Search results for: histopathological grading

Authors: Marina Shargorodsky

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Aim: Gestational weight gain (GWG) has been related to altering future weight-gain curves and increased risks of obesity later in life. Obesity may contribute to vascular atherosclerotic changes as well as excess cardiovascular morbidity and mortality observed in these patients. Noninvasive arterial testing, such as ultrasonographic measurement of carotid IMT, is considered a surrogate for systemic atherosclerotic disease burden and is predictive of cardiovascular events in asymptomatic individuals as well as recurrent events in patients with known cardiovascular disease. Currently, there is no consistent evidence regarding the vascular impact of excessive GWG. The present study was designed to investigate the impact of GWG on early atherosclerotic changes during late pregnancy, using intima-media thickness, as well as placental vascular circulation and inflammatory lesions and pregnancy outcomes. Methods: The study group consisted of 59 pregnant women who gave birth and underwent a placental histopathological examination at the Department of Obstetrics and Gynecology, Edith Wolfson Medical Center, Israel, in 2019. According to the IOM guidelines the study group has been divided into two groups: Group 1 included 32 women with pregnancy weight gain within recommended range; Group 2 included 27 women with excessive weight gain during pregnancy. The IMT was measured from non-diseased intimal and medial wall layers of the carotid artery on both sides, visualized by high-resolution 7.5 MHz ultrasound (Apogee CX Color, ATL). Placental histology subdivided placental findings to lesions consistent with maternal vascular and fetal vascular malperfusion according to the criteria of the Society for Pediatric Pathology, subdividing placental findings to lesions consistent with maternal vascular and fetal vascular malperfusion, as well as the inflammatory response of maternal and fetal origin. Results: IMT levels differed between groups and were significantly higher in Group 1 compared to Group 2 (0.7+/-0.1 vs 0.6+/-0/1, p=0.028). Multiple linear regression analysis of IMT included variables based on their associations in univariate analyses with a backward approach. Included in the model were pre-gestational BMI, HDL cholesterol and fasting glucose. The model was significant (p=0.001) and correctly classified 64.7% of study patients. In this model, pre-pregnancy BMI remained a significant independent predictor of subclinical atherosclerosis assessed by IMT (OR 4.314, 95% CI 0.0599-0.674, p=0.044). Among placental lesions related to fetal vascular malperfusion, villous changes consistent with fetal thrombo-occlusive disease (FTOD) were significantly higher in Group 1 than in Group 2, p=0.034). In Conclusion, the present study demonstrated that excessive weight gain during pregnancy is associated with an adverse effect on early stages of subclinical atherosclerosis, placental vascular circulation and neonatal complications. The precise mechanism for these vascular changes, as well as the overall clinical impact of weight control during pregnancy on IMT, placental vascular circulation as well as pregnancy outcomes, deserves further investigation.

Keywords: obesity, pregnancy, complications, weight gain

Procedia PDF Downloads 31

Authors: J. A. N. Sandamali, R. P. Hewawasam, K. A. P. W. Jayatilaka, L. K. B. Mudduwa

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Introduction: Doxorubicin is widely used in the treatment of solid organ tumors and hematological malignancies, but the dose-dependent cardiotoxicity due to free radical formation compromises its clinical utility. Therapeutic strategies which enhance cellular endogenous defense systems have been identified as promising approaches to combat oxidative stress-associated conditions. Cinnamomum zeylanicum (Ceylon cinnamon) has a number antioxidant compounds, which can effectively scavenge reactive oxygen including superoxide anions, hydroxyl radicals and as well as other free radicals. Therefore, the objective of the study was to elucidate the most effective dose of Cinnamomum bark extract which ameliorates doxorubicin-induced cardiotoxicity. Materials and methods: Wistar rats were divided into seven groups of 10 animals in each. Group 1: normal control (distilled water, orally, for 14 days, 10 mL/kg saline, ip, after 16 hours fast on the 11th day); Group 2: doxorubicin control (distilled water, orally, for 14 days, 18 mg/kg doxorubicin, ip, after 16 hour fast on the 11th day); Groups 3-7: five doses of freeze dried aqueous bark extracts (0.125, 0.25, 0.5, 1.0, 2.0g/kg, orally, daily for 14 days, 18 mg/kg doxorubicin, ip, after 16 hours fast on the 11th day). Animals were sacrificed on the 15th day and blood was collected for the estimation of cardiac troponin I (cTnI), AST and LDH concentrations and myocardial tissues were collected for histopathological assessment of myocardial damage and irreversible changes were graded by developing a score. Results: cTnI concentration of groups 1-7 were 0, 161.9, 128.6, 95.9, 38, 19.41 & 12.36 pg/mL showing significant differences (p<0.05) between group 2 and groups 4-7. In groups 1-7, serum AST concentration were 26.82, 68.1, 37.18, 36.23, 26.8, 26.62 & 22.43U/L and LDH concentrations were 1166.13, 2428.84, 1658.35, 1474.34, 1277.58, 1110.21 & 974.40U/L and a significant difference (p<0.05) was observed between group 2 and groups 3-7. The maximum score for myocardial necrosis was observed in group 2. Parallel to the increase of the dosage of plant extract, a gradual reduction of the score for myocardial necrosis was observed in groups 3-7. Reversible histological changes such as vacuolation, congestion were observed in group 2 and all plant treated groups. Haemorrhages, inflammatory cell infiltrations, and interstitial oedema were observed in group 2, but absent in groups treated with higher doses of the plant extract. Discussion & Conclusion: According to the in vitro antioxidant assays performed, Cinnamomum zeylanicum (Ceylon cinnamon) bark possesses high amounts of polyphenolic substances and high antioxidant activity. The present study showed that Cinnamomum zeylanicum extract at 2.0 g/kg possesses the most significant cardioprotective effect against doxorubicin-induced cardiotoxicity. It can be postulated that pretreatment with Cinnamomum bark extract may replenish the cardiomyocytes with antioxidants that are needed for the defense against oxidative stress induced by doxorubicin.

Keywords: cardioprotection, Cinnamomum zeylanicum, doxorubicin, free radicals

Procedia PDF Downloads 139

Authors: Sajjad H. Kasanagh, Perviz Ahmedzade, Alexander Fainleib, Taylan Gunay

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Modification of asphalt is a fundamental method around the world mainly on the purpose of providing more durable pavements which lead to diminish repairing cost during the lifetime of highways. Various polymers such as styrene-butadiene-styrene (SBS) and ethylene vinyl acetate (EVA) make up the greater parts of the all-over asphalt modifiers generally providing better physical properties of asphalt by decreasing temperature dependency which eventually diminishes permanent deformation on highways such as rutting. However, some waste and low-cost materials such as recycled plastics and ground rubber tire have been attempted to utilize in asphalt as modifier instead of manufactured polymer modifiers due to decreasing the eventual highway cost. On the other hand, the usage of recycled plastics has become a worldwide requirement and awareness in order to decrease the pollution made by waste plastics. Hence, finding an area in which recycling plastics could be utilized has been targeted by many research teams so as to reduce polymer manufacturing and plastic pollution. To this end, in this paper, thermoplastic dynamic vulcanizate (TDV) obtained from recycled post-consumer polyethylene and ground tire rubber (GTR) were used to provide an efficient modifier for asphalt which decreases the production cost as well and finally might provide an ecological solution by decreasing polymer disposal problems. TDV was synthesized by the chemists in the research group by means of the abovementioned components that are considered as compatible physical characteristic of asphalt materials. TDV modified asphalt samples having different rate of proportions of 3, 4, 5, 6, 7 wt.% TDV modifier were prepared. Conventional tests, such as penetration, softening point and roll thin film oven (RTFO) tests were performed to obtain fundamental physical and aging properties of the base and modified binders. The high temperature performance grade (PG) of binders was determined by Superpave tests conducted on original and aged binders. The multiple stress creep and recovery (MSCR) test which is relatively up-to-date method for classifying asphalts taking account of their elasticity abilities was carried out to evaluate PG plus grades of binders. The results obtained from performance grading, and MSCR tests were also evaluated together so as to make a comparison between the methods both aiming to determine rheological parameters of asphalt. The test results revealed that TDV modification leads to a decrease in penetration, an increase in softening point, which proves an increasing stiffness of asphalt. DSR results indicate an improvement in PG for modified binders compared to base asphalt. On the other hand, MSCR results that are compatible with DSR results also indicate an enhancement on rheological properties of asphalt. However, according to the results, the improvement is not as distinct as observed in DSR results since elastic properties are fundamental in MSCR. At the end of the testing program, it can be concluded that TDV can be used as modifier which provides better rheological properties for asphalt and might diminish plastic waste pollution since the material is 100% recycled.

Keywords: asphalt, ground tire rubber, recycled polymer, thermoplastic dynamic vulcanizate

Procedia PDF Downloads 194

Authors: Daniel Rowe, Christopher R. Vogel, Richard H. J. Willden

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The University of Oxford’s recirculating water flume is a combined wave and current test tank with a 1 m depth, 1.1 m width, and 10 m long working section, and is capable of flow speeds up to 1 ms−1 . This study documents the hydrodynamic characteristics of the facility in preparation for experimental testing of horizontal axis tidal stream turbine models. The turbine to be tested has a rotor diameter of 0.6 m and is a modified version of one of two model-scale turbines tested in previous experimental campaigns. An Acoustic Doppler Velocimeter (ADV) was used to measure the flow at high temporal resolution at various locations throughout the flume, enabling the spatial uniformity and turbulence flow parameters to be investigated. The mean velocity profiles exhibited high levels of spatial uniformity at the design speed of the flume, 0.6 ms−1 , with variations in the three-dimensional velocity components on the order of ±1% at the 95% confidence level, along with a modest streamwise acceleration through the measurement domain, a target 5 m working section of the flume. A high degree of uniformity was also apparent for the turbulence intensity, with values ranging between 1-2% across the intended swept area of the turbine rotor. The integral scales of turbulence exhibited a far higher degree of variation throughout the water column, particularly in the streamwise and vertical scales. This behaviour is believed to be due to the high signal noise content leading to decorrelation in the sampling records. To achieve more realistic levels of vertical velocity shear in the flume, a simple procedure to practically generate target vertical shear profiles in open-channel flows is described. Here, the authors arranged a series of non-uniformly spaced parallel bars placed across the width of the flume and normal to the onset flow. By adjusting the resistance grading across the height of the working section, the downstream profiles could be modified accordingly, characterised by changes in the velocity profile power law exponent, 1/n. Considering the significant temporal variation in a tidal channel, the choice of the exponent denominator, n = 6 and n = 9, effectively provides an achievable range around the much-cited value of n = 7 observed at many tidal sites. The resulting flow profiles, which we intend to use in future turbine tests, have been characterised in detail. The results indicate non-uniform vertical shear across the survey area and reveal substantial corner flows, arising from the differential shear between the target vertical and cross-stream shear profiles throughout the measurement domain. In vertically sheared flow, the rotor-equivalent turbulence intensity ranges between 3.0-3.8% throughout the measurement domain for both bar arrangements, while the streamwise integral length scale grows from a characteristic dimension on the order of the bar width, similar to the flow downstream of a turbulence-generating grid. The experimental tests are well-defined and repeatable and serve as a reference for other researchers who wish to undertake similar investigations.

Keywords: acoustic doppler Velocimeter, experimental hydrodynamics, open-channel flow, shear profiles, tidal stream turbines

Procedia PDF Downloads 54

Authors: Waleed Al-Nuaimy, Luke Anastassiou, Manjinder Kainth

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As the process of teaching has evolved with the advent of new technologies over the ages, so has the process of learning. Educators have perpetually found themselves on the lookout for new technology-enhanced methods of teaching in order to increase learning efficiency and decrease ever expanding workloads. Shortly after the invention of the internet, web-based learning started to pick up in the late 1990s and educators quickly found that the process of providing learning material and marking assignments could change thanks to the connectivity offered by the internet. With the creation of early web-based virtual learning environments (VLEs) such as SPIDER and Blackboard, it soon became apparent that VLEs resulted in higher reported computer self-efficacy among students, but at the cost of students being less satisfied with the learning process . It may be argued that the impersonal nature of VLEs, and their limited functionality may have been the leading factors contributing to this reported dissatisfaction. To this day, often faced with the prospects of assigning colossal engineering cohorts their homework and assessments, educators may frequently choose optimally curated assessment formats, such as multiple-choice quizzes and numerical answer input boxes, so that automated grading software embedded in the VLEs can save time and mark student submissions instantaneously. A crucial skill that is meant to be learnt during most science and engineering undergraduate degrees is gaining the confidence in using, solving and deriving mathematical equations. Equations underpin a significant portion of the topics taught in many STEM subjects, and it is in homework assignments and assessments that this understanding is tested. It is not hard to see that this can become challenging if the majority of assignment formats students are engaging with are multiple-choice questions, and educators end up with a reduced perspective of their students’ ability to manipulate equations. Artificial intelligence (AI) has in recent times been shown to be an important consideration for many technologies. In our paper, we explore the use of new AI based software designed to work in conjunction with current VLEs. Using our experience with the software, we discuss its potential to solve a selection of problems ranging from impersonality to the reduction of educator workloads by speeding up the marking process. We examine the software’s potential to increase learning efficiency through its features which claim to allow more customized and higher-quality feedback. We investigate the usability of features allowing students to input equation derivations in a range of different forms, and discuss relevant observations associated with these input methods. Furthermore, we make ethical considerations and discuss potential drawbacks to the software, including the extent to which optical character recognition (OCR) could play a part in the perpetuation of errors and create disagreements between student intent and their submitted assignment answers. It is the intention of the authors that this study will be useful as an example of the implementation of AI in a practical assessment scenario insofar as serving as a springboard for further considerations and studies that utilise AI in the setting and marking of science and engineering assignments.

Keywords: engineering education, assessment, artificial intelligence, optical character recognition (OCR)

Procedia PDF Downloads 100

Authors: Hanan M. Hassan, Laila Abouzeid, Lamya H. Al-Wahaibi, George S. G. Shehatou, Ali A. El-Emam

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Cancer is a major public health problem and the second leading cause of death worldwide. In 2020, cancer diagnosis and treatment have been negatively affected by the coronavirus 2019 (COVID-19) pandemic. During the quarantine, because of the limited access to healthcare and avoiding exposure to COVID-19 as a contagious disease; patients of cancer suffered deferments in follow-up and treatment regimens leading to substantial worsening of disease, death, and increased healthcare costs. Thus, this study is designed to investigate the molecular mechanisms by which adamantne derivatives attenuate hepatocllular carcinoma experimentally and theoretically. There is a close association between increased resistance to anticancer drugs and defective apoptosis that considered a causative factor for oncogenesis. Cancer cells use different molecular pathways to inhibit apoptosis, BAX and Bcl-2 proteins have essential roles in the progression or inhibition of intrinsic apoptotic pathways triggered by mitochondrial dysfunction. Therefore, their balance ratio can promote the cellular apoptotic fate. In this study, the in vitro cytotoxic effects of seven synthetic adamantyl isothiorea derivatives were evaluated against five human tumor cell lines by MTT assay. Compounds 5 and 6 showed the best results, mostly against hepatocellular carcinoma (HCC). Hence, in vivo studies were performed in male Sprague-Dawley (SD) rats in which experimental hepatocellular carcinoma was induced with thioacetamide (TAA) (200 mg/kg, i.p., twice weekly) for 16 weeks. The most promising compounds, 5 and 6, were administered to treat liver cancer rats at a dose of 10 mg/kg/day for an additional two weeks, and the effects were compared with doxorubicin (DR), the anticancer drug. Hepatocellular carcinoma was evidenced by a dramatic increase in liver indices, oxidative stress markers, and immunohistochemical studies that were accompanied by a plethora of inflammatory mediators and alterations in the apoptotic cascade. Our results showed that treatment with adamantane derivatives 5 and 6 significantly suppressed fibrosis, inflammation, and other histopathological insults resulting in the diminished formation of hepatocyte tumorigenesis. Moreover, administration of the tested compounds resulted in amelioration of EGFR protein expression, upregulation of BAX, and lessening down of Bcl-2 levels that prove their role as apoptosis inducers. Also, the docking simulations performed for adamantane showed good fit and binding to the EGFR protein through hydrogen bond formation with conservative amino acids, which gives a shred of strong evidence for its hepatoprotective effect. In most analyses, the effects of compound 6 were more comparable to DR than compound 5. Our findings suggest that adamantane derivatives 5 and 6 are shown to have cytotoxic activity against HCC in vitro and in vivo, by more than one mechanism, possibly by inhibiting the TLR4-MyD88-NF-κB pathway and targeting EGFR signaling.

Keywords: adamantane, EGFR, HCC, apoptosis

Procedia PDF Downloads 127

Authors: Tamar Bikashvili, Tamar Lordkipanidze, Ilia Lazrishvili

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Heavy metals remain one of serious environmental problems due to their toxic effects. The effect of arsenic and manganese compounds on rat behavior and neuromorphology was studied. Wistar rats were assigned to four groups: rats in control group were given regular water, while rats in other groups drank water with final manganese concentration of 10 mg/L (group A), 20 mg/L (group B) and final arsenic concentration 68 mg/L (group C), respectively, for a month. To study exploratory and anxiety behavior and also to evaluate aggressive performance in “home cage” rats were tested in “Open Field” and to estimate learning and memory status multi-branched maze was used. Statistically significant increase of motor and oriental-searching activity in experimental groups was revealed by an open field test, which was expressed in increase of number of lines crossed, rearing and hole reflexes. Obtained results indicated the suppression of fear in rats exposed to manganese. Specifically, this was estimated by the frequency of getting to the central part of the open field. Experiments revealed that 30-day exposure to 10 mg/ml manganese did not stimulate aggressive behavior in rats, while exposure to the higher dose (20 mg/ml), 37% of initially non-aggressive animals manifested aggressive behavior. Furthermore, 25% of rats were extremely aggressive. Obtained data support the hypothesis that excess manganese in the body is one of the immediate causes of enhancement of interspecific predatory aggressive and violent behavior in rats. It was also discovered that manganese intoxication produces non-reversible severe learning disability and insignificant, reversible memory disturbances. Studies of rodents exposed to arsenic also revealed changes in the learning process. As it is known, the distribution of metal ions differs in various brain regions. The principle manganese accumulation was observed in the hippocampus and in the neocortex, while arsenic was predominantly accumulated in nucleus accumbens, striatum, and cortex. These brain regions play an important role in the regulation of emotional state and motor activity. Histopathological analyzes of brain sections illustrated two morphologically distinct altered phenotypes of neurons: (1) shrunk cells with indications of apoptosis - nucleus and cytoplasm were very difficult to be distinguished, the integrity of neuronal cytoplasm was not disturbed; and (2) swollen cells - with indications of necrosis. Pyknotic nucleus, plasma membrane disruption and cytoplasmic vacuoles were observed in swollen neurons and they were surrounded by activated gliocytes. It’s worth to mention that in the cortex the majority of damaged neurons were apoptotic while in subcortical nuclei –neurons were mainly necrotic. Ultrastructural analyses demonstrated that all cell types in the cortex and the nucleus caudatus represent destructed mitochondria, widened neurons’ vacuolar system profiles, increased number of lysosomes and degeneration of axonal endings.

Keywords: arsenic, manganese, behavior, learning, neuron

Procedia PDF Downloads 330

Authors: Akanksha Agrawal, Richa Rathor, Geetha Suryakumar

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Muscle represents about ¾ of the body mass, and a healthy muscular system is required for human performance. A healthy muscular system is dynamically balanced via the catabolic and anabolic process. High altitude associated hypoxia altered this redox balance via producing reactive oxygen and nitrogen species that ultimately modulates protein structure and function, hence, disrupts proteostasis or protein homeostasis. The mechanism by which proteostasis is clinched includes regulated protein translation, protein folding, and protein degradation machinery. Perturbation in any of these mechanisms could increase proteome imbalance in the cellular processes. Altered proteostasis in skeletal muscle is likely to be responsible for contributing muscular atrophy in response to hypoxia. Therefore, we planned to elucidate the mechanism involving altered proteostasis leading to skeletal muscle atrophy under chronic hypobaric hypoxia. Material and Methods-Male Sprague Dawley rats weighing about 200-220 were divided into five groups - Control (Normoxic animals), 1d, 3d, 7d and 14d hypobaric hypoxia exposed animals. The animals were exposed to simulated hypoxia equivalent to 282 torr pressure (equivalent to an altitude of 7620m, 8% oxygen) at 25°C. On completion of chronic hypobaric hypoxia (CHH) exposure, rats were sacrificed, muscle was excised and biochemical, histopathological and protein synthesis signaling were studied. Results-A number of changes were observed with the CHH exposure time period. ROS was increased significantly on 07 and 14 days which were attributed to protein oxidation via damaging muscle protein structure by oxidation of amino acids moiety. The oxidative damage to the protein further enhanced the various protein degradation pathways. Calcium activated cysteine proteases and other intracellular proteases participate in protein turnover in muscles. Therefore, we analysed calpain and 20S proteosome activity which were noticeably increased at CHH exposure as compared to control group representing enhanced muscle protein catabolism. Since inflammatory markers (myokines) affect protein synthesis and triggers degradation machinery. So, we determined inflammatory pathway regulated under hypoxic environment. Other striking finding of the study was upregulation of Akt/PKB translational machinery that was increased on CHH exposure. Akt, p-Akt, p70 S6kinase, and GSK- 3β expression were upregulated till 7d of CHH exposure. Apoptosis related markers, caspase-3, caspase-9 and annexin V was also increased on CHH exposure. Conclusion: The present study provides evidence of disrupted proteostasis under chronic hypobaric hypoxia. A profound loss of muscle mass is accompanied by the muscle damage leading to apoptosis and cell death under CHH. These cellular stress response pathways may play a pivotal role in hypobaric hypoxia induced skeletal muscle atrophy. Further research in these signaling pathways will lead to development of therapeutic interventions for amelioration of hypoxia induced muscle atrophy.

Keywords: Akt/PKB translational machinery, chronic hypobaric hypoxia, muscle atrophy, protein degradation

Procedia PDF Downloads 232

Authors: Shivani Dhande, Sanjiv Choudhary, Adarshlata Singh

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Introduction: Chemical peeling is a popular, relatively inexpensive day procedure and generally safe method for treatment of pigmentary skin disorders and for skin rejuvenation. Chemical peels are classified by the depth of action into superficial, medium, and deep peels.Various facial pigmentary conditions have significant impact on quality of life causing psychological stress, necessitating its safe and effective treatment.Aim & Objectives:To compare the efficacy of Salicylic acid, Trichloroaceticacid & Glycolic Acid in facial melanosis(melasma,photomelanosis& post acne pigmentation).To study the side effects of above mentioned peeling agents. Method and Materials:It was a randomized parallel control single blind study consisting of total of 36 cases, 12 cases each of melasma, photo melanosis and post acne pigmentation within age group 20-50 years having fitzpatrick’s skin type4. Woods lamp examination was done to confirm the type of melasma.Patients with keloidal tendency, active herpes infection or past history of hypersensitivity to salicylic acid, trichloroaceticand glycolic acid as well aspatients on systemic isotretinoin were excluded.Clinical photographs at the beginning of therapy and then serially, were taken to assess the clinical response. Prior to application a written informed consent was obtained. A post auricular test peel was performed. Patients were divided into 3 groups, containing 12 patients each of melasma, photomelanosis and post acnepigmentation.All the three peels SA peel 20% (done once in 2 weeks), GA peel 50% (done once in 3 weeks) and TCA 15% (done once in 3 weeks) were used with total six settings for each patient. Before application of peel patients were counseled to wash the face with soap and water. Then face was dried and cleaned with spirit and acetone to remove all cutaneous oils. GA, TCA, SA were applied with cotton buds/gauze withmild strokes. After a contact period off 5-10mins neutralization was done with cold water. Post peel topical sunscreen application was mandatory. MASI was used pre and post treatment to assess melasma. Investigator’s global improvement scale- overall hyperpigmentation (4-significant, 3-moderate, 2-mild, 1-minimal, 0-no change ) and Patient’s satisfaction grading scale (>70%- excellent response, 50-70%- good response, <50%- average response) was used to assess improvement in all the three facial melanosis.Results:In our study of 12 patients of melasma, 4 (33.33%)patients showed excellent results;3 (25%) with GAand 1(8.33%) of TCA.Good response was seen in 4 (33.33%) patients;1(8.33%) each for GA & SA and 2(16.66%) for TCA.Poor response was seen in 4(33.33%) patients;1(8.33%) for TCA and 3 (25%) for SA.Of 12 patients of photomelanosis, excellent resultswas seen in 3(25%)patients of TCA. Good response was seen in 4 (33.33%) patients, 1(8.33%) each of TCA &SA and 2(16.66%) of GA.Poor responsewas seen in 5(41.66%) patients;3 (25%) for SA and 2(16.66%) of GA.Of 12 patients of post acne pigmentation, excellent responsein 3 (25%) patients;2(16.66%) of SA and 1(8.33%) of TCA.Good responsewas seen in 5(41.66%) patients;2(16.66%) of SA and GA and1(8.33%) of TCA.Poor response was seen in 4 (33.33%) patients; 2 (16.66%) for SA and TCA both. No major side effects in the form of scarring or persistant pigmentation was seen. Transient blackening of skin with burning sensation was seen in cases treated with TCA and SA. Post procedural itching and redness was noted with GA peel. Conclusion- In our study GA(50%),TCA(15%) & SA(20%) peels showed excellent response in melasma, photomelanosis and post-acne pigmentation respectively.All the 3 peeling agents were well tolerated without any significant side-effects in the above specified concentrations.

Keywords: facial melanosis, gycolic acid, salicylic acid, trichloroacetic acid

Procedia PDF Downloads 227

Authors: A. C. Facin, M. C. Maronezi , M. P. Menezes, G. L. Montanhim, L. Pavan, M. A. R. Feliciano, R. P. Nociti, R. A. R. Uscategui, P. C. Moraes

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The incidence of brachycephalic syndrome (BS) in the clinical routine of small animals has increased significantly giving the higher proportion of brachycephalic pets in the last years and has been considered as an animal welfare problem. The treatment of BS is surgical and the clinical signs related can be considerably attenuated. Nevertheless, the systemic effects of the BS are still poorly reported and little is known about these when the surgical correction is not performed early. Affected dogs are more likely to develop cardiopulmonary, gastrointestinal and sleep disorders in which the chronic hypoxemia plays a major role. This syndrome is compared with the obstructive sleep apnea (OSA) in humans, both considered as causes of systemic and metabolic dysfunction. Among the several consequences of the BS little is known if the syndrome also affects the hepatic tissue of brachycephalic patients. Elastography is a promising ultrasound technique that evaluates tissue elasticity and has been recently used with the purpose of diagnosis of liver fibrosis. In medicine, it is a growing concern regarding the hepatic injury of patients affected by OSA. This prospective study hypothesizes if there is any consequence of BS in the hepatic parenchyma of brachycephalic dogs that don’t receive any surgical treatment. This study was conducted following the approval of the Animal Ethics and Welfare Committee of the Faculdade de Ciências Agrárias e Veterinárias, UNESP, Campus Jaboticabal, Brazil (protocol no 17944/2017) and funded by Sao Paulo Research Foundation (FAPESP, process no 2017/24809-4). The methodology was based in ARFI elastography using the ACUSON S2000/SIEMENS device, with convex multifrequential transducer and specific software as well as clinical evaluation of the syndrome, in order to determine if they can be used as a prognostic non-invasive tool. On quantitative elastography, it was collected three measures of shear wave velocity (meters per second) and depth in centimeters in the left lateral, left medial, right lateral, right medial and caudate lobe of the liver. The brachycephalic patients, 16 pugs and 30 french bulldogs, were classified using a previously established 4-point functional grading system based on clinical evaluation before and after a 3-minute exercise tolerance test already established and validated. The control group was based on the same features collected in 22 beagles. The software R version 3.3.0 was used for the analysis and the significance level was set at 0.05. The data were analysed for normality of residuals and homogeneity of variances by Shapiro-Wilks test. Comparisons of parametric continuous variables between breeds were performed by using ANOVA with a post hoc test for pair wise comparison. The preliminary results show significant statistic differences between the brachycephalic groups and the control group in all lobes analysed (p ≤ 0,05), with higher values of shear wave velocities in the hepatic tissue of brachycephalic dogs. In this context, the results obtained in this study contributes to the understanding of BS as well as its consequences in our patients, reflecting in evidence that one more systemic consequence of the syndrome may occur in brachycephalic patients, which was not related in the veterinary literature yet.

Keywords: airway obstruction, brachycephalic airway obstructive syndrome, hepatic injury, obstructive sleep apnea

Procedia PDF Downloads 91

Authors: Olugbenga S. Alebiosu, Olusola H. Adekanmbi, Oluwatoyin T. Ogundipe

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Pollen and spores have been identified as major airborne bio-particles inducing respiratory disorders such as asthma, allergic rhinitis and atopic dermatitis among hypersensitive individuals. An aeropalynological study was conducted within a one year sampling period with a view to investigating the monthly depositional rate of atmospheric pollen and spores; influence of the immediate vegetation on airborne pollen distribution; allergenic potentials of dominant atmospheric pollen types at selected study locations in Bauchi and Taraba states, Northwestern Nigeria. A tauber-like pollen trap was employed in aerosampling with the sampler positioned at a height of 5 feet above the ground, followed by a monthly collection of the recipient solution for the sampling period. The collected samples were subjected to acetolysis treatment, examined microscopically with the identification of pollen grains and spores using reference materials and published photomicrographs. Plants within the surrounding vegetation were enumerated. Crude protein contents extracted from pollen types found to be commonly dominant at both study locations; Senna siamea, Terminalia cattapa, Panicum maximum and Zea mays were used to sensitize Musmusculus. Histopathological studies of bronchi and lung sections from certain dead M.musculus in the test groups was conducted. Blood samples were collected from the pre-orbital vein of M.musculus and processed for serological and haematological (differential and total white blood cell counts) studies. ELISA was used in determining the levels of serological parameters: IgE and cytokines (TNF-, IL-5, and IL-13). Statistical significance was observed in the correlation between the levels of serological and haematological parameters elicited by each test group, differences between the levels of serological and haematological parameters elicited by each test group and those of the control, as well as at varying sensitization periods. The results from this study revealed dominant airborne pollen types across the study locations; Syzygiumguineense, Tridaxprocumbens, Elaeisguineensis, Mimosa sp., Borreria sp., Terminalia sp., Senna sp. and Poaceae. Nephrolepis sp., Pteris sp. and a trilete fern also produced spores. This study also revealed that some of the airborne pollen types were produced by local plants at the study locations. Bronchi sections of M.musculus after first and second sensitizations, as well as lung section after first sensitization with Senna siamea, showed areas of necrosis. Statistical significance was recorded in the correlation between the levels of some serological and haematological parameters produced by each test group and those of the control, as well as at certain sensitization periods. The study revealed some candidate pollen allergens at the study locations allergy sufferers and also established a complexity of interaction between immune cells, IgE and cytokines at varied periods of mice sensitization and forming a paradigm of human immune response to different pollen allergens. However, it is expedient that further studies should be conducted on these candidate pollen allergens for their allergenicity potential in humans within their immediate environment.

Keywords: airborne, hypersensitive, mus musculus, pollen allergens, respiratory, tauber-like

Procedia PDF Downloads 112

Authors: P. J. Sweeney, T. Ahtoniemi, J. Puoliväli, T. Laitinen, K. Lehtimäki, A. Nurmi, D. Wells

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Duchenne muscular dystrophy (DMD) is caused by an X linked mutation in the dystrophin gene; lack of dystrophin causes a progressive muscle necrosis which leads to a progressive decrease in mobility in those suffering from the disease. The MDX mouse, a mutant mouse model which displays a frank dystrophinopathy, is currently widely employed in pre clinical efficacy models for treatments and therapies aimed at DMD. In general the end-points examined within this model have been based on invasive histopathology of muscles and serum biochemical measures like measurement of serum creatine kinase (sCK). It is established that a “critical period” between 4 and 6 weeks exists in the MDX mouse when there is extensive muscle damage that is largely sub clinical but evident with sCK measurements and histopathological staining. However, a full characterization of the MDX model remains largely incomplete especially with respect to the ability to aggravate of the muscle damage beyond the critical period. The purpose of this study was to attempt to aggravate the muscle damage in the MDX mouse and to create a wider, more readily translatable and discernible, therapeutic window for the testing of potential therapies for DMD. The study consisted of subjecting 15 male mutant MDX mice and 15 male wild-type mice to an intense chronic exercise regime that consisted of bi-weekly (two times per week) treadmill sessions over a 12 month period. Each session was 30 minutes in duration and the treadmill speed was gradually built up to 14m/min for the entire session. Baseline plasma creatine kinase (pCK), treadmill training performance and locomotor activity were measured after the “critical period” at around 10 weeks of age and again at 14 weeks of age, 6 months, 9 months and 12 months of age. In addition, kinematic gait analysis was employed using a novel analysis algorithm in order to compare changes in gait and fine motor skills in diseased exercised MDX mice compared to exercised wild type mice and non exercised MDX mice. In addition, a morphological and metabolic profile (including lipid profile), from the muscles most severely affected, the gastrocnemius muscle and the tibialis anterior muscle, was also measured at the same time intervals. Results indicate that by aggravating or exacerbating the underlying muscle damage in the MDX mouse by exercise a more pronounced and severe phenotype in comes to light and this can be picked up earlier by kinematic gait analysis. A reduction in mobility as measured by open field is not apparent at younger ages nor during the critical period, but changes in gait are apparent in the mutant MDX mice. These gait changes coincide with pronounced morphological and metabolic changes by non-invasive anatomical MRI and proton spectroscopy (1H-MRS) we have reported elsewhere. Evidence of a progressive asymmetric pathology in imaging parameters as well as in the kinematic gait analysis was found. Taken together, the data show that chronic exercise regime exacerbates the muscle damage beyond the critical period and the ability to measure through non-invasive means are important factors to consider when performing preclinical efficacy studies in the MDX mouse.

Keywords: Gait, muscular dystrophy, Kinematic analysis, neuromuscular disease

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Authors: R. Pardo, P. Menendez, MA Gil-Olarte, S. Sanchez, E. García, R. Quintana, J. Martín

Abstract:

Introduction : Within oncoplastic breast techniques there is increased interest in immediate partial breast reconstruction. The volume resected is greater than that of conventional conservative techniques. Central tumours of the breast have classically been treated with a mastectomy with regard to oncological safety and cosmetic secondary effects after wide central resection of the nipple and breast tissue beneath. Oncological results for central quadrantectomy have a recurrence level, disease- free period and survival identical to mastectomy. Grissoti flap is an oncoplastic surgical technique that allows the surgeon to perform a safe central quadrantectomy with excellent cosmetic results. Material and methods: The Grissoti flap is a glandular cutaneous advancement rotation flap that can fill the defect in the central portion of the excised breast. If the inferior border is affected by tumour and further surgery is decided upon at the Multidisciplinary Team Meeting, it will be necessary to perform a mastectomy. All patients with a Grisotti flap undergoing surgery since 2009 were reviewed obtaining the following data: age, hystopathological diagnosis, size, operating time, volume of tissue resected, postoperative admission time, re-excisions due to positive margins affected by tumour, wound dehiscence, complications and recurrence. Analysis and results of sentinel node biopsy were also obtained. Results: 12 patients underwent surgery between 2009-2015. The mean age was 54 years (34-67) . All had a preoperative diagnosis of ductal infiltrative carcinoma of less than 2 cm,. Diagnosis was made with Ultrasound, Mamography or both . Magnetic resonance was used in 5 cases. No patients had preoperative positive axilla after ultrasound exploration. Mean operating time was 104 minutes (84-130). Postoperative stay was 24 hours. Mean volume resected was 159 cc (70-286). In one patient the surgical border was affected by tumour and a further procedure with resection of the affected border was performed as ambulatory surgery. The sentinel node biopsy was positive for micrometastasis in only two cases. In one case lymphadenectomy was performed in 2009. In the other, treated in 2015, no lymphadenectomy was performed as the patient had a favourable histopathological prognosis and the multidisciplinary team meeting agreed that lymphadenectomy was not required. No recurrence has been diagnosed in any of the patients who underwent surgery and they are all disease free at present. Conclusions: Conservative surgery for retroareolar central tumours of the breast results in good local control of the disease with free surgical borders, including resection of the nipple areola complex and pectoral major muscle fascia. Reconstructive surgery with the inferior Grissoti flap adequately fills the defect after central quadrantectomy with creation of a new cutaneous disc where a new nipple areola complex is reconstructed with a local flap or micropigmentation. This avoids the need for contralateral symmetrization. Sentinel Node biopsy can be performed without added morbidity. When feasible, the Grissoti flap will avoid skin-sparing mastectomy for central breast tumours that will require the use of an expander, prosthesis or myocutaneous flap, with all the complications of a more complex operation.

Keywords: Grisotti flap, oncoplastic surgery, central tumours, breast

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Authors: J. van Soest, B. Bruneel, J. Smit, N. Williams, P. Swiegers

Abstract:

Selenium (Se) is an essential trace mineral involved in reducing oxidative stress, enhancing immune status, improving reproduction, and regulating growth. During finishing period, selenium supplementation can be applied to improve meat quality. Dietary selenium can be provided in inorganic or organic forms. Specifically, L-selenomethionine (organic selenium) allows for selenium storage in animal protein which supports the animal during periods of high oxidative stress. The objective of this study was to investigate the effects of synthetically produced, single amino acid, L-selenomethionine (Excential Selenium 4000, Orffa Additives BV) on production parameters, health status, and meat quality of Bonsmara bull calves. 24 calves, 7 months of age, completed a 60-day initial growing period at a commercial feedlot, after which they were transported to research station Rumen-8 (Bethlehem, South-Africa). After a ten-day adaptation period, the bulls were allocated to a control (n=12) or treatment (n=12) group. Each group was divided over 3 pens based on weight. Both groups received Total Mixed Ration supplemented with 5.25 mg Se/head per day. The control group was supplemented with sodium selenite as Se source, whilst the treatment group was supplemented with L-selenomethionine (Excential Selenium 4000, Orffa Additives BV). Animals were limited to 10 kg feed intake per head per day to ensure similar Se intake. Treatment period lasted 1.5 months. A beta-adrenergic agonist was included in the feed for the last 30 days. During the treatment period, average daily gain, average daily feed intake, and feed conversion ratio were recorded. Blood parameters were measured at day 1, day 25, and before slaughter (day 47). After slaughter, carcass weight, dressing percentage, grading, and meat quality (pH, tenderness, colour, odour, purge, proximate analyses, acid detergent fibre, and neutral detergent fibre) were determined. No differences between groups were found in performance. A higher number of animals with cortisol levels below detection limit (27.6 nmol/l) was recorded for the treatment group. Other blood parameters showed no differences. No differences were found regarding carcass weight and dressing percentage. Important parameters of meat quality were significantly improved in the treatment group: instrumental tenderness at 14 days ageing was 2.8 and 3.4 for treatment and control respectively (P=0.010), and a 0.5% decrease in purge (of fresh samples) was shown, 1.5% and 2.0% for treatment group and control respectively (p=0.029). Besides, pH was shown to be numerically reduced in the treatment group. In summary, supplementation with L-selenomethionine as selenium source improved meat quality compared to sodium selenite. Lower instrumental tenderness (Warner Bratzler Shear Force, WBSF) was recorded for the treatment group. This indicates less tough meat and highest consumer satisfaction. Regarding purge, control was just below 2.0%, an important threshold for consumer acceptation. Treatment group scored 0.5% lower for purge than control, indicating higher consumer satisfaction. The lower pH in the treatment group could be an indication of higher glycogen reserves in muscle which could contribute to a reduced risk of Dark Firm Dry carcasses. More animals showed cortisol levels below detection limit in the treatment group, indicating lower levels of stress when animals receive L-selenomethionine.

Keywords: calves, meat quality, nutrition, selenium

Procedia PDF Downloads 152

Authors: Mohamed Ahmed Tony, Mohamed Hamoud

Abstract:

The present study was conducted to determine the effect of commercially coated slow-release sodium butyrate (CM3000®) as a feed additive on zootechnical performance, immune status and Clostridium perfringens severity after experimental infection. Three hundred 1-d-old broiler chicks (Cobb 500) were randomly distributed into 3 treatment groups (4 replicates each) using 25 chicks per replicate on floor pens. Control (C) birds were offered non-supplemented basal diets. Treatments 1 and 2 (T1 and T2) were fed diets containing CM3000® at 300 and 500 g/ton feed, respectively, during the entire experimental period (35 days). Feed and water were offered ad-libitum. Feed consumption and body weight were recorded weekly to calculate body weight gain and feed conversion. Blood samples were collected to evaluate the immune status of the birds against Newcastle disease vaccines using HI test. At the end of the experimental period, 20 birds were chosen randomly from each group (5 birds from each pen) to compare carcass yield. At day 16 of age 20 birds from each group (5 birds/replicate) were bacteriologically examined and proved to be free from Clostridium perfringens. The isolated birds were challenged orally with 1 ml buffer containing 106 CFU/ml Clostridium perfringens local isolate and prepared from necrotic enteritis (NE) diseased farms. Birds were observed on a regular basis daily for any signs of NE. Birds that died in the challenged group were necropsied to determine the cause of death. On day 28 of age, the surviving chickens were killed by cervical dislocation and necropsied immediately. Intestinal tracts were removed and intestinal lesions were scored. Tissue samples of the duodenum, jejunum, ileum and cecum for histopathological examination were collected. All collected data were statistically analyzed using IBM SPSS® version 19 software for personal computers. Means were compared by one-way ANOVA (P<0.05) followed by the Duncan Post Hoc test. The results revealed that body weight gain was significantly (P<0.05) improved in chicks fed on both doses of CM3000® compared to the control one. Final body weight gain in T1 and T2 were 2064.94 and 2141.37 g/bird, respectively, while in the control group, the weight gain showed 1952.78 g/bird. In addition, supplementation of diets with CM3000® increased significantly feed intake (P<0.05). Total feed intake in T1 and T2 were 3186.32 and 3273.29 g/bird, respectively; however, feed intake in the control group recorded 3081.95 g/bird. The best feed conversion was recorded in T2 group (1.53). Feed conversion in the control and T1 groups were 1.58 and 1.54, respectively. Dressing percentage, liver weights and the other carcasses yields were not different between treatments. The butyrate significantly enhanced immune responses measured against Newcastle disease vaccines. Sodium butyrate significantly reduced NE lesions and healthy improved the intestinal tissues in the samples collected from T1 and T2-challenged chickens versus those collected from the control group. In conclusion, exogenous administration of slow-release butyrate (CM3000®) is capable of improving performance, enhancing immunity and NE disease resistance in broiler chickens.

Keywords: sodium butyrate, broiler chicken, zootechnical performance, immunity, necrotic enteritis

Procedia PDF Downloads 51

Authors: Imdad Ullah Khan, Yongseok Yoon, Kyeung Uk Choi, Kwang Rae Jo, Namyul Kim, Eunbee Lee, Wan Hee Kim, Oh-Kyeong Kweon

Abstract:

The primary spinal cord injury (SCI) causes mechanical damage to the neurons and blood vessels. It leads to secondary SCI, which activates multiple pathological pathways, which expand neuronal damage at the injury site. It is characterized by vascular disruption, ischemia, excitotoxicity, oxidation, inflammation, and apoptotic cell death. It causes nerve demyelination and disruption of axons, which perpetuate a loss of impulse conduction through the injured spinal cord. It also leads to the production of myelin inhibitory molecules, which with a concomitant formation of an astroglial scar, impede axonal regeneration. The pivotal role regarding the neuronal necrosis is played by oxidation and inflammation. During an early stage of spinal cord injury, there occurs an abundant expression of reactive oxygen species (ROS) due to defective mitochondrial metabolism and abundant migration of phagocytes (macrophages, neutrophils). ROS cause lipid peroxidation of the cell membrane, and cell death. Abundant migration of neutrophils, macrophages, and lymphocytes collectively produce pro-inflammatory cytokines such as tumor necrosis factor-alpha (TNF-α), interleukin-6 (IL-6), interleukin-1beta (IL-1β), matrix metalloproteinase, superoxide dismutase, and myeloperoxidases which synergize neuronal apoptosis. Therefore, it is crucial to control inflammation and oxidation injury to minimize the nerve cell death during secondary spinal cord injury. Therefore, in response to oxidation and inflammation, heme oxygenase-1 (HO-1) is induced by the resident cells to ameliorate the milieu. In the meanwhile, neurotrophic factors are induced to promote neuroregeneration. However, it seems that anti-stress enzyme (HO-1) and neurotrophic factor (BDNF) do not significantly combat the pathological events during secondary spinal cord injury. Therefore, optimum healing can be induced if anti-inflammatory and neurotrophic factors are administered in a higher amount through an exogenous source. During the first experiment, the inflammation and neuroregeneration were selectively targeted. HO-1 expressing MSCs (HO-1 MSCs) and BDNF expressing MSCs (BDNF MSC) were co-transplanted in one group (combination group) of dogs with subacute spinal cord injury to selectively control the expression of inflammatory cytokines by HO-1 and induce neuroregeneration by BDNF. We compared the combination group with the HO-1 MSCs group, BDNF MSCs group, and GFP MSCs group. We found that the combination group showed significant improvement in functional recovery. It showed increased expression of neural markers and growth-associated proteins (GAP-43) than in other groups, which depicts enhanced neuroregeneration/neural sparing due to reduced expression of pro-inflammatory cytokines such as TNF-alpha, IL-6 and COX-2; and increased expression of anti-inflammatory markers such as IL-10 and HO-1. Histopathological study revealed reduced intra-parenchymal fibrosis in the injured spinal cord segment in the combination group than in other groups. Thus it was concluded that selectively targeting the inflammation and neuronal growth with the combined use of HO-1 MSCs and BDNF MSCs more favorably promote healing of the SCI. HO-1 MSCs play a role in controlling the inflammation, which favors the BDNF induced neuroregeneration at the injured spinal cord segment of dogs.

Keywords: HO-1 MSCs, BDNF MSCs, neuroregeneration, inflammation, anti-inflammation, spinal cord injury, dogs

Procedia PDF Downloads 100

Authors: I. Stathopoulos, V. Syrgiamiotis, E. Karavasilis, A. Ploussi, I. Nikas, C. Hatzigiorgi, K. Platoni, E. P. Efstathopoulos

Abstract:

Introduction: Brain and central nervous system (CNS) tumors form the second most common group of cancer in children, accounting for 30% of all childhood cancers. MRI is the key imaging technique used for the visualization and management of pediatric brain tumors. Initial characterization of tumors from MRI scans is usually performed via a radiologist’s visual assessment. However, different brain tumor types do not always demonstrate clear differences in visual appearance. Using only conventional MRI to provide a definite diagnosis could potentially lead to inaccurate results, and so histopathological examination of biopsy samples is currently considered to be the gold standard for obtaining definite diagnoses. Machine learning is defined as the study of computational algorithms that can use, complex or not, mathematical relationships and patterns from empirical and scientific data to make reliable decisions. Concerning the above, machine learning techniques could provide effective and accurate ways to automate and speed up the analysis and diagnosis for medical images. Machine learning applications in radiology are or could potentially be useful in practice for medical image segmentation and registration, computer-aided detection and diagnosis systems for CT, MR or radiography images and functional MR (fMRI) images for brain activity analysis and neurological disease diagnosis. Purpose: The objective of this study is to provide an automated tool, which may assist in the imaging evaluation and classification of brain neoplasms in pediatric patients by determining the glioma type, grade and differentiating between different brain tissue types. Moreover, a future purpose is to present an alternative way of quick and accurate diagnosis in order to save time and resources in the daily medical workflow. Materials and Methods: A cohort, of 80 pediatric patients with a diagnosis of posterior fossa tumor, was used: 20 ependymomas, 20 astrocytomas, 20 medulloblastomas and 20 healthy children. The MR sequences used, for every single patient, were the following: axial T1-weighted (T1), axial T2-weighted (T2), FluidAttenuated Inversion Recovery (FLAIR), axial diffusion weighted images (DWI), axial contrast-enhanced T1-weighted (T1ce). From every sequence only a principal slice was used that manually traced by two expert radiologists. Image acquisition was carried out on a GE HDxt 1.5-T scanner. The images were preprocessed following a number of steps including noise reduction, bias-field correction, thresholding, coregistration of all sequences (T1, T2, T1ce, FLAIR, DWI), skull stripping, and histogram matching. A large number of features for investigation were chosen, which included age, tumor shape characteristics, image intensity characteristics and texture features. After selecting the features for achieving the highest accuracy using the least number of variables, four machine learning classification algorithms were used: k-Nearest Neighbour, Support-Vector Machines, C4.5 Decision Tree and Convolutional Neural Network. The machine learning schemes and the image analysis are implemented in the WEKA platform and MatLab platform respectively. Results-Conclusions: The results and the accuracy of images classification for each type of glioma by the four different algorithms are still on process.

Keywords: image classification, machine learning algorithms, pediatric MRI, pediatric oncology

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Authors: Kakali Roy, Sahana P. Raju, Subhra Dhar, Sandipan Dhar

Abstract:

Introduction: Xeroderma pigmentosa (XP) is a rare inherited (autosomal recessive) disease resulting from impairment in DNA repair that involves recognition and repair of ultraviolet radiation (UVR) induced DNA damage in the nucleotide excision repair pathway. Which results in increased photosensitivity, UVR induced damage to skin and eye, increased susceptibility of skin and ocular cancer, and progressive neurodegeneration in some patients. XP is present worldwide, with higher incidence in areas having frequent consanguinity. Being extremely rare, there is limited literature on XP and associated complications. Here, the clinico-pathological experience (spectrum of clinical presentation, histopathological findings of malignant skin lesions, and progression) of managing 8 cases of XP is presented. Methodology: A retrospective study was conducted in a pediatric tertiary care hospital in eastern India during a ten-year period from 2013 to 2022. A clinical diagnosis was made based on severe sun burn or premature photo-aging and/or onset of cutaneous malignancies at early age (1st decade) in background of consanguinity and autosomal recessive inheritance pattern in family. Results: The mean age of presentation was 1.2 years (range of 7month-3years), while three children presented during their infancy. Male to female ratio was 5:3, and all were born of consanguineous marriage. They presented with dermatological manifestations (100%) followed by ophthalmic (75%) and/or neurological symptoms (25%). Patients had normal skin at birth but soon developed extreme sensitivity to UVR in the form of exaggerated sun tanning, burning, and blistering on minimal sun exposure, followed by abnormal skin pigmentation like freckles and lentiginosis. Subsequently, over time there was progressive xerosis, atrophy, wrinkling, and poikiloderma. Six patients had varied degree of ocular involvement, while three of them had severe manifestation, including madarosis, tylosis, ectropion, Lagopthalmos, Pthysis bulbi, clouding and scarring of the cornea with complete or partial loss of vision, and ophthalmic malignancies. 50% (n=4) cases had skin and ocular pre-malignant (actinic keratosis) and malignant lesions, including melanoma and non melanoma skin cancer (NMSC) like squamous cell carcinoma (SCC) and basal cell carcinoma (BCC) in their early childhood. One patient had simultaneous occurrence of multiple malignancies together (SCC, BCC, and melanoma). Subnormal intelligence was noticed as neurological feature, and none had sensory neural hearing loss, microcephaly, neuroregression, or neurdeficit. All the patients had been being managed by a multidisciplinary team of pediatricians, dermatologists, ophthalmologists, neurologists and psychiatrists. Conclusion: Although till date there is no complete cure for XP and the disease is ultimately fatal. But increased awareness, early diagnosis followed by persistent vigorous protection from UVR, and regular screening for early detection of malignancies along with psychological support can drastically improve patients’ quality of life and life expectancy. Further research is required on formulating optimal management of XP, specifically the role and possibilities of gene therapy in XP.

Keywords: childhood malignancies, dermato-pathological findings, eastern India, Xeroderma pigmentosa

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Authors: Rajeswari Raguraman, Sowmya Parameswaran, Krishnakumar Subramanian, Jagat Kanwar, Rupinder Kanwar

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Background: Tumor microenvironment has been implicated in several cancers to regulate cell growth, invasion and metastasis culminating in outcome of therapy. Tumor stroma consists of multiple cell types that are in constant cross-talk with the tumor cells to favour a pro-tumorigenic environment. Not much is known about the existence of tumor microenvironment in the pediatric intraocular malignancy, Retinoblastoma (RB). In the present study, we aim to understand the multiple stromal cellular subtypes and tumor stromal interactions expressed in RB tumors. Materials and Methods: Immunohistochemistry for stromal cell markers CD31, CD68, alpha-smooth muscle (α-SMA), vimentin and glial fibrillary acidic protein (GFAP) was performed on formalin fixed paraffin embedded tissues sections of RB (n=12). The differential expression of stromal target molecules; fibroblast activation protein (FAP), tenascin-C (TNC), osteopontin (SPP1), bone marrow stromal antigen 2 (BST2), stromal derived factor 2 and 4 (SDF2 and SDF4) in primary RB tumors (n=20) and normal retina (n=5) was studied by quantitative reverse transcriptase polymerase chain reaction (qRT-PCR) and Western blotting. The differential expression was correlated with the histopathological features of RB. The interaction between RB cell lines (Weri-Rb-1, NCC-RbC-51) and Bone marrow stromal cells (BMSC) was also studied using direct co-culture and indirect co-culture methods. The functional effect of the co-culture methods on the RB cells was evaluated by invasion and proliferation assays. Global gene expression was studied by using Affymetrix 3’ IVT microarray. Pathway prediction was performed using KEGG and the key molecules were validated using qRT-PCR. Results: The immunohistochemistry revealed the presence of several stromal cell types such as endothelial cells (CD31+;Vim+/-); macrophages (CD68+;Vim+/-); Fibroblasts (Vim+; CD31-;CD68- );myofibroblasts (α-SMA+/ Vim+) and invading retinal astrocytes/ differentiated retinal glia (GFAP+; Vim+). A characteristic distribution of these stromal cell types was observed in the tumor microenvironment, with endothelial cells predominantly seen in blood vessels and macrophages near actively proliferating tumor or necrotic areas. Retinal astrocytes and glia were predominant near the optic nerve regions in invasive tumors with sparse distribution in tumor foci. Fibroblasts were widely distributed with rare evidence of myofibroblasts in the tumor. Both gene and protein expression revealed statistically significant (P<0.05) up-regulation of FAP, TNC and BST2 in primary RB tumors compared to the normal retina. Co-culture of BMSC with RB cells promoted invasion and proliferation of RB cells in direct and indirect contact methods respectively. Direct co-culture of RB cell lines with BMSC resulted in gene expression changes in ECM-receptor interaction, focal adhesion, IL-8 and TGF-β signaling pathways associated with cancer. In contrast, various metabolic pathways such a glucose, fructose and amino acid metabolism were significantly altered under the indirect co-culture condition. Conclusion: The study suggests that the close interaction between RB cells and the stroma might be involved in RB tumor invasion and progression which is likely to be mediated by ECM-receptor interactions and secretory factors. Targeting the tumor stroma would be an attractive option for redesigning treatment strategies for RB.

Keywords: gene expression profiles, retinoblastoma, stromal cells, tumor microenvironment

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Authors: Shikha Rani, Neeta Sehgal, Vipin Kumar Verma, Om Prakash

Abstract:

Introduction: Fish is an important protein source for humans and has great economic value. Fish cultures are affected due to various anthropogenic activities that lead to bacterial and viral infections. Aeromonas hydrophila is a fish pathogenic bacterium that causes several aquaculture outbreaks throughout the world and leads to huge mortalities. In this study, plants of no commercial value were used to investigate their immunostimulatory, antioxidant, anti-inflammatory, anti-bacterial, and disease resistance potential in fish against Aeromonas hydrophila, through fish feed fortification. Methods: The plant was dried at room temperature in the shade, dissolved in methanol, and analysed for biological compounds through GC-MS/MS. DPPH, FRAP, Phenolic, and flavonoids were estimated following standardized protocols. In silico molecular docking was also performed to validate its broad-spectrum activities based on binding affinity with specific proteins. Fish were divided into four groups (n=6; total 30 in a group): Group 1, non-challenged fish (fed on a non-supplemented diet); Group 2, fish challenged with bacteria (fed on a non-supplemented diet); Group 3 and 4, fish challenged with bacteria (A. hydrophila) and fed on plant supplemented feed at 2.5% and 5%. Blood was collected from the fish on 0, 7th, 14th, 21st, and 28th days. Serum was separated for glutamic-oxaloacetic transaminase (SGOT), serum glutamic pyruvic transaminase (SGPT), alkaline phosphatase assay (ALP), lysozyme activity assay, superoxide dismutase assay (SOD), lipid peroxidation assay (LPO) and molecular parameters (including cytokine levels) were estimated through ELISA. The phagocytic activity of macrophages from the spleen and head kidney, along with quantitative analysis of immune-related genes, were analysed in different tissue samples. The digestive enzymes (Pepsin, Trypsin, and Chymotrypsin) were also measured to evaluate the effect of plant-supplemented feed on freshwater fish. Results and Discussion: GC-MS/MS analysis of a methanolic extract of plant validated the presence of key compounds having antioxidant, anti-inflammatory, anti-bacterial, anti-inflammatory, and immunomodulatory activities along with disease resistance properties. From biochemical investigations like ABTS, DPPH, and FRAP, the amount of total flavonoids, phenols, and promising binding affinities towards different proteins in molecular docking analysis helped us to realize the potential of this plant that can be used for investigation in the supplemented feed of fish. Measurement liver function tests, ALPs, oxidation-antioxidant enzyme concentrations, and immunoglobulin concentrations in the experimental groups (3 and 4) showed significant improvement as compared to the positive control group. The histopathological evaluation of the liver, spleen, and head kidney supports the biochemical findings. The isolated macrophages from the group fed on supplemented feed showed a higher percentage of phagocytosis and a phagocytic index, indicating an enhanced cell-mediated immune response. Significant improvements in digestive enzymes were also observed in fish fed on supplemented feed, even after weekly challenges with bacteria. Hence, the plant-fortified feed can be recommended as a regular feed to enhance fish immunity and disease resistance against the Aeromonas hydrophila infection after confirmation from the field trial.

Keywords: immunostimulation, antipathogen, plant fortified feed, macrophages, GC-MS/MS, in silico molecular docking

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Authors: Magdy I. A. Alshourbagi

Abstract:

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: Aastha Arora, Vikas Bhuria, Saurabh Singh, Uma Pathak, Shweta Mathur, Puja P. Hazari, Rajat Sandhir, Ravi Soni, Anant N. Bhatt, Bilikere S. Dwarakanath

Abstract:

Radiotherapy is an effective curative and palliative option for patients with thoracic malignancies. However, lung injury, comprising of pneumonitis and fibrosis, remains a significant clin¬ical complication of thoracic radiation, thus making it a dose-limiting factor. Also, injury to the lung is often reported as part of multi-organ failure in victims of accidental radiation exposures. Radiation induced inflammatory response in the lung, characterized by leukocyte infiltration and vascular changes, is an important contributing factor for the injury. Therefore, countermeasure agents to attenuate radiation induced inflammatory response are considered as an important approach to prevent chronic lung damage. Although Amifostine, the widely used, FDA approved radio-protector, has been found to reduce the radiation induced pneumonitis during radiation therapy of non-small cell lung carcinoma, its application during mass and field exposure is limited due to associated toxicity and ineffectiveness with the oral administration. The amifostine analogue (DRDE-30) overcomes this limitation as it is orally effective in reducing the mortality of whole body irradiated mice. The current study was undertaken to investigate the potential of DRDE-30 to ameliorate radiation induced lung damage. DRDE-30 was administered intra-peritoneally, 30 minutes prior to 13.5 Gy thoracic (60Co-gamma) radiation in C57BL/6 mice. Broncheo- alveolar lavage fluid (BALF) and lung tissues were harvested at 12 and 24 weeks post irradiation for studying inflammatory and fibrotic markers. Lactate dehydrogenase (LDH) leakage, leukocyte count and protein content in BALF were used as parameters to evaluate lung vascular permeability. Inflammatory cell signaling (p38 phosphorylation) and anti-oxidant status (MnSOD and Catalase level) was assessed by Western blot, while X-ray CT scan, H & E staining and trichrome staining were done to study the lung architecture and collagen deposition. Irradiation of the lung increased the total protein content, LDH leakage and total leukocyte count in the BALF, reflecting endothelial barrier dysfunction. These disruptive effects were significantly abolished by DRDE-30, which appear to be linked to the DRDE-30 mediated abrogation of activation of the redox-sensitive pro- inflammatory signaling cascade, the MAPK pathway. Concurrent administration of DRDE-30 with radiation inhibited radiation-induced oxidative stress by strengthening the anti-oxidant defense system and abrogated p38 mitogen-activated protein kinase activation, which was associated with reduced vascular leak and macrophage recruitment to the lungs. Histopathological examination (by H & E staining) of the lung showed radiation-induced inflammation of the lungs, characterized by cellular infiltration, interstitial oedema, alveolar wall thickening, perivascular fibrosis and obstruction of alveolar spaces, which were all reduced by pre-administration of DRDE-30. Structural analysis with X-ray CT indicated lung architecture (linked to the degree of opacity) comparable to un-irradiated mice that correlated well with the lung morphology and reduced collagen deposition. Reduction in the radiation-induced inflammation and fibrosis brought about by DRDE-30 resulted in a profound increase in animal survival (72 % in the combination vs 24% with radiation) observed at the end of 24 weeks following irradiation. These findings establish the potential of the Amifostine analogue, DRDE-30, in reducing radiation induced pulmonary injury by attenuating the inflammatory and fibrotic responses.

Keywords: amifostine, fibrosis, inflammation, lung injury radiation

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Authors: S. M. A. Ismail, M. I. Ibrahim, H. Masdar, F. M. Effendi, M. F. Suhaimi, A. Suun

Abstract:

Introduction: It is generally known that the rehabilitation process is as important as the reconstruction surgery. Several literature has focused on how early the rehabilitation modalities can be initiated after the surgery to ensure a safe return of patients to sports or at least regaining the pre-injury level of function following an ACL reconstruction. Objectives: The main objective is to study and evaluate the outcome of early balance exercises and agility training in sports rehabilitation for patients post ACL reconstruction. To compare between early balance exercises and agility training as intervention and control. (material or non-material). All of them were recruited for material exercise (balance exercises and agility training with strengthening) and strengthening only rehabilitation protocol (non-material). Followed the prospective intervention trial. Materials and Methods: Post-operative ACL reconstruction patients performed in Selayang and Sg Buloh Hospitals from 2012 to 2014 were selected for this study. They were taken from Malaysian Knee Ligament Registry (MKLR) and all patients had single bundle reconstruction with autograft hamstring tendon (semitendinosus and gracilis). ACL injury from any type of sports were included. Subjects performed various type of physical activity for rehabilitation in every 18 week for a different type of rehab activity. All subject attended all 18 sessions of rehabilitation exercises and evaluation was done during the first, 9th and 18th session. Evaluation format were based on clinical assessment (anterior drawer, Lachmann, pivot shift, laxity with rolimeter, the end point and thigh circumference) and scoring (Lysholm Knee scoring and Tegner Activity Level scale). Rehabilitation protocol initiated from 24 week after the surgery. Evaluation format were based on clinical assessment (anterior drawer, Lachmann, pivot shift, laxity with rolimeter, the end point and thigh circumference) and scoring (Lysholm Knee scoring and Tegner Activity Level scale). Results and Discussion: 100 patients were selected of which 94 patients are male and 6 female. Age range is 18 to 54 year with the average of 28 years old for included 100 patients. All patients are evaluated after 24 week after the surgery. 50 of them were recruited for material exercise (balance exercises and agility training with strengthening) and 50 for strengthening only rehabilitation protocol (non-material). Demographically showed 85% suffering sports injury mainly from futsal and football. 39 % of them have abnormal BMI (26 – 38) and involving of the left knee. 100% of patient had the basic radiographic x-ray of knee and 98% had MRI. All patients had negative anterior drawer’s, Lachman test and Pivot shift test during the post ACL reconstruction after the complete rehabilitation. There was 95 subject sustained grade I injury, 5 of grade II and 0 of grade III with 90% of them had soft end-point. Overall they scored badly on presentation with 53% of Lysholm score (poor) and Tegner activity score level 3/10. After completing 9 weeks of exercises, of material group 90% had grade I laxity, 75% with firm end-point, Lysholm score 71% (fair) and Tegner activity level 5/10 comparing non-material group who had 62% of grade I laxity , 54% of firm end-point, Lyhslom score 62 % (poor) and Tegner activity level 4/10. After completed 18 weeks of exercises, of material group maintained 90% grade I laxity with 100 % with firm end-point, Lysholm score increase 91% (excellent) and Tegner activity level 7/10 comparing non-material group who had 69% of grade I laxity but maintained 54% of firm end-point, Lysholm score 76% (fair) and Tegner activity level 5/10. These showed the improvement were achieved fast on material group who have achieved satisfactory level after 9th cycle of exercises 75% (15/20) comparing non-material group who only achieved 54% (7/13) after completed 18th session. Most of them were grade I. These concepts are consolidated into our approach to prepare patients for return to play including field testing and maintenance training. Conclusions: The basic approach in ACL rehabilitation is to ensure return to sports at post-operative 6 month. Grade I and II laxity has favourable and early satisfactory outcome base on clinical assessment and Lysholm and Tegner scoring point. Reduction of laxity grading indicates satisfactory outcome. Firm end-point showed the adequacy of rehabilitation before starting previous sports game. Material exercise (balance exercises and agility training with strengthening) were beneficial and reliable in order to achieve favourable and early satisfactory outcome comparing strengthening only (non-material).We have identified that rehabilitation protocol varies between different patients. Therefore future post ACL reconstruction rehabilitation guidelines should look into focusing on rehabilitation techniques instead of time.

Keywords: post anterior cruciate ligament (ACL) reconstruction, single bundle, hamstring tendon, sports rehabilitation, balance exercises, agility balance

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Authors: Leila Noori, Rosario Barone, Francesca Rappa, Antonella Marino Gammazza, Alessandra Maria Vitale, Giuseppe Donato Mangano, Giusy Sentiero, Filippo Macaluso, Kathryn H. Myburgh, Francesco Cappello, Federica Scalia

Abstract:

The neuromuscular system controls, directs, and allows movement of the body through the action of neural circuits, which include motor neurons, sensory neurons, and skeletal muscle fibers. Protein homeostasis of the involved cytotypes appears crucial to maintain the correct and prolonged functions of the neuromuscular system, and both neuronal cells and skeletal muscle fibers express significant quantities of protein chaperones, the molecular machinery responsible to maintain the protein turnover. Genetic mutations or defective post-translational modifications of molecular chaperones (i.e., genetic or acquired chaperonopathies) may lead to neuromuscular disorders called as neurochaperonopathies. The limited knowledge of the effects of the defective chaperones on skeletal muscle fibers and neurons impedes the progression of therapeutic approaches. A distinct genetic variation of CCT5 gene encoding for the subunit 5 of the chaperonin CCT (Chaperonin Containing TCP1; also known as TRiC, TCP1 Ring Complex) was recently described associated with severe distal motor neuropathy by our team. In this study, we investigated the histopathological abnormalities of the skeletal muscle biopsy of the pediatric patient affected by the mutation Leu224Val in the CCT5 subunit. We provide molecular and structural features of the diseased skeletal muscle tissue that we believe may be useful to identify undiagnosed cases of this rare genetic disorder. We investigated the histological abnormalities of the affected tissue via hematoxylin and eosin staining. Then we used immunofluorescence and qPCR techniques to explore the expression and distribution of CCT5 in diseased and healthy skeletal muscle tissue. Immunofluorescence and immunohistochemistry assays were performed to study the sarcomeric and structural proteins of skeletal muscle, including actin, myosin, tubulin, troponin-T, telethonin, and titin. We performed Western blot to examine the protein expression of CCT5 and some heat shock proteins, Hsp90, Hsp60, Hsp27, and α-B crystallin, along with the main client proteins of the CCT5, actin, and tubulin. Our findings revealed muscular atrophy, abnormal morphology, and different sizes of muscle fibers in affected tissue. The swollen nuclei and wide interfiber spaces were seen. Expression of CCT5 had been decreased and showed a different distribution pattern in the affected tissue. Altered expression, distribution, and bandage pattern were detected by confocal microscopy for the interested muscular proteins in tissue from the patient compared to the healthy control. Protein levels of the studied Hsps normally located at the Z-disk were reduced. Western blot results showed increased levels of the actin and tubulin proteins in the diseased skeletal muscle biopsy compared to healthy tissue. Chaperones must be expressed at high levels in skeletal muscle to counteract various stressors such as mechanical, oxidative, and thermal crises; therefore, it seems relevant that defects of molecular chaperones may result in damaged skeletal muscle fibers. So far, several chaperones or cochaperones involved in neuromuscular disorders have been defined. Our study shows that alteration of the CCT5 subunit is associated with the damaged structure of skeletal muscle fibers and alterations of chaperone system components and paves the way to explore possible alternative substrates of chaperonin CCT. However, further studies are underway to investigate the CCT mechanisms of action to design applicable therapeutic strategies.

Keywords: molecular chaperones, neurochaperonopathy, neuromuscular system, protein homeostasis

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