Search results for: bone mineral metabolism

Authors: Mohammadjavad Sotoudeheian, Navid Farahmandian

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Kawasaki disease (KD) is the primary cause of acquired pediatric heart disease as an acute vasculitis. In children with prolonged fever, rash, and inflammation of the mucosa KD must be considered as a clinical diagnosis. There is a persuasive suggestion of immune-mediated damage as the pathophysiologic cascade of KD. For example, the invasion of cytotoxic T-cells supports a viral etiology and the inflammasome of the innate immune system is a critical component in the vasculitis formation in KD. Animal models of KD propose the cytokine profiles, such as increased IL-1 and GM-CSF, which cause vascular damage. CRP and IFN-γ elevated expression and the upregulation of IL-6, and IL-10 production are also described in previous studies. Untreated KD is a critical risk factor for coronary artery diseases and myocardial infarction. Vascular damage may encompass amplified T-cell activity. SMAD3 is an essential molecule in down-regulating T-cells and increasing expression of FoxP3. It has a critical effect in the differentiation of regulatory T-cells. The discrepancy of regulatory T-cells and pro-inflammatory Th17 has been studied in acute coronary syndrome during KD. However in the coronary artery damaged lymphocytes and IgA plasma cells are seen at the lesion locations, the major immune cells in the coronary lesions are monocytes/macrophages and neutrophils. These cells secrete TNF-α, and activates matrix metalloprotease (MMP)-9, reducing the integrity of vessels and prompting patients to arise aneurysm. MMPs can break down the components of the extracellular matrix and assist immune cell movement. IVIG as an effective form of treatment clarified the role of the immune system, which may target pathogenic antigens and regulate cytokine production. Several reports have revealed that in the coronary arteries, high expression of MMP-9 in monocyte/macrophage results in pathologic cascades. Curcumin is a potent antioxidant and anti-inflammatory molecule. Curcumin decreases the production of reactive oxygen and nitrogen species and inhibits transcription factors like AP-1 and NF-κB. Curcumin also contains the characteristics of inhibitory effects on MMPs, especially MMP-9. The upregulation of MMP-9 is an important cellular response. Curcumin treatment caused a reverse effect and down-regulates MMP-9 gene expression which may fund the anti-inflammatory effect. Curcumin inhibits MMP-9 expression via PKC and AMPK-dependent pathways in Human monocytes cells. Elevated expression and activity of MMP-9 are correlated with advanced vascular lesions. AMPK controls lipid metabolism and oxidation, and protein synthesis. AMPK is also necessary for the MMP-9 activity and THP-1 cell adhesion to endothelial cells. Curcumin was shown to inhibit the activation of AMPKα. Compound C (AMPK inhibitor) inhibits MMP-9 expression level. Therefore, through inactivating AMPKs and PKC, curcumin decreases the MMP-9 level, which results in inhibiting monocyte/macrophage differentiation. Compound C also suppress the phosphorylation of three major classes of MAP kinase signaling, suggesting that curcumin may suppress MMP-9 level by inactivation of MAPK pathways. MAPK cascades are activated to induce the expression of MMP-9. Curcumin inhibits MAPKs phosphorylation, which contributes to the down-regulation of MMP-9. This study demonstrated that the potential inhibitory properties of curcumin over MMP-9 lead to a therapeutic strategy to reduce the risk of coronary artery involvement during KD.

Keywords: MMP-9, coronary artery aneurysm, Kawasaki’s disease, curcumin, AMPK, immune system, NF-κB, MAPK

Procedia PDF Downloads 275

Authors: Piacentini Diego, Della Rovere Federica, Fattorini Laura, Lanni Francesca, Cittadini Martina, Altamura Maria Maddalena, Falasca Giuseppina

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Plants have evolved sophisticated mechanisms to cope with environmental cues. Changes in intracellular content and distribution of phytohormones, such as the auxin indole-3-acetic acid (IAA), have been involved in morphogenic adaptation to environmental stresses. In addition to phytohormones, plants can rely on a plethora of small signal molecules able to promptly sense and transduce the stress signals, resulting in morpho/physiological responses thanks also to their capacity to modulate the levels/distribution/reception of most hormones. Among these signaling molecules, nitrogen monoxide (nitric oxide – NO) is a critical component in several plant acclimation strategies to both biotic and abiotic stresses. Depending on its levels, NO increases plant adaptation by enhancing the enzymatic or non-enzymatic antioxidant systems or by acting as a direct scavenger of reactive oxygen/nitrogen (ROS/RNS) species produced during the stress. In addition, exogenous applications of NO-specific donor compounds showed the involvement of the signal molecule in auxin metabolism, transport, and signaling, under both physiological and stress conditions. However, the complex mechanisms underlying NO action in interacting with phytohormones, such as auxins, during metal stress responses are still poorly understood and need to be better investigated. Emphasis must be placed on the response of the root system since it is the first plant organ system to be exposed to metal soil pollution. The monocot Oryza sativa L. (rice) has been chosen given its importance as a stable food for some 4 billion people worldwide. In addition, increasing evidence has shown that rice is often grown in contaminated paddy soils with high levels of heavy metal cadmium (Cd) and metalloid arsenic (As). The facility through which these metals are taken up by rice roots and transported to the aerial organs up to the edible caryopses makes rice one of the most relevant sources of these pollutants for humans. This study aimed to evaluate if NO has a mitigatory activity in the roots of rice seedlings against Cd or As toxicity and to understand if this activity requires interactions with auxin. Our results show that exogenous treatments with the NO-donor SNP alleviate the stress induced by Cd, but not by As, in in-vitro-grown rice seedlings through increased intracellular root NO levels. The damages induced by the pollutants include root growth inhibition, root histological alterations and ROS (H2O2, O2●ˉ), and RNS (ONOOˉ) production. Also, SNP treatments mitigate both the root increase in root IAA levels and the IAA alteration in distribution monitored by the OsDR5::GUS system due to the toxic metal exposure. Notably, the SNP-induced mitigation of the IAA homeostasis altered by the pollutants does not involve changes in the expression of OsYUCCA1 and ASA2 IAA-biosynthetic genes. Taken together, the results highlight a mitigating role of NO in the rice root system, which is pollutant-specific, and involves the interaction of the signal molecule with both IAA and brassinosteroids at different (i.e., transport, levels, distribution) and multiple levels (i.e., transcriptional/post-translational levels). The research is supported by Progetti Ateneo Sapienza University of Rome, grant number: RG120172B773D1FF

Keywords: arsenic, auxin, cadmium, nitric oxide, rice, root system

Procedia PDF Downloads 51

Authors: Tatsiana Ihnatovich, Darya Nizheharodava, Mikalai Halabarodzka, Tatsiana Savitskaya, Marina Zafranskaya

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Liver fibrosis is a complex of histological changes resulting from chronic liver disease accompanied by an excessive production and deposition of extracellular matrix components in the hepatic parenchyma. Liver fibrosis is a serious medical and social problem. Hepatic stellate cells (HSCs) make a significant contribution to the extracellular matrix deposition due to liver injury. Mesenchymal stem cells (MSCs) have a pronounced anti-inflammatory, regenerative and immunomodulatory effect; they are able to differentiate into hepatocytes and induce apoptosis of activated HSCs that opens the prospect of their use for preventing the excessive fibro-formation and the development of liver cirrhosis. The aim of the study is to evaluate the effect of MSCs therapy on the expression of fibrogenesis markers genes in liver tissue and HSCs cultures of rats with experimental liver cirrhosis (ELC). Materials and methods: ELC was induced by the common bile duct ligation (CBDL) in female Wistar rats (n = 19) with an average body weight of 250 (220 ÷ 270) g. Animals from the control group (n = 10) were sham-operated. On the 56th day after the CBDL, the rats of the experimental (n = 12) and the control (n = 5) groups received intraportal MSCs in concentration of 1×106 cells/animal (previously obtained from rat’s bone marrow) or saline, respectively. The animals were taken out of the experiment on the 21st day. HSCs were isolated by sequential liver perfusion in situ with following disaggregation, enzymatic treatment and centrifugation of cell suspension on a two-stage density gradient. The expression of collagen type I (Col1a1) and type III (Col3a1), matrix metalloproteinase type 2 (MMP2) and type 9 (MMP9), tissue inhibitor of matrix metalloproteinases type 1 (TIMP1), transforming growth factor β type 1 (TGFβ1) and type 3 (TGFβ3) was determined by real-time polymerase chain reaction. Statistical analysis was performed using Statistica 10.0. Results: In ELC rats compared to sham-operated animals, a significant increase of all studied markers expression was observed. The administration of MSCs led to a significant decrease of all detectable markers in the experimental group compared to rats without cell therapy. In ELC rats, an increased MMP9/TIMP1 ratio after cell therapy was also detected. The infusion of MSCs in the sham-operated animals did not lead to any changes. In the HSCs from ELC animals, the expression of Col1a1 and Col3a1 exceeded the similar parameters of the control group (p <0.05) and statistically decreased after the MSCs administration. The correlation between Col3a1 (Rs = 0.51, p <0.05), TGFβ1 (Rs = 0.6, p <0.01), and TGFβ3 (Rs = 0.75, p <0.001) expression in HSCs cultures and liver tissue has been found. Conclusion: Intraportal administration of MSCs to rats with ELC leads to a decreased Col1a1 and Col3a1, MMP2 and MMP9, TIMP1, TGFβ1 and TGFβ3 expression. The correlation between the expression of Col3a1, TGFβ1 and TGFβ3 in liver tissue and in HSCs cultures indicates the involvement of activated HSCs in the fibrogenesis that allows considering HSCs to be the main cell therapy target in ELC.

Keywords: cell therapy, experimental liver cirrhosis, hepatic stellate cells, mesenchymal stem cells

Procedia PDF Downloads 141

Authors: Dilek Ozturk, Narin Ozturk, Zeliha Pala Kara, Engin Kaptan, Serap Sancar Bas, Nurten Ozsoy, Alper Okyar

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Most physiological processes oscillate in a rhythmic manner in mammals including metabolism and energy homeostasis, locomotor activity, hormone secretion, immune and endocrine system functions. Endocrine body rhythms are tightly regulated by the circadian timing system. The hypothalamic-pituitary-thyroid (HPT) axis is under circadian control at multiple levels from hypothalamus to thyroid gland. Since circadian timing system controls a variety of biological functions in mammals, circadian rhythms of biological functions may modify the drug tolerability/toxicity depending on the dosing time. Selective mTOR (mammalian target of rapamycin) inhibitor everolimus is an immunosuppressant and anticancer agent that is active against many cancers. It was also found to be active in medullary thyroid cancer. The aim of this study was to investigate the dosing time-dependent toxicity of everolimus on the thyroid gland and hormones in mice. Healthy C57BL/6J mice were synchronized with 12h:12h Light-Dark cycle (LD12:12, with Zeitgeber Time 0 – ZT0 – corresponding to Light onset). Everolimus was administered to male (5 mg/kg/day) and female mice (15 mg/kg/day) orally at ZT1-rest period- and ZT13-activity period- for 4 weeks; body weight loss, clinical signs and possible changes in serum thyroid hormone levels (TSH and free T4) were examined. Histological alterations in the thyroid gland were evaluated according to the following criteria: follicular size, colloid density and viscidity, height of the follicular epithelium and the presence of necrotic cells. The statistical significance between differences was analyzed with ANOVA. Study findings included everolimus-related diarrhea, decreased activity, decreased body weight gains, alterations in serum TSH levels, and histopathological changes in thyroid gland. Decreases in mean body weight gains were more evident in mice treated at ZT1 as compared to ZT13 (p < 0.001, for both sexes). Control tissue sections of thyroid glands exhibited well-organized histoarchitecture when compared to everolimus-treated groups. Everolimus caused histopathological alterations in thyroid glands in male (5 mg/kg, slightly) and female mice (15 mg/kg; p < 0.01 for both ZT as compared to their controls) irrespective of dosing-time. TSH levels were slightly decreased upon everolimus treatment at ZT13 in both males and females. Conversely, increases in TSH levels were observed when everolimus treated at ZT1 in both males (5 mg/kg; p < 0.05) and females (15 mg/kg; slightly). No statistically significant alterations in serum free T4 levels were observed. TSH and free T4 is clinically important thyroid hormones since a number of disease states have been linked to alterations in these hormones. Serum free T4 levels within the normal ranges in the presence of abnormal serum TSH levels in everolimus treated mice may suggest subclinical thyroid disease which may have repercussions on the cardiovascular system, as well as on other organs and systems. Our study has revealed the histological damage on thyroid gland induced by subacute everolimus administration, this effect was irrespective of dosing time. However, based on the body weight changes and clinical signs upon everolimus treatment, tolerability for the drug was best following dosing at ZT13 in both male and females. Yet, effects of everolimus on thyroid functions may deserve further studies regarding their clinical importance and chronotoxicity.

Keywords: circadian rhythm, chronotoxicity, everolimus, thyroid gland, thyroid hormones

Procedia PDF Downloads 321

Authors: Narin Ozturk, Xiao-Mei Li, Sylvie Giachetti, Francis Levi, Alper Okyar

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P-glycoprotein (P-gp, MDR1, ABCB1) is a transmembrane protein acting as an ATP-dependent efflux pump and functions as a biological barrier by extruding drugs and xenobiotics out of cells in healthy tissues especially in intestines, liver and brain as well as in tumor cells. The circadian timing system controls a variety of biological functions in mammals including xenobiotic metabolism and detoxification, proliferation and cell cycle events, and may affect pharmacokinetics, toxicity and efficacy of drugs. Selective mTOR (mammalian target of rapamycin) inhibitor everolimus is an immunosuppressant and anticancer drug that is active against many cancers, and its pharmacokinetics depend on P-gp. The aim of this study was to investigate the dosing time-dependent toxicity of everolimus with respect to the intestinal P-gp expression rhythms in mdr1a::Luc mice using Real Time-Biolumicorder (RT-BIO) System. Mdr1a::Luc male mice were synchronized with 12 h of Light and 12 h of Dark (LD12:12, with Zeitgeber Time 0 – ZT0 – corresponding Light onset). After 1-week baseline recordings, everolimus (5 mg/kg/day x 14 days) was administered orally at ZT1-resting period- and ZT13-activity period- to mdr1a::Luc mice singly housed in an innovative monitoring device, Real Time-Biolumicorder units which let us monitor real-time and long-term gene expression in freely moving mice. D-luciferin (1.5 mg/mL) was dissolved in drinking water. Mouse intestinal mdr1a::Luc oscillation profile reflecting P-gp gene expression and locomotor activity pattern were recorded every minute with the photomultiplier tube and infrared sensor respectively. General behavior and clinical signs were monitored, and body weight was measured every day as an index of toxicity. Drug-induced body weight change was expressed relative to body weight on the initial treatment day. Statistical significance of differences between groups was validated with ANOVA. Circadian rhythms were validated with Cosinor Analysis. Everolimus toxicity changed as a function of drug timing, which was least following dosing at ZT13, near the onset of the activity span in male mice. Mean body weight loss was nearly twice as large in mice treated with 5 mg/kg everolimus at ZT1 as compared to ZT13 (8.9% vs. 5.4%; ANOVA, p < 0.001). Based on the body weight loss and clinical signs upon everolimus treatment, tolerability for the drug was best following dosing at ZT13. Both rest-activity and mdr1a::Luc expression displayed stable 24-h periodic rhythms before everolimus and in both vehicle-treated controls. Real-time bioluminescence pattern of mdr1a revealed a circadian rhythm with a 24-h period with an acrophase at ZT16 (Cosinor, p < 0.001). Mdr1a expression remained rhythmic in everolimus-treated mice, whereas down-regulation was observed in P-gp expression in 2 of 4 mice. The study identified the circadian pattern of intestinal P-gp expression with an unprecedented precision. The circadian timing depending on the P-gp expression rhythms may play a crucial role in the tolerability/toxicity of everolimus. The circadian changes in mdr1a genes deserve further studies regarding their relevance for in vitro and in vivo chronotolerance of mdr1a-transported anticancer drugs. Chronotherapy with P-gp-effluxed anticancer drugs could then be applied according to their rhythmic patterns in host and tumor to jointly maximize treatment efficacy and minimize toxicity.

Keywords: circadian rhythm, chronotoxicity, everolimus, mdr1a::Luc mice, p-glycoprotein

Procedia PDF Downloads 311

Authors: Nilam Bano, Uzma Iram

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Globally, the dilemma of undernutrition has become a notable concern for the researchers, academicians, and policymakers because of its severe consequences for many centuries. The nutritional deficiencies create hurdles for the people to achieve goals related to live a better lifestyle. Not only at micro level but also at the macro level, the consequences of undernutrition affect the economic progress of the country. The initial five years of a child’s life are considered critical for the physical growth and brain development. In this regard, children require special care and good quality food (nutrient intake) to fulfill their nutritional demand of the growing body. Having the sensitive stature and health, children specially under the age of 5 years are more vulnerable to the poor economic, housing, environmental and other social conditions. Beside confronting economic challenges and political upheavals, Pakistan is also going through from a rough patch in the context of social development. Majority of the children are facing serious health problems in the absence of required nutrition. The complexity of this issue is getting severe day by day and specially children are left behind with different type of immune problems and vitamins and mineral deficiencies. It is noted that children from the well-off background are less likely affected by the undernutrition. In order to underline this issue, the present study aims to highlight the existing nutritional inequalities among the children of under five years in Pakistan. Moreover, this study strives to decompose those factors that severely affect the existing nutritional inequality and standing in the queue to capture the consideration of concerned authorities. Pakistan Demographic and Health Survey 2012-13 was employed to assess the relevant indicators of undernutrition such as stunting, wasting, underweight and associated socioeconomic factors. The objectives were executed through the utilization of the relevant empirical techniques. Concentration indices were constructed to measure the nutritional inequalities by utilizing three measures of undernutrition; stunting, wasting and underweight. In addition to it, the decomposition analysis following the logistic regression was made to unfold the determinants that severely affect the nutritional inequalities. The negative values of concentration indices illustrate that children from the marginalized background are affected by the undernutrition more than their counterparts who belong from rich households. Furthermore, the result of decomposition analysis indicates that child age, size of a child at birth, wealth index, household size, parents’ education, mother’s health and place of residence are the most contributing factors in the prevalence of existing nutritional inequalities. Considering the result of the study, it is suggested to the policymakers to design policies in a way so that the health sector of Pakistan can stimulate in a productive manner. Increasing the number of effective health awareness programs for mothers would create a notable difference. Moreover, the education of the parents must be concerned by the policymakers as it has a significant association with the present research in terms of eradicating the nutritional inequalities among children.

Keywords: concentration index, decomposition analysis, inequalities, undernutrition, Pakistan

Procedia PDF Downloads 113

Authors: K. A.Veselova, N. V.Gromova, I. N.Antonova, I. N. Kalakutskii

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There are many diseases and incidents that may result facial defects and deformities: cancer, trauma, burns, congenital anomalies, and autoimmune diseases. In some cases, patient may acquire atypically extensive facial defect, including more than one anatomical region or, by contrast, atypically small defect (e.g. partial auricular defect). The anaplastology gives us opportunity to help patient with facial disfigurement in cases when plastic surgery is contraindicated. Using of implant retention for facial prosthesis is strongly recommended because improves both aesthetic and functional results and makes using of the prosthesis more comfortable. Prostheticly oriented fixture position is extremely important for aesthetic and functional long-term result; however, the optimal site for fixture placement is not clear in cases with atypical configuration of facial defect. The objective of this report is to demonstrate challenges in fixture position determination we have faced with and offer the solution. In this report, four cases of implant-supported facial prosthesis are described. Extra-oral implants with four millimeter length were used in all cases. The decision regarding the quantity of surgical stages was based on anamnesis of disease. Facial prostheses were manufactured according to conventional technique. Clinical and technological difficulties and mistakes are described, and prostheticly oriented approach for determination of fixture position is demonstrated. The case with atypically large combined orbital and nasal defect resulting after arteriovenous malformation is described: the correct positioning of artificial eye was impossible due to wrong position of the fixture (with suprastructure) located in medial aspect of supraorbital rim. The suprastructure was unfixed and this fixture wasn`t used for retention in order to achieve appropriate artificial eye placement and better aesthetic result. In other case with small partial auricular defect (only helix and antihelix were absent) caused by squamoized cell carcinoma T1N0M0 surgical template was used to avoid the difficulties. To achieve the prostheticly oriented fixture position in case of extremely small defect the template was made on preliminary cast using vacuum thermoforming method. Two radiopaque markers were incorporated into template in preferable for fixture placement positions taking into account future prosthesis configuration. The template was put on remaining ear and cone-beam CT was performed to insure, that the amount of bone is enough for implant insertion in preferable position. Before the surgery radiopaque markers were extracted and template was holed for guide drill. Fabrication of implant-retained facial prostheses gives us opportunity to improve aesthetics, retention and patients’ quality of life. But every inaccuracy in planning leads to challenges on surgery and prosthetic stages. Moreover, in cases with atypically small or extended facial defects prostheticly oriented approach for determination of fixture position is strongly required. The approach including surgical template fabrication is effective, easy and cheap way to avoid mistakes and unpredictable result.

Keywords: anaplastology, facial prosthesis, implant-retained facial prosthesis., maxillofacil prosthese

Procedia PDF Downloads 74

Authors: Hilal T. Sasmazel, Seda Surucu

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Skin tissue engineering is a promising field for the treatment of skin defects using scaffolds. This approach involves the use of living cells and biomaterials to restore, maintain, or regenerate tissues and organs in the body by providing; (i) larger surface area for cell attachment, (ii) proper porosity for cell colonization and cell to cell interaction, and (iii) 3-dimensionality at macroscopic scale. Recent studies on this area mainly focus on fabrication of scaffolds that can closely mimic the natural extracellular matrix (ECM) for creation of tissue specific niche-like environment at the subcellular scale. Scaffolds designed as ECM-like architectures incorporating into the host with minimal scarring/pain and facilitate angiogenesis. This study is related to combining of synthetic PCL and natural chitosan polymers to form 3D PCL/Chitosan core-shell structures for skin tissue engineering applications. Amongst the polymers used in tissue engineering, natural polymer chitosan and synthetic polymer poly(ε-caprolactone) (PCL) are widely preferred in the literature. Chitosan has been among researchers for a very long time because of its superior biocompatibility and structural resemblance to the glycosaminoglycan of bone tissue. However, the low mechanical flexibility and limited biodegradability properties reveals the necessity of using this polymer in a composite structure. On the other hand, PCL is a versatile polymer due to its low melting point (60°C), ease of processability, degradability with non-enzymatic processes (hydrolysis) and good mechanical properties. Nevertheless, there are also several disadvantages of PCL such as its hydrophobic structure, limited bio-interaction and susceptibility to bacterial biodegradation. Therefore, it became crucial to use both of these polymers together as a hybrid material in order to overcome the disadvantages of both polymers and combine advantages of those. The scaffolds here were fabricated by using electrospinning technique and the characterizations of the samples were done by contact angle (CA) measurements, scanning electron microscopy (SEM), transmission electron microscopy (TEM) and X-Ray Photoelectron spectroscopy (XPS). Additionally, gas permeability test, mechanical test, thickness measurement and PBS absorption and shrinkage tests were performed for all type of scaffolds (PCL, chitosan and PCL/chitosan core-shell). By using ImageJ launcher software program (USA) from SEM photographs the average inter-fiber diameter values were calculated as 0.717±0.198 µm for PCL, 0.660±0.070 µm for chitosan and 0.412±0.339 µm for PCL/chitosan core-shell structures. Additionally, the average inter-fiber pore size values exhibited decrease of 66.91% and 61.90% for the PCL and chitosan structures respectively, compare to PCL/chitosan core-shell structures. TEM images proved that homogenous and continuous bead free core-shell fibers were obtained. XPS analysis of the PCL/chitosan core-shell structures exhibited the characteristic peaks of PCL and chitosan polymers. Measured average gas permeability value of produced PCL/chitosan core-shell structure was determined 2315±3.4 g.m-2.day-1. In the future, cell-material interactions of those developed PCL/chitosan core-shell structures will be carried out with L929 ATCC CCL-1 mouse fibroblast cell line. Standard MTT assay and microscopic imaging methods will be used for the investigation of the cell attachment, proliferation and growth capacities of the developed materials.

Keywords: chitosan, coaxial electrospinning, core-shell, PCL, tissue scaffold

Procedia PDF Downloads 459

Authors: G. Kontochristopoulos, T. Spiliopoulos, V. Markantoni, E. Platsidaki, A. Kouris, E. Balamoti, C. Bokotas, G. Haidemenos

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Introduction: There is a high patient demand for periorbital rejuvenation since the facial area is often the first to show visible signs of aging. With advancing age, there are sometimes marked changes that occur in the skin, fat, muscle and bone of the periorbital region, resulting to wrinkles and skin laxity. These changes are among the easiest areas to correct using several minimally invasive techniques, which have become increasingly popular over the last decade. Lasers, radiofrequency, botulinum toxin, fat grafting and fillers are available treatments sometimes in combination to traditional blepharoplasty. This study attempts to show the benefits of a minimally invasive approach to periorbital wrinkles and skin laxity that combine microneedling and 10% trichloroacetic acid (TCA) peels. Method: Eleven female patients aged 34-72 enrolled in the study. They all gave informed consent after receiving detailed information regarding the treatment procedure. Exclusion criteria in the study were previous treatment for the same condition in the past six months, pregnancy, allergy or hypersensitivity to the components, infection, inflammation and photosensitivity on the affected region. All patients had diffuse periorbital wrinkles and mild to moderate upper or lower eyelid skin laxity. They were treated with Automatic Microneedle Therapy System-Handhold and topical application of 10% trichloroacetic acid solution to each periorbital area for five minutes. Needling at a 0,25 mm depth was performed in both latelar (x-y) directions. Subsequently, the peeling agent was applied to each periorbital area for five minutes. Patients were subjected to the above combination every two weeks for a series of four treatments. Subsequently they were followed up regularly every month for two months. The effect was photo-documented. A Physician's and a Patient's Global Assessment Scale was used to evaluate the efficacy of the treatment (0-25% indicated poor response, 25%-50% fair, 50%-75% good and 75%-100% excellent response). Safety was assessed by monitoring early and delayed adverse events. Results: At the end of the study, almost all patients demonstrated significant aesthetic improvement. Physicians assessed a fair and a good improvement in 9(81.8% of patients) and 2(18.1% of patients) participants respectively. Patients Global Assessment rated a fair and a good response in 6 (54.5%) and 5 (45.4%) participants respectively. The procedure was well tolerated and all patients were satisfied. Mild discomfort and transient erythema were quite common during or immediately after the procedure, however only temporary. During the monthly follow up, no complications or scars were observed. Conclusions: Microneedling is known as a simple, office–based collagen induction therapy. Low concentration TCA solution applied to the epidermis that has been more permeable by microneedling, can reach the dermis more effectively. In the present study, chemical peels with 10% TCA acted as an adjuvant to microneedling, as it causes controlled skin damage, promoting regeneration and rejuvenation of tissues. This combined therapy improved periorbital fine lines, wrinkles, and overall appearance of the skin. Thus it constitutes an alternative treatment of periorbital skin aging, with encouraging results and minor side-effects.

Keywords: chemical peels, microneedling, periorbital wrinkles, skin laxity

Procedia PDF Downloads 325

Authors: Shah Rucksana Akhter Urme

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Agriculture is the main source of food for human consumption and feeding the world huge population, the pressure of food supply is increasing day by day. Undoubtedly, quality strain, improved plantation, farming technology, synthetic fertilizer, readily available irrigation, insecticides and harvesting technology are the main factors those to meet up the huge demand of food consumption all over the world. However, depended on this limited resources and excess amount of consuming lands, water, fertilizers leads to the end of the resources and severe climate effects has been left for our future generation. Agriculture is the most responsible to global warming, emitting more greenhouse gases than all other vehicles largely from nitrous oxide released by from fertilized fields, and carbon dioxide from the cutting of rain forests to grow crops . Farming is the thirstiest user of our precious water supplies and a major polluter, as runoff from fertilizers disrupts fragile lakes, rivers, and coastal ecosystems across the globe which accelerates the loss of biodiversity, crucial habitat and a major driver of wildlife extinction. It is needless to say that we have to more concern on how we can save the nutrients of the soil, storage of the water and avoid excessive depends on synthetic fertilizer and insecticides. In this case, eco- friendly cultivation could be a potential alternative solution to minimize effects of agriculture in our environment. The objective of this review paper is about organic cultivation following in particular biotechnological process focused on bio-fertilizer and bio-pesticides. Intense practice of chemical pesticides, insecticides has severe effect on both in human life and biodiversity. This cultivation process introduces farmer an alternative way which is nonhazardous, cost effective and ecofriendly. Organic fertilizer such as tea residue, ashes might be the best alternative to synthetic fertilizer those play important role in increasing soil nutrient and fertility. Ashes contain different essential and non-essential mineral contents that are required for plant growth. Organic pesticide such as neem spray is beneficial for crop as it is toxic for pest and insects. Recycled and composted crop wastes and animal manures, crop rotation, green manures and legumes etc. are suitable for soil fertility which is free from hazardous chemicals practice. Finally water hyacinth and algae are potential source of nutrients even alternative to soil for cultivation along with storage of water for continuous supply. Inorganic practice of agriculture, consuming fruits and vegetables becomes a threat for both human life and eco-system and synthetic fertilizer and pesticides are responsible for it. Farmers that practice eco-friendly farming have to implement steps to protect the environment, particularly by severely limiting the use of pesticides and avoiding the use of synthetic chemical fertilizers, which are necessary for organic systems to experience reduced environmental harm and health risk.

Keywords: organic farming, biopesticides, organic nutrients, water storage, global warming

Procedia PDF Downloads 35

Authors: Kamyar Tolouei, Ehsan Moosavi

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In open-pit mines, the long-term production scheduling optimization problem (LTPSOP) is a complicated problem that contains constraints, large datasets, and uncertainties. Uncertainty in the output is caused by several geological, economic, or technical factors. Due to its dimensions and NP-hard nature, it is usually difficult to find an ideal solution to the LTPSOP. The optimal schedule generally restricts the ore, metal, and waste tonnages, average grades, and cash flows of each period. Past decades have witnessed important measurements of long-term production scheduling and optimal algorithms since researchers have become highly cognizant of the issue. In fact, it is not possible to consider LTPSOP as a well-solved problem. Traditional production scheduling methods in open-pit mines apply an estimated orebody model to produce optimal schedules. The smoothing result of some geostatistical estimation procedures causes most of the mine schedules and production predictions to be unrealistic and imperfect. With the expansion of simulation procedures, the risks from grade uncertainty in ore reserves can be evaluated and organized through a set of equally probable orebody realizations. In this paper, to synthesize grade uncertainty into the strategic mine schedule, a stochastic integer programming framework is presented to LTPSOP. The objective function of the model is to maximize the net present value and minimize the risk of deviation from the production targets considering grade uncertainty simultaneously while satisfying all technical constraints and operational requirements. Instead of applying one estimated orebody model as input to optimize the production schedule, a set of equally probable orebody realizations are applied to synthesize grade uncertainty in the strategic mine schedule and to produce a more profitable and risk-based production schedule. A mixture of metaheuristic procedures and mathematical methods paves the way to achieve an appropriate solution. This paper introduced a hybrid model between the augmented Lagrangian relaxation (ALR) method and the metaheuristic algorithm, the Harris Hawks optimization (HHO), to solve the LTPSOP under grade uncertainty conditions. In this study, the HHO is experienced to update Lagrange coefficients. Besides, a machine learning method called Random Forest is applied to estimate gold grade in a mineral deposit. The Monte Carlo method is used as the simulation method with 20 realizations. The results specify that the progressive versions have been considerably developed in comparison with the traditional methods. The outcomes were also compared with the ALR-genetic algorithm and ALR-sub-gradient. To indicate the applicability of the model, a case study on an open-pit gold mining operation is implemented. The framework displays the capability to minimize risk and improvement in the expected net present value and financial profitability for LTPSOP. The framework could control geological risk more effectively than the traditional procedure considering grade uncertainty in the hybrid model framework.

Keywords: grade uncertainty, metaheuristic algorithms, open-pit mine, production scheduling optimization

Procedia PDF Downloads 73

Authors: Marcela Parra-Vargas, Ana Sandoval-Rodriguez, Roberto Rodriguez-Echevarria, Jose Dominguez-Rosales, Juan Armendariz-Borunda

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Non-alcoholic fatty liver disease (NAFLD) is characterized by an excess of hepatic lipids, and it is to author’s best knowledge, the most prevalent chronic liver disorder. Anthocyanin-rich food consumption is linked to health benefits in metabolic disorders associated with obesity and NAFLD, although the precise functional role of anthocyanidin delphinidin (Dp) has yet to be established. The aim of this study was to investigate the effect of the Dp in NAFLD metabolic alterations by evaluating prevention or amelioration of hepatic lipid accumulation, as well as molecular mechanisms in two experimental obesity-related models of NALFD. In vitro: HepG2 cells were incubated with sodium palmitate (PA, 1 mM) to induce lipotoxic damage, and concomitantly treated with Dp (180 uM) for 24 h. Subsequently, total lipid accumulation was measured by colorimetric staining with Oil Red O, and total intrahepatic triglycerides were determined by an enzymatic assay. To assess molecular mechanisms, cells were pre-treated with PA for 24 h and then exposed to Dp for 1 h. In vivo: four-week-old male C57BL/6Nhsd mice were allocated in two main groups. Mice were fed with standard diet (control) or high-fat and high-carbohydrate diet (45% fat, HFD) for 16 wk to induce NAFLD. Then HFD was divided into subgroups: one treated orally with Dp (15 mg/kg bw, HFD-Dp) every day for 4 wk, while HFD group treated with vehicle (DMSO). Weight and fasting glucose were recorded weekly, while dietary ingestion was measured daily. Insulin tolerance test was performed at the end of treatment. Liver histology was evaluated with H&E and Masson’s trichrome stain. RT-PCR was used to evaluate gene expression and Western Blot to determine levels of protein in both experimental models. Parametric data were analyzed with one-way ANOVA and Tukey’s post-hoc test. Kruskal-Wallis and Mann-Whitney U test for non-parametric data, and P < 0.5 were considered significant. Dp prevented hepatic lipid accumulation by PA in HepG2 hepatocytes. Furthermore, Dp down-regulated gene expression of SREBP1c, FAS, and CPT1a without modifying AMPK phosphorylation levels. In vivo, Dp oral administration did not ameliorate lipid metabolic alterations raised by HFD. Adiposity, dietary ingestion, fasting glucose, and insulin sensitivity after Dp treatment remained similar to HFD group. Histological analysis showed hepatic damage in HFD groups and no differences between HFD and HFD-Dp groups were found. Hepatic gene expression of ACC and FAS were not altered by HFD. SREBP1c was similar in both HFD and HFD-Dp groups. No significant changes were observed in SREBP1c, ACC, and FAS adipose tissue gene expression by HFD or Dp treatment. Additionally, immunoblotting analysis revealed no changes in pathway SIRT1-LKB-AMPK and PPAR alpha by both HFD groups compared to control. In conclusion, the antioxidant Dp may provoke beneficial effects in the prevention of hepatic lipid accumulation. Nevertheless, the oral dose administrated in mice that simulated the total intake of anthocyanins consumed daily by humans has no effect as a treatment on hepatic lipid metabolic alterations and histological abnormalities associated with exposure to chronic HFD. A healthy lifestyle with regular intake of antioxidants such as anthocyanins may prevent metabolic alterations in NAFLD.

Keywords: anthocyanins, antioxidants, delphinidin, non-alcoholic fatty liver disease, obesity

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Authors: Huan Peng, Chenye Zeng, Zhao Wang

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Alzheimer’s disease (AD) is an age-related neurodegenerative disease that is a leading cause of dementia syndromes and has become a huge burden on society and families. The main pathological features of AD involve excessive deposition of β-amyloid (Aβ) and Tau proteins in the brain, resulting in loss of neurons, expansion of neuroinflammation, and cognitive dysfunction in patients. Researchers have found effective drugs to clear the brain of error-accumulating proteins or to slow the loss of neurons, but their direct administration has key bottlenecks such as single-drug limitation, rapid blood clearance rate, impenetrable blood-brain barrier (BBB), and poor ability to target tissues and cells. Therefore, we are committed to seeking a suitable and efficient delivery system. Inspired by the possibility that exosomes may be involved in the secretion and transport mechanism of many signaling molecules or proteins in the brain, exosomes have attracted extensive attention as natural nanoscale drug carriers. We selected exosomes derived from bone marrow mesenchymal stem cells (MSC-EXO) with low immunogenicity and exosomes derived from hippocampal neurons (HT22-EXO) that may have excellent homing ability to overcome the deficiencies of oral or injectable pathways and bypass the BBB through nasal administration and evaluated their delivery ability and effect on AD. First, MSC-EXO and HT22 cells were isolated and cultured, and MSCs were identified by microimaging and flow cytometry. Then MSC-EXO and HT22-EXO were obtained by gradient centrifugation and qEV SEC separation column, and a series of physicochemical characterization were performed by transmission electron microscope, western blot, nanoparticle tracking analysis and dynamic light scattering. Next, exosomes labeled with lipophilic fluorescent dye were administered to WT mice and APP/PS1 mice to obtain fluorescence images of various organs at different times. Finally, APP/PS1 mice were administered intranasally with two exosomes 20 times over 40 days and 20 μL each time. Behavioral analysis and pathological section analysis of the hippocampus were performed after the experiment. The results showed that MSC-EXO and HT22-EXO were successfully isolated and characterized, and they had good biocompatibility. MSC-EXO showed excellent brain enrichment in APP/PS1 mice after intranasal administration, could improve the neuronal damage and reduce inflammation levels in the hippocampus of APP/PS1 mice, and the improvement effect was significantly better than HT22-EXO. However, intranasal administration of the two exosomes did not cause depression and anxious-like phenotypes in APP/PS1 mice, nor significantly improved the short-term or spatial learning and memory ability of APP/PS1 mice, and had no significant effect on the content of Aβ plaques in the hippocampus, which also meant that MSC-EXO could use their own advantages in combination with other drugs to clear Aβ plaques. The possibility of realizing highly effective non-invasive synergistic treatment for AD provides new strategies and ideas for clinical research.

Keywords: Alzheimer’s disease, exosomes derived from mesenchymal stem cell, intranasal administration, therapy-carrier dual roles

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Authors: M. Fry, L. Fitzpatrick, Julie Considine, R. Z. Shaban, Kate Curtis

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Introduction: The vast majority of older Australians lives independently and are self-managing at home, despite a growing number living with a chronic illness that requires health intervention. Evidence shows that between 50% and 80% of people presenting to the emergency department (ED) are in pain. Australian EDs manage 7.2 million attendances every year and 1.4 million of these are people aged 65 years or more. Research shows that 28% of ED patients aged 65 years or more have Cognitive impairment (CI) associated with dementia, delirium and neurological conditions. Background: Traditional ED service delivery may not be suitable for older people who present with multiple, complex and ongoing illnesses. Likewise, ED clinical staff often perceive that their role should be focused more on immediate and potential lifethreatening illness and conditions which are episodic in nature. Therefore, the needs of older people and their family/carers may not be adequately addressed in the context of an ED presentation. Aim: We aimed to explore the utilisation and characteristics of older people presenting to four metropolitan EDs. Method: The findings being presented are part of a program of research exploring pain management practices for older persons with long bone fractures. The study was conducted across four metropolitan emergency departments of older patients (65years and over) and involved a 12-month randomised medical record audit (n=255). Results: ED presentations across four ED sites in 2012 numbered 168021, with 44778 (26.6%) patients aged 65 and over. Of the 44778 patients, the average age was 79.1 years (SD 8.54). There were more females 23932 (53.5%). The majority (26925: 85.0%) of older persons self-referred to the ED and lived independently. The majority arrived by ambulance (n=18553: 41.4%) and were allocated triage category was 3 (n=19,507:43.65%) or Triage category 4 at (n=15,389: 34.43%). The top five triage symptom presentations involved pain (n=8088; 18.25%), dyspnoea (n=4735; 10.7%), falls (n=4032; 9.1%), other (n=3984; 9.0%), cardiac (n=2987; 6.7%). The top five system based diagnostic presentations involved musculoskeletal (n=8902; 20.1%), cardiac (n=6704:15.0%), respiratory (n=4933; 11.0%), neurological (n=4909; 11.0%), gastroenterology (n=4321; 9.7%). On review of one tertiary hospital database the vital signs on average at time triage: Systolic Blood Pressure 143.6mmHg. Heart Rate 83.4 beats/minute; Respiratory Rate 18.5 breaths/ minute; Oxygen saturation 97.0% and Tympanic temperature 36.7 and Blood Glucose Level 7.4mmols/litre. The majority presented with a Glasgow Coma Score of 14 or higher. On average the older person stayed in the ED 4:56 (SD 3:28minutes).The average time to be seen was 39 minutes (SD 48 minutes). The majority of older persons were admitted (n=27562: 61.5%), did not wait for treatment (n= 8879: 0.02%) discharged home (n=16256: 36.0%). Conclusion: The vast majority of older persons are living independently, although many require admission on arrival to the ED. Many arrived in pain and with musculoskeletal injuries and or conditions. New models of care need to be considered, which may better support self-management and independent living of the older person and the National Emergency Access Targets.

Keywords: chronic, older person, aged care, emergency department

Procedia PDF Downloads 207

Authors: Abdoulaye Maihatchi Ahamed, Zubin Arora, Benjamin Swobada, Jean-yves Lansot, Alexandre Chagnes

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Lithium-ion battery (LiB) is the technology of choice in the development of electric vehicles. But there are still many challenges, including the development of positive electrode materials exhibiting high cycle ability, high energy density, and low environmental impact. For this latter, LiBs must be manufactured in a circular approach by developing the appropriate strategies to reuse and recycle them. Presently, the recycling of LiBs is carried out by the pyrometallurgical route, but more and more processes implement or will implement the hydrometallurgical route or a combination of pyrometallurgical and hydrometallurgical operations. After producing the black mass by mineral processing, the hydrometallurgical process consists in leaching the black mass in order to uptake the metals contained in the cathodic material. Then, these metals are extracted selectively by liquid-liquid extraction, solid-liquid extraction, and/or precipitation stages. However, liquid-liquid extraction combined with precipitation/crystallization steps is the most implemented operation in the LiB recycling process to selectively extract copper, aluminum, cobalt, nickel, manganese, and lithium from the leaching solution and precipitate these metals as high-grade sulfate or carbonate salts. Liquid-liquid extraction consists in contacting an organic solvent and an aqueous feed solution containing several metals, including the targeted metal(s) to extract. The organic phase is non-miscible with the aqueous phase. It is composed of an extractant to extract the target metals and a diluent, which is usually aliphatic kerosene produced from the petroleum industry. Sometimes, a phase modifier is added in the formulation of the extraction solvent to avoid the third phase formation. The extraction properties of the diluent do not depend only on the chemical structure of the extractant, but it may also depend on the nature of the diluent. Indeed, the interactions between the diluent can influence more or less the interactions between extractant molecules besides the extractant-diluent interactions. Only a few studies in the literature addressed the influence of the diluent on the extraction properties, while many studies focused on the effect of the extractants. Recently, new low-carbon footprint aliphatic diluents were produced by catalytic dearomatisation and distillation of bio-based oil. This study aims at investigating the influence of the nature of the diluent on the extraction properties of three extractants towards cobalt, nickel, manganese, copper, aluminum, and lithium: Cyanex®272 for nickel-cobalt separation, DEHPA for manganese extraction, and Acorga M5640 for copper extraction. The diluents used in the formulation of the extraction solvents are (i) low-odor aliphatic kerosene produced from the petroleum industry (ELIXORE 180, ELIXORE 230, ELIXORE 205, and ISANE IP 175) and (ii) bio-sourced aliphatic diluents (DEV 2138, DEV 2139, DEV 1763, DEV 2160, DEV 2161 and DEV 2063). After discussing the effect of the diluents on the extraction properties, this conference will address the development of a low carbon footprint process based on the use of the best bio-sourced diluent for the production of high-grade cobalt sulfate, nickel sulfate, manganese sulfate, and lithium carbonate, as well as metal copper.

Keywords: diluent, hydrometallurgy, lithium-ion battery, recycling

Procedia PDF Downloads 61

Authors: Naresh Kumar, Savita Kumari, Naresh Kochhar

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The objective of the study was to assess the role of mineralogy and subsurface structure on water quality of Tosham, Malani Igneous Suite (MIS), Western Rajasthan, India. MIS is the largest (55,000 km2) A-type, anorogenic and high heat producing acid magmatism in the peninsular India and owes its origin to hot spot tectonics. Apart from agricultural and industrial wastes, geogenic activities cause fluctuations in quality parameters of water resources. Twenty water samples (20) selected from Tosham and surrounding areas were analyzed for As, Pb, B, Al, Zn, Fe, Ni using Inductive coupled plasma emission and F by Ion Chromatography. The concentration of As, Pb, B, Ni and F was above the stipulated level specified by BIS (Bureau of Indian Standards IS-10500, 2012). The concentration of As and Pb in surrounding areas of Tosham ranged from 1.2 to 4.1 mg/l and from 0.59 to 0.9 mg/l respectively which is higher than limits of 0.05mg/l (As) and 0.01 mg/l (Pb). Excess trace metal accumulation in water is toxic to humans and adversely affects the central nervous system, kidneys, gastrointestinal tract, skin and cause mental confusion. Groundwater quality is defined by nature of rock formation, mineral water reaction, physiography, soils, environment, recharge and discharge conditions of the area. Fluoride content in groundwater is due to the solubility of fluoride-bearing minerals like fluorite, cryolite, topaz, and mica, etc. Tosham is comprised of quartz mica schist, quartzite, schorl, tuff, quartz porphyry and associated granites, thus, fluoride is leached out and dissolved in groundwater. In the study area, Ni concentration ranged from 0.07 to 0.5 mg/l (permissible limit 0.02 mg/l). The primary source of nickel in drinking water is leached out nickel from ore-bearing rocks. Higher concentration of As is found in some igneous rocks specifically containing minerals as arsenopyrite (AsFeS), realgar (AsS) and orpiment (As2S3). MIS consists of granite (hypersolvus and subsolvus), rhyolite, dacite, trachyte, andesite, pyroclasts, basalt, gabbro and dolerite which increased the trace elements concentration in groundwater. Nakora, a part of MIS rocks has high concentration of trace and rare earth elements (Ni, Rb, Pb, Sr, Y, Zr, Th, U, La, Ce, Nd, Eu and Yb) which percolates the Ni and Pb to groundwater by weathering, contacts and joints/fractures in rocks. Additionally, geological setting of MIS also causes dissolution of trace elements in water resources beneath the surface. NE–SW tectonic lineament, radial pattern of dykes and volcanic vent at Nakora created a way for leaching of these elements to groundwater. Rain water quality might be altered by major minerals constituents of host Tosham rocks during its percolation through the rock fracture, joints before becoming the integral part of groundwater aquifer. The weathering process like hydration, hydrolysis and solution might be the cause of change in water chemistry of particular area. These studies suggest that geological relation of soil-water horizon with MIS rocks via mineralogical variations, structures and tectonic setting affects the water quality of the studied area.

Keywords: geochemistry, groundwater, malani igneous suite, tosham

Procedia PDF Downloads 187

Authors: Kuladip Jana

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Benzo(a)pyrene [B(a)P] is an environmental toxicant present mostly in cigarette smoke and car exhaust, is an aryl hydrocarbon receptor (AhR) ligand that exerts its toxic effects on both male and female reproductive systems. In this study, the effect of B(a)P at different doses (0.1, 0.25, 0.5, 1 and 5 mg /kg body weight) was studied on male reproductive system of rat. A significant decrease in cauda epididymal sperm count and motility along with the presence of sperm head abnormalities and altered epididymal and testicular histology were documented following B(a)P treatment. B(a)P treatment resulted apoptotic sperm cells as observed by TUNEL and Annexin V-PI assay with increased ROS, altered sperm mitochondrial membrane potential (ΔΨm) with a simultaneous decrease in the activity of antioxidant enzymes and GSH status. TUNEL positive apoptotic cells also observed in testis as well as isolated germ and Leydig cells following B(a)P exposure. Western Blot analysis revealed the activation of p38MAPK, cytosolic translocation of cytochrome-c, up-regulation of Bax and inducible nitric oxide synthase (iNOS) with cleavage of PARP and down-regulation of BCl2 in testis upon B(a)P treatment. The protein and mRNA levels of testicular key steroidogenesis regulatory proteins like StAR, cytochrome P450 IIA1 (CYPIIA1), 3β HSD, 17β HSD showed a significant decrease in a dose dependent manner while an increase in the expression of cytochrome P450 1A1 (CYP1A1), Aryl hydrocarbon Receptor (AhR), active caspase- 9 and caspase- 3 following B(a)P exposure. We conclude that exposure of benzo(a)pyrene caused testicular gamatogenic and steroidogenic disorders by induction of oxidative stress, inhibition of StAR and other steroidogenic enzymes along with activation of p38MAPK and initiated caspase-3 mediated germ and Leydig cell apoptosis.The possible protective role of naturally occurring phytochemicals against B(a)P induced testicular toxicity needs immediate consideration. Curcumin and resveratrol separately were found to protect against B(a)P induced germ cell apoptosis, and their combinatorial effect was more significant. Our present study in isolated testicular germ cell population from adult male Wistar rats, highlighted their synergistic protective effect against B(a)P induced germ cell apoptosis. Curcumin-resveratrol co-treatment decreased the expression of pro-apoptotic proteins like cleaved caspase 3,8,9, cleaved PARP, Apaf1, FasL, tBid. Curcumin-resveratrol co-treatment decreased Bax/Bcl2 ratio, mitochondria to cytosolic translocation of cytochrome c and activated the survival protein Akt. Curcumin-resveratrol decreased the expression of p53 dependent apoptotic genes like Fas, FasL, Bax, Bcl2, Apaf1.Curcumin-resveratrol co-treatment thus prevented B(a)P induced germ cell apoptosis. B(a)P induced testicular ROS generation and oxidative stress were significantly ameliorated with curcumin and resveratrol. Curcumin-resveratrol co-treatment prevented B(a)P induced nuclear translocation of AhR and CYP1A1 production. The combinatorial treatment significantly inhibited B(a)P induced ERK 1/2, p38 MAPK and JNK 1/2 activation. B(a)P treatment increased the expression of p53 and its phosphorylation (p53 ser 15). Curcumin-resveratrol co-treatment significantly decreased p53 level and its phosphorylation (p53 ser 15). The study concludes that curcumin-resveratrol synergistically modulated MAPKs and p53, prevented oxidative stress, regulated the expression of pro and anti-apoptotic proteins as well as the proteins involved in B(a)P metabolism thus protected germ cells from B(a)P induced apoptosis.

Keywords: benzo(a)pyrene, germ cell, apoptosis, oxidative stress, resveratrol, curcumin

Procedia PDF Downloads 230

Authors: Hayden R Schott, John M Felder III

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Introduction: Chronic lower extremity wounds in the diabetic and vasculopathic populations are associated with a high degree of morbidity.When wounds require more extensive treatment than can be offered by wound care centers, more aggressive solutions involve local tissue transfer and microsurgical free tissue transfer for achieving definitive soft tissue coverage. These procedures of autologous tissue transfer (ATT) offer resilient, soft tissue coverage of limb-threatening wounds and confer promising limb salvage rates. However, chronic osteomyelitis and recalcitrant soft tissue infections are common in severe diabetic foot wounds and serve to significantly complicate ATT procedures. Stimulan is a resorbable calcium sulfate antibiotic carrier. The use of stimulan antibiotic beads to treat chronic osteomyelitis is well established in the orthopedic and plastic surgery literature. In these procedures, the beads are placed beneath the skin flap to directly deliver antibiotics to the infection site. The purpose of this study was to quantify the success of Stimulan antibiotic beads in treating recalcitrant infections in patients with diabetic foot wounds receiving ATT. Methods: A retrospective review of clinical and demographic information was performed on patients who underwent ATT with the placement of Stimulan antibiotic beads for attempted limb salvage from 2018-21. Patients were analyzed for preoperative wound characteristics, demographics, infection recurrence, and adverse outcomes as a result of product use. The primary endpoint was 90 day infection recurrence, with secondary endpoints including 90 day complications. Outcomes were compared using basic statistics and Fisher’s exact tests. Results: In this time span, 14 patients were identified. At the time of surgery, all patients exhibited clinical signs of active infection, including positive cultures and erythema. 57% of patients (n=8) exhibited chronic osteomyelitis prior to surgery, and 71% (n=10) had exposed bone at the wound base. In 57% of patients (n=8), Stimulan beads were placed beneath a free tissue flap and beneath a pedicle tissue flap in 42% of patients (n=6). In all patients, Stimulan beads were only applied once. Recurrent infections were observed in 28% of patients (n=4) at 90 days post-op, and flap nonadherence was observed in 7% (n=1). These were the only Stimulan related complications observed. Ultimately, lower limb salvage was successful in 85% of patients (n=12). Notably, there was no significant association between the preoperative presence of osteomyelitis and recurrent infections. Conclusions: The use of Stimulanantiobiotic beads to treat recalcitrant infections in patients receiving definitive skin coverage of diabetic foot wounds does not appear to demonstrate unnecessary risk. Furthermore, the lack of significance between the preoperative presence of osteomyelitis and recurrent infections indicates the successful use of Stimulan to dampen infection in patients with osteomyelitis, as is consistent with the literature. Further research is needed to identify Stimulan as the significant contributor to infection treatment using future cohort and case control studies with more patients. Nonetheless, the use of Stimulan antibiotic beads in patients with diabetic foot wounds demonstrates successful infection suppression and maintenance of definitive soft tissue coverage.

Keywords: wound care, stimulan antibiotic beads, free tissue transfer, plastic surgery, wound, infection

Procedia PDF Downloads 59

Authors: Jae Won Lee, Kyung Hyun Min, Hong Jae Lee, Sang Cheon Lee

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To date, imaging techniques have attracted much attention in medicine because the detection of diseases at an early stage provides greater opportunities for successful treatment. Consequently, over the past few decades, diverse imaging modalities including magnetic resonance (MR), positron emission tomography, computed tomography, and ultrasound (US) have been developed and applied widely in the field of clinical diagnosis. However, each of the above-mentioned imaging modalities possesses unique strengths and intrinsic weaknesses, which limit their abilities to provide accurate information. Therefore, multimodal imaging systems may be a solution that can provide improved diagnostic performance. Among the current medical imaging modalities, US is a widely available real-time imaging modality. It has many advantages including safety, low cost and easy access for patients. However, its low spatial resolution precludes accurate discrimination of diseased region such as cancer sites. In contrast, MR has no tissue-penetrating limit and can provide images possessing exquisite soft tissue contrast and high spatial resolution. However, it cannot offer real-time images and needs a comparatively long imaging time. The characteristics of these imaging modalities may be considered complementary, and the modalities have been frequently combined for the clinical diagnostic process. Biominerals such as calcium carbonate (CaCO3) and calcium phosphate (CaP) exhibit pH-dependent dissolution behavior. They demonstrate pH-controlled drug release due to the dissolution of minerals in acidic pH conditions. In particular, the application of this mineralization technique to a US contrast agent has been reported recently. The CaCO3 mineral reacts with acids and decomposes to generate calcium dioxide (CO2) gas in an acidic environment. These gas-generating mineralized nanoparticles generated CO2 bubbles in the acidic environment of the tumor, thereby allowing for strong echogenic US imaging of tumor tissues. On the basis of this previous work, it was hypothesized that the loading of MR contrast agents into the CaCO3 mineralized nanoparticles may be a novel strategy in designing a contrast agent for dual imaging. Herein, CaCO3 mineralized nanoparticles that were capable of generating CO2 bubbles to trigger the release of entrapped MR contrast agents in response to tumoral acidic pH were developed for the purposes of US and MR dual-modality imaging of tumors. Gd2O3 nanoparticles were selected as an MR contrast agent. A key strategy employed in this study was to prepare Gd2O3 nanoparticle-loaded mineralized nanoparticles (Gd2O3-MNPs) using block copolymer-templated CaCO3 mineralization in the presence of calcium cations (Ca2+), carbonate anions (CO32-) and positively charged Gd2O3 nanoparticles. The CaCO3 core was considered suitable because it may effectively shield Gd2O3 nanoparticles from water molecules in the blood (pH 7.4) before decomposing to generate CO2 gas, triggering the release of Gd2O3 nanoparticles in tumor tissues (pH 6.4~7.4). The kinetics of CaCO3 dissolution and CO2 generation from the Gd2O3-MNPs were examined as a function of pH and pH-dependent in vitro magnetic relaxation; additionally, the echogenic properties were estimated to demonstrate the potential of the particles for the tumor-specific US and MR imaging.

Keywords: calcium carbonate, mineralization, ultrasound imaging, magnetic resonance imaging

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Authors: Ogechi Nzeagwu, Assumpta Osuagwu, Charlse Nkwoala

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Malnutrition in infants due to poverty, poor feeding practices, and high cost of commercial complementary foods among others is a concern in developing countries. The study evaluated the proximate, vitamin and mineral compositions, antinutrients and functional properties, biochemical, haematological and sensory evaluation of complementary food made from sorghum, groundnut, crayfish and paw-paw flour blends using standard procedures. The blends were formulated on protein requirement of infants (18 g/day) using Nutrisurvey linear programming software in ratio of sorghum(S), groundnut(G), crayfish(C) and pawpaw(P) flours as 50:25:10:15(SGCP1), 60:20:10:10 (SGCP2), 60:15:15:10 (SGCP3) and 60:10:20:10 (SGCP4). Plain-pap (fermented maize flour)(TCF) and cerelac (commercial complementary food) served as basal and control diets. Thirty weanling male albino rats aged 28-35 days weighing 33-60 g were purchased and used for the study. The rats after acclimatization were fed with gruel produced with the experimental diets and the control with water ad libitum daily for 35days. Effect of the blends on lipid profile, blood glucose, haematological (RBC, HB, PCV, MCV), liver and kidney function and weight gain of the rats were assessed. Acceptability of the gruel was conducted at the end of rat feeding on forty mothers of infants’ ≥ 6 months who gave their informed consent to participate using a 9 point hedonic scale. Data was analyzed for means and standard deviation, analysis of variance and means were separated using Duncan multiple range test and significance judged at 0.05, all using SPSS version 22.0. The results indicated that crude protein, fibre, ash and carbohydrate of the formulated diets were either comparable or higher than values in cerelac. The formulated diets (SGCP1- SGCP4) were significantly (P>0.05) higher in vitamin A and thiamin compared to cerelac. The iron content of the formulated diets SGCP1- SGCP4 (4.23-6.36 mg/100) were within the recommended iron intake of infants (0.55 mg/day). Phytate (1.56-2.55 mg/100g) and oxalate (0.23-0.35 mg/100g) contents of the formulated diets were within the permissible limits of 0-5%. In functional properties, bulk density, swelling index, % dispersibility and water absorption capacity significantly (P<0.05) increased and compared favourably with cerelac. The essential amino acids of the formulated blends were within the amino acid profile of the FAO/WHO/UNU reference protein for children 0.5 -2 years of age. Urea concentration of rats fed with SGCP1-SGCP4 (19.48 mmol/L),(23.76 mmol/L),(24.07 mmol/L),(23.65 mmol/L) respectively was significantly higher than that of rat fed cerelac (16.98 mmol/L); however, plain pap had the least value (9.15 mmol/L). Rats fed with SGCP1-SGCP4 (116 mg/dl), (119 mg/dl), (115 mg/dl), (117 mg/dl) respectively had significantly higher glucose levels those fed with cerelac (108 mg/dl). Liver function parameters (AST, ALP and ALT), lipid profile (triglyceride, HDL, LDL, VLDL) and hematological parameters of rats fed with formulated diets were within normal range. Rats fed SGCP1 gained more weight (90.45 g) than other rats fed with SGCP2-SGCP4 (71.65 g, 79.76 g, 75.68 g), TCF (20.13 g) and cerelac (59.06 g). In all the sensory attributes, the control was preferred with respect to the formulated diets. The formulated diets were generally adequate and may likely have potentials to meet nutrient requirements of infants as complementary food.

Keywords: biochemical, chemical evaluation, complementary food, quadrimix

Procedia PDF Downloads 133

Authors: Mohammadjavad Sotoudeheian, Navid Farahmandian

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Cardiac hypertrophy arises in response to persistent increases in hemodynamic loads. In comparison, diabetic cardiomyopathy is defined by an abnormal myocardial changes without other cardiac-related risk factors. Pathological cardiac hypertrophy and myocardial remodeling are hallmarks of cardiovascular diseases and are risk factors for heart failure. The transcription factor forkhead box class O (FOXOs) can protect heart tissue by hostile oxidative stress and stimulating apoptosis and autophagy. FOXO proteins, as sensitive elements and mediators in response to environmental changes, have been revealed to prevent and inverse cardiac hypertrophy. FOXOs are inhibited by insulin and are critical mediators of insulin action. Insulin deficiency and uncontrolled diabetes lead to a catabolic state. FOXO1 acts downstream of the insulin-dependent pathways, which are dysregulated in diabetes. It regulates cardiomyocyte hypertrophy downstream of IGF1R/PI3K/Akt activation, which are critical regulators of cardiac hypertrophy. The complex network of signaling pathways comprising insulin/IGF-1 signaling, AMPK, JNK, and Sirtuins regulate the development of cardiovascular dysfunction by modulating the activity of FOXOs. Insulin receptors and IGF1R act via the PI3k/Akt and the MAPK/ERK pathways. Activation of Akt in response to insulin or IGF-1 induces phosphorylation of FOXOs. Increased protein synthesis induced by activation of the IGF-I/Akt/mTOR signaling pathway leads to hypertrophy. This pathway and the myostatin/Smad pathway are potent negative muscle development regulators. In cardiac muscle, insulin receptor substrates (IRS)-1 or IRS-2 activates the Akt signaling pathway and inactivate FOXO1. Under metabolic stress, p38 MAPK promotes degradation of IRS-1 and IRS-2 in cardiac myocytes and activates FOXO1, leading to cardiomyopathy. Sirt1 and FOXO1 interaction play an essential role in starvation-induced autophagy in cardiac metabolism. Inhibition of Angiotensin-II induced cardiomyocyte hypertrophy is associated with reduced FOXO1 acetylation and activation of Sirt1. The NF-κB, ERK, and FOXOs are de-acetylated by SIRT1. De-acetylation of FOXO1 induces the expression of genes involved in autophagy and stimulates autophagy flux. Therefore, under metabolic stress, FOXO1 can cause diabetic cardiomyopathy. The overexpression of FOXO1 leads to decreased cardiomyocyte size and suppresses cardiac hypertrophy through inhibition of the calcineurin–NFAT pathway. Diabetes mellitus is associated with elevation of O-GlcNAcylation. Some of its binding partners regulate the substrate selectivity of O-GlcNAc transferase (OGT). O-GlcNAcylation of essential contractile proteins may inhibit protein-protein interactions, reduce calcium sensitivity, and modulate contractile function. Uridine diphosphate (UDP)-GlcNAc is the obligatory substrate of OGT, which catalyzes a reversible post-translational protein modification. The increase of O-GlcNAcylation is accompanied by impaired cardiac hypertrophy in diabetic hearts. Inhibition of O-GlcNAcylation blocks activation of ERK1/2 and hypertrophic growth. O-GlcNAc modification on NFAT is required for its translocation from the cytosol to the nucleus, where NFAT stimulates the transcription of various hypertrophic genes. Inhibition of O-GlcNAcylation dampens NFAT-induced cardiac hypertrophic growth. Transcriptional activity of FOXO1 is enriched by improved O-GlcNAcylation upon high glucose stimulation or OGT overexpression. In diabetic conditions, the modification of FOXO1 by O-GlcNAc is promoted in cardiac troponin I and myosin light chain 2. Therefore targeting O-GlcNAcylation represents a potential therapeutic option to prevent hypertrophy in the diabetic heart.

Keywords: diabetes, cardiac hypertrophy, O-GlcNAcylation, FOXO1, Akt, PI3K, AMPK, insulin

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Authors: Magdy I. A. Alshourbagi

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Background: The National Institute for Deafness and Communication Disorders defines idiopathic sudden sensorineural hearing loss as the idiopathic loss of hearing of at least 30 dB across 3 contiguous frequencies occurring within 3 days.The most common clinical presentation involves an individual experiencing a sudden unilateral hearing loss, tinnitus, a sensation of aural fullness and vertigo. The etiologies and pathologies of ISSNHL remain unclear. Several pathophysiological mechanisms have been described including: vascular occlusion, viral infections, labyrinthine membrane breaks, immune associated disease, abnormal cochlear stress response, trauma, abnormal tissue growth, toxins, ototoxic drugs and cochlear membrane damage. The rationale for the use of hyperbaric oxygen to treat ISSHL is supported by an understanding of the high metabolism and paucity of vascularity to the cochlea. The cochlea and the structures within it require a high oxygen supply. The direct vascular supply, particularly to the organ of Corti, is minimal. Tissue oxygenation to the structures within the cochlea occurs via oxygen diffusion from cochlear capillary networks into the perilymph and the cortilymph. . The perilymph is the primary oxygen source for these intracochlear structures. Unfortunately, perilymph oxygen tension is decreased significantly in patients with ISSHL. To achieve a consistent rise of perilymph oxygen content, the arterial-perilymphatic oxygen concentration difference must be extremely high. This can be restored with hyperbaric oxygen therapy. Subject and Methods: A 37 year old man was presented at the clinic with a five days history of muffled hearing and tinnitus of the right ear. Symptoms were sudden onset, with no associated pain, dizziness or otorrhea and no past history of hearing problems or medical illness. Family history was negative. Physical examination was normal. Otologic examination revealed normal tympanic membranes bilaterally, with no evidence of cerumen or middle ear effusion. Tuning fork examination showed positive Rinne test bilaterally but with lateralization of Weber test to the left side, indicating right ear sensorineural hearing loss. Audiometric analysis confirmed sensorineural hearing loss across all frequencies of about 70- dB in the right ear. Routine lab work were all within normal limits. Clinical diagnosis of idiopathic sudden sensorineural hearing loss of the right ear was made and the patient began a medical treatment (corticosteroid, vasodilator and HBO therapy). The recommended treatment profile consists of 100% O2 at 2.5 atmospheres absolute for 60 minutes daily (six days per week) for 40 treatments .The optimal number of HBOT treatments will vary, depending on the severity and duration of symptomatology and the response to treatment. Results: As HBOT is not yet a standard for idiopathic sudden sensorineural hearing loss, it was introduced to this patient as an adjuvant therapy. The HBOT program was scheduled for 40 sessions, we used a 12-seat multi place chamber for the HBOT, which was started at day seven after the hearing loss onset. After the tenth session of HBOT, improvement of both hearing (by audiogram) and tinnitus was obtained in the affected ear (right). Conclusions: In conclusion, HBOT may be used for idiopathic sudden sensorineural hearing loss as an adjuvant therapy. It may promote oxygenation to the inner ear apparatus and revive hearing ability. Patients who fail to respond to oral and intratympanic steroids may benefit from this treatment. Further investigation is warranted, including animal studies to understand the molecular and histopathological aspects of HBOT and randomized control clinical studies.

Keywords: idiopathic sudden sensorineural hearing loss (issnhl), hyperbaric oxygen therapy (hbot), the decibel (db), oxygen (o2)

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Authors: Agata Migdalska, Joanna Berczynska, Ewa Bieniek, Jacek Sterna

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Muscle relaxation is considered important during general anesthesia for spine stabilization. In a presented case peripherally acting muscle relaxant was applied during general anesthesia for spine stabilization surgery. The patient was a dog, 11-years old, 26 kg, male, mix breed. Spine fracture was situated between Th13-L1-L2, probably due to the car accident. Preanesthetic physical examination revealed no sign underlying health issues. The dog was premedicated with midazolam 0.2 mg IM and butorphanol 2.4 mg IM. General anesthesia was induced with propofol IV. After the induction, the dog was intubated with an endotracheal tube and connected to an open-ended rebreathing system and maintained with the use of inhalation anesthesia with isoflurane in oxygen. 0,5 mg/ kg of rocuronium was given IV. Use of muscle relaxant was accompanied by an assessment of the degree of neuromuscular blockade by peripheral nerve stimulator. Electrodes were attached to the skin overlying at the peroneal nerve at the lateral cranial tibia. Four electrical pulses were applied to the nerve over a 2 second period. When satisfying nerve block was detected dog was prepared for the surgery. No further monitoring of the effectiveness of blockade was performed during surgery. Mechanical ventilation was kept during anesthesia. During surgery dog maintain stable, and no anesthesiological complication occur. Intraoperatively surgeon claimed that neuromuscular blockade results in a better approach to the spine and easier muscle manipulation which was helpful in order to see the fracture and replace bone fragments. Finally, euthanasia was performed intraoperatively as a result of vast myelomalacia process of the spinal cord. This prevented examination of the recovering process. Neuromuscular blocking agents act at the neuromuscular junction to provide profound muscle relaxation throughout the body. Muscle blocking agents are neither anesthetic nor analgesic; therefore inappropriately used may cause paralysis in fully conscious and feeling pain patient. They cause paralysis of all skeletal muscles, also diaphragm and intercostal muscles when given in higher doses. Intraoperative management includes maintaining stable physiological conditions, which involves adjusting hemodynamic parameters, ensuring proper ventilation, avoiding variations in temperature, maintain normal blood flow to promote proper oxygen exchange. Neuromuscular blocking agent can cause many side effects like residual paralysis, anaphylactic or anaphylactoid reactions, delayed recovery from anesthesia, histamine release, recurarization. Therefore reverse drug like neostigmine (with glikopyrolat) or edrofonium (with atropine) should be used in case of a life-threatening situation. Another useful drug is sugammadex, although the cost of this drug strongly limits its use. Muscle relaxant improves surgical conditions during spinal surgery, especially in heavily muscled individuals. They are also used to facilitate the replacement of dislocated joints as they improve conditions during fracture reduction. It is important to emphasize that in a patient with muscle weakness neuromuscular blocking agents may result in intraoperative and early postoperative cardiovascular and respiratory complications, as well as prolonged recovery from anesthesia. This should not appear in patients with recent spine fracture or luxation. Therefore it is believed that neuromuscular blockers could be useful during spine stabilization procedures.

Keywords: anesthesia, dog, neuromuscular block, spine surgery

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Authors: Shuo Li, Yannick Coffinier, Chann Lagadec, Fabrizio Cleri, Katsuhiko Nishiguchi, Akira Fujiwara, Soo Hyeon Kim, Nicolas Clément

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The need for single cell detection and analysis techniques has increased in the past decades because of the heterogeneity of individual living cells, which increases the complexity of the pathogenesis of malignant tumors. In the search for early cancer detection, high-precision medicine and therapy, the technologies most used today for sensitive detection of target analytes and monitoring the variation of these species are mainly including two types. One is based on the identification of molecular differences at the single-cell level, such as flow cytometry, fluorescence-activated cell sorting, next generation proteomics, lipidomic studies, another is based on capturing or detecting single tumor cells from fresh or fixed primary tumors and metastatic tissues, and rare circulating tumors cells (CTCs) from blood or bone marrow, for example, dielectrophoresis technique, microfluidic based microposts chip, electrochemical (EC) approach. Compared to other methods, EC sensors have the merits of easy operation, high sensitivity, and portability. However, despite various demonstrations of low limits of detection (LOD), including aptamer sensors, arrayed EC sensors for detecting single-cell have not been demonstrated. In this work, a new technique based on 20-nm-thick nanopillars array to support cells and keep them at ideal recognition distance for redox-labeled aptamers grafted on the surface. The key advantages of this technology are not only to suppress the false positive signal arising from the pressure exerted by all (including non-target) cells pushing on the aptamers by downward force but also to stabilize the aptamer at the ideal hairpin configuration thanks to a confinement effect. With the first implementation of this technique, a LOD of 13 cells (with5.4 μL of cell suspension) was estimated. In further, the nanosupported cell technology using redox-labeled aptasensors has been pushed forward and fully integrated into a single-cell electrochemical aptasensor array. To reach this goal, the LOD has been reduced by more than one order of magnitude by suppressing parasitic capacitive electrochemical signals by minimizing the sensor area and localizing the cells. Statistical analysis at the single-cell level is demonstrated for the recognition of cancer cells. The future of this technology is discussed, and the potential for scaling over millions of electrodes, thus pushing further integration at sub-cellular level, is highlighted. Despite several demonstrations of electrochemical devices with LOD of 1 cell/mL, the implementation of single-cell bioelectrochemical sensor arrays has remained elusive due to their challenging implementation at a large scale. Here, the introduced nanopillar array technology combined with redox-labeled aptamers targeting epithelial cell adhesion molecule (EpCAM) is perfectly suited for such implementation. Combining nanopillar arrays with microwells determined for single cell trapping directly on the sensor surface, single target cells are successfully detected and analyzed. This first implementation of a single-cell electrochemical aptasensor array based on Brownian-fluctuating redox species opens new opportunities for large-scale implementation and statistical analysis of early cancer diagnosis and cancer therapy in clinical settings.

Keywords: bioelectrochemistry, aptasensors, single-cell, nanopillars

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Authors: Bensaid A., Mostephaoui T., Nedjai R.

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Nowadays, wetlands are the subject of contradictory debates opposing scientific, political and administrative meanings. Indeed, given their multiple services (drinking water, irrigation, hydrological regulation, mineral, plant and animal resources...), wetlands concentrate many socio-economic and biodiversity issues. In some regions, they can cover vast areas (>100 thousand ha) of the landscape, such as the Camargue area in the south of France, inside the Rhone delta. The high biological productivity of wetlands, the strong natural selection pressures and the diversity of aquatic environments have produced many species of plants and animals that are found nowhere else. These environments are tremendous carbon sinks and biodiversity reserves depending on their age, composition and surrounding environmental conditions, wetlands play an important role in global climate projections. Covering more than 3% of the earth's surface, wetlands have experienced since the beginning of the 1990s a tremendous revival of interest, which has resulted in the multiplication of inventories, scientific studies and management experiments. The geographical and physical characteristics of the wetlands of the central region conceal a large number of natural habitats that harbour a great biological diversity. These wetlands, one of the natural habitats, are still influenced by human activities, especially agriculture, which affects its layout and functioning. In this perspective, decision-makers need to delimit spatial objects (natural habitats) in a certain way to be able to take action. Thus, wetlands are no exception to this rule even if it seems to be a difficult exercise to delimit a type of environment as whose main characteristic is often to occupy the transition between aquatic and terrestrial environment. However, it is possible to map wetlands with databases, derived from the interpretation of photos and satellite images, such as the European database Corine Land cover, which allows quantifying and characterizing for each place the characteristic wetland types. Scientific studies have shown limitations when using high spatial resolution images (SPOT, Landsat, ASTER) for the identification and characterization of small wetlands (1 hectare). To address this limitation, it is important to note that these wetlands generally represent spatially complex features. Indeed, the use of very high spatial resolution images (>3m) is necessary to map small and large areas. However, with the recent evolution of artificial intelligence (AI) and deep learning methods for satellite image processing have shown a much better performance compared to traditional processing based only on pixel structures. Our research work is also based on spectral and textural analysis on THR images (Spot and IRC orthoimage) using two object-oriented approaches, the nearest neighbour approach (k-NN) and the Super Vector Machine approach (SVM). The k-NN approach gave good results for the delineation of wetlands (wet marshes and moors, ponds, artificial wetlands water body edges, ponds, mountain wetlands, river edges and brackish marshes) with a kappa index higher than 85%.

Keywords: land development, GIS, sand dunes, segmentation, remote sensing

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Authors: Ye Xue, Zhenhua Deng

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Objectives: Facial soft tissue thickness (FSTT) data could be obtained from CT scans by measuring the face-to-skull distances at sparsely distributed anatomical landmarks by manually located on face and skull. However, automated measurement using 3D facial and skull models by dense points using open-source software has become a viable option due to the development of computed assisted imaging technologies. By utilizing dense FSTT information, it becomes feasible to generate plausible automated facial approximations. Therefore, establishing a comprehensive and detailed, densely calculated FSTT database is crucial in enhancing the accuracy of facial approximation. Materials and methods: This study utilized head CT scans from 250 Chinese adults of Han ethnicity, with 170 participants originally born and residing in northern China and 80 participants in southern China. The age of the participants ranged from 14 to 82 years, and all samples were divided into five non-overlapping age groups. Additionally, samples were also divided into three categories based on BMI information. The 3D Slicer software was utilized to segment bone and soft tissue based on different Hounsfield Unit (HU) thresholds, and surface models of the face and skull were reconstructed for all samples from CT data. Following procedures were performed unsing MeshLab, including converting the face models into hollowed cropped surface models amd automatically measuring the Hausdorff Distance (referred to as FSTT) between the skull and face models. Hausdorff point clouds were colorized based on depth value and exported as PLY files. A histogram of the depth distributions could be view and subdivided into smaller increments. All PLY files were visualized of Hausdorff distance value of each vertex. Basic descriptive statistics (i.e., mean, maximum, minimum and standard deviation etc.) and distribution of FSTT were analysis considering the sex, age, BMI and birthplace. Statistical methods employed included Multiple Regression Analysis, ANOVA, principal component analysis (PCA). Results: The distribution of FSTT is mainly influenced by BMI and sex, as further supported by the results of the PCA analysis. Additionally, FSTT values exceeding 30mm were found to be more sensitive to sex. Birthplace-related differences were observed in regions such as the forehead, orbital, mandibular, and zygoma. Specifically, there are distribution variances in the depth range of 20-30mm, particularly in the mandibular region. Northern males exhibit thinner FSTT in the frontal region of the forehead compared to southern males, while females shows fewer distribution differences between the northern and southern, except for the zygoma region. The observed distribution variance in the orbital region could be attributed to differences in orbital size and shape. Discussion: This study provides a database of Chinese individuals distribution of FSTT and suggested opening source tool shows fine function for FSTT measurement. By incorporating birthplace as an influential factor in the distribution of FSTT, a greater level of detail can be achieved in facial approximation.

Keywords: forensic anthropology, forensic imaging, cranial facial reconstruction, facial soft tissue thickness, CT, open-source tool

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Authors: David Shengelia, Tamara Tsutsunava, Manana Togonidze, Giorgi Chichinadze, Giorgi Beridze

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Orthoclase gabbro intrusive exposes in the Eastern part of the Dzirula crystalline massif of the Central Transcaucasian microcontinent. It is intruded in the Baikal quartz-diorite gneisses as a stock-like body. The intrusive is characterized by heterogeneity of rock composition: variability of mineral content and irregular distribution of rock-forming minerals. The rocks are represented by pyroxenites, gabbro-pyroxenites and gabbros of different composition – K-feldspar, pyroxene-hornblende and biotite bearing varieties. Scientific views on the genesis and age of the orthoclase gabbro intrusive are considerably different. Based on the long-term pertogeochemical and geochronological investigations of the intrusive with such an extraordinary composition the authors came to the following conclusions. According to geological and geophysical data, it is stated that in the Saurian orogeny horizontal tectonic layering of the Earth’s crust of the Central Transcaucasian microcontinent took place. That is precisely this fact that explains the formation of the orthoclase gabbro intrusive. During the tectonic doubling of the Earth’s crust of the mentioned microcontinent thick tectonic nappes of mafic and sialic layers overlap the sialic basement (‘inversion’ layer). The initial magma of the intrusive was of high-temperature basite-ultrabasite composition, crystallization products of which are pyroxenites and gabbro-pyroxenites. Petrochemical data of the magma attest to its formation in the Upper mantle and partially in the ‘crustal astenolayer’. Then, a newly formed overheated dry magma with phenocrysts of clinopyrocxene and basic plagioclase intruded into the ‘inversion’ layer. From the new medium it was enriched by the volatile components causing the selective melting and as a result the formation of leucocratic quartz-feldspar material. At the same time in the basic magma intensive transformation of pyroxene to hornblende was going on. The basic magma partially mixed with the newly formed acid magma. These different magmas intruded first into the allochthonous basite layer without its significant transformation and then into the upper sialic layer and crystallized here at a depth of 7-10 km. By petrochemical data the newly formed leucocratic granite magma belongs to the S type granites, but the above mentioned mixed magma – to H (hybrid) type. During the final stage of magmatic processes the gabbroic rocks impregnated with high-temperature feldspar-bearing material forming anorthoclase or orthoclase. Thus, so called ‘orthoclase gabbro’ includes the rocks of various genetic groups: 1. protolith of gabbroic intrusive; 2. hybrid rock – K-feldspar gabbro and 3. leucocratic quartz-feldspar bearing rock. Petrochemical and geochemical data obtained from the hybrid gabbro and from the inrusive protolith differ from each other. For the identification of petrogenetic model of the orthoclase gabbro intrusive formation LA-ICP-MS- U-Pb zircon dating has been conducted in all three genetic types of gabbro. The zircon age of the protolith – mean 221.4±1.9 Ma and of hybrid K-feldspar gabbro – mean 221.9±2.2 Ma, records crystallization time of the intrusive, but the zircon age of quartz-feldspar bearing rocks – mean 323±2.9 Ma, as well as the inherited age (323±9, 329±8.3, 332±10 and 335±11 Ma) of hybrid K-feldspar gabbro corresponds to the formation age of Late Variscan granitoids widespread in the Dzirula crystalline massif.

Keywords: The Caucasus, isotope dating, orthoclase-bearing gabbro, petrogenetic model

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Authors: Fouzia Arif, Arif S. Mohammad, Hifsa Altaf, Lubna Raees

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Introduction: The term "disability", refers to any condition that impedes the completion of daily tasks using traditional methods. In developing countries like Pakistan, disable population is usually excluded from the mainstream. In squatter settlements the situation is more critical. Sultanabad is one of the squatter settlements of Karachi. Purpose of case study is to improve the health of disabled children’s, and create awareness among the parents and community. Through a household visit, Shiraz, a young disabled boy of 15.5 years old was identified. Her mother articulated that her son was living normally and happily with his parents two years back. When he was 13 years old and student of class 8th, both his legs were traumatized in a Railway Train Accident while playing cricket. He got both femoral shaft fractured severely. He was taken to Jinnah Post Graduate Medical Centre (JPMC) where his left leg was amputated at above knee level and right leg was opened & fixed by reduction internally, luckily bone healed moderately with the passage of time. Methods: In Squatter settlements of Karachi Sultanabad, a survey was conducted in two sectors. Disability screening questionnaire was developed, collaboration with community through household visits, outreach sessions 23cases of disabled were identified who were socialized through sports, Musical program and get-together was organized with stockholder for creating awareness among community and parent’s. Collaboration was established with different NGOs, Government, stakeholders and community support for establishment of Physiotherapy Center. During home visit it was identified that Shiraz was on bed since last 1 year, his family could not afforded cost of physiotherapist and medical consultation due to poverty. Parents counseling was done mentioning that Shiraz needed to take treatment. After motivation his parents agreed for treatment. He was consulted by an orthopedic surgeon in AKUH, Who referred to DMC University of Health Science for rehabilitation service. There he was assessed and referred for Community Based Physiotherapy Centre Sultanabad. Physiotherapist visited home along with Coordinator for Special children and assessed him regularly, planned Physiotherapy treatment for abdominal, high muscles strutting exercise foot muscles strengthening exercise, knee mobilization weight bearing from partial to full weight gradually, also strengthen exercise were given for residual limb as the boy was dependent on it. He was also provided by an artificial leg and training was done. Result: Shiraz is now fully mobile, he can walk independently even out of home, functional ability progress improved and dependency factors reduced. It was difficult but not impossible. We all have sympathy but if we have empathy then we can rehabilitate the community in a better way. His parents are very happy and also the community is surprised to see him in such better condition. Conclusion: Combined efforts of physiotherapist, Coordinator of special children, community and parents made a drastic change in Shiraz’s case by continuously motivating him for better outcome. He is going to school regularly without support. Since he belongs to a poor family he faces financial constraints for education and clinical follow ups regularly.

Keywords: femoral shaft fracture, trauma, orthopedic surgeon, physiotherapy treatment

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Authors: Shazi Farooqui, Anupam Sharma

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The Mahi River (~600km long) is an important west flowing the river of Central India. It originates in Madhya Pradesh and starts flowing in NW direction and enters into the state of Rajasthan. It flows across southern Rajasthan and then enters into Gujarat and finally debouches in the Gulf of Cambay. In Gujarat state, it flows through all four geomorphic zones i.e. eastern upland zone, shallow buried piedmont zone, alluvial zone and coastal zone. In lower reaches and particularly when it is flowing under the coastal regime, it provides an opportunity to study – 1. Land–Sea interaction and role of relative sea level changes, 2. Coastal/estuarine geological process, 3. Landscape evolution in marginal areas and so on. The Late Quaternary deposits of Mainland Gujarat is appreciably studied by Chamyal and his group of MS University of Baroda, and they have established that the 30-35m thick sediment package of the Mainland Gujarat is comprised of marine, fluvial and aeolian sediments. It is also established that in the estuarine zone, the upper few meter thick sediments package is of marine nature. However, its thickness, characters and the depositional environment including the role of climate and tectonics is still not clearly defined. To understand few aspects of the above mentioned, in the present study, a 17m subsurface sediment core has been retrieved from the estuarine zone of Mahi river basin. The Multiproxy studies which include the textural analysis (grain size), Loss on ignition (LOI), Bulk and clay mineralogy and geochemical studies have been carried out. In the entire sedimentary sequence, the grain size largely varies from coarse sand to clay; however, a solitary gravel bed is also noticed. The lower part (depth 9-17m), is mainly comprised of sub equal proportion of sand and silt. The sediments mainly have bimodal and leptokurtic distribution and deposited in alternate sand-silt package, probably indicating flood deposits. Relatively low moisture (1.8%) and organic carbon (2.4%) with increased carbonate values (12%) indicate that conditions must have to remain oxidizing. The middle part (depth 9–6m) has a 1m thick gravel bed at the bottom and overlain by coarse sand to very fine sand showing fining upward sequence. The presence of gravel bed suggests some kind of tectonic activity resulting into change in base level or enhanced precipitation in the catchment region. The upper part (depth 6–0m; top part of sequence) mainly comprised of fine sand to silt size grains (with appreciable clay content). The sediment of this part is Unimodal and very leptokurtic in nature suggesting wave and winnowing process and deposited in low energy suspension environment. This part has relatively high moisture (2.1%) and organic carbon (2.7%) with decreased carbonate content (4.2%) indicating change in the depositional environment probably under estuarine conditions. The presence of chlorite along with smectite clay mineral further supports the significant marine contribution in the formation of upper part of the sequence.

Keywords: grain size, statistical analysis, clay minerals, late quaternary, LOI

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Authors: Samia A. El-Fiky, F. A. Abou-Zaid, Ibrahim M. Farag, Naira M. Efiky

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Clomipramine hydrochloride is one of the most used tricyclic antidepressant drug in Egypt. This drug contains in its chemical structure on two benzene rings. Benzene is considered to be toxic and clastogenic agent. So, the present study was designed to assess the genotoxic effect of Clomipramine hydrochloride on somatic and germ cells in mice. Three dose levels 0.195 (Low), 0.26 (Medium), and 0.65 (High) mg/kg.b.wt. were used. Seven groups of male mice were utilized in this work. The first group was employed as a control. In the remaining six groups, each of the above doses was orally administrated for two groups, one of them was treated for 5 days and the other group was given the same dose for 30 days. At the end of experiments, the animals were sacrificed for cytogenetic and sperm examination as well as histopathological investigations by using hematoxylin and eosin stains (H and E stains) and electron microscope. Concerning the sperm studies, these studies were confined to 5 days treatment with different dose levels. Moreover, the ultrastructural investigation by electron microscope was restricted to 30 days treatment with drug doses. The results of the dose dependent effect of Clomipramine showed that the treatment with three different doses induced increases of frequencies of chromosome aberrations in bone marrow and spermatocyte cells as compared to control. In addition, mitotic and meiotic activities of somatic and germ cells were declined. The treatments with medium or high doses were more effective for inducing significant increases of chromosome aberrations and significant decreases of cell divisions than treatment with low dose. The effect of high dose was more pronounced for causing such genetic deleterious in respect to effect of medium dose. Moreover, the results of the time dependent effect of Clomipramine observed that the treatment with different dose levels for 30 days led to significant increases of genetic aberrations than treatment for 5 days. Sperm examinations revealed that the treatment with Clomipramine at different dose levels caused significant increase of sperm shape abnormalities and significant decrease in sperm count as compared to control. The adverse effects on sperm shape and count were more obviousness by using the treatments with medium or high doses than those found in treatment with low dose. The group of mice treated with high dose had the highest rate of sperm shape abnormalities and the lowest proportion of sperm count as compared to mice received medium dose. In histopathological investigation, hematoxylin and eosin stains showed that, the using of low dose of Clomipramine for 5 or 30 days caused a little pathological changes in liver tissue. However, using medium and high doses for 5 or 30 days induced severe damages than that observed in mice treated with low dose. The treatment with high dose for 30 days gave the worst results of pathological changes in hepatic cells. Moreover, ultrastructure examination revealed, the mice treated with low dose of Clomipramine had little differences in liver histological architecture as compared to control group. These differences were confined to cytoplasmic inclusions. Whereas, prominent pathological changes in nuclei as well as dilated of rough Endoplasmic Reticulum (rER) were observed in mice treated with medium or high doses of Clomipramine drug. In conclusion, the present study adds evidence that treatments with medium or high doses of Clomipramine have genotoxic effects on somatic and germ cells of mice, as unwanted side effects. However, the using of low dose (especially for short time, 5 days) can be utilized as a therapeutic dose, where it caused relatively similar proportions of genetic, sperm, and histopathological changes as those found in normal control.

Keywords: clomipramine, mice, chromosome aberrations, sperm abnormalities, histopathology

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