexible cystoscopy is an essential diagnostic and therapeutic tool in managing such patients. With the increasing prevalence of mesh-related complications, it is crucial to explore how diagnostic procedures like cystoscopy can aid in identifying mesh-associated issues that contribute to recurrent UTIs. While flexible cystoscopy is commonly used to evaluate lower urinary tract conditions, its necessity in cases involving patients with mesh implants remains under debate. This study aims to determine the value of flexible cystoscopy in identifying complications such as mesh erosion, fistula formation, and chronic inflammation, which may contribute to recurrent infections. The research compares patients who underwent flexible cystoscopy to those managed without this procedure, examining the diagnostic yield of cystoscopy in detecting mesh-related complications. Furthermore, the study investigates the relationship between recurrent UTIs and the mechanical effects of mesh on the urinary tract, as well as the potential for cystoscopy to guide treatment decisions, such as mesh removal or revision. The results indicate that while flexible cystoscopy can identify mesh-related complications in some cases, its routine use may not be necessary for all patients with recurrent UTIs and mesh. The study emphasizes the importance of patient selection, clinical history, and symptom severity in deciding whether to employ cystoscopy. In cases where there are clear signs of mesh erosion or unexplained recurrent infections despite standard treatments, cystoscopy proves valuable. However, the study also highlights potential risks and discomfort associated with the procedure, suggesting that cystoscopy should be reserved for select cases where non-invasive methods fail to provide clarity. The research concludes that while flexible cystoscopy remains a valuable tool in certain cases, its routine use for all patients with recurrent UTIs and mesh is not justified. The paper provides recommendations for clinical guidelines, emphasizing a more personalized approach to diagnostics that considers the patient’s overall condition, infection history, and mesh type.

Keywords: flexible cystoscopy, recurrent urinary tract infections, mesh implants, mesh erosion, diagnostic procedures, urology

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Authors: Rossy G. Olan Villegas, Gerardo Acosta Garcia, Aurea Bernardino Nicanor, Leopoldo Gonzalez Cruz, Humberto Ramirez Medina

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Capsicum annuum is a crop of agricultural and economic importance in Mexico and other countries. The fruit (pepper) contains bioactive components such as carotenoids, phenolic compounds and capsaicinoids that improve health. However, pepper cultivation is affected by biotic and abiotic factors that decrease yield. Some phytohormones like gibberellins and auxins induce the formation and development of fruit in several plants. In this study, we evaluated the effect of the exogenous application of phytohormones like gibberellic acid and indolbutyric acid on fruit development of jalapeno pepper plants, the protein profile of plant tissues, the accumulation of bioactive compounds and antioxidant activity in the pericarp and seeds. For that, plants were sprinkled with these phytohormones. The fruit collection for the control, indolbutyric acid and gibberellic acid treatments was 7 peppers per plant; however, for the treatment that combines indolbutyric acid and gibberellic acid, a fruit with the shortest length (1.52 ± 1.00 cm) and weight (0.41 ± 1.0 g) was collected compared to fruits of plants grown under other treatments. The length (4,179 ± 0,130 cm) and weight of the fruit (8,949 ± 0.583 g) increased in plants treated with indolbutyric acid, but these characteristics decreased with the application of GA3 (length of 3,349 ± 0.127 cm and a weight 4,429 ± 0.144 g). The content of carotenes and phenolic compounds increased in plants treated with GA3 (1,733 ± 0.092 and 1,449 ± 0.009 mg / g, respectively) or indolbutyric acid (1,164 ± 0.042 and 0.970 ± 0.003 mg / g). However, this effect was not observed in plants treated with both phytohormones (0.238 ± 0.021 and 0.218 ± 0.004 mg / g). Capsaicin content was higher in all treatments; but it was more noticeable in plants treated with both phytohormones, the value being 0.913 ± 0.001 mg / g (three times greater in amount). The antioxidant activity was measured by 3 different assays, 2,2-diphenyl-1-picrylhydrazyl (DPPH), antioxidant power of ferric reduction (FRAP) and 2,2'-Azinobis-3-ethyl-benzothiazoline-6-sulfonic acid ( ABTS) to find the minimum inhibitory concentration of the reducing radical (IC50 and EC50). Significant differences were observed from the application of the phytohormone, being the fruits treated with gibberellins, which had a greater accumulation of bioactive compounds. Our results suggest that the application of phytohormones modifies the development of fruit and its content of bioactive compounds.

Keywords: auxins, capsaicinoids, carotenoids, gibberellins

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Authors: Aphinan Phukaoluan, Surachai Dechkunakorn, Niwat Anuwongnukroh, Anak Khantachawana, Pongpan Kaewtathip, Julathep Kajornchaiyakul, Peerapong Tua-Ngam

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Aims: The objectives of this study was to determine the load-deflecting characteristics of a fabricated orthodontic wire with alloy composition of 50.6% (atomic weight) Ni and 49.4% (atomic weight) Ti and to compare the results with Ormco, a commercially available pre-formed NiTi orthodontic archwire. Materials and Methods: The ingots alloys with atomic weight ratio 50.6 Ni: 49.4 Ti alloy were used in this study. Three specimens were cut to have wire dimensions of 0.016 inch x0.022 inch. For comparison, a commercially available pre-formed NiTi archwire, Ormco, with dimensions of 0.016 inch x 0.022 inch was used. Three-point bending tests were performed at the temperature 36+1 °C using a Universal Testing Machine on the newly fabricated and commercial archwires to assess the characteristics of the load-deflection curve with loading and unloading forces. The loading and unloading features at the deflection points 0.25, 0.50, 0.75. 1.0, 1.25, and 1.5 mm were compared. Descriptive statistics was used to evaluate each variables, and independent t-test at p < 0.05 was used to analyze the mean differences between the two groups. Results: The load-deflection curve of the 50.6Ni: 49.4Ti wires exhibited the characteristic features of superelasticity. The curves at the loading and unloading slope of Ormco NiTi archwire were more parallel than the newly fabricated NiTi wires. The average deflection force of the 50.6Ni: 49.4Ti wire was 304.98 g and 208.08 g for loading and unloading, respectively. Similarly, the values were 358.02 g loading and 253.98 g for unloading of Ormco NiTi archwire. The interval difference forces between each deflection points were in the range 20.40-121.38 g and 36.72-92.82 g for the loading and unloading curve of 50.6Ni: 49.4Ti wire, respectively, and 4.08-157.08 g and 14.28-90.78 g for the loading and unloading curve of commercial wire, respectively. The average deflection force of the 50.6Ni: 49.4Ti wire was less than that of Ormco NiTi archwire, which could have been due to variations in the wire dimensions. Although a greater force was required for each deflection point of loading and unloading for the 50.6Ni: 49.4Ti wire as compared to Ormco NiTi archwire, the values were still within the acceptable limits to be clinically used in orthodontic treatment. Conclusion: The 50.6Ni: 49.4Ti wires presented the characteristics of a superelastic orthodontic wire. The loading and unloading force were also suitable for orthodontic tooth movement. These results serve as a suitable foundation for further studies in the development of new orthodontic NiTi archwires.

Keywords: 50.6 ni 49.4 Ti alloy wire, load deflection curve, loading and unloading force, orthodontic

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Authors: Richa Sinha, Mohammad Irfan Javed, Sanjay Singh

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Introduction: Good antimicrobial prescribing reduces length of stay in hospital, risk of adverse events, antimicrobial resistance, and unnecessary hospital expenditure. The aim of this prospective audit was to identify any problems with antimicrobial prescribing including documentation of the relevant aspects as well as appropriateness of antibiotics use. The audit was conducted on the surgical wards in a teaching hospital in the UK. Methods: Standards included the indication, duration, choice, and prescription of antibiotic should be in line with current Regional Guidelines and should be clearly documented on the prescription chart. There should be an entry in each patients’ medical record of the diagnosis and indication for each acute antibiotic prescription issued. All prescriptions should clearly document the route, frequency and dose of antibiotic. Data collection was done for 2 weeks in the month of March 2014. A proforma including all the questions above was completed for all the patients. The results were analysed using Excel. Results: 35 patients in total were selected for the audit. 85.7% of patients had indication of antibiotic documented on the prescription chart and 68.5% of patients had indication documented in the notes. The antibiotic used was in line with hospital guidelines in 45.7% of patients, however, in a further 28.5% of patients the reason for the antibiotic prescription was microbiology approved. Therefore, in total 74.2% of patients had been prescribed appropriate antibiotics. The duration of antibiotic was documented in 68.6% of patients and the antibiotic was reviewed in 37.1% of patients. The dose, frequency and route was documented clearly in 100% of patients. Conclusion: Overall, prescribing can be improved on the surgical wards in this hospital. Only 37.1% of patients had clear documentation of a review of antibiotics. It may be that antibiotics have been reviewed but this should be clearly highlighted on the prescription chart or the notes. Failure to review antibiotics can lead to poor patient care and antimicrobial resistance and therefore it is important to address this. It is also important to address the appropriateness of antibiotics as inappropriate antibiotic prescription can lead to failure of treatment as well as antimicrobial resistance. The good points from the audit was that all patients had clear documentation of dose, route and frequency which is extremely important in the administration of antibiotics. Recommendations from this audit included to emphasize good antimicrobial prescribing at induction (twice yearly), an antimicrobial handbook for junior doctors, and re-audit in 6 months time.

Keywords: prescribing, antimicrobial, indication, duration

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Authors: Chouahda Salima, Soltani Noureddine

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The present study is a part of biological control against mosquitoes. It aims to assess the impact of two xenobiotics (a selective insect growth regulator: halofenozide and heavy metals: cadmium, more toxic and widespread in the region) in mosquitofish: Gambusia affinis. Several approaches were examined: Acute toxicity of cadmium and halofenozide: The acute toxicity of cadmium and halofenozide was examined in juvenile and adult males and females of G. affinis at different concentrations, cadmium causes mortality of the species studied with a relation dose-response. In laboratory conditions, the impact of cadmium was determined on two biomarkers of environmental stress: glutathione and acetylcholinesterase. The results show that the juvenile followed by adult males are more susceptible than adult females, while the halofenozide does not have any effect on the mortality of juvenile and adult males and females of G.affinis. Chronic toxicity of cadmium and halofenozide: both xenobiotics were added to the water fish raising at different doses tested in juveniles and adults males and females during two months of experience. Growth and metric indices; results show that halofenozide added to the water juveniles of G. affinis has no effect on their growth (length and weight). On the other side, the cadmium at the dose 5 µg/L shows a higher toxicity against juvenile, where he appears to reduce significantly their linear growth and weight. In females, the both xenobiotics have significant effects on metric indices, but these effects are more important on the hepatosomatic index that the gonadosomatic index and the coefficient of condition. Biomarkers; acetylcholinesterase (AChE), glutathione S-transferase (GST) and glutathione (GSH) used in assessing of environmental stress were measured in juveniles and adults males and females. The response of these biomarkers reveals an inhibition of AChE specific activity, an induction of GST activity, and decrease of GSH rates in juveniles in the end of experiment and during chronic treatment adult males and females. The effect of these biomarkers is more pronounced in females compared to males and juveniles. These different biomarkers have a similar profile for the duration of exposure.

Keywords: gambusia affinis, insecticide, heavy metal, morphology, biomarkers, chronic toxicity, acute toxicity, pollution

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Authors: Abdulwahhab Khedr, Tamer Shehata, Hanaa El-Ghamry

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Venlafaxine HCl is a novel antidepressant drug used in the treatment of major depressive disorder, generalized anxiety disorder, social anxiety disorder and panic disorder. Conventional therapeutic regimens with venlafaxine HCl immediate-release dosage forms require frequent dosing due to short elimination half-life of the drug and reduced bioavailability. Hence, this study was carried out to develop sustained-release dosage forms of venlafaxine HCl to reduce its dosing frequency, to improve patient compliance and to reduce side effects of the drug. The polymers used were hydroxypropylmethyl cellulose, xanthan gum, sodium alginate, sodium carboxymethyl cellulose, Carbopol 940 and ethyl cellulose. The physical properties of the prepared tablets including tablet thickness, diameter, weight uniformity, content uniformity, hardness and friability were evaluated. Also, the in-vitro release of venlafaxine HCl from different matrix tablets was studied. Based on physical characters and in-vitro release profiles, certain formulae showing promising sustained-release profiles were subjected to film coating with 15% w/v EC in dichloromethane/ethanol mixture (1:1 ratio) using 1% w/v HPMC as pore former and 30% w/w dibutyl phthalate as plasticizer. The optimized formulations were investigated for drug-excipient compatibility using FTIR and DSC studies. Physical evaluation of the prepared tablets fulfilled the pharmacopoeial requirements for tablet friability test, where the weight loss of the prepared formulae did not exceed 1% of the weight of the tested tablets. Moderate release was obtained from tablets containing HPMC. FTIR and DSC studies for such formulae revealed the absence of any type of chemical interaction between venlafaxine HCl and the used polymers or excipients. Forced swimming test in rats was used to evaluate the antidepressant activity of the selected matrix tablets of venlafaxine HCl. Results showed that formulations significantly decreased the duration of animals’ immobility during the 24 hr-period of the test compared to non-treated group.

Keywords: antidepressant, sustained-release, matrix tablet, venlafaxine hydrochloride

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Authors: Sayed M. Ahmed, Sawsan S. Darwish, Nagib A. Elmarzugi, Mohammad A. Al-Dosari, Mahmoud A. Adam, Nadia A. Al-Mouallimi

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The preservation of cultural heritage is a worldwide problem. Stone monuments represent an important part of this heritage, but due to their prevalently outdoor location, they are generally subject to a complex series of weathering and decay processes, in addition to physical and chemical factors, also biological agents usually play an important role in deterioration phenomena. The aim of this paper is to experimentally verify applicability and feasibility of titanium dioxide (TiO2) nanoparticles for the preservation of historical (architectural, monumental, archaeological) stone surfaces which enables to reduce the deterioration behaviors mentioned above. TiO2 nanoparticles dispersed in an aqueous colloidal suspension were applied directly on travertine (Marble and limestone often used in historical and monumental buildings) by spray-coating in order to obtain a nanometric film on stone samples. SEM, coupled with EDX microanalysis. (SEM-EDX), in order to obtain information oncoating homogeneity, surface morphology before and after aging and penetration depth of the TiO2 within the samples. Activity of the coated surface was evaluated with UV accelerated aging test. Capillary water absorption, thermal aging and colorimetric measurements have been performed on on coated and uncoated samples to evaluate their properties and estimate change of appearance with colour variation. Results show Tio2 nanoparticles good candidate for coating applications on calcareous stone, good water-repellence was observed on the samples after treatment; analyses were carried out on both untreated and freshly treated samples as well as after artificial aging. Colour change showed negligible variations on the coated or uncoated stone as well as after aging. Results showed that treated stone surfaces seem to be not affected after 1000 hours of exposure to UV radiation, no alteration of the original features.

Keywords: architectural and archaeological heritage, calcareous stone, photocatalysis TiO2, self-cleaning, thermal aging

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Authors: Maha Azzam, Mahmoud Gabr, Mahmoud Zakaria, Ayman Refaie, Amani Ismail, Sherry Khater, Sylvia Ashamallah, Mohamed Ghoniem

Abstract:

Evidence was provided that human bone marrow-derived mesenhymal stem cells (HBM-MSCs) could be differentiated to form insulin-producing cells (IPCs). Transplantation of these cells was able to cure chemically-induced diabetes in nude mice. The efficacy of these cells to control diabetes in large animals was carried out to evaluate the sufficient number of cells needed/Kg body weight and to determine the functional longevity in vivo. Materials/Methods: Ten male mongrel dogs weighing 15-20 Kg were used in this study. Diabetes was chemically-induced in 7 dogs by a mixture of alloxan and streptozotocin. Three non-diabetic served as normal controls. Differentiated HBM-MSCs (5 million/Kg) were encapsulated in theracyte capsules and transplanted beneath the rectus sheath. Each dog received 2 capsules. One dog died 4 days postoperative from inhalation pneumonia. The remaining 6 dogs were followed up for 6-18 months. Results: Four dogs became normoglycemic within 6-8 weeks with normal glucose tolerance curves providing evidence that the transplanted cells were glucose-sensitive and insulin-responsive. In the remaining 2 dogs, fasting blood glucose was reduced but did not reach euglycemic levels. The sera of all transplanted dogs contained human insulin and c-peptide but negligible levels of canine insulin. When the HBM-MSCs loaded capsules were removed, rapid return of diabetic state was noted. The harvested capsules were examined by immunofluorescence. IPCs were seen and co-expression of with c-peptide was confirmed. Furthermore, all the pancreatic endocrine genes were expressed by the transplanted cells. Conclusions: This study provided evidence that theracyte capsules could protect the xenogenic HBM-MSCs from the host immune response. This is an important issue when clinical stem cell therapy is considered for definitive treatment for T1DM.

Keywords: diabetes, mesenchymal stem cells, dogs, Insulin-producing cells

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Authors: Reena K., Mamatha H. G., Somshekarayya, P. Kumar

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Objectives: The annual proficiency testing of intermediate reference laboratories is conducted by the National Reference Laboratory (NRL) to assess the efficiency of the laboratories to correctly identify Mycobacterium tuberculosis and to determine its drug susceptibility pattern. The proficiency testing results from 2013 to 2017 were analyzed to determine laboratories that were consistent in reporting quality results and those that had difficulty in doing so. Methods: A panel of twenty cultures were sent out to each of these laboratories. The laboratories were expected to grow the cultures in their own laboratories, set up drug susceptibly testing by all the methods they were certified for and report the results within the stipulated time period. The turnaround time for reporting results, specificity, sensitivity positive and negative predictive values and efficiency of the laboratory in identifying the cultures were analyzed. Results: Most of the laboratories had reported their results within the stipulated time period. However, there was enormous delay in reporting results from few of the laboratories. This was mainly due to improper functioning of the biosafety level III laboratory. Only 40% of the laboratories had 100% efficiency in solid culture using Lowenstein Jensen medium. This was expected as a solid culture, and drug susceptibility testing is not used for diagnosing drug resistance. Rapid molecular methods such as Line probe assay and Genexpert are used to determine drug resistance. Automated liquid culture system such as the Mycobacterial growth indicator tube is used to determine prognosis of the patient while on treatment. It was observed that 90% of the laboratories had achieved 100% in the liquid culture method. Almost all laboratories had achieved 100% efficiency in the line probe assay method which is the method of choice for determining drug-resistant tuberculosis. Conclusion: Since the liquid culture and line probe assay technologies are routinely used for the detection of drug-resistant tuberculosis the laboratories exhibited higher level of efficiency as compared to solid culture and drug susceptibility testing which are rarely used. The infrastructure of the laboratory should be maintained properly so that samples can be processed safely and results could be declared on time.

Keywords: annual proficiency testing, drug susceptibility testing, intermediate reference laboratory, national reference laboratory

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Authors: Christophe Spaas, Lies Pottel, Joke De Ceulaer, Johan Abeloos, Philippe Lamoral, Tom De Backer, Calix De Clercq

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We aimed to evaluate the accuracy of an in-house developed low-cost computer-assisted surgery (CAS) protocol for osseous free flap mandibular reconstruction. All patients who underwent primary or secondary mandibular reconstruction with a free (solely or composite) osseous flap, either a fibula free flap or iliac crest free flap, between January 2014 and December 2017 were evaluated. The low-cost protocol consisted out of a virtual surgical planning, a prebend custom reconstruction plate and an individualized free flap positioning guide. The accuracy of the protocol was evaluated through comparison of the postoperative outcome with the 3D virtual planning, based on measurement of the following parameters: intercondylar distance, mandibular angle (axial and sagittal), inner angular distance, anterior-posterior distance, length of the fibular/iliac crest segments and osteotomy angles. A statistical analysis of the obtained values was done. Virtual 3D surgical planning and cutting guide design were performed with Proplan CMF® software (Materialise, Leuven, Belgium) and IPS Gate (KLS Martin, Tuttlingen, Germany). Segmentation of the DICOM data as well as outcome analysis were done with BrainLab iPlan® Software (Brainlab AG, Feldkirchen, Germany). A cost analysis of the protocol was done. Twenty-two patients (11 fibula /11 iliac crest) were included and analyzed. Based on voxel-based registration on the cranial base, 3D virtual planning landmark parameters did not significantly differ from those measured on the actual treatment outcome (p-values >0.05). A cost evaluation of the in-house developed CAS protocol revealed a 1750 euro cost reduction in comparison with a standard CAS protocol with a patient-specific reconstruction plate. Our results indicate that an accurate transfer of the planning with our in-house developed low-cost CAS protocol is feasible at a significant lower cost.

Keywords: CAD/CAM, computer-assisted surgery, low-cost, mandibular reconstruction

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Authors: Sungpil Ha, Ju Yong Kang, Sangbaek Park, Seung-Ju Lee, Soo-Won Chae

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The growing number of obese patients in aging societies has led to an increase in the number of patients with knee medial osteoarthritis (OA). Artificial joint insertion is the most common treatment for knee medial OA. Surgery is effective for patients with serious arthritic symptoms, but it is costly and dangerous. It is also inappropriate way to prevent a disease as an early stage. Therefore Non-operative treatments such as toe-in gait are proposed recently. Toe-in gait is one of non-surgical interventions, which restrain the progression of arthritis and relieves pain by reducing knee adduction moment (KAM) to facilitate lateral distribution of load on to knee medial cartilage. Numerous studies have measured KAM in various foot progression angle (FPA), and KAM data could be obtained by motion analysis. However, variations in stress at knee cartilage could not be directly observed or evaluated by these experiments of measuring KAM. Therefore, this study applied motion analysis to major gait points (1st peak, mid –stance, 2nd peak) with regard to FPA, and to evaluate the effects of FPA on the human lower extremity, the finite element (FE) method was employed. Three types of gait analysis (toe-in, toe-out, baseline gait) were performed with markers placed at the lower extremity. Ground reaction forces (GRF) were obtained by the force plates. The forces associated with the major muscles were computed using GRF and marker trajectory data. MRI data provided by the Visible Human Project were used to develop a human lower extremity FE model. FE analyses for three types of gait simulations were performed based on the calculated muscle force and GRF. We observed the maximum stress point during toe-in gait was lower than the other types, by comparing the results of FE analyses at the 1st peak across gait types. This is the same as the trend exhibited by KAM, measured through motion analysis in other papers. This indicates that the progression of knee medial OA could be suppressed by adopting toe-in gait. This study integrated motion analysis with FE analysis. One advantage of this method is that re-modeling is not required even with changes in posture. Therefore another type of gait simulation or various motions of lower extremity can be easily analyzed using this method.

Keywords: finite element analysis, gait analysis, human model, motion capture

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Authors: Ravan Samadov

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Mentally disabled people are the most discriminated against among other disabled people and face much stronger negative attitudes across many cultures. The most complex and severe form of exclusion of these people is deprivation of liberty on the grounds of their disability. This problem was for many years overlooked to a great extent by the core human rights instruments. However, the United Nations (UN) Convention on the Rights of Persons with Disabilities (CRPD), adopted in 2006, is considered a potential tool to successfully fill the gap. It is especially vital for the developing countries with the vast majority of disabled people of the world and the CRPD is presumed to be able to trigger drastic positive changes. Article 14 of the mentioned human rights treaty has brought into the international forum a new notion, as prohibits deprivation of liberty on the grounds of disability. It is to be understood as an absolute prohibition of deprivation of liberty on the grounds of disability, including mental disability, which manifests in the form of non-consensual psychiatric hospitalisation. The interpretation by the CRPD Committee indicates that this prohibition well embraces all types of non-consensual psychiatric hospitalisation – whether it is based on illness, impairment or disability. This prohibition also extends to such justifications as ‘dangerousness’, ‘need for treatment’ and ‘diminished capacity’. Moreover, providing due substantive and/or procedural safeguards does not render any legitimacy to application of deprivation of liberty on the grounds of mental disability. Logically, this new prohibition form was to be duly considered by different UN human rights bodies, and was subsequently to bring changes to their practices. However, the analyses of post-CRPD work of those bodies allows for asserting the contrary, as they have continued displaying the position which recognises deprivation of liberty on the grounds of disability to be legitimate. While such a position could be justified in the pre-CRPD time as stemming from the silence of human rights documents about it, the continuation of this course after the CRPD entered into force may call the integrity and coherence of the UN human rights treaty system into question. The non-coherent approaches of different UN bodies to this novelty give grounds for misinterpretation thereof, and hinder its due implementation by the States Parties. The paper will discuss the nature of the mentioned new prohibition and the controversial approaches to that notion by different UN human rights bodies.

Keywords: CRPD, deprivation of liberty, mental disability, non-consensual psychiatric hospitalisation, UN bodies

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Authors: Ashleigh Beales, Anne Whitworth, Jade Cartwright

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Background: While significant benefits of lexical retrieval intervention are evident within the Primary Progressive Aphasia (PPA) and Alzheimer’s disease (AD) literature, an understanding of the mechanisms that underlie change or improvement is limited. Change mechanisms have been explored in the non-progressive post-stroke literature that may offer insight into how interventions affect change with progressive language disorders. The potential influences of cognitive factors may also play a role here, interacting with the aims of intervention. Exploring how such processes have been applied is likely to grow our understanding of how interventions have, or have not, been effective, and how and why generalisation is likely, or not, to occur. Aims: This review of the literature aimed to (1) investigate the proposed mechanisms of change which underpin lexical interventions, mapping the PPA and AD lexical retrieval literature to theoretical accounts of mechanisms that underlie change within the broader intervention literature, (2) identify whether and which nonlinguistic cognitive functions have been engaged in intervention with these populations and any proposed influence, and (3) explore evidence of linguistic generalisation, with particular reference to change mechanisms employed in interventions. Main contribution: A search of Medline, PsycINFO, and CINAHL identified 36 articles that reported data for individuals with PPA or AD following lexical retrieval intervention. A review of the mechanisms of change identified 10 studies that used stimulation, 21 studies utilised relearning, three studies drew on reorganisation, and two studies used cognitive-relay. Significant treatment gains, predominantly based on linguistic performance measures, were reported for all client groups for each of the proposed mechanisms. Reorganisation and cognitive-relay change mechanisms were only targeted in PPA. Eighteen studies incorporated nonlinguistic cognitive functions in intervention; these were limited to autobiographical memory (16 studies), episodic memory (three studies), or both (one study). Linguistic generalisation outcomes were inconsistently reported in PPA and AD studies. Conclusion: This review highlights that individuals with PPA and AD may benefit from lexical retrieval intervention, irrespective of the mechanism of change. Thorough application of a theory of intervention is required to gain a greater understanding of the change mechanisms, as well as the interplay of nonlinguistic cognitive functions.

Keywords: Alzheimer's disease, lexical retrieval, mechanisms of change, primary progressive aphasia

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Authors: Khemakhem Nahed, Hammami Fatma, Trabelsi Houaida, Neji Sourour, Sellami Hayet, Makni Fattouma, Turki Hamida, Ayadi Ali

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Dermatophytoses are considered a public health problem and represent 10% of dermatological consultations in our region. Their epidemiology is influenced by various factors, such as lifestyle, human migration patterns, changes in the environment and the host relationship. The understanding of epidemiology has a major impact on their prevention and treatment. The aim of the study is to determine the prevalence pattern of aetiological agents and to describe the clinical characteristics of dermatophytoses between 1999 and 2019. Out of 65 059 subjects suspected to have superficial mycoses, 36 220 (55.67%) were affected with dermatophytoses. The mean age was 40.1 years (range: 10 days to 99 years). The sex ratio was 0.8. Our patients were from urban regions in 80.9% of cases. The most common type of infection was onychomycosis (42.64%), followed by tinea pedis (20.8%), intertrigo (18.3%), tinea corporis (8.48%) and tinea capitis (7.87%). The most isolated dermatophyte was Trichophyton rubrum (76.5%), followed by T. mentagrophytes complex (6.3%), Microsporum canis (5.8%), T. violaceum (5.3%), T. verrucosum (0.83%) and Epidermophyton floccosum (0.3%). Zoophilic agents have become more prevalent and their frequency has been increased from 6.46% in 1999 to 13% in 2019. It is interesting to note that M. canis has been on the rise since 2010 and it was the first etiological agent of tinea capitis (48%), while infections caused by T. violaceum continued to decrease from 1999 (16.2%) to 2019 (4.7%). Other dermatophytes have been rarely isolated: T. tonsurans (9 cases), T. schoenleinii (3 cases), T. soudanense (2 cases), M. fulvum (1 case), M. audouinii (1 case) and M. ferrugineum (2 cases).T. mentagrophytes var. quinckeanum was isolated from an inflammatory tinea capitis lesion in an a-3-year-old girl. T. mentagrophytes var. erinacei was isolated from the first case of tinea manuum, in-a-10-year-old girl. The same fungus was isolated from the hair and scales of the hedgehog. Our study showed significant changes in the dermatophytes spectrum in our region. The prevalence of zoophilic species increased in recent years due to people's behavioral changes with the adoption of pets and animal husbandry in urban settings. Molecular methods are often crucial that help us to refine the identification strains of dermatophytes and to identify their origin of the contamination.

Keywords: dermatophytoses, PCR-sequencing, spectrum, Sfax, Tunisia

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Authors: Yemane Hailu Fissuh, Zhongzhan Zhang

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In biomedical researches and randomized clinical trials, the most commonly interested outcomes are time-to-event so-called survival data. The importance of robust models in this context is to compare the effect of randomly controlled experimental groups that have a sense of causality. Causal estimation is the scientific concept of comparing the pragmatic effect of treatments conditional to the given covariates rather than assessing the simple association of response and predictors. Hence, the causal effect based semiparametric transformation model was proposed to estimate the effect of treatment with the presence of possibly time-varying covariates. Due to its high flexibility and robustness, the semiparametric transformation model which shall be applied in this paper has been given much more attention for estimation of a causal effect in modeling left-truncated and right censored survival data. Despite its wide applications and popularity in estimating unknown parameters, the maximum likelihood estimation technique is quite complex and burdensome in estimating unknown parameters and unspecified transformation function in the presence of possibly time-varying covariates. Thus, to ease the complexity we proposed the modified estimating equations. After intuitive estimation procedures, the consistency and asymptotic properties of the estimators were derived and the characteristics of the estimators in the finite sample performance of the proposed model were illustrated via simulation studies and Stanford heart transplant real data example. To sum up the study, the bias of covariates was adjusted via estimating the density function for truncation variable which was also incorporated in the model as a covariate in order to relax the independence assumption of failure time and truncation time. Moreover, the expectation-maximization (EM) algorithm was described for the estimation of iterative unknown parameters and unspecified transformation function. In addition, the causal effect was derived by the ratio of the cumulative hazard function of active and passive experiments after adjusting for bias raised in the model due to the truncation variable.

Keywords: causal estimation, EM algorithm, semiparametric transformation models, time-to-event outcomes, time-varying covariate

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Authors: Mohd Shazad, Kamal Kumar Gupta

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Aedes aegypti (Diptera: Culicidae), commonly known as tiger mosquito is the vector of dengue fever, yellow fever, chikungunya and zika virus. In the absence of any effective vaccine against these diseases, control the mosquito population is the only promising mean to prevent the diseases. Currently used chemical insecticides cause environmental contamination, high mammalian toxicity and hazards to non-target organisms, insecticide resistance and vector resurgence. Present research work aimed to explore the potentials of phytochemicals present in the Ocimum sanctum in management of mosquito population. The leaves of Ocimum were extracted with ethanol by ‘cold extraction method’. 0-24h old fourth instar larvae of Aedes aegypti were treated with the extract of concentrations 50ppm, 100ppm, 200ppm and 400ppm for 24h. Survival, growth and development of the treated larvae were evaluated. The adults emerged from the treated larvae were used for the reproductive fitness studies. Our results indicate 77.2% mortality in the larvae exposed to 400 ppm. At lower doses, although there was no significant reduction in the survival after 24h however, it decreased during subsequent days of observations. In control experiments, no mortality was observed. It was also observed that the larvae survived after treatment showed severe growth and developmental abnormalities. There was significant increase in larval duration. In control, fourth instar moulted into pupa after 3 days while larvae treated with 400 ppm extract were moulted after 4.6 days. Larva-pupa intermediates and the pupa-adult intermediates were observed in many cases. The adults emerged from the treated larvae showed impaired mating and oviposition behaviour. The females exhibited longer preoviposition period, reduced oviposition rate and decreased egg output. GCMS analysis of the ethanol extract revealed presence of JH mimics and intermediates of JH biosynthetic pathway. Potentials of Ocimum sanctum in integrated vector management programme of Aedes aegypti were discussed.

Keywords: Aedes aegypti, Ocimum sanctum, oviposition, survival

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Authors: Mathodzi Nditsheni, Olawole Emmanuel Aina, Joshua Oluwole Olowoyo

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The ever-increasing world population is putting extreme pressure on the already limited agricultural resources for food production. Different soil enhancers were introduced by famers to meet the need of the ever-increasing population demand for food. One of the soil enhancers is the municipal waste sludge. This research investigated the differences in the concentrations of trace metals and levels of phytochemicals in four different tomato varieties cultivated on soil treated with municipal waste sludge in Pretoria, South Africa. Fruits were harvested at maturity and analyzed for trace metals and phytochemicals contents using Inductively Coupled Plasma Optical Emission Spectrometry (ICP-OES) and a High-Performance Liquid Chromatography (HPLC) respectively. A one-way analysis of variance (ANOVA) was used to determine the differences in the concentrations of trace metals and phytochemical from different tomato varieties were significant. From the study, Rodade tomato bioaccumulated the highest concentrations of Mn, Cr, Cu and Ni, Roma bioaccumulated the highest concentrations of, Cd, Fe and Pb while Heinz bioaccumulated the highest concentrations of As and Zn. Cherry tomato on the other hand, recorded the lowest concentrations for most metals, Cd, Cr, Cu, Mn, Ni, Pb and Zn. The results of the study further showed that phenolic and flavonoids content were higher in the Solanum lycopersicum fruit grown in soils treated with municipal waste sludge. The study also showed that there was an inverse relationship between the levels of trace metals and phytochemicals. The calculated contamination factor values of trace metals like Cr, Cu, Pb and Zn were above the safe value of 1 which indicated that the tomato fruits may be unsafe for human consumption. However, the contamination factor values for the remaining trace metals were well below the safe value of 1. From the results obtained either for the control group or the treatment, the tomato varieties used in the study, bioaccumulated the toxic trace metals in their fruits and some of the values obtained were higher than the acceptable limit, which may then imply that the varieties of tomato used in this study bio accumulated the toxic trace metals from the soil, hence care should be taken when these tomato varieties are either cultivated or harvested from polluted areas

Keywords: trace metals, flavonoids, phenolics, waste sludge, tomato, contamination factors

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Authors: Chiara Della Rocca, Gavino Piras, Andrea Berti, Alessandro Mameli

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DNA identification of human skeletal remains plays a valuable role in the forensic field, especially in missing persons and mass disaster investigations. Hard tissues, such as bones and teeth, represent a very common kind of samples analyzed in forensic laboratories because they are often the only biological materials remaining. However, the major limitation of using these compact samples relies on the extremely time–consuming and labor–intensive treatment of grinding them into powder before proceeding with the conventional DNA purification and extraction step. In this context, a DNA extraction assay called the TBone Ex kit (DNA Chip Research Inc.) was developed to digest bone chips without powdering. Here, we simultaneously analyzed bone and tooth samples that arrived at our police laboratory and belonged to 15 different forensic casework that occurred in Sardinia (Italy). A total of 27 samples were recovered from different scenarios and were exposed to extreme environmental factors, including sunlight, seawater, soil, fauna, vegetation, and high temperature and humidity. The TBone Ex kit was used prior to the EZ2 DNA extraction kit on the EZ2 Connect Fx instrument (Qiagen), and high-quality autosomal and Y-chromosome STRs profiles were obtained for the 80% of the caseworks in an extremely short time frame. This study provides additional support for the use of the TBone Ex kit for digesting bone fragments/whole teeth as an effective alternative to pulverization protocols. We empirically demonstrated the effectiveness of the kit in processing multiple bone samples simultaneously, largely simplifying the DNA extraction procedure and the good yield of recovered DNA for downstream genetic typing in highly compromised forensic real specimens. In conclusion, this study turns out to be extremely useful for forensic laboratories, to which the various actors of the criminal justice system – such as potential jury members, judges, defense attorneys, and prosecutors – required immediate feedback.

Keywords: DNA, skeletal remains, bones, tbone ex kit, extreme conditions

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Authors: Allan F. F. Alves, Fernando A. Bacchim Neto, Guilherme Giacomini, Marcela de Oliveira, Ana L. M. Pavan, Maria E. D. Rosa, Diana R. Pina

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Stroke is a worldwide concern, only in Brazil it accounts for 10% of all registered deaths. There are 2 stroke types, ischemic (87%) and hemorrhagic (13%). Early diagnosis is essential to avoid irreversible cerebral damage. Non-enhanced computed tomography (NECT) is one of the main diagnostic techniques used due to its wide availability and rapid diagnosis. Detection depends on the size and severity of lesions and the time spent between the first symptoms and examination. The Alberta Stroke Program Early CT Score (ASPECTS) is a subjective method that increases the detection rate. The aim of this work was to implement an image segmentation system to enhance ischemic stroke and to quantify the area of ischemic and hemorrhagic stroke lesions in CT scans. We evaluated 10 patients with NECT examinations diagnosed with ischemic stroke. Analyzes were performed in two axial slices, one at the level of the thalamus and basal ganglion and one adjacent to the top edge of the ganglionic structures with window width between 80 and 100 Hounsfield Units. We used different image processing techniques such as morphological filters, discrete wavelet transform and Fuzzy C-means clustering. Subjective analyzes were performed by a neuroradiologist according to the ASPECTS scale to quantify ischemic areas in the middle cerebral artery region. These subjective analysis results were compared with objective analyzes performed by the computational algorithm. Preliminary results indicate that the morphological filters actually improve the ischemic areas for subjective evaluations. The comparison in area of the ischemic region contoured by the neuroradiologist and the defined area by computational algorithm showed no deviations greater than 12% in any of the 10 examination tests. Although there is a tendency that the areas contoured by the neuroradiologist are smaller than those obtained by the algorithm. These results show the importance of a computer aided diagnosis software to assist neuroradiology decisions, especially in critical situations as the choice of treatment for ischemic stroke.

Keywords: ischemic stroke, image processing, CT scans, Fuzzy C-means

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Authors: E. Kilicay, Z. Karahaliloglu, B. Hazer, E. B. Denkbas

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In this study, we have prepared concanavaline A (ConA) functionalized curcumin (CUR) loaded PHBHHx (poly(3-hydroxybutyrate-co-3-hydroxyhexanoate)) nanoparticles as a novel and efficient drug delivery system. CUR is a promising anticancer agent for various cancer types. The aim of this study was to evaluate therapeutic potential of curcumin loaded PHBHHx nanoparticles (CUR-NPs) and concanavaline A conjugated curcumin loaded NPs (ConA-CUR NPs) for ovarian cancer treatment. ConA was covalently connected to the carboxylic group of nanoparticles by EDC/NHS activation method. In the ligand attachment experiment, the binding capacity of ConA on the surface of NPs was found about 90%. Scanning electron microscopy (SEM) and atomic force microscopy (AFM) analysis showed that the prepared nanoparticles were smooth and spherical in shape. The size and zeta potential of prepared NPs were about 228±5 nm and −21.3 mV respectively. ConA-CUR NPs were characterized by FT-IR spectroscopy which confirmed the existence of CUR and ConA in the nanoparticles. The entrapment and loading efficiencies of different polymer/drug weight ratios, 1/0.125 PHBHHx/CUR= 1.25CUR-NPs; 1/0.25 PHBHHx/CUR= 2.5CUR-NPs; 1/0.5 PHBHHx/CUR= 5CUR-NPs, ConA-1.25CUR NPs, ConA-2.5CUR NPs and ConA-5CUR NPs were found to be ≈ 68%-16.8%; 55%-17.7 %; 45%-33.6%; 70%-15.7%; 60%-17%; 51%-30.2% respectively. In vitro drug release showed that the sustained release of curcumin was observed from CUR-NPs and ConA-CUR NPs over a period of 19 days. After binding of ConA, the release rate was slightly increased due to the migration of curcumin to the surface of the nanoparticles and the matrix integrities was decreased because of the conjugation reaction. This functionalized nanoparticles demonstrated high drug loading capacity, sustained drug release profile, and high and long term anticancer efficacy in human cancer cell lines. Anticancer activity of ConA-CUR NPs was proved by MTT assay and reconfirmed by apoptosis and necrosis assay. The anticancer activity of ConA-CUR NPs was measured in ovarian cancer cells (SKOV-3) and the results revealed that the ConA-CUR NPs had better tumor cells decline activity than free curcumin. The nacked nanoparticles have no cytotoxicity against human ovarian carcinoma cells. Thus the developed functionalized nanoformulation could be a promising candidate in cancer therapy.

Keywords: curcumin, curcumin-PHBHHx nanoparticles, concanavalin A, concanavalin A-curcumin PHBHHx nanoparticles, PHBHHx nanoparticles, ovarian cancer cell

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Authors: Les Moncrieff

Abstract:

In a world awash with potent opioids flaming an international crisis, the need to explore safe alternatives has never been more urgent. Bio-electrode Therapy is a novel adjunctive treatment method for relieving acute opioid withdrawal symptoms and many types of complex acute and chronic pain (often the underlying cause of opioid dependence). By combining the science of developmental bioelectricity with Traditional Chinese Medicine’s theory of meridians, rapid relief from pain is routinely being achieved in the clinical setting. Human body functions are dependent on electrical factors, and acupuncture points on the body are known to have higher electrical conductivity than surrounding skin tissue. When tiny gold- and silver-plated electrodes are secured to the skin at specific acupuncture points using established Chinese Medicine principles and protocols, an enhanced microcurrent and electrical field are created between the electrodes, influencing the entire meridian and connecting meridians. No external power source or electrical devices are required. Endogenous DC electric fields are an essential fundamental component for development, regeneration, and wound healing. Disruptions in the normal ion-charge in the meridians and circulation of blood will manifest as pain and development of disease. With the application of these simple electrodes (gold acting as cathode and silver as anode) according to protocols, the resulting microcurrent is directed along the selected meridians to target injured or diseased organs and tissues. When injured or diseased cells have been stimulated by the microcurrent and electrical fields, the permeability of the cell membrane is affected, resulting in an immediate relief of pain, a rapid balancing of positive and negative ions (sodium, potassium, etc.) in the cells, the restoration of intracellular fluid levels, replenishment of electrolyte levels, pH balance, removal of toxins, and a re-establishment of homeostasis.

Keywords: bioelectricity, electrodes, electrical fields, acupuncture meridians, complex pain, opioid withdrawal management

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Authors: J. D. Cabral, E. Murray, P. Turner, E. Hewitt, A. Ali, M. McConnell

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Worldwide demand for organ replacement and tissue regeneration is progressively increasing. Three-dimensional (3D) bioprinting, where a physical construct is produced using computer-aided design, is a promising tool to advance the tissue engineering and regenerative medicine fields. In this paper we describe two different approaches to developing 3D bioprinted constructs for use in tissue regeneration. Bioink development is critical in achieving the 3D biofabrication of functional, regenerative tissues. Hydrogels, cross-linked macromolecules that absorb large amounts of water, have received widespread interest as bioinks due to their relevant soft tissue mechanics, biocompatibility, and tunability. In turn, not only is bioink optimisation crucial, but the creation of vascularized tissues remains a key challenge for the successful fabrication of thicker, more clinically relevant bioengineered tissues. Among the various methodologies, cell-laden hydrogels are regarded as a favorable approach; and when combined with novel core/shell 3D bioprinting technology, an innovative strategy towards creating new vessel-like structures. In this work, we investigate this cell-based approach by using human umbilical endothelial cells (HUVECs) entrapped in a viscoelastic chitosan/dextran (CD)-based core hydrogel, printed simulataneously along with a gelatin methacrylate (GelMA) shell. We have expanded beyond our previously reported FDA approved, commercialised, post-surgical CD hydrogel, Chitogel®, by functionalizing it with cell adhesion and proteolytic peptides in order to promote bone marrow-derived mesenchymal stem cell (immortalized BMSC cell line, hTERT) and HUVECs growth. The biocompatibility and biodegradability of these cell lines in a 3D bioprinted construct is demonstrated. Our studies show that particular peptide combinations crosslinked within the CD hydrogel was found to increase in vitro growth of BMSCs and HUVECs by more than two-fold. These gels were then used as a core bioink combined with the more mechanically robust, UV irradiated GelMA shell bioink, to create 3D regenerative, vessel-like scaffolds with high print fidelity. As well, microporous MEW scaffolds made from milk proteins blended with PCL were found to show promising bioactivity, exhibiting a significant increase in keratinocyte (HaCaTs) and fibroblast (normal human dermal fibroblasts, NhDFs) cell migration and proliferation when compared to PCL only scaffolds. In conclusion, our studies indicate that a peptide functionalized CD hydrogel bioink reinforced with a GelMA shell is biocompatible, biodegradable, and an appropriate cell delivery vehicle in the creation of regenerative 3D constructs. In addition, a novel 3D printing technique, melt electrowriting (MEW), which allows fabrication of micrometer fibre meshes, was used to 3D print polycaprolactone (PCL) and bioactive milk protein, lactorferrin (LF) and whey protein (WP), blended scaffolds for potential skin regeneration applications. MEW milk protein/PCL scaffolds exhibited high porosity characteristics, low overall biodegradation, and rapid protein release. Human fibroblasts and keratinocyte cells were seeded on to the scaffolds. Scaffolds containing high concentrations of LF and combined proteins (LF+WP) showed improved cell viability over time as compared to PCL only scaffolds. This research highlights two scaffolds made using two different 3D printing techniques using a combination of both natural and synthetic biomaterial components in order to create regenerative constructs as potential chronic wound treatments.

Keywords: biomaterials, hydrogels, regenerative medicine, 3D bioprinting

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