Search results for: treatment gap

Authors: Svitlana Antonenko, Gennady Telegeev

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Introductive statement: The development of chronic myeloid leukemia (CML) is caused by Bcr-Abl oncoprotein. Modern treatments with tyrosine kinase inhibitors are greatly complicated by the mutational variability of the Bcr-Abl oncoprotein, which causes drug resistance. Therefore, there is an urgent need to develop new approaches to the treatment of the disease, which will allow modeling the level of Bcr-Abl oncoprotein in the cell. Promising in this direction is the identification of proteases that can selectively promote cellular proteolysis of oncoproteins. The aim of the study was to study the effect of the interaction of Bcr-Abl with deubiquitinase USP1 on the level of oncoprotein in CML cells. Methodology: K562 cells were selected for the experiment. Сells were incubated with ML323 inhibitor for 24 hours. Precipitation of endogenous proteins from K562 cell lysate was performed using anti-Bcr-Abl antibodies. Cell lysates and precipitation results were studied by Western blot. Subcellular localization of proteins was studied by immunofluorescence analysis followed by confocal microscopy. The results were analyzed quantitatively and statistically. Major findings: The Bcr-Abl/USP1 protein complex was detected in CML cells, and it was found that inhibition of USP1 deubiquitinating activity by the compound ML323 leads to disruption of this protein complex and a decrease in the level of Bcr-Abl oncoprotein in cells. The interaction of Bcr-Abl with USP1 may result in deubiquitination of the oncoprotein, which disrupts its proteasomal degradation and leads to the accumulation of CML in cells. Conclusion: We believe that the interaction of oncoprotein with USP1 may be one of the prerequisites that contribute to malignant cell transformation due to the deubiquitination of oncoprotein, which leads to its accumulation and disease progression. A correlation was found between the deubiquitinating activity of USP1 and the level of oncoprotein in CML cells. Thus, we identify deubiquitinase USP1 as a promising therapeutic target for the development of a new strategy for the treatment of CML by modulating the level of Bcr-Abl in the cell.

Keywords: chronic myeloid leukemia, Bcr-Abl, USP1, deubiquitination Bcr-Abl, K562 cell

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Authors: Tanyaporn Chairoch

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Introduction: Cannabis is a drug to treat patients with many diseases such as Multiple sclerosis, Alzheimer’s disease, and Epilepsy, where theycontain many active compounds such as delta-9 tetrahydrocannabinol (THC) and cannabidiol (CBD). Especially, THC is the primary psychoactive ingredient in cannabis and binds to cannabinoid 1 (CB1) receptors. Moreover, CB1 is located on the neocortex, hippocampus, basal ganglia, cerebellum, and brainstem. In previous study, we found the association between the variant of CB1recptors gene (rs2023239) and decreased effect of nicotine reinforcement in patients. However, there are no data describing whether the distribution of CB1 receptor gene is a genetic marker for Thai patients who are treated with cannabis. Objective: Thus, the aim of this study we want to investigate the frequency of the CB1 receptor gene in Thai patients. Materials and Methods: All of sixty Thai patients received the medical cannabis for treatment who were recruited in this study. DNA will be extracted from EDTA whole blood by Genomic DNA Mini Kit. The genotyping of CNR1 gene (rs 2023239) was genotyped by the TaqMan real time PCR assay (ABI, Foster City, CA, USA).and using the real-time PCR ViiA7 (ABI, Foster City, CA, USA). Results: We found thirty-eight (63.3%) Thai patients were female, and twenty-two (36.70%) were male in this study with median age of 45.8 (range19 – 87 ) years. Especially, thirty-two (53.30%) medical cannabis tolerant controls were female ( 55%) and median age of52.1 (range 27 – 79 ) years. The most adverse effects for medical cannabis treatment was tachycardia. Furthermore, the number of rs 2023239 (TT) carriers was 26 of 27 (96.29%) in medical cannabis-induced adverse effects and 32 of 33 (96.96%) in tolerant controls. Additionally, rs 2023239 (CT) variant was found just only one of twenty-seven (3.7%) in medical cannabis-induced adverse effects and 1 of 33 (3.03%) in tolerant controls. Conclusions: The distribution of genetic variant in CNR1 gene might serve as a pharmacogenetics markers for screening before initiating the therapy with medical cannabis in Thai patients.

Keywords: cannabis, pharmacogenetics, CNR1 gene, thai patient

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Authors: Lai Gwen Chan, Yining Ong, Audrey Yoke Poh Wong

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Background. The efficacy of electroconvulsive therapy (ECT) as a form of treatment to a range of mental disorders is well-established. However, ECT is often associated with either temporary or persistent cognitive side-effects, resulting in the failure of wider prescription. Of which, retrograde amnesia is the most commonly reported cognitive side-effect. Most studies found a recalling deficit in autobiographical memories to be short-term, although a few have reported more persistent amnesic effects. Little is known about ECT-related amnesic effects in Asian population. Hence, this study aims to resolve conflicting findings, as well as to better elucidate the effects of ECT on cognitive functioning in a local sample. Method: 12 patients underwent bilateral ECT under the care of Psychological Medicine Department, Tan Tock Seng Hospital, Singapore. Participants’ cognition and level of functioning were assessed at four time-points: before ECT, between the third and fourth induced seizure, at the end of the whole course of ECT, and two months after the index course of ECT. Results: It was found that Global Assessment of Functioning scores increased significantly at the completion of ECT. Case-by-case analyses also revealed an overall improvement in Personal Semantic and Autobiographical memory two months after the index course of ECT. A transient dip in both personal semantic and autobiographical memory scores was observed in one participant between the third and fourth induced seizure, but subsequently resolved and showed better performance than at baseline. Conclusions: The findings of this study suggest that ECT is an effective form of treatment to alleviate the severity of symptoms of the diagnosis. ECT does not affect attention, language, executive functioning, personal semantic and autobiographical memory adversely. The findings suggest that Asian patients may respond to bilateral ECT differently from Western samples.

Keywords: electroconvulsive therapy (ECT), autobiographical memory, cognitive impairment, psychiatric disorder

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Authors: Bernice Lottering, Yi-Wen Lin

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Chronic pain and depression have an estimated 80% rate of comorbidity with unsatisfactory treatment interventions signifying the importance of developing effective therapeutic interventions for a serious chronic condition affecting a large majority of the global population. Chronic pain is defined as persistent pain presenting for over 3 months. This disease state increases the risk of developing depression in comparison to healthy individuals. In the current study, complete Freund’s adjuvant (CFA) was used to induce cell-mediated chronic inflammatory pain in a murine model. Significant mechanical and thermal hyperalgesia was induced, alongside observable depression-like behaviors. These conditions were attenuated through the use of electroacupuncture (EA). Similarly, these effects were also investigated with respect to the transient receptor potential vanilloid 1 (TRPV1), by analyzing the effects of TRPV1 gene deletion on the comorbidity of chronic pain and depression. The expression of the TRPV1 inflammatory response, and related downstream molecules, including protein kinases (PKs), mitogen-activated protein kinase (MAPKs), and transcriptional factors, were significantly reduced in the thalamus, prefrontal cortex (PFC), hippocampus, and periaqueductal gray (PAG) of CFA-treated mice. In addition, phosphorylated N-methyl-D-aspartate (NMDA) receptor 1 was also found to be reduced in the aforementioned areas, suggesting potential application and validity in a clinical setting. Our study determined the prospective therapeutic effects of EA in the treatment of chronic inflammatory pain and depression comorbidity and provides a novel and detailed mechanism underlying EA-mediated analgesia. These findings may be relevant in the utilization of clinical intervention approaches related to chronic pain and depression comorbidity.

Keywords: chronic pain, depression, NMDA, prefrontal cortex, TRPV1

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Authors: N. S. El-Mougy, M. M. Abdel-Kader, H. M. Abouelnasr

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The efficacy of two essential oils applied as a bean seed dressing followed by seedlings foliar spray with four commercial disinfectants against root rot and wilt incidence was evaluated under field conditions. The essential oils, grape seed and peppermint oils and the disinfectants, Gold, Revarest, Klenva, Malva were applied. Chitosan and the fungicide Topsin-M were used as comparison treatment. Essential oils individually or combined with disinfectants were applied as a bean seed dressing. Furthermore, emerged bean plants were sprayed with the same treatments. Under laboratory conditions, growth inhibition effect was observed for the isolated, tested fungi R. solani and F. oxysporum when exposed to essential oils individually or combined with disinfectants. A high inhibitor effect was recorded for peppermint followed by grape seed oils. Concentrations of 1% and 2% of chitosan as well as Topsin M at 400 ppm showed complete reduction (100%) in the two fungal growths. Under field conditions, the obtained results showed that the applied treatments of chitosan had a superior effect on root rot and wilt disease incidence compared with other tested treatments. It was found that seed coating treatment provides good protection of emerged green bean seeds against the root pathogens attack compared with the fungicide and control treatments. Also, the application of seed dressing with essential oils accompanied by seedling spray demonstrated similar results. It was observed that essential oils had an enhancing effect against disease incidence when combined with disinfectants compared with their application. The obvious yield increase was significantly higher in all applied treatments than in fungicide and control.

Keywords: bean, disinfectants, essential oils, root rot, wilt

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Authors: Ismail I. Abo-Ghanema, Faheim E. Wehaish, Rasha M. Saleh , Walaa F. Awadin, Mohamed F. Elshal

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The antidiabetic activity of myrrh and ginseng ethanolic extracts were investigated in streptozotocin (STZ)-induced diabetic rats. Thirty male albino rats were divided into five groups, each consisted of six rats. The first group (G1) is the negative control that was fed basal diet, the second group (G2) was injected with STZ and received no treatment, the third group (G3) injected with STZ and received metformin (50 mg/kg, b.wt) as standard anti-diabetic drug, the fourth group (G4) injected with STZ and ginseng (50 mg/kg, b.wt), the fifth group (G5) injected with STZ and received myrrh (500 mg/kg, b.wt). As compared with G1-group, STZ injection increased blood concentrations of glucose (6.2 fold), glycated hemoglobin (HbA1c) (2.51 fold), aspartateaminotransferase (AST), and alanine aminotransferase (ALT) (2.64, 4.60 fold respectively), creatinine (2.91 fold), cholesterol (1.79 fold), triglycerides (2.06 fold), low density lipoprotein-cholesterol (LDL) (2.92 fold), nitric oxide (NO) (20.18 fold), and malondialdehyde (MDA) (2.25 fold), whereas it decreased blood insulin (0.40 fold), albumin (0.60 fold), high density lipoprotein-cholesterol (HDL) (0.33 fold), and reduced glutathione (GSH) (0.49 fold). Vascular permeability index (VPI as measured by Evan's Blue; EB extravasations test) was significantly increased in the skin of diabetic animals (9.6 fold) when compared with the G1-group. In addition, histological alterations in liver, pancreas, kidneys and heart were observed. After 4 weeks of treatment, rats in G4 and G5 showed significant corrections in the all measured parameters and indices. In conclusions, the ethanolic extracts of ginseng and myrrh exhibited promising and safe anti-diabetic activity especially on peripheral circulation as manifested by decreased vascular permeability and improved histopathological alterations of examined organs and insulin secretion. Hence, it may be pursued for their clinical usefulness in the management of diabetes mellitus (DM) and associated vascular complications.

Keywords: diabetic rats, peripheral circulation, natural plants, myrrh, ginseng

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Authors: Koninika Mukherjee, Dilwar Hussain

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Introduction: One of the most prevalent psychopathologies among the youth is social anxiety. The presence of comorbid disorders further complicates diagnosis and treatment. One of the most commonly co-occurring disorders, along with social anxiety, is related to eating behavior. Objective: Identifying the risk and protective factors and the mechanism through which the effect of these disorders might help in treatment and prevention. So, the stated objective of the present study is to investigate the role of fear of negative evaluation and social appearance anxiety in the relationship of parental bonding with social anxiety and comorbid disordered eating. Method: A cross-sectional study was conducted with 411 Indian undergraduates. Data collection was done with the help of self-report measures like the social interaction anxiety scale, parental bonding instrument, brief fear of negative evaluation, social appearance anxiety scale, and the eating attitudes test. SPSS Amos 22.0 version was used for path analyses. Results: Out of the different dimensions of parental bonding, only maternal care and the father’s granting of behavioural freedom proved significant in the development and maintenance of social anxiety and disordered eating behaviour and symptoms. Fear of negative evaluation and social appearance anxiety mediated the impact of the mother’s care on social anxiety and comorbid disordered eating. However, only fear of negative evaluation seemed to mediate the effect of paternal granting of behavioral freedom on social anxiety and comorbid issues. Implications: One of the vital contributions of this study is looking at perceived maternal and paternal bonding separately in the path model. Identifying parenting dimensions significantly related to social anxiety and comorbid disorders can aid in establishing consensus around operational definitions and in the formulation of comprehensive assessments. Future Directions: Future research can include both participant and parental perceptions of parental bonding.

Keywords: social anxiety, disordered eating, fear of negative evaluation, social appearance anxiety

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Authors: N. M. Sani, E. D. Jatau, O. S. Olonitola, M. Y. Gwarzo, P. Moodley, N. S. Mujahid

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Haemoglobin (HB) indicates anaemia level and by extension may reflect the nutritional level and perhaps the immunity of an individual. Some antiretroviral drugs like zidovudine are known to cause anaemia in People living with HIV/AIDS (PLWHA). A cross-sectional study using demographic data and blood specimen from 218 female commercial sex workers attending antiretroviral therapy (ART) clinics was conducted between December 2009 and July 2011 to assess the effect of zidovudine on haematologic and RNA viral load of female sex workers receiving antiretroviral treatment in north-western Nigeria. Anaemia is a common and serious complication of both HIV infection and its treatment. In the setting of HIV infection, anaemia has been associated with decreased quality of life, functional status, and survival. Antiretroviral therapy, particularly the highly active antiretroviral therapy (HAART), has been associated with a decrease in the incidence and severity of anaemia in HIV-infected patients who have received a HAART regimen for at least 1 year. In this study, result has shown that out of 218 patients, 26 with haemoglobin count between 5.1–10 g/dl were observed to have the highest viral load count of 300,000–350,000 copies/ml. It was also observed that most patients (190) with HB of 10.1–15.0 g/dl had viral load count of 200,000–250,000 copies/ml. An inverse relationship therefore exists, i.e. the lower the haemoglobin level, the higher the viral load count, even though the test statistics did not show any significance between the two (P=0.206). This shows that multivariate logistic regression analysis demonstrated that anaemia was associated with a CD4+ cell count below 50/µL in female sex workers with a viral load above 100,000 copies/mL who use zidovudine. Severe anaemia was less prevalent in this study population than in historical comparators; however, mild to moderate anaemia rates remain high. The study, therefore, recommends that hematological and virologic parameters be monitored closely in patients receiving first line ART regimen.

Keywords: anaemia, female sex worker, haemoglobin, Zidovudine

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Authors: Jae-Ho Jang, Jung-Soo Kim, Byung-Jun Kim, Dae-Geun Nam, Uoo-Chang Jung, Yoon-Suk Choi

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Low alloy steels are widely used for pressure vessels, spent fuel storage, and steam generators required to withstand the internal pressure and prevent unexpected failure in nuclear power plants, which these may suffer embrittlement by high levels of radiation and heat for a long period. Therefore, it is important to improve mechanical properties of low alloy steels for the integrity of structure materials at an early stage of fabrication. Recently, it showed that a double austenitizing and tempering (DTA) process resulted in a significant improvement of strength and toughness by refinement of prior austenite grains. In this study, it was investigated that the mechanism of improving mechanical properties according to the change of microstructure by the second fully austenitizing temperature of the DAT process for low alloy steel required the structural integrity. Compared to conventional single austenitizing and tempering (SAT) process, the tensile elongation properties have improved about 5%, DBTTs have obtained result in reduction of about -65℃, and grain size has decreased by about 50% in the DAT process conditions. Grain refinement has crack propagation interference effect due to an increase of the grain boundaries and amount of energy absorption at low temperatures. The higher first austenitizing temperature in the DAT process, the more increase the spheroidized carbides and strengthening the effect of fine precipitates in the ferrite grain. The area ratio of the dimple in the transition area has increased by proportion to the effect of spheroidized carbides. This may the primary mechanisms that can improve low-temperature toughness and elongation while maintaining a similar hardness and strength.

Keywords: double austenitizing, Ductile Brittle transition temperature, grain refinement, heat treatment, low alloy steel, low-temperature toughness

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Authors: Maha Atout, Pippa Hemingway, Jane Seymour

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A preliminary systematic review shows that health professionals experience a tension when communicating with the parents and family members of children with life-threatening and life-limiting conditions. On the one hand, they want to promote open and honest communication, while on the other, they are apprehensive about fostering an unrealistic sense of hope. Defining the boundaries between information that might offer reasonable hope versus that which results in false reassurance is challenging. Some healthcare providers worry that instilling a false sense of hope could motivate parents to seek continued aggressive treatment for their child, which in turn might cause the patient further unnecessary suffering. To date, there has been a lack of research in the Middle East regarding how healthcare providers do or should communicate bad news; in particular, the issue of hope in the field of paediatric palliative care has not been researched thoroughly. This study aims to explore, from the perspective of patients’ mothers, physicians, and nurses, the experience of communicating and receiving bad news in the care of children with palliative care needs. Data were collected using a collective qualitative case study approach across three paediatric units in a Jordanian hospital. Two data collection methods were employed: participant observation and semi-structured interviews. The overall number of cases was 15, with a total of 56 interviews with mothers (n=24), physicians (n=12), and nurses (n=20) completed, as well as 197 observational hours logged. The findings demonstrate that mothers wanted their doctors to provide them with hopeful information about the future progression of their child’s illness. Although some mothers asked their doctors to provide them with honest information regarding the condition of their child, they still considered a sense of hope to be essential for coping with caring for their child. According to mothers, hope was critical to treatment as it helped them to stay committed to the treatment and protected them to some extent from the extreme emotional suffering that would occur if they lost hope. The health professionals agreed with the mothers on the importance of hope, so long as it was congruent with the stage and severity of each patient’s disease. The findings of this study conclude that while parents typically insist on knowing all relevant information when their child is diagnosed with a severe illness, they considered hope to be an essential part of life, and they found it very difficult to handle suffering without any glimmer of it. This study finds that using negative terms has extremely adverse effects on the parents’ emotions. Hence, although the mothers asked the doctors to be as honest as they could, they still wanted the physicians to provide them with a positive message by communicating this information in a sensitive manner including hope.

Keywords: health professionals, children, communication, hope, information, mothers, palliative care

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Authors: Delband Yekta Moazami

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Background: For proper care and treatment of HIV patients and drug users, the medical staff and physicians must have a correct and positive attitude and knowledge towards such patients. We aimed to assess the attitudes in a sample of health care workers (HCW) working in different hospitals and clinics and medical students in Georgia towards HIV infected people and drug users in Tbilisi. Method: We conducted a cross-sectional study to assess attitudes of health care workers towards people living with HIV and drug users in hospitals and clinics in Tbilisi. The study was carried out from 1st of May 2020 till 30th of September 2020. Data were collected using a self-administered structured online questionnaire. With this tool we evaluated four facets of attitudes: Discrimination, Acceptance of HIV/AIDS patients, Acceptance of drug users and Fear. All data were imported and analyzed with the software SPSS 22 for windows. Results: In total data was collected from168 respondents, that among them 107 (65%) were women and majority of the participants were medical doctors. Women had more acceptance attitudes rather than men towards drug abusers. We found significant differences regarding expressing negative attitudes among HCW who were more than 50 years old comparing with other age groups in all four aspects. Medical doctors expressed more acceptances towards people with HIV and drug users comparing two other groups. Also our study revealed that the group with working experience 21 years and more, showed more discriminatory attitudes comparing other groups. Conclusion: Based on our study findings, there are significant differences regarding respondent’s attitudes based on gender, medical specialty and working experience in health care system. People struggling with HIV and drug use need nonjudgmental and positive behaviors from health care workers and physicians in order to help them for harm reduction and receiving appropriate treatment.

Keywords: hiv, addiction, attitudes, healthcare workers

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Authors: Mohammed Badereldien, Rezk Diab, Mohamoud Ali, Ayman Aboelkassem

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The stone surfaces of historical architectural heritage in Egypt are under threat from of various environmental factors such as temperature fluctuation, humidity, pollution, and microbes. Due to these factors, the facades of buildings are deteriorating deformation and disfiguration of external decoration and the formation of black accretion also often from the stone works. The aim of this study is to evaluate the effectiveness of CaCO₃ nano-particles as consolidation and protection material for calcareous stone monuments. Selected tests were carried out in order to estimate the superficial consolidating and protective effect of the treatment. When applied the nanoparticles dispersed in the acrylic copolymer; poly ethylmethacrylate (EMA)/methylacrylate (MA) (70/30, respectively) (EMA)/methylacrylate (MA) (70/30, respectively). The synthesis process of CaCO₃ nanoparticles/polymer nano-composite was prepared using in situ emulsion polymerization system. The consolidation and protection were characterized by TEM, while the penetration depth, re-aggregating effects of the deposited phase, and the surface morphology before and after treatment were examined by SEM (Scanning Electron Microscopy). Improvement of the stones' mechanical properties was evaluated by compressive strength tests. Changes in water-interaction properties were evaluated by water absorption capillarity measurements, and colorimetric measurements were used to evaluate the optical appearance. Together the results appear to demonstrate that CaCO₃/polymer nanocomposite is an efficient material for the consolidation of limestone architecture and monuments. As compared with samples treated with pure acrylic copolymer without Calcium carbonate nanoparticles, for example, CaCO₃ nanoparticles are completely compatible, strengthening limestone against thermal aging and improving its mechanical properties.

Keywords: calcium carbonate nanoparticles, consolidation, nanocomposites, calcareous stone, colorimetric measurements, compressive strength

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Authors: Syed Ameer Haider Jafri

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The primary goal of a root canal treatment in deciduous teeth is to eliminate infection and to retain the tooth in a functional state until it gets physiologically exfoliated and replaced by permanent successor. Important requisite of a root canal filling material for primary teeth is that, it should resorb at a similar rate as the roots of primary tooth, be harmless to the periapical tissue and to the permanent tooth germ, resorb readily if pushed beyond the apex, be antiseptic, radio-opaque, should not shrink, adhere to the walls, not discolor the tooth and easy to fill & remove, if required at any stage. Presently available, commonly used obturating materials for primary teeth are zinc oxide eugenol, calcium hydroxide and iodoform based pastes. None of these materials so far meet the ideal requirement of root canal filling material. So in search of ideal obturating material, this study was planed, in which mixture of calcium hydroxide, zinc oxide & sodium fluoride and mixture of calcium hydroxide & sodium fluoride was compared clinically and radiographically with calcium hydroxide for the obturation of root canals of 75 carious exposed primary mandibular second molars of 59 children aged 4-9 years. All the three material shows good results, but after a follow-up of 9 months mixture of calcium hydroxide, two percent sodium fluoride & zinc oxide powder closely follow the resorption of root, mixture of calcium hydroxide, two percent sodium fluoride follow resorption of root in the beginning but later on majority of cases shows faster resorption whereas calcium hydroxide starts depleting from the canal from the beginning even as early as 3 months. Thus mixture of calcium hydroxide, two percent sodium fluoride & zinc oxide found to be best obturaring material for primary tooth.

Keywords: obturating material, primary teeth, root canal treatment, success rate

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Authors: Ekaterina Zubkova, Irina Beloglazova, Iurii Stafeev, Konsyantin Dergilev, Yelena Parfyonova, Mikhail Menshikov

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Mesenchymal stromal cells from adipose tissue (MSC) currently are widely used in regenerative medicine to restore the function of damaged tissues, but that is significantly hampered by their heterogeneity. One of the modern approaches to overcoming this obstacle is the polarization of cell subpopulations into a specific phenotype under the influence of cytokines and other factors that activate receptors and signal transmission to cells. We polarized MSC with factors affecting the inflammatory signaling and functional properties of cells, followed by verification of their expression profile and ability to affect the polarization of macrophages. RT-PCR evaluation showed that cells treated with LPS, interleukin-17, tumor necrosis factor α (TNF α), primarily express pro-inflammatory factors and cytokines, and after treatment with polyninosin polycytidic acid and interleukin-4 (IL4) anti-inflammatory factors and some proinflammatory factors. MSC polarized with pro-inflammatory cytokines showed a more robust pro-angiogenic effect in fibrin gel bead 3D angiogenesis assay. Further, we evaluated the possibility of paracrine effects of MSCs on the polarization of intact macrophages. Polarization efficiency was assesed by expression of M1/M2 phenotype markers CD80 and CD206. We showed that conditioned media from MSC preincubated in the presence of IL-4 cause an increase in CD206 expression similar to that observed in M2 macrophages. Conditioned media from MSC polarized in the presence of LPS or TNF-α increased the expression of CD80 antigen in macrophages, similar to that observed in M1 macrophages. In other cases, a pronounced paracrine effect of MSC on the polarization of macrophages was not detected. Thus, our study showed that the polarization of MSC along the pro-inflammatory or anti-inflammatory pathway allows us to obtain cell subpopulations that have a multidirectional modulating effect on the polarization of macrophages. (RFBR grants 20-015-00405 and 18-015-00398.)

Keywords: angiogenesis, cytokines, mesenchymal, polarization, inflammation

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Authors: Suvidha Gupta, R. A. Pandey, Sanjay Pawar

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The effluents from various food processing industries are found with high BOD, COD, suspended solids, nitrate, and phosphate. Mixotrophic growth of microalgae using food processing industrial wastewater as an organic carbon source has emerged as more effective and energy intensive means for the nutrient removal and COD reduction. The present study details the treatment of non-sterilized unfiltered food processing industrial wastewater by microalgae for nutrient removal as well as to determine the tolerance to COD by taking different dilutions of wastewater. In addition, the effect of different inoculum percentages of microalgae on removal efficiency of the nutrients for given dilution has been studied. To see the effect of dilution and COD tolerance, the wastewater having initial COD 5000 mg/L (±5), nitrate 28 mg/L (±10), and phosphate 24 mg/L (±10) was diluted to get COD of 3000 mg/L and 1000 mg/L. The experiments were carried out in 1L conical flask by intermittent aeration with different inoculum percentage i.e. 10%, 20%, and 30% of Chlorella sp. isolated from nearby area of NEERI, Nagpur. The experiments were conducted for 6 days by providing 12:12 light- dark period and determined various parameters such as COD, TOC, NO3-- N, PO4-- P, and total solids on daily basis. Results revealed that, for 10% and 20% inoculum, over 90% COD and TOC reduction was obtained with wastewater containing COD of 3000 mg/L whereas over 80% COD and TOC reduction was obtained with wastewater containing COD of 1000 mg/L. Moreover, microalgae was found to tolerate wastewater containing COD 5000 mg/L and obtained over 60% and 80% reduction in COD and TOC respectively. The obtained results were found similar with 10% and 20% inoculum in all COD dilutions whereas for 30% inoculum over 60% COD and 70% TOC reduction was obtained. In case of nutrient removal, over 70% nitrate removal and 45% phosphate removal was obtained with 20% inoculum in all dilutions. The obtained results indicated that Microalgae assisted nutrient removal gives maximum COD and TOC reduction with 3000 mg/L COD and 20% inoculum. Hence, microalgae assisted wastewater treatment is not only effective for removal of nutrients but also can tolerate high COD up to 5000 mg/L and solid content.

Keywords: Chlorella sp., chemical oxygen demand, food processing industrial wastewater, mixotrophic growth

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Authors: Sally A. El Awdan

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Objective and Design: The purpose of this study was to evaluate the anti inflammatory, anti-arthritic and analgesic effects of antidepressants. Methods: Carrageenan model was used to assess effect on acute inflammation. Paw volume were measured at 1, 2, 3 and 4th hour post challenge. Anti-nociceptive effect was evaluated by hot plate method. Chronic inflammation was developed using Complete Freund's Adjuvant (CFA). The animals were injected with Freund’s adjuvant in sub-plantar tissue of the right posterior paw. Paw volume, ankle flexion scores, adjuvant-induced hyperalgesia and serum cytokine levels were assessed. Results: Results obtained demonstrate that mirtazapine, venalfaxine and escitalopram significantly and dose-dependently inhibited carrageenan-induced rat paw oedema. Mirtazapine, venalfaxine and escitalopram increased the reaction time of rats in hot plate test. We observed an increase in paw volume, ankle flexion scores, thermal hyperalgesia, serum levels of interleukin-1β, PGE2 and TNF-α, induced by intraplantar CFA injection. Regular treatment up to 28 days of adjuvant-induced arthritic rats with mirtazapine, venalfaxine and escitalopram showed anti anti-inflammatory and analgesic activities by suppressing the paw volume, recovering the paw withdrawal latency, and by inhibiting the ankle flexion scores in CFA-induced rats. In addition significant reduction in serum levels of interleukin-1β, PGE2 and TNF-α level in arthritic rats was reduced by treatment with drugs. Conclusion: These results suggest that antidepressants have significant anti-inflammatory and anti-nociceptive effects in acute and chronic models in rats, which may be associated with the reduction of interleukin-1β, PGE2 and TNF-α levels.

Keywords: antidepressants, carrageenan, anti-nociceptive, Complete Freund's Adjuvant

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Authors: Washaya Soul, Mupangwa John, Mapfumo Lizwell, Muchenje Voster

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Ruminant animals contribute a considerable amount of methane to the atmosphere, which is a cause of concern for global warming. Two studies were conducted in beef and goats where the studies aimed to determine the enteric CH₄ levels from a herd of beef cows raised on semi-arid rangelands and to evaluate the effect of supplementing goats with forage legumes: Vigna unguiculata and Lablab purpureus on enteric methane production. A total of 24 cows were selected from Boran and Nguni cows (n = 12 per breed) from two different farms; parity (P1 – P4) and season (dry vs. wet) were considered predictor variables in the first experiment. Eighteen goats (weaners, 9 males, 9 females) were used, in which sex and forage species were predictor variables in the second experiment. Three treatment diets were used in goats. Methane was measured using a Laser methane detector [LMD] for six consecutive days and repeated once after every three months in beef cows and once every week for 6 weeks in goats during the post-adaptation period. Parity and breed had no effects on CH₄ production in beef cows; however, season significantly influenced CH₄ outputs. Methane production was higher (P<0.05) in the dry compared to the wet season, 31.1CH₄/DMI(g/kg) and 28.8 CH₄/DMI(g/kg) for the dry and wet seasons, respectively. In goats, forage species and sex of the animal affected enteric methane production (P<0.05). Animals produce more gas when ruminating than feeding or just standing for all treatments. The control treatment exhibited higher (P<0.05) methane emissions per kg of DMI. Male goats produced more methane compared to females (17.40L/day; 12.46 g/kg DMI and 0.126g/day) versus (15.47L/day, 12.28 g/kg DMI, 0.0109g/day) respectively. It was concluded that cows produce more CH₄/DMI during the dry season, while forage legumes reduce enteric methane production in goats, and male goats produce more gas compared to females. It is recommended to introduce forage legumes, particularly during the dry season, to reduce the amount of gas produced.

Keywords: beef cows, extensive grazing system, forage legumes, greenhouse gases, goats Laser methane detector.

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Authors: Antonio Munar-Frau, Sascha Klismoch, Manfred Schmolz, Federico Hernandez-Alfaro, Jordi Caballe-Serrano

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Introduction: Biocompatibility of biomaterials has been proposed as one of the main criteria for treatment success. For guided bone regeneration (GBR), barrier membranes present a conflict given the number of origins and modifications of these materials. The biologic response to biomaterials is orchestrated by a series of events leading to the integration or rejection of the biomaterial, posing questions such as if a longer occlusive property may trigger an inflammatory reaction. Whole blood cultures are a solution to study the immune response to drugs or biomaterials during the first 24-48 hours. The aim of this study is to determine the early immune response of different origins and chemical modifications of barrier membranes. Materials & Methods: 5 different widely used barrier membranes were included in this study: Acellular dermal matrix (AlloDerm, LifeCell®), Porcine Peritoneum (BioGide, Geistlich Pharma®), Porcine Pericardium (Jason, Botiss Biomaterials GmbH®), Porcine Cross-linked collagen (Ossix Plus, Datum Dental®) and d-PTFE (Cytoplast TXT, Osteogenics Biomedical®). Blood samples were extracted from 3 different healthy donors and incubated with the different samples of barrier membranes for 24 hours. After the incubation time, serum samples were obtained and analyzed by means of biocompatibility assays taking into account 42 markers. Results: In an early stage of the inflammatory response, the Acellular dermal matrix, porcine peritoneum and porcine cross-linked collagen expressed similar patterns of cytokine expression with a great manifestation of ENA 78. Porcine pericardium and d-PTFE presented similar cytokine activation, especially for MMP-3 and MMP-9, although other cytokines were highlighted with lower expression. For the later immune response, Porcine peritoneum and acellular dermal matrix MCP-1 and IL-15 were evident. Porcine pericardium, porcine cross-linked collagen and d-PTFE presented a high expression of IL-16 and lower manifestation of other cytokines. Different behaviors depending on an earlier or later stage of the inflammation process were observed. Barrier membrane inflammatory expression does not only differ depending on the origin, variables such as treatment of the collagen and polymers may also have a great impact on the cytokine expression of the studied barrier membranes during inflammation. Conclusions: Surface treatment and modifications might affect the biocompatibility of the membranes, as different cytokine expressions were evidently depending on the origin of the biomaterial. This study is only a brushstroke regarding the biocompatibility of materials, as it is one of the pioneer studies for ex vivo barrier membranes assays. Studies regarding surface modification are needed in order to clarify mystifications of barrier membrane science.

Keywords: biomaterials, bone regeneration, biocompatibility, inflammation

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Authors: Viviana Manzulli, Luigina Serrecchia, Adelia Donatiello, Valeria Rondinone, Sabine Zange, Alina Tscherne, Antonio Parisi, Antonio Fasanella

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Anthrax is a zoonotic disease that affects a wide range of animal species (primarily ruminant herbivores), and can be transmitted to humans through consumption or handling of contaminated animal products. The etiological agent B.anthracis is able to survive in unfavorable environmental conditions by forming endospore which remain viable in the soil for many decades. Furthermore, B.anthracis is considered as one of the most feared agents to be potentially misused as a biological weapon and the importance of the disease and its treatment in humans has been underscored before the bioterrorism events in the United States in 2001. Due to the often fatal outcome of human cases, antimicrobial susceptibility testing plays especially in the management of anthrax infections an important role. In Italy, animal anthrax is endemic (predominantly found in the southern regions and on islands) and is characterized by sporadic outbreaks occurring mainly during summer. Between 2012 and 2017 single human cases of cutaneous anthrax occurred. In this study, 90 diverse strains of B.anthracis, isolated in Italy from 2001 to 2017, were screened to their susceptibility to sixteen clinically relevant antimicrobial agents by using the broth microdilution method. B.anthracis strains selected for this study belong to the strain collection stored at the Anthrax Reference Institute of Italy located inside the Istituto Zooprofilattico Sperimentale of Puglia and Basilicata. The strains were isolated at different time points and places from various matrices (human, animal and environmental). All strains are a representative of over fifty distinct MLVA 31 genotypes. The following antibiotics were used for testing: gentamicin, ceftriaxone, streptomycin, penicillin G, clindamycin, chloramphenicol, vancomycin, linezolid, cefotaxime, tetracycline, erythromycin, rifampin, amoxicillin, ciprofloxacin, doxycycline and trimethoprim. A standard concentration of each antibiotic was prepared in a specific diluent, which were then twofold serial diluted. Therefore, each wells contained: bacterial suspension of 1–5x104 CFU/mL in Mueller-Hinton Broth (MHB), the antibiotic to be tested at known concentration and resazurin, an indicator of cell growth. After incubation overnight at 37°C, the wells were screened for color changes caused by the resazurin: a change from purple to pink/colorless indicated cell growth. The lowest concentration of antibiotic that prevented growth represented the minimal inhibitory concentration (MIC). This study suggests that B.anthracis remains susceptible in vitro to many antibiotics, in addition to doxycycline (MICs ≤ 0,03 µg/ml), ciprofloxacin (MICs ≤ 0,03 µg/ml) and penicillin G (MICs ≤ 0,06 µg/ml), recommend by CDC for the treatment of human cases and for prophylactic use after exposure to the spores. In fact, the good activity of gentamicin (MICs ≤ 0,25 µg/ml), streptomycin (MICs ≤ 1 µg/ml), clindamycin (MICs ≤ 0,125 µg/ml), chloramphenicol(MICs ≤ 4 µg/ml), vancomycin (MICs ≤ 2 µg/ml), linezolid (MICs ≤ 2 µg/ml), tetracycline (MICs ≤ 0,125 µg/ml), erythromycin (MICs ≤ 0,25 µg/ml), rifampin (MICs ≤ 0,25 µg/ml), amoxicillin (MICs ≤ 0,06 µg/ml), towards all tested B.anthracis strains demonstrates an appropriate alternative choice for prophylaxis and/or treatment. All tested B.anthracis strains showed intermediate susceptibility to the cephalosporins (MICs ≥ 16 µg/ml) and resistance to trimethoprim (MICs ≥ 128 µg/ml).

Keywords: Bacillus anthracis, antibiotic susceptibility, treatment, minimum inhibitory concentration

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Authors: András Fülöp, Lejla Heilmann, Zsolt Szabó, Ákos Koós

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Microbial fuel cells (MFCs) present a sustainable biotechnological solution to future energy demands. The aim of this study was to construct soil based, single cell, membrane-less MFC systems, operated without treatment to continuously power on-site monitoring and control systems during the soil bioremediation processes. Our Pseudomonas aeruginosa 541 isolate is an ideal choice for MFCs, because it is able to produce pyocyanin which behaves as electron-shuttle molecule, furthermore, it also has a significant antimicrobial effect. We tested several materials and structural configurations to obtain long term high power output. Comparing different configurations, a proton exchange membrane-less, 0.6 m long with 0.05 m diameter MFC tubes offered the best long-term performances. The long-term electricity production were tested from starch, yeast extract (YE), carboxymethyl cellulose (CMC) with humic acid (HA) as a mediator. In all cases, 3 kΩ external load have been used. The two best-operated systems were the Pseudomonas aeruginosa 541 containing MFCs with 1 % carboxymethyl cellulose and the MFCs with 1% yeast extract in the anode area and 35% hydrogel in the cathode chamber. The first had 3.3 ± 0.033 mW/m2 and the second had 4.1 ± 0.065 mW/m2 power density values. These systems have operated for 230 days without any treatment. The addition of 0.2 % HA and 1 % YE referred to the volume of the anode area resulted in 1.4 ± 0.035 mW/m2 power densities. The mixture of 1% starch with 0.2 % HA gave 1.82 ± 0.031 mW/m2. Using CMC as retard carbon source takes effect in the long-term bacterial survivor, thus enable the expression of the long term power output. The application of hydrogels in the cathode chamber significantly increased the performance of the MFC units due to their good water retention capacity.

Keywords: microbial fuel cell, bioremediation, Pseudomonas aeruginosa, biotechnological solution

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Authors: Simran Gill, Samuel Bartels

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Turfgrass is an important component of urban and rural lawns and landscapes. However, broadleaf weeds such as dandelions (Taraxacum officinale) and white clovers (Trifolium repens) pose major challenges to the health and aesthetics of turfgrass fields. Chemical weed control methods, such as 2,4-D weedicides, have been widely deployed; however, their safety and environmental impacts are often debated. Alternative, environmentally friendly control methods have been considered, but experimental tests for their effectiveness have been limited. This study investigates the use and effectiveness of nitrogen and iron compounds as nutrient management methods of weed control. In a two-phase experiment, the first conducted on a blend of cool season turfgrasses in plastic containers, the blend included Perennial ryegrass (Lolium perenne), Kentucky bluegrass (Poa pratensis) and Creeping red fescue (Festuca rubra) grown under controlled conditions in the greenhouse, involved the application of different combinations of nitrogen (urea and ammonium sulphate) and iron (chelated iron and iron sulphate) compounds and their combinations (urea × chelated iron, urea × iron sulphate, ammonium sulphate × chelated iron, ammonium sulphate × iron sulphate) contrasted with chemical 2, 4-D weedicide and a control (no application) treatment. There were three replicates of each of the treatments, resulting in a total of 30 treatment combinations. The parameters assessed during weekly data collection included a visual quality rating of weeds (nominal scale of 0-9), number of leaves, longest leaf span, number of weeds, chlorophyll fluorescence of grass, the visual quality rating of grass (0-9), and the weight of dried grass clippings. The results drawn from the experiment conducted over the period of 12 weeks, with three applications each at an interval of every 4 weeks, stated that the combination of ammonium sulphate and iron sulphate appeared to be most effective in halting the growth and establishment of dandelions and clovers while it also improved turf health. The second phase of the experiment, which involved the ammonium sulphate × iron sulphate, weedicide, and control treatments, was conducted outdoors on already established perennial turf with weeds under natural field conditions. After 12 weeks of observation, the results were comparable among the treatments in terms of weed control, but the ammonium sulphate × iron sulphate treatment fared much better in terms of the improved visual quality of the turf and other quality ratings. Preliminary results from these experiments thus suggest that nutrient management based on nitrogen and iron compounds could be a useful environmentally friendly alternative for controlling broadleaf weeds and improving the health and quality of turfgrass.

Keywords: broadleaf weeds, nitrogen, iron, turfgrass

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Authors: Daniel Afolayan, Christina Olawepo, Francis Olowookanga, Nguhemen Tingir, Olawale Fadare, John Oko

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In Nigeria, traditional birth attendants (TBAs) can play an important role in the prevention of mother-to-child transmission of HIV. However, their role in improving access to antiretroviral therapy (ART) is unclear. Catholic Caritas Foundation of Nigeria (Caritas Nigeria) is an implementing agency supporting increased access to HIV testing and treatment services in Lagos state through health facilities including Mother Theresa Hospital. Despite intra-facility testing and community outreaches, ART uptake at Mother Theresa Hospital, Lagos was low with 6 individuals on antiretroviral drugs 3 months post-activation. This study explored improving access to ART through linkages with TBAs for ART uptake at the facility. Plan-Do-Study-Act model was used. The goal was to improve uptake of ART from 6 to 80 in 5 months (end of project year). Scanning revealed a network of 15 TBAs with potential as satellites for HIV testing. Caritas Nigeria linked the facility with 15 TBAs who were provided with HIV test kits and trained on HIV testing services for provider-initiated testing and outreaches. Weekly reports and referrals of positives were received, tracked and feedback given on testing yield. These TBAs serve individuals of various age and gender at their trado-medical centres. At the end of 5 months, HIV testing increased by 10,575 (78% from TBAs) and HIV positives obtained improved by 77 (44.2% from TBAs). 55 new individuals were enrolled and commenced on ART (61.8% from TBAs). There was a successful linkage of all clients with escort services due to incentives. Total uptake of ART was 61 (76.3% of target). Structured partnerships between TBAs and HIV care and treatment centers should be strengthened to improve access to ART.

Keywords: access improvement, antiretroviral therapy, traditional birth attendants, uptake

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Authors: Shamim Mushtaq, Moazzam Shahid

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Breast cancer (BC) claims the lives of half a million women every year and is the most common cause of death in the developing world. In 2019, it was estimated that BC alone accounts for 15% of all cancer deaths in younger women (aged < 45 years old) with advanced-stage lung metastasis. According to the World Health Organization & International Union against Cancer, in Asia, a high number of cancer-related deaths will be observed in 2020, whereas the burden will be reduced in Western countries due to awareness about the disease, better health facilities and advanced treatments. In the last 15 years, it has been reported that the incidence of BC has increased by 1.1% among Asian compared to the US population from 2003 to 2012. To date, several BC biological subtypes have been reported so far, which are associated with different treatment responses. The heterogeneity and diversity of BC reflected these different subtypes, including Luminal A (23.7% prevalence) and B (38.8% prevalence) that have pathological estrogen receptor (ER+)-positive tumors, the human epidermal growth factor receptor 2 (HER2) (11.2% prevalence) and triple-negative breast cancer (TNBC) (25% prevalence). According to Shaukat Khanum Memorial Cancer Hospital and Research Centre – Pakistan, ten years of data showed that among 636 BC patients, 30.5% had TNBC who were <40 years of age, which is an extremely alarming situation. Therefore, there is a dire need to explore and develop therapeutic targets for the treatment of early TNBC. Since the last decade, unfortunately, there has been little success in understanding the complexity of TNBC and in discovering new biological therapeutic targets. However, conventional chemotherapy is the only choice of treatment for TNBC patients. Many investigators revealed advances in multi-omics (multiple "omes", e.g., genome, proteome, transcriptome, epigenome, and microbiome) which were later identified as actionable targets and increased prevalence in TNBC patients. However, various drugs have been identified so far which are related to a particular diagnostic and prognostic biomarker. For example, Epidermal growth factor receptor ( EGFR or ErbB-1), HER-2/neu (ErbB-2), HER-3 (ErbB-3), and HER-4 (ErbB-4). Protein Transglin-2 (TAGLN 2 ) and Profilins-1 (Pfn-1 ) are the ubiquitously expressed large family of proteins present in all eukaryotes, enabling actin cytoskeletal reorganization. It is known that the oncogenic transformation of cells is accompanied by alteration in the actin cytoskeleton. There are causal connections between altered expression of actin cytoskeletal regulators and cancer progression. Our case-control study identified TAGLN-2 and Pfn-1 proteins in TNBC blood by mass spectrometry. Both TAGLN-2 and Pfn-1 proteins are differentially expressed in early and advanced stages of TNBS patients, which could be potential predictors or therapeutic targets for TNBC.

Keywords: TNBC, blood biomarkers, mass spectrometry, qPCR, ELISA

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Authors: Marina S. Basta, Kirollos S. Basta

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Cosmetic dermatology procedures have witnessed exponential growth and diversification over the last 10 years. Thus, the purpose of this study was to collect data about the latest trends for cosmetic procedures reported by dermatologists during the year 2018. This study was performed by American Society for Dermatologic Surgery (ASDS) in 2018 through sending survey invitations to 3,358 practicing dermatologists in the U.S. containing streamline questions as well as statistical questions targeted to specific analysis of cosmetic dermatology trends. Out of the targeted physicians, only 596 dermatologists reply to the survey invitation (15% overall response rate). It was noted that data collected from that survey was generalized to represent all ASDS members. Results show that there is an increase in cosmetic dermatology procedures since 12.5 million procedures were reported for 2018 compared to only 7.8 million for 2012. Injectable neuromodulators and soft tissue fillers have topped the list with a 3.7 million procedure count. Body sculpting, chemical peeling, hair transplantation, and microneedling procedures were reported to be 1.57 million cases combined. Also, the top two procedures using laser were represented in wrinkle treatment as well as sun damage correction, while the lowest two trends for laser usage were for treatments of tattoos and birthmarks. Cryolipolysis was found to be at the head of body sculpting procedures with 287,435 cases, while tumescent liposuction was reported as the least performed body sculpting procedure (18,286 cases). In conclusion, comparing the procedural trends for the last 7 years has indicated that there has been a 78% increase in soft tissue filler treatment compared to 2012. In addition, it was further noted that laser procedures scored 74% increase in the last 7 years while body contouring procedures have had four folds increase in general compared to 2012.

Keywords: cosmetic dermatology, ASDS procedure survey, laser, body sculpting

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Authors: R. Suresh, C. B. Singh, A. K. Sarda

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Background: Over the decades, several surgical techniques have been developed to treat anal fistulas with variable success rates and complications. Large amount of work has been done in radiofrequency excision of the fistula for several years but no work has been done for ablating the tract. Therefore one can consider for obliteration ofanal fistula by Radiofrequency ablation (RFA). Material and Methods: A randomized controlled clinical trial was conducted at Lok Nayak Hospital, where a total of 40 patients were enrolled in the study and they were randomly assigned to Group I (fistulectomy)(n=20) and Group II (RFA) (n=20). Aim of the study was to compare the efficacy of RFA of fistula versus fistulectomy in the treatment of a low anal fistula and to evaluate RFA as an effective alternative to fistulectomy with respect to time taken for wound healing as primary outcome and post-operative pain, time taken to return to work as secondary outcomes. Patients with simple low anal fistulas, single internal and external opening, not more than two secondary tracts were included. Patients with high complex fistula, fistulas communicating with cavity, fistula due to condition like tuberculosis, Crohn's, malignancy were excluded from the study. Results: Both groups were comparable with respect to age, sex ratio, type of fistula. Themean healing time was significantly shorter in group II (41.02 days) than in group I(62.68 days).The mean operative time was significantly shorter in groupII (21.40 min) than in group I(28.50 min). The mean time taken to return to work was significantly shorter in group II(8.30 days)than in group I(12.01 days).There was no significant difference in the post operative hospital stay, mean postoperative pain score, wound infection and recurrence between the two groups. Conclusion: The patients who underwent RFA of fistula had shorter wound healing time, operative time and time taken to return to work when compared to those who underwent fistulectomy and therefore RFA shows outcome comparable to fistulectomy in the treatment of low anal fistula.

Keywords: fistulectomy, low anal fistula, radio frequency ablation, wound healing

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Authors: Sharif Abdelghany

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Polymeric nanoparticles have been widely investigated as a controlled release drug delivery platform for the treatment of tuberculosis (TB). These nanoparticles were also readily internalised into macrophages, leading to high intracellular drug concentration. In this study two anti-TB drugs, amikacin and moxifloxacin were encapsulated into PLGA nanoparticles. The novelty of this work appears in: (1) the efficient encapsulation of two hydrophilic second-line anti-TB drugs, and (2) intramacrophage delivery of this synergistic combination potentially for rapid treatment of multi-drug resistant TB (MDR-TB). Two water-oil-water (w/o/w) emulsion strategies were employed in this study: (1) alginate coated PLGA nanoparticles, and (2) alginate entrapped PLGA nanoparticles. The average particle size and polydispersity index (PDI) of the alginate coated PLGA nanoparticles were found to be unfavourably high with values of 640 ± 32 nm and 0.63 ± 0.09, respectively. In contrast, the alginate entrapped PLGA nanoparticles were within the desirable particle size range of 282 - 315 nm and the PDI was 0.08 - 0.16, and therefore were chosen for subsequent studies. Alginate entrapped PLGA nanoparticles yielded a drug loading of over 10 µg/mg powder for amikacin, and more than 5 µg/mg for moxifloxacin and entrapment efficiencies range of approximately 25-31% for moxifloxacin and 51-59% for amikacin. To study macrophage uptake efficiency, the nanoparticles of alginate entrapped nanoparticle formulation were loaded with acridine orange as a marker, seeded to THP-1 derived macrophages and viewed under confocal microscopy. The particles were readily internalised into the macrophages and highly concentrated in the nucleus region. Furthermore, the anti-mycobacterial activity of the drug-loaded particles was evaluated using M. tuberculosis-infected macrophages, which revealed a significant reduction (4 log reduction) of viable bacterial count compared to the untreated group. In conclusion, the amikacin-moxifloxacin alginate entrapped PLGA nanoparticles are promising for further in vivo studies.

Keywords: moxifloxacin and amikacin, nanoparticles, multidrug resistant TB, PLGA

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Authors: Drago Bratkovic, Curtis Gravance, David Ketteridge, Ravi Krishnan, Michael Imperiale

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The mucopolysaccharidoses (MPSs) are a group of lysosomal storage diseases that have a common defect in the catabolism of glycosaminoglycans (GAGs). MPS I is the most common of the MPS diseases. Manifestations of MPS I include coarsening of facial features, corneal clouding, developmental delay, short stature, skeletal manifestations, hearing loss, cardiac valve disease, hepatosplenomegaly, and umbilical and inguinal hernias. Treatments for MPS I restore or activate the missing or deficient enzyme in the case of enzyme replacement therapy (ERT) and haematopoietic stem cell transplantation (HSCT). Pentosan polysulfate sodium (PPS) is a potential treatment to improve bone and joint manifestations of MPS I. The mechanisms of action of PPS that are relevant to the treatment of MPS I are the ability to: (i) Reduce systemic and accumulated GAG, (ii) Reduce inflammatory effects via the inhibition of NF-kB, resulting in the reduction in pro-inflammatory mediators. (iii) Reduce the expression of the pain mediator nerve growth factor in osteocytes from degenerating joints. (iv) Inhibit the cartilage degrading enzymes related to joint dysfunction in MPS I. PPS is being evaluated as an adjunctive therapy to ERT and/or HSCT in an open-label, single-centre, phase 2 study. Patients are ≥ 5 years of age with a diagnosis of MPS I and previously received HSCT and/or ERT. Three white, female, patients with MPS I-Hurler, ages 14, 15, and 19 years, and one, white male patient aged 15 years are enrolled. All were diagnosed at ≤2 years of age. All patients received HSCT ≤ 6 months after diagnosis. Two of the patients were treated with ERT prior to HSCT, and 1 patient received ERT commencing 3 months prior to HSCT. Two patients received 0.75mg/kg and 2 patients received 1.5mg/kg of PPS. PPS was well tolerated at doses of 0.75 and 1.5 mg/kg to 47 weeks of continuous dosing. Of the 19 adverse events (AEs), 2 were related to PPS. One AE was moderate (pre-syncope) and 1 was mild (injection site bruising), experienced in the same patient. All AEs were reported as mild or moderate. There have been no SAEs. One subject experienced a COVID-19 infection and PPS was interrupted. The MPS I signature GAG fragments, sulfated disaccharide and UA-HNAc S, tended to decrease in 3 patients from baseline through Week 25. Week 25 GAG data are pending for the 4th patient. Overall, most biomarkers (inflammatory, cartilage degeneration, and bone turnover) evaluated in the 3 patients with 25-week assessments have indicated either no change or a reduction in levels compared to baseline. In 3 patients, there was a trend toward improvement in the 2MWT from baseline to Week 48 with > 100% increase in 1 patient (01-201). In the 3 patients that had Week 48 assessments, patients and proxies reported improvement in PGIC, including “worthwhile difference” (n=1), or “made all the difference” (n=2).

Keywords: MPS I, pentosan polysulfate sodium, clinical study, 2MWT, QoL

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Authors: Kaling Taki, Rohit Gahlot, Manish Kumar

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Disposal of Sewage Sludge (SS) is a big issue especially in developing nation like India, where there is no control in the dynamicity of SS produced. The present research work demonstrates the potential application of SS amended with varying percentage (0-100%) of Fly Ash (FA) for brick manufacturing as an alternative of SS management. SS samples were collected from Jaspur sewage treatment plant (Ahmedabad, India) and subjected to different preconditioning treatments: (i) atmospheric drying (ii) pulverization (iii) heat treatment in oven (110°C, moisture removal) and muffle furnace (440°C, organic content removal). Geotechnical parameters of the SS were obtained as liquid limit (52%), plastic limit (24%), shrinkage limit (10%), plasticity index (28%), differential free swell index (DFSI, 47%), silt (68%), clay (27%), organic content (5%), optimum moisture content (OMC, 20%), maximum dry density (MDD, 1.55gm/cc), specific gravity (2.66), swell pressure (57kPa) and unconfined compressive strength (UCS, 207kPa). For FA liquid limit, plastic limit and specific gravity was 44%, 0% and 2.2 respectively. Initially, for brick casting pulverized SS sample was heat treated in a muffle furnace around 440℃ (5 hours) for removal of organic matter. Later, mixing of SS, FA and water by weight ratio was done at OMC. 7*7*7 cm3 sample mold was used for casting bricks at MDD. Brick samples were then first dried in room temperature for 24 hours, then in oven at 100℃ (24 hours) and finally firing in muffle furnace for 1000℃ (10 hours). The fired brick samples were then cured for 3 days according to Indian Standards (IS) common burnt clay building bricks- specification (5th revision). The Compressive strength of brick samples (0, 10, 20, 30, 40, 50 ,60, 70, 80, 90, 100%) of FA were 0.45, 0.76, 1.89, 1.83, 4.02, 3.74, 3.42, 3.19, 2.87, 0.78 and 4.95MPa when evaluated through compressive testing machine (CTM) for a stress rate of 14MPa/min. The highest strength was obtained at 40% FA mixture i.e. 4.02MPa which is much higher than the pure SS brick sample. According to IS 1077: 1992 this combination gives strength more than 3.5 MPa and can be utilized as common building bricks. The loss in weight after firing was much higher than the oven treatment, this might be due to degradation temperature higher than 100℃. The thermal conductivity of the fired brick was obtained as 0.44Wm-1K-1, indicating better insulation properties than other reported studies. TCLP (Toxicity characteristic leaching procedure) test of Cr, Cu, Co, Fe and Ni in raw SS was found as 69, 70, 21, 39502 and 47 mg/kg. The study positively concludes that SS and FA at optimum ratio can be utilized as common building bricks such as partitioning wall and other small strength requirement works. The uniqueness of the work is it emphasizes on utilization of FA for stabilizing SS as construction material as a replacement of natural clay as reported in existing studies.

Keywords: Compressive strength, Curing, Fly Ash, Sewage Sludge.

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Authors: Oluyomi Stephen Adeyemi, Kentaro Kato

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Toxoplasma gondii is the etiological agent of toxoplasmosis, a common parasitic disease capable of infecting a range of hosts, including nearly one-third of the human population. Current treatment options for toxoplasmosis patients are limited. In consequence, toxoplasmosis represents a large global burden that is further enhanced by the shortcomings of the current therapeutic options. These factors underscore the need for better anti-T. gondii agents and/or new treatment approach. In the present study, we sought to find out whether preparing and capping nanoparticles (NPs) in amino acids, would enhance specificity toward the parasite versus the host cell. The selection of amino acids was premised on the fact that T. gondii is auxotrophic for some amino acids. The amino acid-nanoparticles (amino-NPs) were synthesized, purified and characterized following established protocols. Next, we tested to determine the anti-T. gondii activity of the amino-NPs using in vitro experimental model of infection. Overall, our data show evidence that supports enhanced and excellent selective action against the parasite versus the host cells by amino-NPs. The findings are promising and provide additional support that warrants exploring the prospects of NPs as alternative anti-parasite agents. In addition, the anti-parasite action by amino-NPs indicates that nutritional requirement of parasite may represent a viable target in the development of better alternative anti-parasite agents. Furthermore, data suggest the anti-parasite mechanism of the amino-NPs involves multiple cellular processes including the production of reactive oxygen species (ROS), modulation of hypoxia-inducing factor-1 alpha (HIF-1α) as well as the activation of kynurenine pathway. Taken together, findings highlight further, the prospects of NPs as alternative source of anti-parasite agents.

Keywords: drug discovery, infectious diseases, mode of action, nanomedicine

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Authors: Chioma J. Nwakamma, Blessing O. Oyedemi, Garuba Omosun

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This research surveys and documents information on medicinal plants and their botanical preparations used in the treatment of children’s ailments in South-Eastern Nigeria. Children under the age of 5 in developing countries suffer from diseases with high morbidity and mortality rate yearly due to inaccessible and unaffordable healthcare. Structured questionnaires were administered to herbal sellers, traditional medicine practitioners, nursing mothers, and adult dwellers to collect data on the names of plants used to treat the conditions, methods of preparation, duration of treatment, adverse effects, and the methods of administration of the plant materials. A total of 135 plants belonging to 55 families were identified for the management of children’s health in the area. Common pediatric ailments which were said to be treated with herbal remedies by the respondents included malaria, pneumonia, stomach ache, diarrhea, dysentery, measles, chickenpox/smallpox, convulsion, jaundice, pile, ringworm, scabies, eczema, stubborn cough, scurvy, catarrh, wounds, boils, insect bites, food poison, cholera, and umbilical cord complications. Percentages of respondents were; herbal sellers (48.2%), traditional medical practitioners (21.6%), nursing mothers (11.1%), and others (19.1%). The most occurring plant families were Euphorbiaceae, Fabaceae, and Apocynaceae, with 8 species of plants each followed by Annonaceae and Asteriaceae with 7 and 6 species, respectively. The recipes were made from the combination of different parts of two or more plant species, and others were made from single plant parts. Methods of extraction were mostly decoction and raw-squeezing out of the juice and infusion, while oral administration was the main route of administration.

Keywords: ethno-botanicals, children’s health, medicinal plants, South-Eastern Nigeria

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