Search results for: veterinary treatment
Commenced in January 2007
Frequency: Monthly
Edition: International
Paper Count: 8405

Search results for: veterinary treatment

5915 Habituation on Children Mental Retardation through Practice of Behaviour Therapy in Great Aceh, Aceh Province

Authors: Marini Kristina Situmeang, Siti Hazar Sitorus, Mukhammad Fatkhullah, Arfan Fadli

Abstract:

This study aims to identify and explain how forms of treatment and community action include parents who have children with mental retardation while undergoing behavioral therapy that leads to habituation processes. Based on observations made there is inappropriate treatment such as labeling that child mental retardation is considered ‘crazy’ by some people in Aceh Besar region. Reflecting on the phenomenon of discriminatory treatment, the existence of children with mental retardation should be realized in concrete actions that can encourage the development of cognitive abilities, language, motor, and social, one of them through behavioral. The purpose of this research is to find out and explain how the social practices of children with mental retardation when undergoing behavioral therapy that leads to habituation process. This study focuses on families or parents who have children with mental retardation and do therapy of behavioral therapy at home or at physiotherapy clinics in Aceh Besar. The research method is qualitative with case study approach. Data collection techniques are conducted with in-depth interviews and Focus Group Discussion (FGD). The results showed that habituation process which is conducted by parents at home and in fisotherapy clinic have a positive effect on the development of children behavior of mental retardation, especially when dealing with the environment of the community around the residence. Habituation processes conducted through behavioral therapy practices are influenced by Habitus (Gestational and childcare at therapy) and Reinforcement (in this case family and social support). Habituation process is done in the form of habituation, the creation of the situation, and strengthening the character. For example, when a child's mental retardation commits a wrong act (disgraceful or inappropriate behavior) then the child gets punishment in accordance with the form of punishment in a normal child generally, and when he performs a good deed, then he is given a prize such as praise or a thing he likes. Through some of these actions, the child with mental retardation can behave in accordance with the character formed and expected by the community. The process of habituation done by parents accompanied by continuous support of physiotherapy can be one of the alternative booster of cognitive and social development of children mental retardation to then out of the ‘crazy’ label that has been given.

Keywords: behaviour therapy, habituation, habitus, mental retardation

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5914 Silver Nanoparticles Loaded Cellulose Nanofibers (Cnf)/mesoporous Bioactive Glass Hydrogels For Periodontitis Treatment

Authors: Anika Pallapothu

Abstract:

Periodontitis, a severe gum disease, poses a significant threat to the integrity of bone and soft tissues supporting teeth, primarily initiated by bacterial accumulation around the gum line. Conventional treatments like scaling/root planning and plaque removal are widely employed, but integrating modern technologies such as nanotechnology holds promise for innovative therapeutic approaches. This study explores the utilization of silver nanoparticles encapsulated within cellulose nanofiber (CNF) and mesoporous bioactive glass hydrogel matrices for periodontitis management. Silver nanoparticles exhibit potent antimicrobial properties by disrupting microbial cell membranes, inducing reactive oxygen species (ROS) generation, and interfering with vital cellular processes like ATP production and nucleic acid synthesis. Mesoporous bioactive glass, renowned for its high surface area, osteoconductive, and bioactivity, presents a favorable platform for pharmaceutical applications. Incorporating CNF enhances the properties of the hydrogel due to its biocompatibility, biodegradability, and water absorption capacity. The proposed composite material is anticipated to exert beneficial effects in periodontitis treatment by demonstrating antibacterial and anti-inflammatory activities, offering a promising avenue for future therapeutic interventions.

Keywords: periodontitis, cellulose nanofibers, silver nanoparticles, mesoporous bioactive glass, antibacterial activity, anti-inflammatory activity

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5913 Recycling Waste Product for Metal Removal from Water

Authors: Saidur R. Chowdhury, Mamme K. Addai, Ernest K. Yanful

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The research was performed to assess the potential of nickel smelter slag, an industrial waste, as an adsorbent in the removal of metals from aqueous solution. An investigation was carried out for Arsenic (As), Copper (Cu), lead (Pb) and Cadmium (Cd) adsorption from aqueous solution. Smelter slag was obtain from Ni ore at the Vale Inco Ni smelter in Sudbury, Ontario, Canada. The batch experimental studies were conducted to evaluate the removal efficiencies of smelter slag. The slag was characterized by surface analytical techniques. The slag contained different iron oxides and iron silicate bearing compounds. In this study, the effect of pH, contact time, particle size, competition by other ions, slag dose and distribution coefficient were evaluated to measure the optimum adsorption conditions of the slag as an adsorbent for As, Cu, Pb and Cd. The results showed 95-99% removal of As, Cu, Pb, and almost 50-60% removal of Cd, while batch experimental studies were conducted at 5-10 mg/L of initial concentration of metals, 10 g/L of slag doses, 10 hours of contact time and 170 rpm of shaking speed and 25oC condition. The maximum removal of Arsenic (As), Copper (Cu), lead (Pb) was achieved at pH 5 while the maximum removal of Cd was found after pH 7. The column experiment was also conducted to evaluate adsorption depth and service time for metal removal. This study also determined adsorption capacity, adsorption rate and mass transfer rate. The maximum adsorption capacity was found to be 3.84 mg/g for As, 4 mg/g for Pb, and 3.86 mg/g for Cu. The adsorption capacity of nickel slag for the four test metals were in decreasing order of Pb > Cu > As > Cd. Modelling of experimental data with Visual MINTEQ revealed that saturation indices of < 0 were recorded in all cases suggesting that the metals at this pH were under- saturated and thus in their aqueous forms. This confirms the absence of precipitation in the removal of these metals at the pHs. The experimental results also showed that Fe and Ni leaching from the slag during the adsorption process was found to be very minimal, ranging from 0.01 to 0.022 mg/L indicating the potential adsorbent in the treatment industry. The study also revealed that waste product (Ni smelter slag) can be used about five times more before disposal in a landfill or as a stabilization material. It also highlighted the recycled slags as a potential reactive adsorbent in the field of remediation engineering. It also explored the benefits of using renewable waste products for the water treatment industry.

Keywords: adsorption, industrial waste, recycling, slag, treatment

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5912 Forensic Necropsy-Importance in Wildlife Conservation

Authors: G. V. Sai Soumya, Kalpesh Solanki, Sumit K. Choudhary

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Necropsy is another term used for an autopsy, which is known as death examination in the case of animals. It is a complete standardized procedure involving dissection, observation, interpretation, and documentation. Government Bodies like National Tiger Conservation Authority (NTCA) have given standard operating procedures for commencing the necropsies. Necropsies are rarely performed as compared to autopsies performed on human bodies. There are no databases which maintain the count of autopsies in wildlife, but the research in this area has shown a very small number of necropsies. Long back, wildlife forensics came into existence but is coming into light nowadays as there is an increase in wildlife crime cases, including the smuggling of trophies, pooching, and many more. Physical examination in cases of animals is not sufficient to yield fruitful information, and thus postmortem examination plays an important role. Postmortem examination helps in the determination of time since death, cause of death, manner of death, factors affecting the case under investigation, and thus decreases the amount of time required in solving cases. Increasing the rate of necropsies will help forensic veterinary pathologists to build standardized provision and confidence within them, which will ultimately yield a higher success rate in solving wildlife crime cases.

Keywords: necropsy, wildlife crime, postmortem examination, forensic application

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5911 Investigation of Rifampicin and Isoniazid Resistance Mutated Genes in Mycobacterium Tuberculosis Isolated From Patients

Authors: Seyyed Mohammad Amin Mousavi Sagharchi, Alireza Mahmoudi Nasab, Tim Bakker

Abstract:

Introduction: Mycobacterium tuberculosis (MTB) is the most intelligent bacterium that existed in the world to our best knowledge. This bacterium can cause tuberculosis (TB) which is responsible for its spread speed and murder of millions of people around the world. MTB has the practical function to escape from anti-tuberculosis drugs (AT), for this purpose, it handles some mutations in the main genes and creates new patterns for inhibited genes. Method and materials: Researchers have their best tries to safely isolate MTB from the sputum specimens of 35 patients in some hospitals in the Tehran province and detect MTB by culture on Löwenstein-Jensen (LJ) medium and microscopic examination. DNA was extracted from the established bacterial colony by enzymatic extraction method. It was amplified by the polymerase chain reaction (PCR) method, reverse hybridization, and evaluation for detection of resistance genes; generally, researchers apply GenoType MTBDRplus assay. Results: Investigations of results declare us that 21 of the isolated specimens (about 60%) have mutation in rpoB gene, which resisted to rifampicin (most prevalence), and 8 of them (about 22.8%) have mutation in katG or inhA genes which resisted to isoniazid. Also, 4 of them (about 11.4%) don't have any mutation, and 2 of them (about 5.7%) have mutation in every three genes, which makes them resistant to the two drugs mentioned above. Conclusion: Rifampicin and isoniazid are two essential AT that using in the first line of treatment. Resistance in rpoB, and katG, and inhA genes related to mentioned drugs lead to ineffective treatment.

Keywords: mycobacterium tuberculosis, tuberculosis, drug resistance, isoniazid, rifampicin

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5910 Synergistic Effect of Platelet-Rich Plasma with Hyaluronic Acid Injection Following Arthrocentesis to Reduce Pain and Improve Function in Temporomandibular joint (TMJ) Osteoarthritis

Authors: Ayman Hegab

Abstract:

Increasing evidence supports the use of platelet-rich plasma (PRP) combined with hyaluronic acid (HA) for the treatment of knee osteoarthritis, which effectively promotes cartilage repair. This study aimed to determine whether injection of PRP+HA following arthrocentesis reduces pain and improves maximum incisal opening. This was a single-blind, prospective, randomized control study. The patients were selected based on the Hegab classification: Group I: patients treated with arthrocentesis followed by a single PRP injection; Group II (Control): patients treated with arthrocentesis followed by a single HA injection; and Group III: patients treated with arthrocentesis followed by a single PRP+HA combination injection. The primary predictor variable was the medication used for injection. The primary outcome variables were the maximum voluntary mouth opening and pain index scores. The secondary outcome variable was joint sounds. All outcome variables were assessed and compared among the three groups at baseline and at 1-, 3-, 6-, and 12-month intervals. Other variables, including patients’ age and sex, were evaluated in relation to the patient outcomes. Injecting PRP+HA showed statistically significant improvement in the primary and secondary treatment outcomes over PRP or HA injection throughout the study period (P<0.005). Injection of PRP+HA following arthrocentesis had significant long-term clinical efficacy regarding pain relief that was considered the main concern of both the patient and clinician.

Keywords: TMJ, HA, PRP, osteoarthritis

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5909 Microstructure and Properties of Cu-Bearing Hypereutectic High Chromium Cast Iron

Authors: Liqiang Gong, Hanguang Fu

Abstract:

In order to further improve the wear resistance of Hypereutectic High Chromium Cast iron (HHCCI), the effects of different Cu contents on the microstructure and properties of HHCCI were systematically studied. It was found that with the increase of Cu content, the carbide size was refined, and the increase of Cu content led to the increase of austenite and the decrease of hardness in as-cast HHCCI. After heat treatment at 1050 °C, the hardness of HHCCI increased significantly compared with as-cast. And with the increase of Cu content, the hardness of HHCCI increased first and then decreased, and the hardness was the highest when 0.5 wt.% Cu was added. The increase of copper content promotes the precipitation of secondary carbides and makes the interface between α-Fe and M23C6-type secondary carbides a semi-coherent boundary. With the increase of Cu content, the wear loss of HHCCI decreased after heat treatment at 1050 °C, and the wear resistance improved. When the Cu content increased to 1.0 wt.%, the wear resistance of HHCCI was the best, which was 2.6 times that of copper-free HHCCI. The continued increase of copper content has no obvious effect on the wear resistance of HHCCI. In addition, a small amount of Cu tends to adsorb on the (0001) preferential growth surface of M₇C₃-type carbides, thereby refining the carbides. From the First-principles calculations, the solid solution strengthening effect of Cu on the matrix and the adsorption and refinement of carbides were revealed, and the influence mechanism on the wear resistance of HHCCI was characterized.

Keywords: hypereutectic high chromium cast iron, cu alloying, carbides, wear resistance, first-principles calculations

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5908 The out of Proportion - Pulmonary Hypertension in Indians with Chronic Lung Disease

Authors: S. P. Chintan, A. M. Khoja, M. Modi, R. K. Chopra, S. Garde, D. Jain, O. Kajale

Abstract:

Pulmonary Hypertension is a rare but debilitating disease that affects individuals of all ages and walks of life. As recent as 15 years ago, a patient diagnosed with PH was given an average survival rate of 2.8 years. Recent advances in treatment options have allowed patients to improve quality o and quantity of life. Initial screening for PH is through echocardiography with final diagnosis confirmed through right heart catheterization. PH is now considered to have five major classifications with subgroups among each. The mild to moderate PH is common in chronic lung diseases like Chronic obstructive pulmonary diseases and Interstitial lung disease. But very severe PH is noted in few cases. In COPD patients, PH is associated with an increased risk of severe exacerbations and a reduced life expectancy. Similarly, in patients with ILD, the presence of PH correlates with a poor prognosis. Early diagnosis is essential to slow disease progression. We report here five cases of severe PH (Out of Proportion) of which four cases were of COPD and another one of IPF (UIP pattern). There echocardiography showed gross RA/RV dilatation, interventricular septum bulging to the left and mPAP of more than 100 mmHg in all the five cases. These patients were put on LTOT, pulmonary rehabilitation, combination pharmacotherapy of vasodilators and diuretics in continuation to the treatment of underlying disease. As these patients have grave prognosis close monitoring and follow up is required. Physicians associated with respiratory care and treating chronic lung disease should have knowledge in the diagnosis and management of patients with PH.

Keywords: COPD, pulmonary hypertension, chronic lung disease, India

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5907 The Roles of Non-Codified Traditional Medicine in a Suburban Village in Kerala, India

Authors: Sachi Matsuoka

Abstract:

This study aimed at implicating a current community health in South India focusing on a Vaidya, a non-codified traditional doctor, based on long-term field works. As the prevalence of colonic diseases is increasing in all over the world, it is needed to know the potential of non-codified medicines and how they can effectively take in a part in community health. Describing the people’s treatment seeking behaviours in a suburban village which is susceptible to modernization can give us a new insight for studying Indian medicines, that is included not only non-codified but also codified traditional ones, affected by global, national and local communities. Both qualitative and quantitative data were gathered via participatory fieldworks and open-ended interviews to a Vaidya and his 97 patients and 31 individuals who lived in a community near the Vaidya’s station. It was found that the community members seldom consulted the Vaidya while a number of patients outside the village (mainly from urban nearby area) daily visited the Vaidya. Thus, the role of the Vaidya as the community’ s primary health care provider had nearly disappeared. Nonetheless, the Vaidya was deeply respected as one of the community’ s leaders by its members because of the spiritual and financial support he provided to them. The reasons for choosing the Vaidya for the patients from urban area are characterized by several social factors of the patients such as their religious belief, seriousness, occupation and medical history. Meanwhile, not only the Vaidya but also other codified traditional medicines, e.g., Ayurveda, were less popular among the community members. It sounds paradoxical given that the traditional Indian medical system has been becoming popular as an alternative medicine in societies outside of India, such as in Europe. The community members who are less educated and engaged in religious activities in daily life preferred to allopathy, the biomedicine in Indian context. It is thus concluded that roles of non-codified medicine has changed depending on its cultural and social contexts, even though its medical system is not authorized by the government. Nowadays, traditional medical effectiveness is recognized as evidenced by scientific survey and the codified medical doctors treats diseases rather than people. However, this study implicated that people’s treatment seeking behaviors are likely based on the social context in which people live their lives even though evidenced based codified medicine is provided in their community.

Keywords: medical pluralism, non-codified medicine, south india, treatment-seeking behaviours

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5906 Effect of Microwave Radiations on Natural Dyes’ Application on Cotton

Authors: Rafia Asghar, Abdul Hafeez

Abstract:

The current research was related with natural dyes’ extraction from the powder of Neem (Azadirachta indica) bark and studied characterization of this dye under microwave radiation’s influence. Both cotton fabric and dyeing powder were exposed to microwave rays for different time intervals (2minutes, 4 minutes, 6 minutes, 8 minutes and 10 minutes) using conventional oven. Aqueous, 60% Methanol and Ethyl Acetate solubilized extracts obtained from Neem (Azadirachta indica) bark were also exposed to different time intervals (2minutes, 4 minutes, 6 minutes, 8 minutes and 10 minutes) of microwave rays exposure. Pre, meta and post mordanting with Alum (2%, 4%, 6%, 8%, and 10%) was done to improve color strength of the extracted dye. Exposure of Neem (Azadirachta indica) bark extract and cotton to microwave rays enhanced the extraction process and dyeing process by reducing extraction time, dyeing time and dyeing temperature. Microwave rays treatment had a very strong influence on color fastness and color strength properties of cotton that was dyes using Neem (Azadirachta indica) bark for 30 minutes and dyeing cotton with that Neem bark extract for 75 minutes at 30°C. Among pre, meta and post mordanting, results indicated that 5% concentration of Alum in meta mordanting exhibited maximum color strength.

Keywords: dyes, natural dyeing, ecofriendly dyes, microwave treatment

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5905 Digestibility in Yankasa Rams Fed Brachiaria ruziziensis – Centrosema pascuorum Hay Mixtures with Concentrate

Authors: Ibrahim Sani, J. T. Amodu, M. R. Hassan, R. J. Tanko, N. Adamu

Abstract:

This study investigated the digestibility of Brachiaria ruziziensis and Centrosema pascuorum hay mixtures at varying proportions in Yankasa rams. Twelve Yankasa rams with average initial weight 10.25 ± 0.1 kg were assigned to three dietary treatments of B. ruziziensis and C. pascuorum hay at different mixtures (75BR:25CP, 50BR:50CP and 25BR:75CP, respectively) in a Completely Randomized Design (CRD) for a period of 14 days. Concentrate diet was given to the experimental animals as supplement at fixed proportion, while the forage mixture (basal diet) was fed at 3% body weight. Animals on 50BR:50CP had better nutrient digestibility (crude protein, acid and neutral detergent fibre, ether extract and nitrogen free extract) than other treatment diets, except in dry matter digestibility (87.35%) which compared with 87.54% obtained in 25BR:75CP treatment diet and also organic matter digestibility. All parameters taken on nitrogen balance with the exception of nitrogen retained were significantly higher (P < 0.05) in animals fed 25BR:75CP diet, but were statistically similar with values obtained for animals on 50BR:50CP diet. From results obtained in this study, it is concluded that mixture of 25%BR75%CP gave the best nutrient digestibility and nitrogen balance in Yankasa rams. It is therefore recommended that B. ruziziensis and C. pascuorum should be fed at 50:50 mixture ratio for enhanced animal growth and performance in Nigeria.

Keywords: B. ruziziensis, C. pascuorum, digestibilty, rams, Yankasa

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5904 The Effect of Tribulus Terresteris on Histomorphometrical Changes of Testis Induced by Ethanol Administration in Male Wistar Rats

Authors: Arash Esfandiari, Ebrahim Parsaei

Abstract:

The purpose of this research was to survey the effect of tribulus terresteris on histomorphometrical changes of testis induced by ethanol administration in male wistar rats. Fifteen male wistar rats divided into three groups: 1- control group (n=5). 2- Experimental group I (IP received 1 mg/gr Alcohole 20% for 30 days) (n=5). 3- Experimental group II (IP received 1 mg/gr Alcohole 20% for 30 days and IP received 100 mg/kg tribulus terresteris 15 days before received Alcohole for 45 days) (n=5). All procedures and care of the animals were conducted following protocols approved by the ethical committee (Iranian Society for the Prevention of cruelty to animal, and Iranian Veterinary Organization). Results showed that the thickness of the wall of seminiferous tubule, the weight of testis, the number of spermatogenic cells were decreased in experimental group I. In addition, all of these parameters were increased in experimental group II compared with experimental group I. These decrement of all of parameters in experimental group I with significant difference in comparison control group (p≤ 0.05). But all of parameters had increment in experimental group II with no significant difference compared with control group (p≥ 0.05) and significant difference with experimental group I (p≤ 0.05).It is concluded that tribulus terresteris may prevent from reducing the number of spermatogenic cell that has been created by the consumption of alcohole.

Keywords: ethanol, histomorphometric, testis, teribulus terresteris

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5903 Alumina Supported Copper-Manganese Catalysts for Combustion of Exhaust Gases: Effect of Preparation Method

Authors: Krasimir Ivanov, Elitsa Kolentsova, Dimitar Dimitrov

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The development of active and stable catalysts without noble metals for low temperature oxidation of exhaust gases remains a significant challenge. The purpose of this study is to determine the influence of the preparation method on the catalytic activity of the supported copper-manganese mixed oxides in terms of VOCs oxidation. The catalysts were prepared by impregnation of γ-Al2O3 with copper and manganese nitrates and acetates and the possibilities for CO, CH3OH and dimethyl ether (DME) oxidation were evaluated using continuous flow equipment with a four-channel isothermal stainless steel reactor. Effect of the support, Cu/Mn mole ratio, heat treatment of the precursor and active component loading were investigated. Highly active alumina supported Cu-Mn catalysts for CO and VOCs oxidation were synthesized. The effect of preparation conditions on the activity behavior of the catalysts was discussed. The synergetic interaction between copper and manganese species increases the activity for complete oxidation over mixed catalysts. Type of support, calcination temperature and active component loading along with catalyst composition are important factors, determining catalytic activity. Cu/Mn molar ratio of 1:5, heat treatment at 450oC and 20 % active component loading are the best compromise for production of active catalyst for simultaneous combustion of CO, CH3OH and DME.

Keywords: copper-manganese catalysts, CO, VOCs oxidation, exhaust gases

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5902 Placebo Analgesia in Older Age: Evidence from Event-Related Potentials

Authors: Angelika Dierolf, K. Rischer, A. Gonzalez-Roldan, P. Montoya, F. Anton, M. Van der Meulen

Abstract:

Placebo analgesia is a powerful cognitive endogenous pain modulation mechanism with high relevance in pain treatment. Older people would benefit, especially from non-pharmacologic pain interventions, since this age group is disproportionately affected by acute and chronic pain, while pharmacological treatments are less suitable due to polypharmacy and age-related changes in drug metabolism. Although aging is known to affect neurobiological and physiological aspects of pain perception, as for example, changes in pain threshold and pain tolerance, its effects on cognitive pain modulation strategies, including placebo analgesia, have hardly been investigated so far. In the present study, we are assessing placebo analgesia in 35 older adults (60 years and older) and 35 younger adults (between 18 and 35 years). Acute pain was induced with short transdermal electrical pulses to the inner forearm, using a concentric stimulating electrode. Stimulation intensities were individually adjusted to the participant’s threshold. Next to the stimulation site, we applied sham transcutaneous electrical nerve stimulation (TENS). Participants were informed that sometimes the TENS device would be switched on (placebo condition), and sometimes it would be switched off (control condition). In reality, it was always switched off. Participants received alternating blocks of painful stimuli in the placebo and control condition and were asked to rate the intensity and unpleasantness of each stimulus on a visual analog scale (VAS). Pain-related evoked potentials were recorded with a 64-channel EEG. Preliminary results show a reduced placebo effect in older compared to younger adults in both behavioral and neurophysiological data. Older people experienced less subjective pain reduction under sham TENS treatment compared to younger adults, as evidenced by the VAS ratings. The N1 and P2 event-related potential components were generally reduced in the older group. While younger adults showed a reduced N1 and P2 under sham TENS treatment, this reduction was considerably smaller in older people. This reduced placebo effect in the older group suggests that cognitive pain modulation is altered in aging and may at least partly explain why older adults experience more pain. Our results highlight the need for a better understanding of the efficacy of non-pharmacological pain treatments in older adults and how these can be optimized to meet the specific requirements of this population.

Keywords: placebo analgesia, aging, acute pain, TENS, EEG

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5901 The Impact of Stigma on the Course of Mental Illness: A Brief Review

Authors: Mariana Mangas, Yaroslava Martins, Ana Matos Pires

Abstract:

Introduction: Stigmatization is a common problem to overcome for people suffering from chronic diseases. It usually follows mental disorders and complicates the course of illness and reduces quality of life for people with mental illness. Objective: unsystematic review concerning stigma and mental illness, its impact on psychiatric disease and strategies to eradicate stigma. Methods: A search was conducted on PubMed, using keywords 'stigma' and 'mental illness'. Results and Discussion: Stigma is a psychosocial process that identifies individuals by the negative label of their differences. Stigma often brings a loss of occupational success and social support, reduced functioning and lower quality of life. The sense of stigma is common in individuals with mental illness and has considerable negative repercussions: delays treatment achievement, promotes social isolation, stress and maladaptive coping behaviors and it is associated with higher symptom levels, placing these individuals at higher risk for a poorer outcome and prognoses. Conclusion: Given the interrelation between stigma, symptoms, treatment seeking and disease management, stigma is a key construct in mental illness upon which anti-stigma initiatives may have considerable therapeutic potential. It will take multidisciplinary interventions to overcome mental illness stigma, including changes in social policy, attitudes and practices among mental health professionals, liaison between general public and people with a mental illness under conditions of equity and parity, family support, and easy access to evidence-based treatments.

Keywords: discrimination, stigma, mental illness, quality of life

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5900 Controlled Release of Glucosamine from Pluronic-Based Hydrogels for the Treatment of Osteoarthritis

Authors: Papon Thamvasupong, Kwanchanok Viravaidya-Pasuwat

Abstract:

Osteoarthritis affects a lot of people worldwide. Local injection of glucosamine is one of the alternative treatment methods to replenish the natural lubrication of cartilage. However, multiple injections can potentially lead to possible bacterial infection. Therefore, a drug delivery system is desired to reduce the frequencies of injections. A hydrogel is one of the delivery systems that can control the release of drugs. Thermo-reversible hydrogels can be beneficial to the drug delivery system especially in the local injection route because this formulation can change from liquid to gel after getting into human body. Once the gel is in the body, it will slowly release the drug in a controlled manner. In this study, various formulations of Pluronic-based hydrogels were synthesized for the controlled release of glucosamine. One of the challenges of the Pluronic controlled release system is its fast dissolution rate. To overcome this problem, alginate and calcium sulfate (CaSO4) were added to the polymer solution. The characteristics of the hydrogels were investigated including the gelation temperature, gelation time, hydrogel dissolution and glucosamine release mechanism. Finally, a mathematical model of glucosamine release from Pluronic-alginate-hyaluronic acid hydrogel was developed. Our results have shown that crosslinking Pluronic gel with alginate did not significantly extend the dissolution rate of the gel. Moreover, the gel dissolution profiles and the glucosamine release mechanisms were best described using the zeroth-order kinetic model, indicating that the release of glucosamine was primarily governed by the gel dissolution.

Keywords: controlled release, drug delivery system, glucosamine, pluronic, thermoreversible hydrogel

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5899 Anti-Anxiety Activity of Ethyl Acetate Extract of Flowers Nerium indicum

Authors: Deepak Suresh Mohale, Anil V. Chandewar

Abstract:

Anxiety is defined as an exaggerated feeling of apprehension, uncertainty and fear. Nerium indicum is a well-known ornamental and medicinal plant belonging to the family Apocynaceae. A wide spectrum of biological activities has been reported with various constituents isolated from different parts of the plant. This study was conducted to investigate antianxiety activity of flower extract. Flowers were collected and dried in shade and coarsely powdered. Powdered mixture was extracted with ethyl acetate by maceration process. Extract of flowers obtained was subsequently dried in oven at 40-50 °C. This extract is then tested for antianxiety activity at low and high dose using elevated plus maze and light & dark model. Rats shown increased open arm entries and time spent in open arm in elevated Plus maze with treatment low and high dose of extract of Nerium indicum flower as compared to their respective control groups. In Light & dark Model, light box entries and time spent in light box increased with treatment low and high dose of extract of Nerium indicum flower as compared to their respective control groups. From result it is concluded that ethyl acetate extract of flower of Nerium indicum possess antianxiety activity at low and high dose.

Keywords: antianxiety, anxiety, kaner, nerium indicum, social isolation

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5898 Effect of Quenching Medium on the Hardness of Dual Phase Steel Heat Treated at a High Temperature

Authors: Tebogo Mabotsa, Tamba Jamiru, David Ibrahim

Abstract:

Dual phase(DP) steel consists essentially of fine grained equiaxial ferrite and a dispersion of martensite. Martensite is the primary precipitate in DP steels, it is the main resistance to dislocation motion within the material. The objective of this paper is to present a relation between the intercritical annealing holding time and the hardness of a dual phase steel. The initial heat treatment involved heating the specimens to 1000oC and holding the sample at that temperature for 30 minutes. After the initial heat treatment, the samples were heated to 770oC and held for a varying amount of time at constant temperature. The samples were held at 30, 60, and 90 minutes respectively. After heating and holding the samples at the austenite-ferrite phase field, the samples were quenched in water, brine, and oil for each holding time. The experimental results proved that an equation for predicting the hardness of a dual phase steel as a function of the intercritical holding time is possible. The relation between intercritical annealing holding time and hardness of a dual phase steel heat treated at high temperatures is parabolic in nature. Theoretically, the model isdependent on the cooling rate because the model differs for each quenching medium; therefore, a universal hardness equation can be derived where the cooling rate is a variable factor.

Keywords: quenching medium, annealing temperature, dual phase steel, martensite

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5897 Characterization of InGaAsP/InP Quantum Well Lasers

Authors: K. Melouk, M. Dellakrachaï

Abstract:

Analytical formula for the optical gain based on a simple parabolic-band by introducing theoretical expressions for the quantized energy is presented. The model used in this treatment take into account the effects of intraband relaxation. It is shown, as a result, that the gain for the TE mode is larger than that for TM mode and the presence of acceptor impurity increase the peak gain.

Keywords: InGaAsP, laser, quantum well, semiconductor

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5896 Gut Microbiota in Patients with Opioid Use Disorder: A 12-week Follow up Study

Authors: Sheng-Yu Lee

Abstract:

Aim: Opioid use disorder is often characterized by repetitive drug-seeking and drug-taking behaviors with severe public health consequences. Animal model showed that opioid-induced perturbations in the gut microbiota causally relate to neuroinflammation, deficits in reward responding, and opioid tolerance, possibly due to changes in gut microbiota. Therefore, we propose that the dysbiosis of gut microbiota can be associated with pathogenesis of opioid dependence. In this current study, we explored the differences in gut microbiota between patients and normal controls and in patients before and after initiation of methadone treatment program for 12 weeks. Methods: Patients with opioid use disorder between 20 and 65 years were recruited from the methadone maintenance outpatient clinic in 2 medical centers in the Southern Taiwan. Healthy controls without any family history of major psychiatric disorders (schizophrenia, bipolar disorder and major depressive disorder) were recruited from the community. After initial screening, 15 patients with opioid use disorder joined the study for initial evaluation (Week 0), 12 of them completed the 12-week follow-up while receiving methadone treatment and ceased heroin use (Week 12). Fecal samples were collected from the patients at baseline and the end of 12th week. A one-time fecal sample was collected from the healthy controls. The microbiota of fecal samples were investigated using 16S rRNA V3V4 amplicon sequencing, followed by bioinformatics and statistical analyses. Results: We found no significant differences in species diversity in opioid dependent patients between Week 0 and Week 12, nor compared between patients at both points and controls. For beta diversity, using principal component analysis, we found no significant differences between patients at Week 0 and Week 12, however, both patient groups showed significant differences compared to control (P=0.011). Furthermore, the linear discriminant analysis effect size (LEfSe) analysis was used to identify differentially enriched bacteria between opioid use patients and healthy controls. Compared to controls, the relative abundance of Lactobacillaceae Lactobacillus (L. Lactobacillus), Megasphaera Megasphaerahexanoica (M. Megasphaerahexanoica) and Caecibacter Caecibactermassiliensis (C Caecibactermassiliensis) were increased in patients at Week 0, while Coriobacteriales Atopobiaceae (C. Atopobiaceae), Acidaminococcus Acidaminococcusintestini (A. Acidaminococcusintestini) and Tractidigestivibacter Tractidigestivibacterscatoligenes (T. Tractidigestivibacterscatoligenes) were increased in patients at Week 12. Conclusion: In conclusion, we suggest that the gut microbiome community maybe linked to opioid use disorder, such differences may not be altered even after 12-week of cessation of opioid use.

Keywords: opioid use disorder, gut microbiota, methadone treatment, follow up study

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5895 Mathematical Modelling of Ultrasound Pre-Treatment in Microwave Dried Strawberry (Fragaria L.) Slices

Authors: Hilal Uslu, Salih Eroglu, Betul Ozkan, Ozcan Bulantekin, Alper Kuscu

Abstract:

In this study, the strawberry (Fragaria L.) fruits, which were pretreated with ultrasound (US), were worked on in the microwave by using 90W power. Then mathematical modelling was applied to dried fruits by using different experimental thin layer models. The sliced fruits were subjected to ultrasound treatment at a frequency of 40 kHz for 10, 20, and 30 minutes, in an ultrasonic water bath, with a ratio of 1:4 to fruit/water. They are then dried in the microwave (90W). The drying process continued until the product moisture was below 10%. By analyzing the moisture change of the products at a certain time, eight different thin-layer drying models, (Newton, page, modified page, Midilli, Henderson and Pabis, logarithmic, two-term, Wang and Singh) were tested for verification of experimental data. MATLAB R2015a statistical program was used for the modelling, and the best suitable model was determined with R²adj (coefficient of determination of compatibility), and root mean square error (RMSE) values. According to analysis, the drying model that best describes the drying behavior for both drying conditions was determined as the Midilli model by high R²adj and low RMSE values. Control, 10, 20, and 30 min US for groups R²adj and RMSE values was established as respectively; 0,9997- 0,005298; 0,9998- 0,004735; 0,9995- 0,007031; 0,9917-0,02773. In addition, effective diffusion coefficients were calculated for each group and were determined as 3,80x 10⁻⁸, 3,71 x 10⁻⁸, 3,26 x10⁻⁸ ve 3,5 x 10⁻⁸ m/s, respectively.

Keywords: mathematical modelling, microwave drying, strawberry, ultrasound

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5894 IoT Continuous Monitoring Biochemical Oxygen Demand Wastewater Effluent Quality: Machine Learning Algorithms

Authors: Sergio Celaschi, Henrique Canavarro de Alencar, Claaudecir Biazoli

Abstract:

Effluent quality is of the highest priority for compliance with the permit limits of environmental protection agencies and ensures the protection of their local water system. Of the pollutants monitored, the biochemical oxygen demand (BOD) posed one of the greatest challenges. This work presents a solution for wastewater treatment plants - WWTP’s ability to react to different situations and meet treatment goals. Delayed BOD5 results from the lab take 7 to 8 analysis days, hindered the WWTP’s ability to react to different situations and meet treatment goals. Reducing BOD turnaround time from days to hours is our quest. Such a solution is based on a system of two BOD bioreactors associated with Digital Twin (DT) and Machine Learning (ML) methodologies via an Internet of Things (IoT) platform to monitor and control a WWTP to support decision making. DT is a virtual and dynamic replica of a production process. DT requires the ability to collect and store real-time sensor data related to the operating environment. Furthermore, it integrates and organizes the data on a digital platform and applies analytical models allowing a deeper understanding of the real process to catch sooner anomalies. In our system of continuous time monitoring of the BOD suppressed by the effluent treatment process, the DT algorithm for analyzing the data uses ML on a chemical kinetic parameterized model. The continuous BOD monitoring system, capable of providing results in a fraction of the time required by BOD5 analysis, is composed of two thermally isolated batch bioreactors. Each bioreactor contains input/output access to wastewater sample (influent and effluent), hydraulic conduction tubes, pumps, and valves for batch sample and dilution water, air supply for dissolved oxygen (DO) saturation, cooler/heater for sample thermal stability, optical ODO sensor based on fluorescence quenching, pH, ORP, temperature, and atmospheric pressure sensors, local PLC/CPU for TCP/IP data transmission interface. The dynamic BOD system monitoring range covers 2 mg/L < BOD < 2,000 mg/L. In addition to the BOD monitoring system, there are many other operational WWTP sensors. The CPU data is transmitted/received to/from the digital platform, which in turn performs analyses at periodic intervals, aiming to feed the learning process. BOD bulletins and their credibility intervals are made available in 12-hour intervals to web users. The chemical kinetics ML algorithm is composed of a coupled system of four first-order ordinary differential equations for the molar masses of DO, organic material present in the sample, biomass, and products (CO₂ and H₂O) of the reaction. This system is solved numerically linked to its initial conditions: DO (saturated) and initial products of the kinetic oxidation process; CO₂ = H₂0 = 0. The initial values for organic matter and biomass are estimated by the method of minimization of the mean square deviations. A real case of continuous monitoring of BOD wastewater effluent quality is being conducted by deploying an IoT application on a large wastewater purification system located in S. Paulo, Brazil.

Keywords: effluent treatment, biochemical oxygen demand, continuous monitoring, IoT, machine learning

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5893 Effects of Lipoic Acid Supplementation on Activities of Cyclooxygenases and Levels of Prostaglandins E2 and F2 Alpha Metabolites in the Offspring of Rats with Streptozocin-Induced Diabetes

Authors: H. Y. Al-Matubsi, G. A. Oriquat, M. Abu-Samak, O. A. Al Hanbali, M. Salim

Abstract:

Background: Uncontrolled diabetes mellitus (DM) is an etiological factor for recurrent pregnancy loss and major congenital malformations in the offspring. Antioxidant therapy has been advocated to overcome the oxidant-antioxidant disequilibrium inherent in diabetes. The aims of this study were to evaluate the protective effect of lipoic acid (LA) on fetal outcome and to elucidate changes that may be involved in the mechanism(s) implicit diabetic fetopathy. Methods: Female rats were rendered hyperglycemic using streptozocin and then mated with normal male rat. Pregnant non-diabetic (group1; n=9; and group2; n=7) or pregnant diabetic (group 3; n=10; and group 4; n=8) rats were treated daily with either lipoic acid (LA) (30 mg/kg body weight; groups 2 and 4) or vehicle (groups 1 and 3) between gestational days 0 and 15. On day 15 of gestation, the rats were sacrificed, and the fetuses, placentas and membranes dissected out of the uterine horns. Following morphological examination, the fetuses, placentas and membranes were homogenized, and used to measure cyclooxygenases (COX) activities and metabolisms of prostaglandin (PG) E2 (PGEM) and PGF2 (PGFM) levels. Maternal liver and plasma total glutathione levels were also determined. Results: Supplementation of diabetic rats with LA was found to significantly (P<0.05) reduce resorption rates in diabetic rats and increased mean fetal weight compared to diabetic group. Treatment of diabetic rats with LA leads to a significant (P<0.05) increase in liver and plasma total glutathione, in comparison with diabetic rats. Decreased levels of PGEM and elevated levels of PGFM in the fetuses, placentas and membranes were characteristic of experimental diabetic gestation associated with malformation. LA treatment to diabetic mothers failed to normalize levels of PGEM to the non-diabetic control rats. However, the levels of PGEM in malformed fetuses from LA-treated diabetic mothers was significantly (P < 0.05) higher than those in malformed fetuses from diabetic rats. Conclusions: We conclude that LA can reduce congenital malformations in the offspring of diabetic rats at day 15 of gestation. However, LA treatment did not completely prevent the occurrence of malformations, other factors, such as arachidonic acid deficiency and altered prostaglandin metabolismmay be involved in the pathogenesis of diabetes-induced congenital malformations.

Keywords: diabetes, lipoic acid, pregnancy, prostaglandins

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5892 A Radiographic Superimposition in Orthognathic Surgery of Class III Skeletal Malocclusion

Authors: Albert Suryaprawira

Abstract:

Patients requiring correction of severe Class III skeletal discrepancy historically has been among the most challenging treatments for orthodontists. Correction of an aesthetic and functional problem is crucially important. This is a case report of an adult male aged 18 years who complained of difficulty in chewing and speaking. Patient has a prominent profile with mandibular excess. The pre-treatment cephalometric radiograph was taken to analyse the skeletal problem and to measure the amount of bone movement and the prediction soft tissue response. The panoramic radiograph was also taken to analyse bone quality, bone abnormality, third molar impaction, etc. Before the surgery, the pre-surgical cephalometric radiograph was taken to re-evaluate the plan and to settle the final amount of bone cut. After the surgery, the post-surgical cephalometric radiograph was taken to confirm the result with the plan. The superimposition between those radiographs was performed to analyse the outcome. It includes the superimposition of the cranial base, maxilla, and mandible. Superimposition is important to describe the amount of hard and soft tissue movement. It is also important to predict the possibility of relapse after the surgery. The patient needs to understand all the surgical plan, outcome and relapse prevention. The surgery included mandibular set back by bilateral sagittal split osteotomies. Although the discrepancy was severe using this combination of treatment and the use of radiographic superimposition, an aesthetically pleasing and stable result was achieved.

Keywords: cephalometric, mandibular set back, orthognathic, superimposition

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5891 Comparative Analysis of Pet-parent Reported Pruritic Symptoms in Cats: Data from Social Media Listening and Surveys Similar

Authors: Georgina Cherry, Taranpreet Rai, Luke Boyden, Sitira Williams, Andrea Wright, Richard Brown, Viva Chu, Alasdair Cook, Kevin Wells

Abstract:

Estimating population-level burden, abilities of pet-parents to identify disease and demand for veterinary services worldwide is challenging. The purpose of this study is to compare a feline pruritus survey with social media listening (SML) data discussing this condition. Surveys are expensive and labour intensive to analyse, but SML data is freeform and requires careful filtering for relevancy. This study considers data from a survey of owner-observed symptoms of 156 pruritic cats conducted using Pet Parade® and SML posts collected through web-scraping to gain insights into the characterisation and management of feline pruritus. SML posts meeting a feline body area, behaviour and symptom were captured and reviewed for relevance representing 1299 public posts collected from 2021 to 2023. The survey involved 1067 pet-parents who reported on pruritic symptoms in their cats. Among the observed cats, approximately 18.37% (n=196) exhibited at least one symptom. The most frequently reported symptoms were hair loss (9.2%), bald spots (7.3%) and infection, crusting, scaling, redness, scabbing, scaling, or bumpy skin (8.2%). Notably, bald spots were the primary symptom reported for short-haired cats, while other symptoms were more prevalent in medium and long-haired cats. Affected body areas, according to pet-parents, were primarily the head, face, chin, neck (27%), and the top of the body, along the spine (22%). 35% of all cats displayed excessive behaviours consistent with pruritic skin disease. Interestingly, 27% of these cats were perceived as non-symptomatic by their owners, suggesting an under-identification of itch-related signs. Furthermore, a significant proportion of symptomatic cats did not receive any skin disease medication, whether prescribed or over the counter (n=41). These findings indicate a higher incidence of pruritic skin disease in cats than recognized by pet owners, potentially leading to a lack of medical intervention for clinically symptomatic cases. The comparison between the survey and social media listening data revealed bald spots were reported in similar proportions in both datasets (25% in the survey and 28% in SML). Infection, crusting, scaling, redness, scabbing, scaling, or bumpy skin accounted for 31% of symptoms in the survey, whereas it represented 53% of relevant SML posts (excluding bumpy skin). Abnormal licking or chewing behaviours were mentioned by pet-parents in 40% of SML posts compared to 38% in the survey. The consistency in the findings of these two disparate data sources, including a complete overlap in affected body areas for the top 80% of social media listening posts, indicates minimal biases in each method, as significant biases would likely yield divergent results. Therefore, the strong agreement across pruritic symptoms, affected body areas, and reported behaviours enhances our confidence in the reliability of the findings. Moreover, the small differences identified between the datasets underscore the valuable insights that arise from utilising multiple data sources. These variations provide additional depth in characterising and managing feline pruritus, allowing for more comprehensive understanding of the condition. By combining survey data and social media listening, researchers can obtain a nuanced perspective and capture a wider range of experiences and perspectives, supporting informed decision-making in veterinary practice.

Keywords: social media listening, feline pruritus, surveys, felines, cats, pet owners

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5890 The Effect of Particulate Matter on Cardiomyocyte Apoptosis Through Mitochondrial Fission

Authors: Tsai-chun Lai, Szu-ju Fu, Tzu-lin Lee, Yuh-Lien Chen

Abstract:

There is much evidence that exposure to fine particulate matter (PM) from air pollution increases the risk of cardiovascular morbidity and mortality. According to previous reports, PM in the air enters the respiratory tract, contacts the alveoli, and enters the blood circulation, leading to the progression of cardiovascular disease. PM pollution may also lead to cardiometabolic disturbances, increasing the risk of cardiovascular disease. The effects of PM on cardiac function and mitochondrial damage are currently unknown. We used mice and rat cardiomyocytes (H9c2) as animal and in vitro cell models, respectively, to simulate an air pollution environment using PM. These results indicate that the apoptosis-related factor PUMA, a regulator of apoptosis upregulated by p53, is increased in mice treated with PM. Apoptosis was aggravated in cardiomyocytes treated with PM, as measured by TUNEL assay and Annexin V/PI. Western blot results showed that CASPASE3 was significantly increased and BCL2 (B-cell lymphoid 2) was significantly decreased under PM treatment. Concurrent exposure to PM increases mitochondrial reactive oxygen species (ROS) production by MitoSOX Red staining. Furthermore, using Mitotracker staining, PM treatment significantly shortened mitochondrial length, indicating mitochondrial fission. The expression of mitochondrial fission-related proteins p-DRP1 (phosphodynamics-related protein 1) and FIS1 (mitochondrial fission 1 protein) was significantly increased. Based on these results, the exposure to PM worsens mitochondrial function and leads to cardiomyocyte apoptosis.

Keywords: particulate matter, cardiomyocyte, apoptosis, mitochondria

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5889 Cardiotoxicity Associated with Radiation Therapy: The Role of Bone Marrow Mesenchymal Cells in Improvement of Heart Function

Authors: Isalira Peroba Ramos, Cherley Borba Vieira de Andrade, Grazielle Suhett, Camila Salata, Paulo Cesar Canary, Guilherme Visconde Brasil, Antonio Carlos Campos de Carvalho, Regina Coeli dos Santos Goldenberg

Abstract:

Background: The therapeutic options for patients with cancer now include increasingly complex combinations of medications, radiation therapy (RT), and surgical intervention. Many of these treatments have important potential adverse cardiac effects and are likely to have significant effects on patient outcomes. Cell therapy appears to be promising for the treatment of chronic and degenerative diseases, including cardiomyopathy induced by RT, as the current therapeutic options are insufficient. Aims: To evaluate the potential of bone marrow mesenchymal cells (BMMCs) in radioinduced cardiac damage Methods: Female Wistar rats, 3 months old (Ethics Committee 054/14), were divided into 2 groups, non-treated irradiated group (IR n=15) and irradiated and BMMC treated (IRT n=10). Echocardiography was performed to evaluate heart function. After euthanasia, 3 months post treatment; the left ventricle was removed and prepared for RT-qPCR (VEGF and Pro Collagen I) and histological (picrosirius) analysis. Results: In both groups, 45 days after irradiation, ejection fraction (EF) was in the normal range for these animals (> 70%). However, the BMMC treated group had EF (83.1%±2.6) while the non-treated IR group showed a significant reduction (76.1%±2.6) in relation to the treated group. In addition, we observed an increase in VEGF gene expression and a decrease in Pro Collagen I in IRT when compared to IR group. We also observed by histology that the collagen deposition was reduced in IRT (10.26%±0.83) when compared to IR group (25.29%±0.96). Conclusions: Treatment with BMMCs was able to prevent ejection fraction reduction and collagen deposition in irradiated animals. The increase of VEGF and the decrease of pro collagen I gene expression might explain, at least in part, the cell therapy benefits. All authors disclose no financial or personal relationships with individuals or organizations that could be perceived to bias their work. Sources of funding: FAPERJ, CAPES, CNPq, MCT.

Keywords: mesenchymal cells, radioation, cardiotoxicity, bone marrow

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5888 Intervention Guide for Holistic Needs and Coping Strategies of Cancer Patients

Authors: Arvin Baes

Abstract:

This study was conducted to assess the holistic needs of cancer patients in terms of physiological, psychological, social, and spiritual needs and to determine how they respond through coping. It was conducted from January-April 2018 from various hospitals in Laguna, with 20 respondents. It utilized a survey descriptive type of research, a checklist type of questionnaire, and purposive sampling in selecting the respondents. It was found out that in terms of physiological needs, fatigue is the most common symptoms they experienced. In terms of psychological, social, and spiritual needs, most of the patients experienced a significant concern. Meanwhile, in coping, religion dominates among the 14 strategies followed by Use of Emotional Support and Positive Reframing, and Substance Use obtained the lowest response. Most of the respondents were female, and its significant relationship in terms of Positive Reframing agrees significantly. In coping and civil status, Positive Reframing and Humor are significant among married respondents. In coping and stage of cancer, 'Positive Reframing' and 'Humor' are significant with the stage of cancer. In coping and treatment modalities, Active Coping, Use of Emotional Support, and Religion are significantly related to patients’ treatment modalities. There is also a significant relationship between Active Coping and Physiological Needs, Religion and Psychological Needs, and Self-blaming and Psychological, Social, and Spiritual Needs. Thus, it is concluded that holistic needs and coping are essential to each other to meet the wholeness of cancer patients. A formulated care intervention program would be beneficial among this group of patients.

Keywords: coping strategies, cancer, cancer patients, holistic needs

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5887 MANIFEST-2, a Global, Phase 3, Randomized, Double-Blind, Active-Control Study of Pelabresib (CPI-0610) and Ruxolitinib vs. Placebo and Ruxolitinib in JAK Inhibitor-Naïve Myelofibrosis Patients

Authors: Claire Harrison, Raajit K. Rampal, Vikas Gupta, Srdan Verstovsek, Moshe Talpaz, Jean-Jacques Kiladjian, Ruben Mesa, Andrew Kuykendall, Alessandro Vannucchi, Francesca Palandri, Sebastian Grosicki, Timothy Devos, Eric Jourdan, Marielle J. Wondergem, Haifa Kathrin Al-Ali, Veronika Buxhofer-Ausch, Alberto Alvarez-Larrán, Sanjay Akhani, Rafael Muñoz-Carerras, Yury Sheykin, Gozde Colak, Morgan Harris, John Mascarenhas

Abstract:

Myelofibrosis (MF) is characterized by bone marrow fibrosis, anemia, splenomegaly and constitutional symptoms. Progressive bone marrow fibrosis results from aberrant megakaryopoeisis and expression of proinflammatory cytokines, both of which are heavily influenced by bromodomain and extraterminal domain (BET)-mediated gene regulation and lead to myeloproliferation and cytopenias. Pelabresib (CPI-0610) is an oral small-molecule investigational inhibitor of BET protein bromodomains currently being developed for the treatment of patients with MF. It is designed to downregulate BET target genes and modify nuclear factor kappa B (NF-κB) signaling. MANIFEST-2 was initiated based on data from Arm 3 of the ongoing Phase 2 MANIFEST study (NCT02158858), which is evaluating the combination of pelabresib and ruxolitinib in Janus kinase inhibitor (JAKi) treatment-naïve patients with MF. Primary endpoint analyses showed splenic and symptom responses in 68% and 56% of 84 enrolled patients, respectively. MANIFEST-2 (NCT04603495) is a global, Phase 3, randomized, double-blind, active-control study of pelabresib and ruxolitinib versus placebo and ruxolitinib in JAKi treatment-naïve patients with primary MF, post-polycythemia vera MF or post-essential thrombocythemia MF. The aim of this study is to evaluate the efficacy and safety of pelabresib in combination with ruxolitinib. Here we report updates from a recent protocol amendment. The MANIFEST-2 study schema is shown in Figure 1. Key eligibility criteria include a Dynamic International Prognostic Scoring System (DIPSS) score of Intermediate-1 or higher, platelet count ≥100 × 10^9/L, spleen volume ≥450 cc by computerized tomography or magnetic resonance imaging, ≥2 symptoms with an average score ≥3 or a Total Symptom Score (TSS) of ≥10 using the Myelofibrosis Symptom Assessment Form v4.0, peripheral blast count <5% and Eastern Cooperative Oncology Group performance status ≤2. Patient randomization will be stratified by DIPSS risk category (Intermediate-1 vs Intermediate-2 vs High), platelet count (>200 × 10^9/L vs 100–200 × 10^9/L) and spleen volume (≥1800 cm^3 vs <1800 cm^3). Double-blind treatment (pelabresib or matching placebo) will be administered once daily for 14 consecutive days, followed by a 7 day break, which is considered one cycle of treatment. Ruxolitinib will be administered twice daily for all 21 days of the cycle. The primary endpoint is SVR35 response (≥35% reduction in spleen volume from baseline) at Week 24, and the key secondary endpoint is TSS50 response (≥50% reduction in TSS from baseline) at Week 24. Other secondary endpoints include safety, pharmacokinetics, changes in bone marrow fibrosis, duration of SVR35 response, duration of TSS50 response, progression-free survival, overall survival, conversion from transfusion dependence to independence and rate of red blood cell transfusion for the first 24 weeks. Study recruitment is ongoing; 400 patients (200 per arm) from North America, Europe, Asia and Australia will be enrolled. The study opened for enrollment in November 2020. MANIFEST-2 was initiated based on data from the ongoing Phase 2 MANIFEST study with the aim of assessing the efficacy and safety of pelabresib and ruxolitinib in JAKi treatment-naïve patients with MF. MANIFEST-2 is currently open for enrollment.

Keywords: CPI-0610, JAKi treatment-naïve, MANIFEST-2, myelofibrosis, pelabresib

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5886 Endoscopic Treatment of Patients with Large Bile Duct Stones

Authors: Yuri Teterin, Lomali Generdukaev, Dmitry Blagovestnov, Peter Yartcev

Abstract:

Introduction: Under the definition "large biliary stones," we referred to stones over 1.5 cm, in which standard transpapillary litho extraction techniques were unsuccessful. Electrohydraulic and laser contact lithotripsy under SpyGlass control have been actively applied for the last decade in order to improve endoscopic treatment results. Aims and Methods: Between January 2019 and July 2022, the N.V. Sklifosovsky Research Institute of Emergency Care treated 706 patients diagnosed with choledocholithiasis who underwent biliary stones removed from the common bile duct. Of them, in 57 (8, 1%) patients, the use of a Dormia basket or Biliary stone extraction balloon was technically unsuccessful due to the size of the stones (more than 15 mm in diameter), which required their destruction. Mechanical lithotripsy was used in 35 patients, and electrohydraulic and laser lithotripsy under SpyGlass direct visualization system - in 26 patients. Results: The efficiency of mechanical lithotripsy was 72%. Complications in this group were observed in 2 patients. In both cases, on day one after lithotripsy, acute pancreatitis developed, which resolved on day three with conservative therapy (Clavin-Dindo type 2). The efficiency of contact lithotripsy was in 100% of patients. Complications were not observed in this group. Bilirubin level in this group normalized on the 3rd-4th day. Conclusion: Our study showed the efficacy and safety of electrohydraulic and laser lithotripsy under SpyGlass control in a well-defined group of patients with large bile duct stones.

Keywords: contact lithotripsy, choledocholithiasis, SpyGlass, cholangioscopy, laser, electrohydraulic system, ERCP

Procedia PDF Downloads 83