Search results for: oral submucous fibrosis

Authors: Sam Yurdakul, Nick Baverstock, Jim Mills

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TDT 064 (FLEXISEQ®) is a drug-free gel used to treat osteoarthritis (OA)-associated pain and joint stiffness. It contains ultra-deformable phospholipid Sequessome™ vesicles, which can pass through the skin barrier intact. In six randomized OA studies, topical TDT 064 was well tolerated and improved joint pain, physical function and stiffness. In the largest study, these TDT 064-mediated effects were statistically significantly greater than oral placebo and equivalent to celecoxib. To understand the therapeutic effects of TDT 064, we investigated the localisation of the drug-free vesicles within rat synovial joints. TDT 064 containing DiO-labelled Sequessome™ vesicles was applied to the knees of four 6-week-old CD® hairless rats (10 mg/kg/ joint), 2–3 times/day, for 3 days (representing the recommended clinical dose). Eighteen hours later, the animals and one untreated control were sacrificed, and the knee joints isolated, flash frozen and embedded in Acrytol Mounting Media™. Approximately 15 sections (10 µm) from each joint were analysed by fluorescence microscopy. To investigate whether the localisation of DiO fluorescence was associated with intact vesicles, an anti-PEG monoclonal antibody (mAb) was used to detect Tween, a constituent of Sequessome™ vesicles. Sections were visualized at 484 nm (DiO) and 647 nm (anti-PEG mAb) and analysed using inForm 1.4 (Perkin Elmer, Inc.). Significant fluorescence was observed at 484 nm in sections from TDT 064-treated animals. No non-specific fluorescence was observed in control sections. Fluorescence was detected as discrete vesicles on the cartilage surfaces, inside the cartilaginous matrix and within the synovial space. The number of DiO-labelled vesicles in multiple fields of view was consistent and >100 in sections from four different treated knees. DiO and anti-PEG mAb co-localised within the collagenous tissues in four different joint sections. Under higher magnification (40x), vesicles were seen in the intercellular spaces of the synovial joint tissue, but no fluorescence was seen inside cells. These data suggest that the phospholipid vesicles in TDT 064 localize at the surface of the joint cartilage; these vesicles may therefore be supplementing the phospholipid deficiency reported in OA and acting as a biolubricant within the synovial joint.

Keywords: joint pain, osteoarthritis, phospholipid vesicles, TDT 064

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Authors: Kim Kennedy, Daren Gibson, Stephanie Flukes, Chandra Diwakarla, Lisa Spalding, Leanne Pilkington, Andrew Redfern

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Introduction: It is well known that patients with Head and Neck Cancer (HNC) are at increased risk of subsequent head and neck cancers due to various aetiologies. Aim: We sought to determine the factors contributing to an increased risk of subsequent HNC primaries, and also to evaluate whether Aboriginal patients are at increased risk. Methods: We performed a retrospective cohort analysis of 320 HNC patients from a single centre in Western Australia, identifying 80 Aboriginal patients and 240 non-Aboriginal patients matched on a 1:3 ratio by site, histology, rurality, and age. We collected patient data including smoking and alcohol consumption, tumour and treatment data, and data on subsequent HNC primaries. Results: A subsequent HNC primary was seen in 37 patients (11.6%) overall. There was no significant difference in the rate of second primary HNCs between Aboriginal patients (12.5%) and nonAboriginal patients (11.2%) (p=0.408). Subsequent HNCs, were strongly associated with smoking and alcohol consumption however, with 95% of patients with a second primary being ever-smokers, and 54% of patients with a second primary having a history of excessive alcohol consumption. In the 37 patients with multiple HNC primaries, there were a total of 57 HNCs, with 29 patients having two primaries, six patients having 3 HNC primaries, one patient with four, and one with six. 54 out of the 57 cancers were in ever smokers (94.7%). There were only two multiple HNC primaries in a never smoker, non-drinker, and these cases were of unknown etiology with HPV/p16 status unknown in both cases. In the whole study population, there were 32 HPV-positive HNCs, and 67 p16-positive HNCs, with only two 2 nd HNCs in a p16-positive case, giving a rate of 3% in the p16+ population, which is actually much lower than the rate of second primaries seen in the overall population (11.6%), and was highest in the p16-negative population (15.7%). This suggests that p16-positivity is not a strong risk factor for subsequent primaries, and in fact p16-negativity appeared to be associated with increased risk, however this data is limited by the large number of patients without documented p16 status (45.3% overall, 12% for oropharyngeal, and 59.6% for oral cavity primaries had unknown p16 status). Summary: Subsequent HNC primaries were strongly associated with smoking and alcohol excess. Second and later HNC primaries did not appear to occur at increased rates in Aboriginal patients compared with non-Aboriginal patients, and p16-positivity did not predict increased risk, however p16-negativity was associated with an increased risk of subsequent HNCs.

Keywords: head and neck cancer, multiple primaries, aboriginal, p16 status, smoking, alcohol

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Authors: Akhigbe Mark, Abang Roger, Mwoltu Nanaribet, Edet Blessing

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Introduction.: The introduction of pre- exposure prophylaxis (PrEP) as a biomedical prevention method for HIV/AIDS has been around for more than a decade since the first confirmed evidence of its effectiveness when used daily as an oral pill. It is now a very valuable addition for people who are at higher risk of contracting HIV. Although globalacceptanceof PrEP hasincreased, PrEP is still highly concentrated in a small number of countries and within a small sub-population, with Kenya and South Africa accounting for only 19% of people who have received PrEP in Africa region, there is still a significant regionGap in PrEP availability and use, with only 28% of the target of 3 million in low-and middle countries currently using PrEP. Description: The purpose of this study is to find out if serum creatinine could be used as an incentive to improve PrEP uptake among Key population.Numerous approaches to increasing the uptake ofPrEP as a prevention mechanism for HIV in KPs has beenemployed, and one of them is serum creatinine. This approach is a biomarker of renal function, which was used in study as an incentive to increase PrEP uptake among key population groups (female sex workers, men who have sex with men, persons who inject drugs, transgender) in 3 states from South-South Nigeria. Whole blood samples are collected from clients, analysis of the samples is done using the clinical chemistry analyzer before they are initiated onto PrEP. Lessons learned and Recommendations: Secondary data was extracted from 3 states of HALG Implementing facilities in Southern part of Nigeria, PrEP uptake before and afterthe introduction of serum creatinine between March 2020 and August 2020 among key populationsin Nigeria. A total of 5664 patients were initiated on PrEP before, and after the introduction of serum creatinine, the PrEP uptake rate before (March 2020 to May 2020) introduction of serum creatinine accounted for only 5% of the total onset, and after (June 2020 to August 2020) introduction of serum creatinine, the uptake rate accounted for 95% of the total onset. These finding shows that increased uptake of PrEP before/after serum creatineindicates that serum creatine may be an effective stimulus for promoting PrEP in key populations.

Keywords: serum creatinine, incentives, PrEP, key populations, Nigeria

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Authors: Mimoza Canga, Irene Malagnino, Giulia Malagnino, Alketa Qafmolla, Ruzhdie Qafmolla, Vito Antonio Malagnino

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The goal of the present study was to analyze the risk factors regarding dental fear. This observational study was conducted during the period of February 2020 - April 2022 in Albania. The sample was composed of 200 participants, of which 40% were males and 60% were females. The participants' age range varied from 35 to 75 years old. We divided them into four age groups: 35-45, 46-55, 56-65, and 66-75 years old. Statistical analysis was performed using IBM SPSS Statistics 23.0. Data were scrutinized by the Post Hoc LSD test in analysis of variance (ANOVA). The P ≤ 0.05 values were considered significant. Data analysis included Confidence Interval (95% CI). The prevailing age range in the sample was mostly from 55 to 65 years old, 35.6% of the patients. In all, 50% of the patients had extreme fear about the fact that the dentist may be infected with Covid-19, 12.2% of them had low dental fear, and 37.8% had extreme dental fear. However, data collected from the current study indicated that a large proportion of patients 49.5% of them had high dental fear regarding the dentist not respecting the quarantine due to COVID-19, in comparison with 37.2% of them who had low dental fear and 13.3% who had extreme dental fear. The present study confirmed that 22.2% of the participants had an extreme fear of poor hygiene practices of the dentist that have been associated with the transmission of COVID-19 infection, 57.8% had high dental fear, and 20% of them had low dental fear. The present study showed that 50% of the patients stated that another factor that causes extreme fear was that the patients feel pain after interventions in the oral cavity. Strong associations were observed between dental fear and pain 95% CI; 0.24-0.52, P-value ˂ .0001. The results of the present study confirmed strong associations between dental fear and the fact that the dentist may be infected with Covid-19 (95% CI; 0.46-0.70, P-value ˂ .0001). Similarly, the analysis of the present study demonstrated that there was a statistically significant correlation between dental fear and poor hygiene practices of the dentist with 95% CI; 0.82-1.02, P-value ˂ .0001. On the basis of our statistical data analysis, the dentist did not respect the quarantine due to COVID-19 having a significant impact on dental fear with a P-value of ˂ .0001. This study shows important risk factors that significantly increase dental fear.

Keywords: Covid-19, dental fear, pain, past dreadful experiences

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Authors: Malay K. Das, Bhupen Kalita

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The poor oral bioavailability of resveratrol (RSV) due to presystemic metabolism can be avoided via dermal route of administration. The hydrophilic-lipophilic nature of resveratrol-phospholipid complex (RSVPs) favors the delivery of resveratrol via the skin. The RSVPs embedded polymeric patch with moderate adhesiveness was developed for dermal application for sustained anti-inflammatory effect. The prepared patches were evaluated for various physicochemical properties, surface morphology by SEM, TEM, and compatibility of patch components by FT-IR and DSC studies. The dermal flux of the optimized patch formulation was found to be at 4.28 ± 0.48 mg/cm2/24 h. The analysis of skin extract after permeation study revealed the presence of resveratrol, which confirmed the localization of RSVPs in the skin. The stability of RSVPs in the polymeric patch and the physiologic environment was confirmed by FE-SEM studies on the patches after drug release and skin permeation studies. The RSVPs particles released from the polymer matrix maintaining the structural integrity and permeate the keratinized horney layer of skin. The optimized patch formulation showed sustained anti-inflammatory effect (84.10% inhibition of inflammation at 24 h) in carrageenan-induced rat paw edema model compared to marketed diclofenac sodium gel (39.58% inhibition of inflammation at 24 h). The CLSM study confirmed the localization of RSVPs for a longer period, thus enabling drug targeting to the dermis for sustained anti-inflammatory effect. Histological studies with phase contrast trinocular microscope suggested no alteration of skin integrity and no evidence of the presence of inflammatory cells after exposure to the permeants. The patch was found to be safe for skin application as evaluated by Draize method for skin irritation scoring in a rabbit model. These results suggest the therapeutic efficacy of the developed patch in both acute and chronic inflammatory diseases.

Keywords: resveratrol-phospholipid complex, skin delivery, sustained anti-inflammatory effect, inflammatory diseases, dermal patch

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Authors: Hassan Nour, Nouh Mounadi, Oussama Abchir, Belaidi Salah, Samir Chtita

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Cholinesterase enzymes are biological catalysts essential for the transformation of acetylcholine, which is a neurotransmitter implicated in memory and learning, into acetic acid and choline, altering the neurotransmission process in Alzheimer’s disease patients. Therefore, inhibition of cholinesterase enzymes is a relevant strategy for the symptomatic treatment of Alzheimer’s disease. The current investigation aims to explore potential cholinesterase (ChE) inhibitors through a comprehensive computational approach. Forty-nine phytoconstituents extracted from Cannabis sativa L. were in-silico screened using molecular docking and pharmacokinetic and toxicological analysis to evaluate their possible inhibitory effect on the cholinesterase enzymes. Two phytoconstituents belonging to cannabinoid derivatives were revealed to be promising candidates for Alzheimer's therapy by acting as cholinesterase inhibitors. They have exhibited high binding affinities towards the cholinesterase enzymes and showed their ability to interact with key residues involved in cholinesterase enzymatic activity. In addition, they presented good ADMET profiles allowing them to be promising oral drug candidates. Furthermore, molecular dynamics (MD) simulations were executed to explore their interaction stability under mimetic biological conditions and thus support our findings. To corroborate the docking results, the binding free energy corresponding to the more stable ligand-ChE complexes was re-estimated by applying the MM-PBSA method. MD and MM-PBSA studies affirmed that the ligand-ChE recognition is a spontaneous reaction leading to stable complexes. The conducted investigations have led to great findings that would strongly guide the pharmaceutical industries toward the rational development of potent anti-Alzheimer agents.

Keywords: Alzheimer’s disease, molecular docking, Cannabis sativa L., cholinesterase inhibitors, molecular dynamics, ADMET, MM-PBSA

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Authors: Ranjot Kaur, Om P. Katare, Anupama Sharma, Sarah R. Dennison, Kamalinder K. Singh, Bhupinder Singh

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Respiratory microbial infections being among the top leading cause of death worldwide are difficult to treat as the microbes reside deep inside the airways, where only a small fraction of drug can access after traditional oral or parenteral routes. As a result, high doses of drugs are required to maintain drug levels above minimum inhibitory concentrations (MIC) at the infection site, unfortunately leading to severe systemic side-effects. Therefore, delivering antimicrobials directly to the respiratory tract provides an attractive way out in such situations. In this context, current study embarks on the systematic development of lung lia pid-modified chitosan nanoparticles for inhalation of voriconazole. Following the principles of quality by design, the chitosan nanoparticles were prepared by ionic gelation method and further coated with major lung lipid by precipitation method. The factor screening studies were performed by fractional factorial design, followed by optimization of the nanoparticles by Box-Behnken Design. The optimized formulation has a particle size range of 170-180nm, PDI 0.3-0.4, zeta potential 14-17, entrapment efficiency 45-50% and drug loading of 3-5%. The presence of a lipid coating was confirmed by FESEM, FTIR, and X-RD. Furthermore, the nanoparticles were found to be safe upto 40µg/ml on A549 and Calu-3 cell lines. The quantitative and qualitative uptake studies also revealed the uptake of nanoparticles in lung epithelial cells. Moreover, the data from Spraytec and next-generation impactor studies confirmed the deposition of nanoparticles in lower airways. Also, the interaction of nanoparticles with DPPC monolayers signifies its biocompatibility with lungs. Overall, the study describes the methodology and potential of lipid-coated chitosan nanoparticles in futuristic inhalation nanomedicine for the management of pulmonary aspergillosis.

Keywords: dipalmitoylphosphatidylcholine, nebulization, DPPC monolayers, quality-by-design

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Authors: Sadeq Al Yaari, Muhammad Alkhunayn, Aayah Al Yaari, Ayman Al Yaari, Montaha Al Yaari, Sajedah Al Yaari, Fatehi Eissa

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The recent rise of smart educational aids and the move away from traditional listening aids are leading to a fundamental shift in the way in which individuals with attention and listening problems (ALP) manipulate listening inputs and/or act appropriately to the spoken information presented to them. A total sample of twenty-six ALP pupils (m=20 and f=6) between 7-12 years old was selected from different strata based on gender, region and school. In the sample size, thirteen (10 males and 3 females) received the treatment in terms of smart classes provided with smart educational aids in a listening course that lasted for four month-semester while others did not (they studied the same course by the same instructor but in ordinary class). A pretest was administered to assess participants’ levels, and a posttest was given to evaluate their attention and listening comprehension performance, namely in phonetic and phonological tests with sociolinguistic themes that have been designed for this purpose. Test results were analyzed both psychoneurolinguistically and statistically. Results reveal a remarkable change in pupils’ behavioral listening where scores witnessed a significant difference in the performance of the experimental ALP group in the pretest compared to the posttest (Pupils performed better at the pretest-posttest on phonetics than at the two tests on phonology). It is concluded that smart educational aids designed for listening skills help not only increase the listening command of pupils with ALP to understand what they listen to but also develop their interactive listening capability and, at the same rate, are responsible for increasing concentrated and in-depth listening capacity. Plus, ALP pupils become able to grasp the audio content of text recordings, including educational audio recordings, news, oral stories and tales, views, spiritual/religious text and general knowledge. However, the pupils have not experienced individual smart audio-visual aids that connect listening to other language receptive and productive skills, which could be the future area of research.

Keywords: language skills, implementing, listening skill, attention, smart aids

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Authors: Baishali Deb, Hari Om Pandey, Shrilla Elangbam, Mukesh Singh, Ayon Tarafdar, A. K. S. Tomar, A. K. Pandey, Triveni Dutt

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The goal of the present investigation was to determine the impact of social stress on behavioural characteristics, physiological responses, and haemato-biochemical indicators under various social environments in Tharparkar cattle. Serum cortisol and faecal cortisol metabolites analysis were used to determine the stress level of Tharparkar cattle. Social isolation and social mixing were the two different social circumstances used to evaluate the animals. In both the experiments i.e., social isolation and social mixing, the lying period of animals decreased significantly (p<0.05) while standing period significantly (p<0.05) increased. Frequency and duration of activities like idling, walking, exploration, oral manipulation, and elimination increased significantly (p<0.05) in Tharparkar cattle after being subjected to social isolation and social mixing. Time spent in grooming (self-grooming and allo-grooming) in respect to social isolation significantly increased during isolation and post-reunion, whereas there was a significant (p<0.05) decline in the grooming behaviour especially allo-grooming during mixing of the animals. Feeding and rumination time also decreased significantly (p<0.05) in animals during both the experiments. Physiological parameters such as respiration rate, heart rate and pulse rate increased during the treatment periods. There was no significant difference in the haematological parameters for both the experiments. There was significant (p<0.05) increase in serum cortisol and faecal cortisol metabolites (FCM) concentration in animals subjected to social stress. Therefore, it can be concluded that social stress strongly impacts the behaviour and physiological parameters of the animals, causing stress and nervousness, proving that social stress is a valid psychological stress in animals. The higher concentration of FCM in Tharparkar cattle subjected to social stress, further supported by higher serum cortisol and behaviour manifestations, suggest that FCM could be used to assess stress response as a non-invasive method.

Keywords: social stress, fecal cortisol metabolites, non-invasive, animal welfare, behaviour

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Authors: Shizrah Jamal, Robia Ghafoor, Farhan Raza

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Porcelain fused to metal crown is the most versatile variety of crown that is commonly placed worldwide. Various complications have been reported in the PFM crowns with use over the period of time. These include chipping of the porcelain, recurrent caries, loss of retention, open contacts, and tooth fracture. The objective of the present study was to determine the frequency of these complications in crowns cemented over a period of five years in a tertiary care hospital and also to report the survival of these crowns. A retrospective study was conducted in Dental clinics, Aga Khan University Hospital in which 150 PFM crowns cemented over a period of five years were evaluated. Patient demographics, oral hygiene habits, para-functional habits, crown insertion and follow-up dates were recorded in a specially designed proforma. All PFM crowns fulfilling the inclusion criteria were assessed both clinically and radiographically for the presence of any complication. SPSS version 22.0 was used for statistical analysis. Frequency distribution and proportion of complications were determined. Chi-square test was used to determine the association of complications of PFM crowns with multiple variables including tooth wear, opposing dentition and betel nut chewing. Kaplan- meier survival analysis was used to determine the survival of PFM crowns over the period of five years. Level of significance was kept at 0.05. A total of 107 patients, with a mean age of 43.51 + 12.4 years, having 150 PFM crowns were evaluated. The most common complication observed was open proximal contacts (8.7%) followed by porcelain chipping (6%), decementation (5.3%), and abutment fracture (1.3%). Chi square test showed that there was no statistically significant association of PFM crown complication with tooth wear, betel nut and opposing dentition (p-value <0.05). The overall success and survival rates of PFM crowns turned out to be 78.7 and 84.7% respectively. Within the limitations of the study, it can be concluded that PFM crowns are an effective treatment modality with high success and survival rates. Since it was a single centered study; the results should be generalized with caution.

Keywords: chipping, complication, crown, survival rate

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Authors: Sathvika Reddy, Devi Revathi

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Background: In India, deliberate self-harm (DSH) with poisoning agents carries a significant impact on morbidity and mortality. Changes in the patterns of poisoning vary across various geographical locations. It is important to know the patterns in a given region in order to facilitate rapid clinical diagnosis, appropriate treatment to reduce associated morbidity and mortality. Aim and Objective: To study the patterns, treatment outcomes of acute poisoning in patients admitted to emergency wards in a tertiary care hospital and to provide poison information services. Materials and Methods: This study was conducted at M.S Ramaiah Memorial and Teaching Hospital from November 2016 to March 2017. The patient’s data was obtained from patient case sheet, interaction with health care professionals, interviewing patients and their caretakers (if possible), and were documented in a suitably designed form. Results: The study involved 131 patients with a mean age of 27.76 ± 15.5 years. Majority of the patients were in the age group 21-30 years, literates (n=53) dwelling in urban (n=113) areas belonging to upper middle class (n=50). Analgesics and antipyretics were commonly utilized in intentional drug overdosage (n=49). Envenomation constituted n=21(16.03%). Furthermore, a significant relationship was observed between marital status and self-poisoning (n=64) (P < 0.001) which commonly occurred through oral ingestion. The outcomes were correlated with the GCS and PSS system and n=85 recovered, n=17 were discharged against medical advice, and n=4 died, and n=4 were lost to follow up respectively. The poison information queries include drug overdose (n=29) and management related queries (n=22) provided majorly by residents (n=45) to update knowledge (n=11) and for better patient care (n=40). Conclusion: The trend in poisoning is dynamic. Medications were identified as the main cause of poisoning in urban areas of India. Educational programs with more emphasis on preventive measures are necessary to create awareness among the general public.

Keywords: poisoning, suicides, clinical pharmacist, envenomation, poison information services

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Authors: Takaharu Hirai, Yuta Mitobe, Hiromi Hirai

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Introduction: Eating disorders (ED) are serious psychiatric disorders that affect individuals, especially adolescents. It has been suggested that nonclinical ED-like characteristics are related to sleep problems. However, studies exploring the association between potential ED and sleep disorders have primarily been conducted in Europe and the United States. We conducted a survey of Japanese adolescents to investigate this claim. Method: In this cross-sectional study, 398 school-aged adolescents, aged 12–18 years old, matched for gender ratio, responded to a self-administered questionnaire survey. We used the Eating Attitudes Test-26 (EAT-26) and the Athens Insomnia Scale (AIS) to measure potential ED and sleep problems, respectively. In this study, participants with an EAT-26 total score of 0–19 points were classified as non-ED, while those with scores of 20 points or higher were classified as potential ED. Result: Of the 398 participants, 17 (4.3%) had an EAT-26 total score of 20 or higher. Among boys, the rate was 6 of 199 participants (3%), and among girls, the rate was 11 of 182 participants (6%). There were 89 participants (22.4%) with an AIS score of 6 points or higher, of which 36 (17.6%) were boys, and 53 (27.5%) were girls. Adolescents with potential ED had significantly higher rates of daytime sleep problems than those without ED. Further, while examining the types of sleep problems, adolescents with potential ED had greater problems with a sense of well-being and physical and mental functioning during the day. In contrast, no significant associations were found between potential ED and sleep initiation, awakenings during the night, early morning awakening, total sleep duration, or overall quality of sleep. Finally, nocturnal and daytime sleep scores were significantly associated with dieting, bulimia, and oral control EAT-26 sub-scores. Discussion: While Japanese adolescents with possible ED do not experience nighttime sleep problems, they do experience problems related to well-being and mental and physical functioning, which are indicators of daytime sleep problems. This may assist with early detection of disordered eating in adolescents. The study suggested that professionals working towards adolescent mental health issues need an approach that comprehensively integrates both sleep problems and potential ED.

Keywords: adolescents, potential eating disorders, sleep problems, eating attitudes test-26

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Authors: Kerry Hull, Mark Wright

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This paper brings light to ethnobotanical medicines used by the Maya of Belize to treat snake bites. The varying ecological zones of Belize boast over fifty species of snakes, nine of which are poisonous and dangerous to humans. Two distinct Maya groups occupy neighboring regions of Belize, the Q’eqchi’ and the Mopan. With Western medical care often far from their villages, what traditional methods are used to treat poisonous snake bites? Based primarily on data gathered with native consultants during the authors’ fieldwork with both groups, this paper details the ethnobotanical resources used by the Q’eqchi’ and Mopan traditional healers. The Q’eqchi’ and Mopan most commonly rely on traditional ‘bush doctors’ (ilmaj in Mopan), both male and female, and specialized ‘snake doctors’ to heal bites from venomous snakes. First, this paper presents each plant employed by healers for bites for the nine poisonous snakes in Belize along with the specific botanical recipes and methods of application for each remedy. Individual chemical and therapeutic qualities of some of those plants are investigated in an effort to explain their possible medicinal value for different toxins or the symptoms caused by those toxins. In addition, this paper explores mythological associations with certain snakes that inform local understanding regarding which plants are considered efficacious in each case, arguing that numerous oral traditions (recorded by the authors) help to link botanical medicines to episodes within their mythic traditions. Finally, the use of plants to counteract snakebites brought about through sorcery is discussed inasmuch as some snakes are seen as ‘helpers’ of sorcerers. Snake bites given under these circumstances can only be cured by those who know both the proper corresponding plant(s) and ritual prayer(s). This paper provides detailed documentation of traditional ethnomedicines and practices from the dying art of traditional Maya healers and argues for multi-faceted diagnostic techniques to determine toxin severity, the presence or absence of sorcery, and the appropriate botanical remedy.

Keywords: ethnobotany, Maya, medicine, snake bites

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Authors: Floyd Misheck Mwanza, Paul Boniface Majura

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The paper looked at highways/ roadside waste generation, disposal and the consequent environmental impacts. The dramatic increase in vehicular and paved roads in the recent past in Zambia, has given rise to the indiscriminate disposal of litter that now poses a threat to health and the environment. Primary data was generated by carrying out oral interviews and field observations for holistic and in–depth assessment of the environment and the secondary data was obtained from desk review method, information on effects of roadside wastes on environment were obtained from relevant literatures. The interviews were semi structured and a purposive sampling method was adopted and analyzed descriptively. The results of the findings showed that population growth and unplanned road expansion has exceeded the expected limit in recent time with resultant poor system of roadside wastes disposal. Roadside wastes which contain both biodegradable and non-biodegradable roadside wastes are disposed at the shoulders of major highways in temporary dumpsites and are never collected by a road development agency (RDA). There is no organized highway to highway or street to street collection of the wastes in Zambia by the key organization the RDA. The study revealed that roadside disposal of roadside wastes has serious impacts on the environment. Some of these impacts include physical nuisance of the wastes to the environment, the waste dumps also serve as hideouts for rodents and snakes which are dangerous. Waste are blown around by wind making the environment filthy, most of the wastes are also been washed by overland flow during heavy downpour to block drainage channels and subsequently lead to flooding of the environment. Most of the non- biodegradable wastes contain toxic chemicals which have serious implications on the environmental sustainability and human health. The paper therefore recommends that Government/ RDA should come up with proper orientation and environmental laws should be put in place for the general public and also to provide necessary facilities and arrange for better methods of collection of wastes.

Keywords: biodegradable, disposal, environment, impacts

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Authors: Muhammad Jum’at Dasuki

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This study investigates the ethical implications of post-fuel subsidy removal support initiatives in Kwara State, Nigeria, with a focus on the application of Islamic principles. The contentious issue of subsidy removal carries significant social and economic consequences, emphasizing the crucial role of ethical considerations in policy implementation. The research provides a comprehensive background on fuel subsidy removal in Nigeria and its implications. Examining post-fuel subsidy removal palliative measures in Kwara State, the study focuses on design and implementation challenges, ethical considerations, transparency, equity, and public trust. Utilizing a case study approach offers insights and best practices. The methodology includes primary sources through in-depth oral interviews and secondary sources like textbooks and journals, aiming for a holistic understanding of the ethical dimensions of support initiatives within the context of Islamic principles in Kwara State. The objective is to contribute to policy decisions and community development. The study recommends an ethically sound implementation of post-fuel subsidy removal support initiatives, emphasizing transparency, accountability, and inclusivity. It advocates for the inclusiveness of governmental palliatives, reaching both civil servants and common individuals in the state. Continuous distribution during fuel subsidy removal challenges is deemed vital. Additionally, extending free or subsidized transportation beyond higher institutions to the general populace is suggested. Consideration should also be given to reducing governmental hospital bills or providing free health services. The study underscores the importance of Islamic ethics in Nigerian governance and employs a case study approach to assess palliative measures in Kwara State, offering practical insights for policymakers and stakeholders.

Keywords: considerations, ethical, palliative, post-fuel subsidy removal

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Authors: Mohd Asharf Ganie, Aafia Rashid, Mohd Afzal Zargar, Showkat Ali Zargar, Syed Mudasar, Tabasum Parvaiz, Zafar Amin Shah

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Accumulating evidence suggests that Vitamin D deficiency (VDD) might at least contribute to the metabolic co-morbidities in PCOS. Hence, we aimed to study the effect of vitamin D supplementation in co-prescription with insulin sensitizers like metformin and pioglitazone on clinical, hormonal and metabolic parameters in women with PCOS. In this open label randomized, controlled trial a total of 120 women with PCOS diagnosis (AE-PCOS 2009 Criteria) were assigned to four treatment groups (n= 30 in each): group I (metformin 1 gm/day in combination with cholecalciferol 4000 IU/day), group II (pioglitazone 30 mg/day in combination with cholecalciferol 4000 IU/day), group III (metformin 1 gm /day) and group IV (pioglitazone 30 mg/day). Vitamin D supplementation was given as 60,000 units every two weeks for 24 weeks. All the subjects were routinely evaluated for clinical, biochemical, hormonal and insulin sensitivity parameters in addition to various safety parameters especially serum calcium levels at baseline and after 24 weeks of the treatment. Our results indicate that 95.5% of PCOS women were vitamin D deficient at baseline. Serum 25 (OH) D levels increased significantly (p < 0.001) in groups I and II without any adverse effects after 24 weeks of oral administration of 4000 IU cholecalciferol daily. However, serum 25 (OH) D levels remained unchanged in group III and IV. By six months, number of menstrual cycles per year increased whereas Ferriman-Gallwey score, serum total testosterone and HOMA-IR decreased significantly (P < 0.001) in the treatment groups supplemented with cholecalciferol as compared to those treated either drug alone. No significant beneficial changes were observed on weight, BMI, blood pressure, glucose tolerance and serum lipids in any of the groups supplemented with cholecalciferol. We conclude that daily dose of 4000 IU cholecalciferol might be a useful adjunct in complex treatment of PCOS with fewer adverse events. Furthermore, pioglitazone and cholecalciferol combination seems to be marginally better although there was no statistical significance.

Keywords: PCOS, vitamin D supplementation, insulin resistance, spironolactone, metformin, pioglitazone

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Authors: Sanjay Singh, Karunanithi Priyanka, Ramoji Kosuru, Raju Prasad Sharma

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Herbal drugs are well known for their mixed pharmacological activities with the benefit of no harmful side effects. The use of herbal drugs is limited because of their higher dose requirement, frequent drug administration, poor bioavailability of phytochemicals and delayed onset of action. Ficus religiosa, a potent anti-oxidant plant useful in the treatment of diabetes and cancer was selected for the study. Solid lipid nanoparticles (SLN) of Ficus religiosa extract was developed for the enhancement in oral bioavailability of stigmasterol and β-sitosterol-d-glucoside, principal components present in the extract. Hot homogenization followed by ultrasonication method was used to develop extract loaded SLN. Developed extract loaded SLN were characterized for particle size, PDI, zeta potential, entrapment efficiency, in vitro drug release and kinetics, fourier transform infra-red spectroscopy, differential scanning calorimetry, powder X-ray diffractrometry and stability studies. Entrapment efficiency of optimized extract loaded SLN was found to be 68.46 % (56.13 % of stigmasterol and 12.33 % of β-sitosteryl-d-glucoside, respectively). RP HPLC method development was done for simultaneous estimation of stigmasterol and β-sitosterol-d-glucoside in Ficus religiosa extract in rat plasma. Bioavailability studies were carried out for extract in suspension form and optimized extract loaded SLN. AUC of stigmasterol and β-sitosterol-d-glucoside were increased by 6.7-folds by 9.2-folds, respectively in rats treated with extract loaded SLN compared to extract suspension. Also, Cmax of stigmasterol and β-sitosterol-d-glucoside were increased by 4.3-folds by 3.9-folds, respectively in rats treated with extract loaded SLN compared to extract suspension. Mean residence times (MRT) for stigmasterol were found to be 12.3 ± 0.67 hours from extract and 7.4 ± 2.1 hours from SLN and for β-sitosterol-d-glucoside, 10.49 ± 2.9 hours from extract and 6.4 ± 0.3 hours from SLN. Hence, it was concluded that SLN enhanced the bioavailability and reduced the MRT of stigmasterol and β-sitosterol-d-glucoside in Ficus religiosa extract which in turn may lead to reduction in dose of Ficus religiosa extract, prolonged duration of action and also enhanced therapeutic efficacy.

Keywords: Ficus religiosa, phytosterolins, bioavailability, solid lipid nanoparticles, stigmasterol and β-sitosteryl-d-glucoside

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Authors: Elisabeth Louise Ndjengue Mindang, Charline Florence Awounfack, Derek Tantoh Ndinteh, Rui W. M. Krause, Dieudonne Njamen

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The evolution of human fertility over the last 50 years has shown considerable problems due to a growing number of couples that find it difficult to procreate without medical assistance. In Africa, this inability to conceive affect 30 to 40% of couples. A number of contaminants in the environment are thought to contribute significantly to the observed infertility epidemic. Methods: On this basis, the impact of 40-days unique oral administration (between 9 and 10 am) of potassium sorbate (at of 12.5, 45, and 78 mg/kg BW doses) was evaluated on sexual maturation and hematologic parameters on immature Wistar rats (21-22 days of age). At the end of the treatment, animals were sacrificed. Vaginal opening was evaluated before the sacrifice. After the sacrifice, relative weight of reproductive organs, pituitary gonadotrophin level (LH and FSH), and sexuals steroids (estrogen and progesterone), cholesterol level in ovaries, folliculogenesis, and some hematological parameters were evaluated. Results: Compared to the control group, no significant variation was observed in the body weight of the animals treated with patassium sorbate. On the other hand, potassium sorbate, a significantly lower percentage (25%) of vaginal-opening in these rats, was observed from day 46 of age (p <0.01); likewise, a significant decrease was observed on the relative weight of the ovaries (p <0.01), number of primary follicles (p <0.01), and a significant increase of follicle number (p <0.001) at 78 mg/kg BW have been obseved. Potassium sorbate always decreased the number of white blood cells (p <0.05). Taken together, these results confirm the disturbing effects on the endocrine system, causing a decrease in fertility by increasing the number of follicles in atresia. A deleterious effect on the immune system was also observed. Overall, these results validate at least in part the global observations on the growing decline in fertility in populationsfeeding increasingly on industrial processed foods.

Keywords: potassium sorbate, early puberty, folliculogenesis, endocrine disruptor, immatur wistar rat

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Authors: Hugo Espinosa-Andrews

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Introduction: Yogurt is widely accepted worldwide due to its high nutritional value, consistency, and texture. Their rheological properties play a significant role in consumer acceptance and are related to the manufacturing process and formulation. Typically, the viscoelastic characteristics of yogurts are studied using the small amplitude oscillatory shear test; however, the initial stages of flow and oral processing are described in the nonlinear zone, in which a large amplitude oscillatory stress test is applied. The objective of this work was to analyze the nonlinear viscoelastic behavior of commercial yogurts using Lissajous curves. Methods: Two commercial yogurts were purchased in a local store in Guadalajara Jalisco Mexico: a natural Greek-style yogurt and a low-fat traditional yogurt. Viscoelastic properties were evaluated using a large amplitude oscillatory stress procedure (LAOS). A crosshatch geometry of 40 mm and a truncation of 1000 µm were used. Stress sweeps were performed at 6.28 rad/s from 1 to 250 Pa at 5°C. The nonlinear viscoelastic properties were analyzed using the Lissajous curves. Results: The yogurts showed strain-viscoelastic behavior related to deformation-dependent materials. In the low-strain region, the elastic modulus predominated over the viscous modulus, showing gel-elastic properties. The sol-gel transitions were observed at approximately 66.5 Pa for the Greek yogurt, double that detected for traditional yogurt. The viscoelastic behavior of the yogurts was characteristic of weak excess deformation: behavior indicating a stable molecular structure at rest, and moderate structure at medium shear-forces. The normalized Lissajous curves characterized viscoelastic transitions of the yogurt as the stress increased. Greater viscoelasticity deformation was observed in Greek yogurt than in traditional yogurt, which is related to the presence of a protein network with a greater degree of crosslinking. Conclusions: The yogurt composition influences the viscoelastic properties of the material. Yogurt with the higher percentage of protein has greater viscoelastic and viscous properties, which describe a product of greater consistency and creaminess.

Keywords: yogurt, viscoelastic properties, LAOS, elastic modulus

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Authors: Eimar Yadir Quintero Tapias

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Background: Science is not generally self-correcting; many clinical studies end with the same conclusion "more research is needed." This study hypothesizes that first, we need a better appraisal of the available (and unavailable) evidence instead of creating more of the same false inquiries. Methods: Systematic review of ClinicalTrials.gov study records using the following Boolean operators: (food OR nut OR milk OR egg OR shellfish OR wheat OR peanuts) AND (allergy OR allergies OR hypersensitivity OR hypersensitivities). Variables included the status of the study (e g., active and completed), availability of results, sponsor type, sample size, among others. To determine the rates of non-publication in journals indexed by PubMed, an advanced search query using the specific Number of Clinical Trials (e.g., NCT000001 OR NCT000002 OR...) was performed. As a prophylactic measure to prevent P-hacking, data analyses only included descriptive statistics and not inferential approaches. Results: A total of 2092 study records matched the search query described above (date: September 13, 2019). Most studies were interventional (n = 1770; 84.6%) and the remainder observational (n = 322; 15.4%). Universities, hospitals, and research centers sponsored over half of these investigations (n = 1208; 57.7%), 308 studies (14.7%) were industry-funded, and 147 received NIH grants; the remaining studies got mixed sponsorship. Regarding completed studies (n = 1156; 55.2%), 248 (21.5%) have results available at the registry site, and 417 (36.1%) matched NCT numbers of journal papers indexed by PubMed. Conclusions: The internal and external validity of human research is critical for the appraisal of medical evidence. It is imperative to analyze the entire dataset of clinical studies, preferably at a patient-level anonymized raw data, before rushing to conclusions with insufficient and inadequate information. Publication bias and non-registration of clinical trials limit the evaluation of the evidence concerning therapeutic interventions for food allergy, such as oral and sublingual immunotherapy, as well as any other medical condition. Over half of the food allergy human research remains unpublished.

Keywords: allergy, clinical trials, immunology, systematic reviews

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Authors: Vinay Kant Shankhdhar

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Purpose: Maxillary defects are three dimensional and require complex bone and soft tissue reconstruction. Maxillary reconstruction using fibula osteocutaneous flaps in situation requiring orbital floor, orbital wall, palatal defects, and external skin, all at the same time require special planning and multiple osteotomies. We tried to improvise our reconstruction using multiple osteotomies and skin paddle designs for fibula and Flexor Hallucis Longus Muscle. This study aims at discussing the planning and outcome in complex maxillary reconstructions using fibula flaps and soft tissue flaps with or without bone grafts. Material and Methods: From 2011 to 2017 a total of 129 Free fibula flaps were done, 67 required two or more struts, 164 Anterolateral Thigh Flaps, 11 Deep Inferior Epigastric Artery perforator flaps and 3 vertical rectus abdominis muscle flaps with iliac crest bone graft. The age range was 2 to 70 years. The reconstruction was evaluated based on the post-operative rehabilitation including orbital support (prevention of diplopia), oral diet, speech and cosmetic appearance. Results: The follow- up is from 5 years to 1 year. In this series, we observed that the common complications were the de-vascularisation of most distal segment of osteotomised fibula and native skin necrosis. Commonest area of breakdown is the medial canthal region. Plate exposure occurs most commonly at the pyriform sinus. There was extrusion of one non-vascularized bone graft. All these complications were noticed post-radiotherapy. Conclusions: The use of free fibula osteocutaneous flap gives very good results when only alveolar reconstruction is required. The reconstruction of orbital floor with extensive skin loss with post operative radiotherapy has maximum complication rate in long term follow up. A soft tissue flap with non vascularized bone graft may be the best option in such cases.

Keywords: maxilla reconstruction, fibula maxilla, post cancer maxillary reconstruction

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Authors: Sunil K. Jena, Sanjaya K. Samal, Mahesh Chand, Abhay T. Sangamwar

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Tamoxifen (TMX) and its analogues are approved as a first line therapy for the treatment of estrogen receptor-positive tumors. However, clinical development of TMX has been hampered by its low bioavailability and severe hepatotoxicity. Herein, we attempt to design a new drug delivery vehicle that could enhance the pharmacokinetic performance of TMX. Initially, high-molecular weight carboxymethyl chitosan was hydrolyzed to low-molecular weight carboxymethyl chitosan (LMW CMC) with hydrogen peroxide under the catalysis of phosphotungstic acid. Amphiphilic block copolymers of LMW CMC were synthesized via amidation reaction between the carboxyl group of α-tocopherol succinate (TS) and an amine group of LMW CMC. These amphiphilic block copolymers were self-assembled to nanosize core-shell-structural micelles in the aqueous medium. The critical micelle concentration (CMC) decreased with the increasing substitution of TS on LMW CMC, which ranged from 1.58 × 10-6 to 7.94 × 10-8 g/mL. Maximum TMX loading up to 8.08 ± 0.98% was achieved with Cmc-TS4.5 (TMX/Cmc-TS4.5 with 1:8 weight ratio). Both blank and TMX-loaded polymeric micelles (TMX-PM) of Cmc-TS4.5 exhibits spherical shape with the particle size below 200 nm. TMX-PM has been found to be stable in the gastrointestinal conditions and released only 44.5% of the total drug content by the first 72 h in simulated gastric fluid (SGF), pH 1.2. However, the presence of pepsin does not significantly increased the TMX release in SGF, pH 1.2, released only about 46.2% by the first 72 h suggesting its inability to cleave the peptide bond. In contrast, the release of TMX from TMX-PM4.5 in SIF, pH 6.8 (without pancreatin) was slow and sustained, released only about 10.43% of the total drug content within the first 30 min and nearly about 12.41% by the first 72 h. The presence of pancreatin in SIF, pH 6.8 led to an improvement in drug release. About 28.09% of incorporated TMX was released in the presence of pancreatin in 72 h. A cytotoxicity study demonstrated that TMX-PM exhibited time-delayed cytotoxicity in human MCF-7 breast cancer cells. Pharmacokinetic studies on Sprague-Dawley rats revealed a remarkable increase in oral bioavailability (1.87-fold) with significant (p < 0.0001) enhancement in AUC0-72 h, t1/2 and MRT of TMX-PM4.5 than that of TMX-suspension. Thus, the results suggested that CMC-TS micelles are a promising carrier for TMX delivery.

Keywords: carboxymethyl chitosan, d-α-tocopherol succinate, pharmacokinetic, polymeric micelles, tamoxifen

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Authors: Min-Chien Su, Tzu-Hsuan Hsu, Guan-Xuan Wu, Shyh-Ming Kuo

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Lung cancer is one of the clinically challenging malignant diseases worldwide. For efficient therapeutics in cancer, combination therapy has developed to acquire a better outcome. PLK-1 was one of the major factors affecting cell mitosis in cancer cells, its inhibitor Bi6727 was proven effective in treating several different cancers namely oral cancer, colon cancer and lung cancer. Despite its low toxicity toward normal cells compared to traditional chemotherapy, it is still yet to be evaluated in detail. Livistona Chinensis (LC) is a Chinese herb that used as a traditional prescription to treat lung cancer. Due to the uncertainty of the efficacy of LC, we utilized a water extraction method to extract the Livistona Chinensis and then lyophilized into powder for further study. In this study we investigated the antiproliferation activities of Bi6727 and LC extracts (LCE) on A549 non-small lung cancer cells. The IC50 of Bi6727 and LCE on A549 are 60 nM and 0.8 mg/mL, respectively. The fluorescent staining images shown nucleolus damage in cells treated with Bi6727 and mitochondrial damage after treated with LCE. A549 cells treated with Bi6727 and LCE showed increased expression of Bax, Caspase-3 and Caspase-9 proteins from Western blot assay. LCE also inhibited A549 cells growth keeping cells at G2-M phase from cell cycle assay. Apoptosis assay results showed that LCE induced late apoptosis of A549 cells. JC-1 assay showed that the mitochondria damaged at the LCE concentration of 0.4 mg/mL. In our preliminary anti-proliferation test of combined LCE and Bi-6727 on A549 cells, we found a dramatically decrease in proliferation after treated with LCE first for 24-h and then Bi-6727 for extra 24-h. This was an important finding regarding synergistic anti-proliferation effect of these drugs, However, the usage, the application sequence of LCE and Bi-6727 on A549 cells and their related mechanisms still need to be evaluated. In summary, the drugs exerted anti-proliferation effect on A549 cells independently. We hopefully combine the usage of these two drugs will bring a different and potential outcome in treating lung cancer.

Keywords: anti-proliferation, A549, Livistona Chinensis fruit extracts, PLK-1 inhibitor

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Authors: Fang Tang

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A major Confucian masterpiece and the earliest-known poetry anthology (composed approximately 1046-771 BCE), The Classic of Poetry, reflects different cultures in ancient China. It is regarded as a Chinese classic and one of the world’s most significant written works, an essential part of our global cultural heritage. This paper explores how the ancient Chinese classic became transformed into part of popular culture, found in folk songs circulated in Fangxian county, a mountainous location in Hubei province in central mainland China. It is the hometown of one of the most well-known authors of The Classic of Poetry, whose name is Yin Jifu. Local villagers process, refine, and recreate these poems into popular folk songs, which have been handed down from generation to generation. The folk songs based on The Classic of Poetry vividly reflect local customs, life styles, and various cultural activities. After thousands of years of singing these traditional songs, the region has become an important area to maintain part of Chinese cultural heritages; here, the original high culture is converted into a popular culture that is absorbed into people’s daily life. Based on a year’s field research and many interviews with local singers, this paper explores the ways in which locals have transformed the contents of The Classic of Poetry. It examines how today these popular folk songs become part of much-treasured culture heritage, illustrating the transformation of traditional high culture into popular culture. The paper argues that the modern adaptations of the traditional poems of The Classic of Poetry combine both oral and written cultural heritage and reflects the interaction between ancient Chinese official literature and folk literature. The paper also explores the reasons why the folk songs of The Classic of Poetry are so popular in the area, including the influences of its author Yin Jifu, the impact of ancient diasporic culture from the political centre to remote rural areas, and the interactions of local cultures (famous as Chu culture) and Chinese mainstream cultural policies.

Keywords: high/low culture, The Classic of Poetry, the functions of media, cultural policy

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Authors: Rasha Alsabbah

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This study explores the relationship between polite language use and religion in the Iraqi culture in computer mediated communication. It tackles the speech acts where these expressions are employed, the frequency of their occurrence and the aims behind them. It also investigates if they have equivalent expressions in English and the possibility of translating them in intercultural communication. Despite the wide assumption that language is a reflection of culture and religion, it started to grant the attention sociologists during the recent 40 years when scholars have questioned the possible interconnection between religion and language in which religion is used as a mean of producing language and performing pragmatic functions. It is presumed that Arabs in general, and Iraqis in particular, have an inclination to use religious vocabulary in showing politeness in their greeting and other speech acts. Due to Islamic religion and culture’s influences, it is observed that Iraqis are very much concerned of maintaining social solidarity and harmonious relationships which make religion a politeness strategy that operates as the key point of their social behaviours. In addition, religion has found to influence almost all their interactions in which they have a tendency of invoking religious expressions, the lexicon of Allah (God), and Qur’anic verses in their daily politeness discourse. This aspect of Islamic culture may look strange, especially to people who come from individualist societies, such as England. Data collection in this study is based on messaging applications like Viber, WhatsApp, and Facebook. After gaining the approval of the participants, there was an investigation for the different aims behind these expressions and the pragmatic function that they perform. It is found that Iraqis tend to incorporate the lexicon of Allah in most of their communication. Such employment is not only by religious people but also by individuals who do not show strong commitment to religion. Furthermore, the social distance and social power between people do not play a significant role in increasing or reducing the rate of using these expressions. A number of these expressions, though can be translated into English, do not have one to one counterpart or reflect religious feeling. In addition, they might sound odd upon being translated or transliterated in oral and written communication in intercultural communication.

Keywords: computer mediated communication (CMC), intercultural communication, politeness, religion, situation bound utterances rituals, speech acts

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Authors: Moulay Driss Mellaoui, Khadija Zaki, Khalid Abbiche, Abdallah Imjjad, Rachid Boutiddar, Abdelouahid Sbai, Aaziz Jmiai, Souad El Issami, Al Mokhtar Lamsabhi, Hanane Zejli

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This study presents a comprehensive analysis of six isoxazolidine and isoxazoline derivatives, leveraging a multifaceted approach that combines Density Functional Theory (DFT), AdmetSAR analysis, and molecular docking simulations to explore their electronic, pharmacokinetic, and anticancer properties. Through DFT analysis, using the B3LYP-D3BJ functional and the 6-311++G(d,p) basis set, we optimized molecular geometries, analyzed vibrational frequencies, and mapped Molecular Electrostatic Potentials (MEP), identifying key sites for electrophilic attacks and hydrogen bonding. Frontier Molecular Orbital (FMO) analysis and Density of States (DOS) plots revealed varying stability levels among the compounds, with 1b, 2b, and 3b showing slightly higher stability. Chemical potential assessments indicated differences in binding affinities, suggesting stronger potential interactions for compounds 1b and 2b. AdmetSAR analysis predicted favorable human intestinal absorption (HIA) rates for all compounds, highlighting compound 3b superior oral effectiveness. Molecular docking and molecular dynamics simulations were conducted on isoxazolidine and 4-isoxazoline derivatives targeting the EGFR receptor (PDB: 1JU6). Molecular docking simulations confirmed the high affinity of these compounds towards the target protein 1JU6, particularly compound 3b, among the isoxazolidine derivatives, compound 3b exhibited the most favorable binding energy, with a g score of -8.50 kcal/mol. Molecular dynamics simulations over 100 nanoseconds demonstrated the stability and potential of compound 3b as a superior candidate for anticancer applications, further supported by structural analyses including RMSD, RMSF, Rg, and SASA values. This study underscores the promising role of compound 3b in anticancer treatments, providing a solid foundation for future drug development and optimization efforts.

Keywords: isoxazolines, DFT, molecular docking, molecular dynamic, ADMET, drugs.

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Authors: Irfan Abdulrahman Sheth, Sohil Pothiawala

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Dermatomyositis is an idiopathic inflammatory myopathy, traditionally characterized by a progressive, symmetrical proximal muscle weakness and pathognomonic or characteristic cutaneous manifestations. We report a case of a 60-year old Chinese female who was referred from polyclinic for allergic rash over the body after applying hair dye 3 weeks ago. It was associated with puffiness of face, shortness of breath and hoarse voice since last 2 weeks with decrease effort tolerance. She also complained of dysphagia/ myalgia with progressive weakness of proximal muscles and palpitations. She denied chest pain, loss of appetite, weight loss, orthopnea or fever. She had stable vital signs and appeared cushingoid. She was noted to have rash over the scalp/ face and ecchymosis over the right arm with puffiness of face and periorbital oedema. There was symmetrical muscle weakness and other neurological examination was normal. Initial impression was of allergic reaction and underlying nephrotic syndrome and Cushing’s syndrome from TCM use. Diagnostic tests showed high Creatinine kinase (CK) of 1463 u/l, CK–MB of 18.7 ug/l and Troponin –T of 0.09 ug/l. The Full blood count and renal panel was normal. EMG showed inflammatory myositis. Patient was managed by rheumatologist and discharged on oral prednisolone with methotrexate/ ergocalciferol capsule and calcium carb, vitamin D tablets and outpatient follow up. In some patients, cutaneous disease exists in the absence of objective evidence of muscle inflammation. Management of dermatomyositis begins with careful investigation for the presence of muscle disease or of additional systemic involvement, particularly of the pulmonary, cardiac or gastrointestinal systems, and for the possibility of an accompanying malignancy. Muscle disease and systemic involvement can be refractory and may require multiple sequential therapeutic interventions or, at times, combinations of therapies. Thus, we want to highlight to the physicians that the cutaneous disease of dermatomyositis should not be confused with allergic reaction. It can be particularly challenging to diagnose. Early recognition aids appropriate management of this group of patients.

Keywords: dermatomyositis, myopathy, allergy, cutaneous disease

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Authors: Omolola R. Ayepola, Nicole L. Brooks, Oluwafemi O. Oguntibeju

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The liver plays an important role in the regulation of blood glucose and is a target organ of hyperglycaemia. Hyperglycemia plays a crucial role in the onset of various liver diseases and may culminate into hepatopathy if untreated. Alteration in antioxidant defense and increase in oxidative stress that results in tissue injury is characteristic of diabetes. We evaluated the protective effects of kolaviron-a biflavonoid complex, on hepatic antioxidants, lipid peroxidation and apoptosis in the liver of diabetic rats. To induce type I diabetes, rats were injected with streptozotocin intraperitoneally at a single dose of 50 mg/kg. Oral treatment of diabetic rats with kolaviron (100 mg/kg) started on the 6th day after diabetes induction and continued for 6 weeks (5 times weekly). Diabetic rats exhibited a significant increase in the peroxidation of hepatic lipids as observed from the elevated level of malondialdehyde (MDA) estimated by High-Performance Liquid Chromatography. In addition, Oxygen Radical Absorbance Capacity (ORAC), ratio of reduced to oxidized glutathione (GSH/GSSG) and catalase (CAT) activity was decreased in the liver of diabetic rats. TUNEL assay revealed increased apoptotic cell death in the liver of diabetic rats. Examination of Pancreatic beta-cells by immunohistochemical methods revealed beta cell degeneration and reduction in beta cell/ islet area in the diabetic controls. Kolaviron-treatment increased the area of insulin immunoreactive beta-cells significantly. Kolaviron attenuated lipid peroxidation and apoptosis in the liver of diabetic rats, increased CAT activity GSH levels and the resultant GSH: GSSG. The ORAC of kolaviron-treated diabetic liver was restored to near-normal values. Kolaviron protects the liver against oxidative and apoptotic damage induced by hyperglycemia. The antidiabetic effect of kolaviron may also be related to its beneficial effects on beta-cell function.

Keywords: diabetes mellitus, kolaviron, oxidative stress, liver, apoptosis

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Authors: Michal Krecichwost, Zauzanna Miodonska, Pawel Badura

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The diagnosis of sigmatism is mostly based on the observation of articulatory organs. It is, however, not always possible to precisely observe the vocal apparatus, in particular in the oral cavity of the patient. Speech processing can allow to objectify the therapy and simplify the verification of its progress. In the described study the methodology for classification of incorrectly pronounced phoneme [s] is proposed. The recordings come from adults. They were registered with the speech recorder at the sampling rate of 44.1 kHz and the resolution of 16 bit. The database of pathological and normative speech has been collected for the study including reference assessments provided by the speech therapy experts. Ten adult subjects were asked to simulate a certain type of stigmatism under the speech therapy expert supervision. In the recordings, the analyzed phone [s] was surrounded by vowels, viz: ASA, ESE, ISI, SPA, USU, YSY. Thirteen MFCC (mel-frequency cepstral coefficients) and RMS (root mean square) values are calculated within each frame being a part of the analyzed phoneme. Additionally, 3 fricative formants along with corresponding amplitudes are determined for the entire segment. In order to aggregate the information within the segment, the average value of each MFCC coefficient is calculated. All features of other types are aggregated by means of their 75th percentile. The proposed method of features aggregation reduces the size of the feature vector used in the classification. Binary SVM (support vector machine) classifier is employed at the phoneme recognition stage. The first group consists of pathological phones, while the other of the normative ones. The proposed feature vector yields classification sensitivity and specificity measures above 90% level in case of individual logo phones. The employment of a fricative formants-based information improves the sole-MFCC classification results average of 5 percentage points. The study shows that the employment of specific parameters for the selected phones improves the efficiency of pathology detection referred to the traditional methods of speech signal parameterization.

Keywords: computer-aided pronunciation evaluation, sibilants, sigmatism diagnosis, speech processing

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Authors: Muhammad Naeem, Juho Lee, Jin-Wook Yoo

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In this study, we hypothesized that prolonged gastrointestinal transit at the inflamed colon conferred by a pH-triggered mucoadhesive smart nanoparticulate drug delivery system aids in achieving selective and sustained levels of the drug within the inflamed colon for the treatment of ulcerative colitis. We developed budesonide-loaded pH-sensitive charge-reversal solid lipid nanoparticles (SLNs) using a hot homogenization method. Polyetylenimine (PEI) was used to render SLNs cationic (PEI-SLNs). Eudragit S100 (ES) was coated on PEI-SLNs for pH-trigger charge-reversal SLNs (ES-PEI-SLNs). Therapeutic potential of the prepared SNLs formulation was evaluated in ulcerative colitis in mice. The transmission electron microscopy, zeta size and zeta potential data showed the successful formation of SLNs formulations. SLNs and PEI-SLNs showed burst drug release in acidic pH condition mimicking stomach and early small intestine environment which limiting their application as oral delivery systems. However, ES-PEI-SLNs prevented a burst drug release in acidic pH conditions and showed sustained release at a colonic pH. Most importantly, the surface charge of ES-PEI-SLNs switched from negative to positive in colonic conditions by pH-triggered removal of ES coating and accumulated selectively in inflamed colon. Furthermore, a charge reversal ES-PEI-SLNs showed a superior mitigation of dextran sulfate sodium (DSS)-induced acute colitis in mice as compared to SLNs and PEI-SLNs treated groups. Moreover, histopathological analysis of distal colon sections stained with hematoxylin/eosin and E-cadherin immunostaining revealed attenuated inflammation in an ES-PEI-SLNs-treated group. We also found that ES-PEI-SLNs markedly reduced the myeloperoxidase level and expression of TNF-alpha in colon tissue. Our results suggest that the pH-triggered charge reversal SLNs presented in this study would be a promising approach for ulcerative colitis therapy.

Keywords: solid lipid nanoparticles, stimuli-triggered charge-reversal, ulcerative colitis, methacrylate copolymer, budesonide

Procedia PDF Downloads 248