Search results for: muscle dysfunction

Authors: Ravinder Kaur

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Introduction Global cerebrovascular reactivity (CVR) mapping is a promising clinical assessment for stress-testing the brain using physiological challenges, such as CO₂, to elicit changes in perfusion. It enables real-time assessment of cerebrovascular integrity and health. Conventional imaging approaches solely use steady-state parameters, like cerebral blood flow (CBF), to evaluate the integrity of the resting parenchyma and can erroneously show a healthy brain at rest, despite the underlying pathogenesis in the presence of cerebrovascular disease. Conversely, coupling CO₂ inhalation with phase-contrast MRI neuroimaging interrogates the capacity of the vasculature to respond to changes under stress. It shows promise in providing prognostic value as a novel health marker to measure neurovascular function in disease and to detect early brain vasculature dysfunction. Objective This exploratory study was established to:(a) quantify the CBF response to CO₂ in hypocapnia and hypercapnia,(b) evaluate disparities in CVR between internal carotid (ICA) and vertebral artery (VA), and (c) assess sex-specific variation in CVR. Methodology Phase-contrast MRI was employed to measure the cerebrovascular reactivity to CO₂ (±10 mmHg). The respiratory interventions were presented using the prospectively end-tidal targeting RespirActTM Gen3 system. Post-processing and statistical analysis were conducted. Results In 9 young, healthy subjects, the CBF increased from hypocapnia to hypercapnia in all vessels (4.21±0.76 to 7.20±1.83 mL/sec in ICA, 1.36±0.55 to 2.33±1.31 mL/sec in VA, p < 0.05). The CVR was quantitatively higher in ICA than VA (slope of linear regression: 0.23 vs. 0.07 mL/sec/mmHg, p < 0.05). No statistically significant effect was observed in CVR between male and female (0.25 vs 0.20 mL/sec/mmHg in ICA, 0.09 vs 0.11 mL/sec/mmHg in VA, p > 0.05). Conclusions The principal finding in this investigation validated the modulation of CBF by CO₂. Moreover, it has indicated that regional heterogeneity in hemodynamic response exists in the brain. This study provides scope to standardize the quantification of CVR prior to its clinical translation.

Keywords: cerebrovascular disease, neuroimaging, phase contrast MRI, cerebrovascular reactivity, carbon dioxide

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Authors: Eman A. Embaby, Amira A. A. Abdallah

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Background: Occupational standing is associated with low back pain (LBP) development. Yet, trunk and gluteus-medius muscles’ fatigability has not been extensively studied during occupational standing. This study examined and correlated the rectus abdominus (RA), erector-spinae (ES), external oblique (EO), and gluteus-medius (GM) muscles’ fatigability on both sides while standing in a confined area for 30 min Methods: Median frequency EMG data were collected from 15 female clinical instructors with chronic LBP (group A) and 15 asymptomatic controls (group B) (mean age 29.53±2.4 vs. 29.07±2.4 years, weight 63.6±7 vs. 60±7.8 kg, and height 162.73±4 vs. 162.8±6 cm respectively) using a spectrum analysis program. Data were collected in the first and last 5min of the standing task. Results: Using Mixed three-way ANOVA, group A showed significantly (p<0.05) lower frequencies for the right and left ES, and right GM in the last 5 min and significantly higher frequencies for the left RA in the first and last 5min than group B. In addition, the left ES and right EO, ES and GM in group B showed significantly higher frequencies and the left ES in group A showed significantly lower frequencies in the last 5min compared with the first. Moreover, the right RA showed significantly higher frequencies than the left in the last 5min in group B. Finally, there were significant (p<0.05) correlations among the median frequencies of the tested four muscles on the same side and between both sides in both groups. Discussion/Conclusions: Clinical instructors with LBP are more liable to have higher trunk and gluteus-medius muscle fatigue than asymptomatic individuals. Thus, endurance training for these muscles should be included in the rehabilitation of such patients.

Keywords: EMG, fatigability, gluteus-medius, LBP, standing, trunk

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Authors: Zak Maas, Daniel Carson, Rachel McIntyre, Mark Omundsen, Teresa Holm

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Aim: After hemicolectomy a period of obligatory bowel dysfunction is expected, termed postoperative ileus (POI). Prolonged postoperative ileus (PPOI), typically four or more days, is associated with higher morbidity and extended inpatient stay. This leads to significant financial and resource-related burdens on healthcare systems. Several studies including a meta-analysis have compared rates of PPOI in left vs right hemicolectomy, which suggest that right-sided resections may be more likely to result in PPOI. Our study aims to further investigate whether significant differences in PPOI and obligatory POI exist between right versus extended right hemicolectomy. Methods: This is a retrospective review assessing rates of PPOI in patients who underwent right vs extended right hemicolectomy at Tauranga Hospital. Patients were divided and compared depending on approach (open versus laparoscopic) and acuity (acute versus elective). Exclusion criteria included synchronous major operations and patients preoperatively on parenteral nutrition. Primary outcome was PPOI as pre-defined in contemporary literature. Secondary outcomes were time to passage of flatus, passage of stool, toleration of oral diet and rate of complications. Results: There were 669 patients identified for analysis (507 laparoscopic vs 162 open; 194 acute vs 475 elective). Early analysis indicates rates of PPOI was significantly increased in patients undergoing extended right hemicolectomy. Factors including age, gender, ethnicity, preoperative haemaglobin, preoperative albumin and diagnosis of inflammatory bowel disease were examined by multivariate analysis to determine correlation with PPOI. Conclusion: PPOI is a common complication of hemicolectomy surgery. Higher rates of PPOI in extended right vs right hemicolectomy warrants further research into determining the cause. This study examines some other factors which may contribute to PPOI.

Keywords: hemicolectomy, colorectal, complications, postoperative ileus

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Authors: Ahmad Rasyadan Arshad, A. Rahman A. Jamal, N. Mohamed Ibrahim, Nor Azian Abdul Murad

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Introduction: Parkinson’s disease (PD) is a complex and asymptomatic disease where patients are usually diagnosed at late stage where about 70% of the dopaminergic neurons are lost. Therefore, identification of molecular biomarkers is crucial for early diagnosis of PD. MicroRNA (miRNA) is a short nucleotide non-coding small RNA which regulates the gene expression in post-translational process. The involvement of these miRNAs in neurodegenerative diseases includes maintenance of neuronal development, necrosis, mitochondrial dysfunction and oxidative stress. Thus, miRNA could be a potential biomarkers for diagnosis of PD. Objective: This study aim to identify the miRNA involved in Late Onset PD (LOPD) and Early Onset PD (EOPD) compared to the controls. Methods: This is a case-control study involved PD patients in the Chancellor Tunku Muhriz Hospital at the UKM Medical Centre. miRNA samples were extracted using miRNeasy serum/plasma kit from Qiagen. The quality of miRNA extracted was determined using Agilent RNA 6000 Nano kit in the Bioanalyzer. miRNA expression was performed using GeneChip miRNA 4.0 chip from Affymetrix. Microarray was performed in EOPD (n= 7), LOPD (n=9) and healthy control (n=11). Expression Console and Transcriptomic Analyses Console were used to analyze the microarray data. Result: miR-129-5p was significantly downregulated in EOPD compared to LOPD with -4.2 fold change (p = <0.050. miR-301a-3p was upregulated in EOPD compared to healthy control (fold = 10.3, p = <0.05). In LOPD versus healthy control, miR-486-3p (fold = 15.28, p = <0.05), miR-29c-3p (fold = 12.21, p = <0.05) and miR-301a-3p (fold = 10.01, p =< 0.05) were upregulated. Conclusion: Several miRNA have been identified to be differentially expressed in EOPD compared to LOPD and PD versus control. These miRNAs could serve as the potential biomarkers for early diagnosis of PD. However, these miRNAs need to be validated in a larger sample size.

Keywords: early onset PD, late onset PD, microRNA (miRNA), microarray

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Authors: Isabella Jabbour

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The world's population is expected to reach over 10 billion by 2050, creating a significant demand for food production, particularly in the agricultural industry. Cellular agriculture presents a solution to this challenge by producing meat that resembles traditionally produced meat, but with significantly less land use. Decellularized plant scaffolds, such as spinach leaves, have been shown to be a suitable edible scaffold for growing animal muscle, enabling cultured cells to grow and organize into three-dimensional structures that mimic the texture and flavor of conventionally produced meat. However, the use of freshwater to remove the intact extracellular material from these plants remains a concern, particularly when considering scaling up the production process. In this study, two protocols were used, 1X SDS and Boom Sauce, to decellularize spinach leaves with both distilled water and ocean water. The decellularization process was confirmed by histology, which showed an absence of cell nuclei, DNA and protein quantification. Results showed that spinach decellularized with ocean water contained 9.9 ± 1.4 ng DNA/mg tissue, which is comparable to the 9.2 ± 1.1 ng DNA/mg tissue obtained with DI water. These findings suggest that decellularized spinach leaves using ocean water hold promise as an eco-friendly and cost-effective scaffold for laboratory-grown meat production, which could ultimately transform the meat industry by providing a sustainable alternative to traditional animal farming practices while reducing freshwater use.

Keywords: cellular agriculture, plant scaffold, decellularization, ocean water usage

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Authors: Asma Naseer Cheema, Attya Bhatti, Jabar Ali, John Peter

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Background: High cholesterol levels, endothelial dysfunction, inefficient coagulation cascade and hyper inflammatory response all are the basis of coronary artery disease (CAD). Several studies are carried out to see the genetic influence of these factors on disease outcome. Objective: The objective of our study was to see the association of 10 putative loci with coronary artery disease in our population. Materials & Methods: We screened our population for 10 putative loci of CAD showing significant association (p < 5x10-8) with candidate genes (regulating the cholesterol metabolism, endothelial function, coagulation cascade and inflammatory response of body). Hardy-Weinberg equilibrium and linkage disequilibrium in cases and controls s were estimated separately. Approximately 5-10 ng of dried DNA in 384 well plate format was used to genotype each sample on the Sequenom iPLEX assay at University of Pittsburgh Genomics and Proteomics Core Laboratories. It was built on single-base primer extension with the MALDI-TOF MS detection possessing high sensitivity and specificity. The SNPs were genotyped through Taqman assay. Hardy Weinberg test was applied. The 10 SNPs were selected as genetic markers for this study (rs579459, rs1561198, rs2954029, rs1122608, rs17114036, rs9515203, rs10947789, rs7173743, rs2895811, rs2075650). Results: Mean age of the patient was 52 ± 11 years. Blood pressure and positive family history was found a significant risk factor for CAD. None of the selected SNPs showed significant association with coronary artery disease in our population (p>0.05). Conclusion: rs579459, rs1561198, rs2954029, rs1122608, rs17114036, rs9515203, rs10947789, rs7173743, rs2895811, rs2075650 are not significant genetic markers for CAD in our population.

Keywords: CAD, genetic markers, loci, risk factors

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Authors: Mohamed M. Diab, Fahmy E. Mohamed, Alaa Balbaa

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Background: Myofascial pain syndrome a common type of non-articular musculoskeletal pain, is a condition associated with regional pain and muscle tenderness characterized by the presence of hypersensitive nodules. Objectives: the purpose of this study is to compare between the effects of manual progressive ischemic pressure versus the effect of post isometric facilitation in the treatment of Rhomboid latent myofascial trigger points. Methods: six patients had participated in this study. Patients divided into two groups. Group A treated by manual progressive ischemic pressure and traditional physical therapy program. Group B treated by post isometric facilitation and traditional physical therapy program. Treatment program was for 6 sessions over two week’s period. Result: Statistical analysis revealed that there is no significant difference in post treatment from pretreatment in pain severity (VAS) in myofascial trigger points with Rhomboid muscles) and Pain pressure threshold (PPT) for tenderness at both groups (A,B). Conclusion: ischemic pressure technique appear to be no more effective than post isometric facilitation in treatment of rhomboids latent myofacial trigger point.

Keywords: Rhmoiboid trigger point, myofacila trigger point, ischemic pressure, post isometric facilitation

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Authors: Eftychia Pappa, Heleni Vastardis, Christos Rahiotis, Andriani Vazaiou

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The aim of this study was to evaluate the prevalence of dry-mouth symptoms (xerostomia) and compare it with alterations in salivary characteristics of children and adolescents with type 1 diabetes (DM1), as measured with the use of chair-side saliva tests. This study also investigated the possible association between salivary dysfunction and incidence of caries, in relation to the level of metabolic control. A cross-sectional study was performed on young patients (6-18 years old) allocated among 3 groups: 40 patients poorly-controlled (DM1-A, HbA1c>8%), 40 well-controlled (DM1-B, HbA1c≤8%) and 40 age- and sex-matched healthy controls. The study was approved by the Research Ethics Committee of University of Athens and the parents signed written informed consent. All subjects were examined for dental caries, oral hygiene and salivary factors. Assessments of salivary function included self-reported xerostomia, quantification of resting and stimulated whole saliva flow rates, pH values, buffering capacity and saliva’s viscosity. Salivary characteristics were evaluated with the use of GC Saliva Check Buffer (3Μ ESPE). Data were analysed by chi-square and Kruskal-Wallis tests. Subjects with diabetes reported xerostomia more frequently than healthy controls (p<0.05). Unstimulated salivary flow rate and pH values remained significantly lower in DM1-A compared to DM1-B and controls. Low values of resting salivary flow rate were associated with a higher prevalence of dental caries in children and adolescents with poorly-controlled DM1 (p<0.05). The results suggested that diabetes-induced alterations in salivary characteristics are indicative of higher caries susceptibility of diabetics and chair-side saliva tests are a useful tool for the evaluation of caries risk assessment.

Keywords: caries risk assessment, saliva diagnostic tests, type 1 diabetes, xerostomia

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Authors: Ramada R. Khasawneh, Mohammed Z. Allouh, Ejlal Abu-El Rub

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The quadriceps angle (Q angle), formed between the quadriceps muscles and the patella tendon, is considered clinically as a very important parameter which displays the biomechanical effect of the quadriceps muscle on the knee, and it is also regarded as a crucial factor for the proper posture and movement of the knee patella. This study had been conducted to measure the normal Q angle values range in the Arab nationalities and determine the correlation between Q angle values and several body parameters, including gender, height, weight, dominant side, and the condylar distance of the femur. The study includes 500 healthy Arab students from Yarmouk University and Jordan University of Science and Technology. The Q angle of those volunteers was measured using a universal manual Goniometer with the subjects in the upright weight-bearing position. It was found that the Q angle was greater in women than in men. The analysis of the data revealed an insignificant increase in the dominant side of the Q angle. In addition, the Q was significantly higher in the taller people of both sexes. However, the Q angle did not present any considerable correlation with weight in the study population; conversely, it was observed that there was a link with the condylar distance of the femur in both sexes. It was also noticed that the Q angle increased remarkably when there was an increase in the condylar distance. Consequently, it turned out that the gender, height, and the condylar distance were momentous factors that had an impact on the Q angle in our study samples. However, weight and dominance factors did not show to have any influence on the values in our study.

Keywords: Q angle, Jordanian, anatomy, condylar distance

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Authors: Ediati Budi Cahyono, Triana Hertiani, Nauval Arrazy Asawimanda, Wahyu Puji Pratomo

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Background: Doxorubicin is widely used as a chemotherapeutic drug despite having many side effects. It may cause macrophage dysfunction and decreasing proliferation of lymphocyte. Noni (Morinda citrifolia) fruit which has rich of polysaccharide content has potential as antitumor and immunostimulant effect. The isolation of polysaccharide from Noni fruit has been optimized according to four different methods based on macrophage and lymphocyte activities. We found the highest polysaccharide content from one of the four methods isolation. A method of polysaccharide isolation which has the highest immunostimulant effect was used for further observation as co-chemotherapy. The aim of the study: was to evaluate the isolated polysaccharide from the method of choice as co-chemotherapy of doxorubicin for the growth of Vero, He-La, and T47D cell lines in vitro. The method: in vitro growth assay of Vero, He-La, and T47D cell lines was done using MTT-reduction method, and apoptosis test was done by double staining method to evaluate the induction apoptotic effect of the combination. Every group was treated with doxorubicin and isolated polysaccharide from method of choice with 4 variances of concentrations (25 µg/ml, 50 µg/ml, 100 µg/ml and 200 µg/ml) a long with negative control (doxorubicin only) and normal control (without doxorubicin or polysaccharide administration). Results: The combination of polysaccharide fraction in the concentration of 100μg/ml with 2μmol of doxorubicin against He-La and T47D cell lines influenced the highest cytotoxic effect by suppressing cell viability comparing with doxorubicin only. The combination of polysaccharide fraction in the concentration of 100μg/ml with 2μmol of doxorubicin-induced apoptotic effect the He-La cell line comparing with doxorubicin only. The result of the study: it can be concluded that the combination of polysaccharide fraction and doxorubicin effect more selective toward He-La and T47D cell lines than to Vero cell line. It can be suggested isolated polysaccharide from the method of choice has co-chemotherapy activity against doxorubicin.

Keywords: polysaccharide, noni fruit, doxorubicin, cancer cell lines, vero cell line

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Authors: Ammara Khan

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Sepsis is characterized by an overwhelming surge of cytokines and oxidative stress to one of many factors, gram-negative bacteria commonly implicated. Despite major expansion and elaboration of sepsis pathophysiology and therapeutic approach; death rate remains very high in septic patients due to multiple organ damages including hepatotoxicity.The present study was aimed to ascertain the adequacy of three different drugs delivered separately and collectively- low dose steroid-dexamethasone (3mg/kg i.p) ,antioxidant-melatonin(10 mg/kg i.p) ,and phosphodiesterases inhibitor - pentoxifylline (75 mg/kg i.p)in endotoxin-induced hepatotoxicity in mice. Endotoxin/lipopolysaccharides induced hepatotoxicity was reproduced in mice by giving lipopolysaccharide of serotype E.Coli intraperitoneally. The preventive role was questioned by giving the experimental agent half an hour prior to LPS injection whereas the therapeutic potential of the experimental agent was searched out via post-LPS delivering. The extent of liver damage was adjudged via serum alanine aminotransferases (ALT) and aspartate aminotransferase (AST) estimation along with a histopathological examination of liver tissue. Dexamethasone is given before (Group 3) and after LPS (group 4) significantly attenuated LPS generated liver injury.Pentoxifylline generated similar results and serum ALT; AST histological alteration abated considerably (p≤ 0.05) both in animals subjected to pentoxifylline pre (Group 5) and post-treatment(Group 6). Melatonin was also prosperous in aversion (Group 7) and curation (Group 8) of LPS invoked hepatotoxicity as evident by lessening of augmented ALT (≤0.01) and AST (≤0.01) along with restoration of pathological changes in liver sections (p≤0.05). Combination therapies with dexamethasone in conjunction with melatonin (Group 9), dexamethasone together with pentoxifylline (Group 10), and pentoxifylline along with melatonin (Group 11) after LPS administration tapered LPS evoked hepatic dysfunction statistically considerably. In conclusion, both melatonin and pentoxifylline set up promising results in endotoxin-induced hepatotoxicity and can be used therapeutic adjuncts to conventional treatment strategies in sepsis-induced liver failure.

Keywords: endotoxin/lipopolysacchride, dexamethasone, hepatotoxicity, melatonin, pentoxifylline

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Authors: Elnaz Sabzehparvar, Pouya Rabiei, Houman Rezaei

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Few studies have been conducted about the effects of compound exercises emphasizing local stability and global stabilization subsystems on the performance of athletes. The present research aimed to study the effect of 6 weeks of compound exercises emphasizing local and global stability on the dynamic balance of elite male Taekwondo athletes. Twenty-seven elite male Taekwondo athletes (with a mean age, mass, and height of 24.4 ± 4.9 years, 75.7 ± 15.1kg, and 181.4 ± 7.8 cm, respectively) were assigned to two groups of control (n=12) and exercise (n=15). 6 weeks of compound exercises in 2 local and global phases. The first phase included activation exercises which were done separately and locally for 3 weeks. Then, integrative exercises specific to the global stabilization subsystems (longitudinal-depth, posterior oblique and anterior, and lateral) was carried out for next 3 weeks. The dynamic balance of subjects was measured in the pre-test and post-test using the Y Balance Test (YBT). After 6 weeks of compound exercises, scores of the YBT in the exercise group showed a significant improvement in all three anterior (p=0.035), posterolateral (p=0.017) and medial (p=0.001) directions in the post-test compared to the control group (p ≤ 0.05 for all comparisons). The findings of the present study suggested that compound exercises focusing on muscle as separate units and then as interdependent chains (muscular subsystems) can significantly increase YBT on elite male Taekwondo athletes in all three directions.

Keywords: Taekwondo, compound exercises, local and global stability, muscular subsystems

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Authors: D: Gupta, M. Radhakrishnan, Y. Kurhe, D. Thangaraj

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Depression is among the leading causes of death worldwide. The current pharmacotherapy is associated with poor compliance, resistance and relapse, which necessitate the development of novel compounds with better efficacy. The present study designed and synthesized EQC-34 (N-cyclohexyl-3-ethoxyquinoxalin-2-carboxamide) as novel serotonin type-3 (5HT3) antagonist and evaluated its antidepressant-like effects using neurobehavioral mouse model. 5HT3 antagonism (as pA2 value) was determined on the longitudinal smooth muscle of guinea-pig ileum against 2-methyl-5HT (a 5HT3 agonist). The doses were calculated by dose response of basal locomotor activity. Consequently, effects of EQC-34 on neurobehavioral parameters were measured in forced swim (FST) and tail suspension test (TST). The possible mechanism was estimated by interaction study with fluoxetine (a selective serotonin reuptake inhibitor) and mCPBG (1-(m-chlorophenyl)-biguanide, a selective 5HT3 agonist), and confirmed by potentiation of head twitch response by 5hydroxy-L-tryptophan (5HTP). EQC-34 (1-4 mg/kg, i.p.) produced significant decreased behavioral despair effects in FST and TST. It potentiated fluoxetine response, while mCPBG reduced EQC-34 activity in FST. Further, EQC-34 potentiated 5HTP induced head twitch response. EQC-34 revealed potential antidepressant-like effects, which may involve 5HT3 receptor mediated facilitation of 5HT neurotransmission, thereby reversing the pathological deficiency of monoamines (5HT) observed in depression. Thus, it may be further investigated as promising agent to improve therapeutics of depression.

Keywords: depression, forced swim test, 5HT3 receptor antagonist, serotonin

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Authors: Kinjal H. Shah, Piyush M. Patel

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Diabetes mellitus is considered to be a serious endocrine syndrome. Synthetic hypoglycemic agents can produce serious side effects including hematological effects, coma, and disturbances of the liver and kidney. In addition, they are not suitable for use during pregnancy. In recent years, there have been relatively few reports of short-term side effects or toxicity due to sulphonylureas. Published figures and frequency of side effects in large series of patient range from about 1 to 5%, with symptoms severe enough to lead to the withdrawal of the drug in less than 1 to 2%. Adverse effects, in general, have been of the following type: allergic skin reactions, gastrointestinal disturbances, blood dyscrasias, hepatic dysfunction, and hypoglycemia. The associated disadvantages with insulin and oral hypoglycemic agents have led to stimulation in the research for locating natural resources showing antidiabetic activity and to explore the possibilities of using traditional medicines with proper chemical and pharmacological profiles. Literature survey reveals that the inhabitants of Abbottabad district of Pakistan use the dried leaf powder along with table salt and water orally for treating diabetes, skin allergy, wounds and as a blood purifier, where they pronounced the plant locally as ‘Nem.' The detailed phytochemical investigation of the Cedrela toona Roxb. leaves for antidiabetic activity has not been documented. Hence, there is a need for phytochemical investigation of the leaves for antidiabetic activity. The collection of fresh leaves and authentification followed by successive extraction, phytochemical screening, and testing of antidiabetic activity. The blood glucose level was reduced maximum in ethanol extract at 5th and 7th h after treatment. Blood glucose was depressed by 8.2% and 10.06% in alloxan – induced diabetic rats after treatment which was comparable to the standard drug, Glibenclamide. This may be due to the activation of the existing pancreatic cells in diabetic rats by the ethanolic extract.

Keywords: antidiabetic, Cedrela toona Roxb., phytochemical screening, blood glucose

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Authors: E. Abustam, M. I. Said, M. Yusuf, H. M. Ali

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This study aims to examine the sensory quality of meatballs made from Balinese beef and buffalo meat after the addition of smoke powder prior to storage at the temperatures of 2-5°C for 7 days. This study used meat from Longissimus dorsi muscle of male Balinese cattle aged 3 years and of male buffalo aged 5 years as the main raw materials, and smoke powder as a binder and preservative in making meatballs. The study was based on completely randomized design (CRD) of factorial pattern of 2 x 3 x 2 where factors 1, 2 and 3 included the types of meat (cattle and buffalo), types of smoke powder (oven dried, freeze dried and spray dried) with a level of 2% of the weight of the meat (b/b), and storage duration (0 and 7 days) with three replications respectively. The parameters measured were the meatball sensory quality (scores of tenderness, firmness, chewing residue, and intensity of flavor). The results of this study show that each type of meat has produced different sensory characteristics. The meatballs made from buffalo meat have higher tenderness and elasticity scores than the Balinese beef. Meanwhile, the buffalo meatballs have a lower residue mastication score than the Balinese beef. Each type of smoke powders has produced a relatively similar sensory quality of meatballs. It can be concluded that the smoke powder of 2% of the weight of the meat (w/w) could maintain the sensory quality of the meatballs for 7 days of storage.

Keywords: Balinese beef meatballs, buffalo meatballs, sensory quality, smoke powder

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Authors: Elisa Maître

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The redeployment of tram networks in French cities has considerably modified public spaces and the way citizens use them. Above and beyond the image that trams have of contributing to the sustainable urban development, the question of safety for users in these spaces has not been studied much. This study is based on an analysis of use of public spaces laid out for trams, from the standpoint of legibility and safety concerns. The study also examines to what extent the complexity of the design process, with many interactions between numerous and varied players in this process has a role in the genesis of these problems. This work is mainly based on the analysis of links between the uses of these re-designed public spaces (through observations, interviews of users and accident studies) and the analysis of the design conditions and processes of the projects studied (mainly based on interviews with the actors of these projects). Practical analyses were based three points of view: that of the planner, that of the user (based on observations and interviews) and that of the road safety expert. The cities of Montpellier, Marseille and Nice are the three fields of study on which the demonstration of this thesis is based. On part, the results of this study allow showing that the insertion of tram poses some problems complication of public areas of French cities. These complications related to the restructuring of public spaces for the tram, create difficulties of use and safety concerns. On the other hand, interviews depth analyses, fully transcribed, have led us to develop particular dysfunction scenarios in the design process. These elements lead to question the way the legibility and safety of these new forms of public spaces are taken into account. Then, an in-depth analysis of the design processes of public spaces with trams systems would also be a way of better understanding the choices made, the compromises accepted, and the conflicts and constraints at work, weighing on the layout of these spaces. The results presented concerning the impact that spaces laid out for trams have on the difficulty of use, suggest different possibilities for improving the way in which safety for all users is taken into account in designing public spaces.

Keywords: public spaces, road layout, users, design process of urban projects

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Authors: Moncayo Donoso Miguelangel, Guevara Morales Johana, Kalenia Flores Kalenia, Barrera Avellaneda Luis Alejandro, Garzon Alvarado Diego Alexander

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In mammals, long bones are formed by ossification of a cartilage mold during early embryonic development, forming structures called secondary ossification centers (SOCs), a primary ossification center (POC) and growth plates. This last structure is responsible for long bone growth. During the femur growth, the morphology of the growth plate and the SOCs may vary during different developmental stages. So far there are no detailed morphological studies of the development process from embryonic to adult stages. In this work, we carried out a morphological characterization of femur development from embryonic period to adulthood in mice. 15, 17 and 19 days old embryos and 1, 7, 14, 35, 46 and 52 days old mice were used. Samples were analyzed by a computational approach, using 3D images obtained by micro-CT imaging. Results obtained in this study showed that femur, its growth plates and SOCs undergo morphological changes during different stages of development, including changes in shape, position and thickness. These variations may be related with a response to mechanical loads imposed for muscle development surrounding the femur and a high activity during early stages necessary to support the high growth rates during first weeks and years of development. This study is important to improve our knowledge about the ossification patterns on every stage of bone development and characterize the morphological changes of important structures in bone growth like SOCs and growth plates.

Keywords: development, femur, growth plate, mice

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Authors: Selena Ferrian, Erin Mccaffrey, Toshie Saito, Aiqin Cao, Noah Greenwald, Mark Robert Nicolls, Trevor Bruce, Roham T. Zamanian, Patricia Del Rosario, Marlene Rabinovitch, Michael Angelo

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Recent experimental and clinical observations are advancing immunotherapies to clinical trials in pulmonary arterial hypertension (PAH). However, comprehensive mapping of the immune landscape in pulmonary arteries (PAs) is necessary to understand how immune cell subsets interact to induce pulmonary vascular pathology. We used multiplexed ion beam imaging by time-of-flight (MIBI-TOF) to interrogate the immune landscape in PAs from idiopathic (IPAH) and hereditary (HPAH) PAH patients. Massive immune infiltration in I/HPAH was observed with intramural infiltration linked to PA occlusive changes. The spatial context of CD11c+DCs expressing SAMHD1, TIM-3 and IDO-1 within immune-enriched microenvironments and neutrophils were associated with greater immune activation in HPAH. Furthermore, CD11c-DC3s (mo-DC-like cells) within a smooth muscle cell (SMC) enriched microenvironment were linked to vessel score, proliferating SMCs, and inflamed endothelial cells. Experimental data in cultured cells reinforced a causal relationship between neutrophils and mo-DCs in mediating pulmonary arterial SMC proliferation. These findings merit consideration in developing effective immunotherapies for PAH.

Keywords: pulmonary arterial hypertension, vascular remodeling, indoleamine 2-3-dioxygenase 1 (IDO-1), neutrophils, monocyte-derived dendritic cells, BMPR2 mutation, interferon gamma (IFN-γ)

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Authors: Mitra Assadi, Md. Faan

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Background: Autism Spectrum Disorder (ASD) in a common neurodevelopmental disorder with limited pharmacological interventions. Transcranial Magnetic Stimulation (rTMS) has produced promising results in ASD, although there is no consensus regarding optimal targets or stimulation paradigms. A prevailing theory in ASD attributes the core deficits to dysfunction of the mirror neurons located in the inferior parietal lobule (IPL) and inferior frontal gyrus (IFG). Methods: Thus far, 11 subjects with ASD, 10 boys and 1 girl with the mean age of 13.36 years have completed the study by receiving 10 session of high frequency rTMS to the IPL. The subjects were randomized to receive stimulation on the left or right IPL and sham stimulation to the opposite side. The outcome measures included the Social Responsiveness Scale – Second Edition (SRS-2) and Delis-Kaplan Executive Function System (D-KEFS) Verbal Fluency task. Results: None of the 11 subjects experienced any adverse effects. The rTMS did not produce any improvement in verbal fluency, nor there was any statistically significant difference between the right versus left sided stimulation. Analysis of social awareness on SRS-2 (SRS-AWR) indicated a close to significant effect of the treatment with a small to medium effect size. After removing a single subject with Level 3 ASD, we demonstrated a close to significant improvement on SRS-AWR with a large effect size. The analysis of the data 3-month post TMS demonstrated return of the SRS-AWR values to baseline. Conclusion: This preliminary analysis of the 11 subjects who have completed our study thus far shows a favorable response to high frequency rTMS stimulation of the mirror neurons/IPL on social awareness. While the decay of the response noted during the 3-month follow-up may be considered a limitation of rTMS, the presence of the improvement, especially the effect size despite the small sample size, is indicative of the efficacy of this technique.

Keywords: rTMS, autism, scoial cognition, mirror neurons

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Authors: Renato André S. Silva, Nana L. F. Sampaio, Carlos J. G. Cruz, Bruno Vianna, Flávio O. Pires

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multiple stage bicycle races require high physiological loads from professional cyclists. Such demands can lead to immunosuppression and health problems. However, in this type of competition, little is known about its physiological effects on amateur athletes, who generally receive less medical support. Thus, this study analyzes the hematological effects of a multiple stage bicycle race on amateur cyclists. Seven Brazilian national amateur cyclists (34 ± 4.21 years) underwent a laboratory test to evaluate VO2Max (69.89 ± 7.43 ml⋅kg-1⋅min-1). Six days later, these volunteers raced in the Tour of Goiás, participating in five races in four days (435 km) of competition. Arterial blood samples were collected one day before and one day after the competition. The Kolmogorov-Smirnov tests were used to evaluate the data distribution and Wilcoxon to compare the two moments (p <0.05) of data collection. The results show: Red cells ↓ 7.8% (5.1 ± 0.28 vs 4.7 ± 0.37 106 / mm 3, p = 0.01); Hemoglobin ↓ 7.9% (15.1 ± 0.31 vs 13.9 ± 0.27 g / dL, p = 0.01); Leukocytes ↑ 9.5% (4946 ± 553 versus 5416 ± 1075 / mm 3, p = 0.17); Platelets ↓ 7.0% (200.2 ± 51.5 vs 186.1 ± 39.5 / mm 3, p = 0.01); LDH ↑ 11% (164.4 ± 28.5 vs 182.5 ± 20.5 U / L, p = 0.17); CK ↑ 13.5% (290.7 ± 206.1 vs 330.1 ± 90.5 U / L, p = 0.39); CK-MB ↑ 2% (15.7 ± 3.9 vs. 20.1 ± 2.9 U / L, p = 0.06); Cortizol ↓ 13.5% (12.1 ± 2.4 vs 9.9 ± 1.9 μg / dL, p = 0.01); Total testosterone ↓ 7% (453.6 ± 120.1 vs 421.7 ± 74.3 ng / dL, p = 0.12); IGF-1 ↓ 15.1% (213.8 ± 18.8 vs 181.5 ± 34.7 ng / mL, p = 0.04). This means that there was significant reductions in O2 allocation / transport capacities, vascular injury disruption, and a fortuitous reduction of muscle skeletal anabolism along with maintenance and / or slight elevation of immune function, glucose and lipid energy and myocardial damage. Therefore, the results suggest that no abnormal health effect was identified among the athletes after participating in the Tour de Goiás.

Keywords: cycling, health effects, cycling stages races, haematology

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Authors: S. Abbasi, M. R. Hadian, M. Abdolvahab, M. Jalili, S. H. Jalaei

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Background: Rehabilitation treatments have significant role in reducing the disabilities of Cerebro Vascular Accident (CVA). Due to great role of upper limb in the function of individuals particularly in Activity of Daily Living and the effect of stability of shoulder girdle on hand function, the aim of this study was to study the effects of Progressive Resistive Exercise on shoulder extensor and abductor muscles isometric strengths in adult hemiplegic. Methods: 17 adult hemiplegics patients (50-70 yrs., mean 60/52, SD7/22); with RT side dominancy and 6 months after stroke, participated in this study. All procedures were approved by ethical committee of TUMS and written consents were also taken. Patients were familiarized with the procedure and shoulder extensor and abductor muscles isometric strengths were measured by dynamometer. Results: according to result to our study, shoulder extensor and abductor muscles isometric strengths showed Significant differences between mean scores of pre and post intervention (P<0/05). Progressive Resistive Exercise improved 34% shoulder extensor muscles isometric strength and 27% shoulder abductor muscle isometric strength. Conclusion: Results of our research showed that progressive resistive exercise approach is a useful method for increasing the isometric strength of shoulder extensor and abductor muscles. Therefore, it might be concluded that improvement of strength of shoulder muscles could result in stability in shoulder girdle and consequently might effect on hand function in hemiplegic patients.

Keywords: shoulder extensor muscles isometric strength, shoulder abductor muscles isometric strength, hemiplegic, physical therapy

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Authors: Peter David Reiss

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The concept of the psychosis prodrome has allowed for the identification of adolescent and young adult patients who have a significantly elevated risk of developing schizophrenia spectrum disorders. A number of different interventions have been tested in order to prevent or delay progression of symptoms. To date, there has been no consistent meta-analytical evidence to support efficacy of antipsychotic treatment for patients in the prodromal state, and their use remains therefore inconclusive. Although antipsychotics may manage symptoms transiently, they have not been found to prevent or delay onset of psychotic disorders. Furthermore, pharmacological intervention in high-risk individuals remains controversial, because of the antipsychotic side effect profile in a population in which only about 20 to 35 percent will eventually convert to psychosis over a two-year period, with even after two years conversion rates not exceeding 30 to 40 percent. This general estimate is additionally problematic, in that it ignores the fact that there is significant variation in individual risk among clinical high-risk cases. The current lack of reliable tests for at-risk patients makes it difficult to justify individual treatment decisions. Preventive treatment should ideally be dictated by an individual’s risk while minimizing potentially harmful medication exposure. This requires more accurate predictive assessments by using valid and accessible prognostic markers. The following will compare prediction and risk modification potential of behavioral biomarkers such as disturbances of basic sense of self and emotion awareness, neurocognitive biomarkers such as attention, working and declarative memory, and neurophysiological biomarkers such as glutamatergic abnormalities and NMDA receptor dysfunction. Identification of robust biomarkers could therefore not only provide more reliable means of psychosis prediction, but also help test and develop new clinical interventions targeted at the prodromal state.

Keywords: at-risk mental state, biomarkers, glutamatergic system, NMDA receptor, psychosis prodrome, schizophrenia

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Authors: A. Elmajdoub, A. El-Mahmoudy

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The present study was designed to investigate the neurotransmitters that mediate the excitatory response of the circular muscle of final branches of mesenteric artery in bovine calves. Mesentery was dissected and the iliac branches were separated and used. The final mesenteric branches of diameter 400 micrometers and less responded strongly to norepinephrine and moderately to ATP. However, the mesenteric branches of wider diameters were gradually less responsive to norepinephrine and those of diameter 700 micrometers were exclusively nonresponsive. These arteries were strongly responsive to ATP (100 µM). Norepinephrine response was sensitive to phentolamine (3 µM) and prazosin (5 µM) indicating that it is mediated by α1 receptor; while ATP response was sensitive to suramin (200 µM), PPADS (50 µM), but not to cibacron blue (100 µM) indicating that it is mediated via P2X receptor. Further confirmatory experiments were performed including application of α1 and P2X receptor specific agonists which are methoxamine and α,β-methylene ATP. Methoxamine (1 µM) showed effects similar to norepinephrine in final branches and was without effect in wider branches. α,β-methylene ATP (1 µM), exhibited more pronounced effects on both wide and narrow branches but in parallel manner to that of ATP. Agonists for α2 and P2Y receptors as clonidine (10 µM) and 2-meThio ATP (10 µM), respectively, were without effect indicating that involvement of these receptors is unlikely. The neuropeptide-Y (200 nM) did not have any effects on either the narrow or the wide rings. Conclusion: These data may imply that in the most peripheral mesenteric arteries a strong vasopressor power represented by norepinephrine and ATP integration is needed for maintaining peripheral resistance; on the other hand a mild vasopressor power mediated only by ATP is enough to maintain the vascular tone in the relatively central mesenteric branches.

Keywords: ATP, calves, mesenteric artery, norepinephrine

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Authors: Afsaneh Soltani, Zahra Mohajer

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Migraine is one of the most common chronic neurological diseases. Migraines affect different aspects of life. Severe migraine headaches lead to dysfunction, a reduced presence at work, and decreased ability to think and make decisions. Non-pharmacological treatments play a very important role in controlling and preventing migraine headaches. A healthy lifestyle helps control migraine headaches. Migraine headaches can be reduced by following these steps: Avoiding stress, eating regularly and avoiding hunger and thirst, avoiding stimulants such as chocolate, caffeine, and cigarettes, following a regular bedtime routine, or avoiding sleep deprivation. Exercise a lot, and do regular exercise (and prevent obesity). Non-pharmacological treatment is especially important in pregnant women and children because in these cases, medical treatments are not preferred due to the many side effects. Exercise is one of the most effective and uncomplicated non-pharmacological alternatives in the treatment of migraine headaches. Exercising for episodic migraines is a safe, effective, and promising complementary treatment option. Numerous studies have shown that aerobic exercise reduces the severity and duration of migraine headaches. Effective aerobic exercise includes cycling and brisk walking. Exercise improves the quality of life and reduces the use of medication in people with migraines. Patients who exercise have fewer migraine days, resulting in better personal, social, and occupational performance. Several studies have shown that pain intensity and frequency in patients who exercise regularly decreased significantly after exercise compared to controls who did not exercise. According to a study, regular exercise reduces the levels of interleukins, especially IL-12P70, which reduces anxiety and reduces the number of days of migraine in patients. An article has shown that endurance exercise reduces the number of migraine days and also increases cerebrovascular health in migraine patients. According to studies, the minimum duration of exercise to achieve a positive effect of exercise in patients with migraine is 3 months (12 weeks) and 40 minutes three times a week.

Keywords: exercise, headache, migraine, physical activity

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Authors: Saidia Houari

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The game of football is one of the global sports activities that have witnessed a remarkable development in recent years in the physical, technical, rhetorical and psychological aspects, so the modern play in different teams and international teams quickly and forcefully in the exact technical performance, and this is due to the interest of international coaches. The good training of the players during the youth stage at the level of various aspects to develop all the techniques that have a great effectiveness in competitions according to scientific methods studied. The muscle strength plays a very important role achieving the performance player during the game and it is clear the need for the player in many situations, especially when jumping to hit the ball head or the goal on the goal or long passes of different types and in the performance of various skills by force and speed appropriate to the possession of the ball or the control of the court of the court while overcoming the body weight during the game it is known that the stronger the muscles of the athlete and the reduced joints injuries, and the strength increases energy saving such as Latin phosphate and glycogen, and develop the player for a game football volitional qualities of the most important of courage, determination And self-confidence. There are also some skill movements that can not be performed without a certain level of strength, so the development of power may affect the effectiveness of the long-term training system.

Keywords: trainning program, maximum force and expolosive force, lowers limbs, under 17 years

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Authors: Rona Hanani Simamora, Bahagia Loebis, M. Surya Husada

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Background: The exact cause of schizophrenia is not known, although several etiology theories have been proposed for the disease, including immune dysfunction or autoimmune mechanisms. Cytokines including Tnf-α has an important role in the pathophysiology of schizophrenia and the effects of pharmacological treatment with antipsychotics. Nicotine is widespread effects on the brain, immune system and cytokine levels. Smoking among schizophrenic patients could play a role in the altered cytokine profiles of schizophrenia such as Tnf-α. Aims: To determine differences of serum Tnf-α levels between schizophrenic patients with smoking in male and healthy control. Methods: This study was a comparative analytic study, divided into two groups: 1) group of male schizophrenic patients with smoking (n1=30) with inclusion criteria were patients who have been diagnosed schizophrenic based PPDGJ-III, 20-60 years old, male, smoking, chronic schizophrenic patients in the stable phase and willing to participate this study. Exclusion criteria were having other mental disorders and comorbidity with other medical illnesses. 2) healthy control group (n2=30) with inclusion criteria were 20-60 years old, male, smoking, willing to participate this study. Exclusion criteria were having mental disorder, a family history of psychiatric disorders, the other medical illnesses, a history of alcohol and other substances abuse (except caffeine and nicotine). Serum Tnf-α were analyzed using the Quantikine HS Human Tnf –α Immunoassay. Results: Serum Tnf-α level measure in patient schizophrenia male with smoking and compared with the healthy control subjects. Tnf-α levels were significantly higher in patients schizophrenic male with smoking (25,79±27,96) to healthy control subjects (2,74±2,19), by using the Mann Whitney U test showed a statistically significant difference was observed for serum Tnf-α level (p < 0,001). Conclusions: Schizophrenia is a highly heterogeneous disorder, and this study shows an increase Tnf-α as pro-inflammation cytokines in schizophrenics. These results suggest an immune abnormalities may be involved in the etiology and pathophysiology of schizophrenia.

Keywords: male, schizophrenic, smoking, Tnf Alpha

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Authors: Nino KItoshvili

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The family is an integral part of society, which plays a major role in the socialization and the formation of a person as a full member of society. The marital conflict even harms family members and finds a different effect on each member of the family, especially on children. There is a significant difference in the behavior of adolescents in conflict and non-conflict families. In times of marital conflict, adolescent psycho-social well-being is significantly dependent on socio-cultural mediating variables such as; Family income; Parenting style; The functioning of the family, and the existence of psycho-social support. In a family with low economic performance, low psychosocial harassment, family dysfunction, and bad parenting style, marital conflict significantly increases the risk of deteriorating adolescent psycho-social well-being. At this time, to support the well-being of the child, a special role is played by improving the marital relationship, which must be supported by state and community services. There are very few family studies in this field in Georgia, the therapeutic direction of the family is at an early stage, and there are no family-supporting psycho-social programs. This increases the chances of adolescent psycho-social well-being deteriorating amd socialization problems. The study will examine the mediating variables of marital conflict and adolescent psycho-social well-being and will attempt to determine their mediating and moderating role. Research suggests that an increase in the rate of marital conflict is associated with a decrease in child well-being. The well-being of children in conflict families is lower than that of children in non-conflict families and depends on the variables of mediating variables. Quantitative research will be conducted to study this phenomenon through a questionnaire developed and standardized in the research process. The study will be attended by families living in Georgia - spouses (married) and their adolescent children. By analyzing the data obtained from the research, we will be able to determine in which cases the intensity of the relationship between the marital conflict and the well-being of the adolescent increases or decreases; To conclude the mediating and moderating role of mediating variables and also to make relevant recommendations to reduce the negative impact on the psycho-social well-being of a child of marital conflict.

Keywords: adolescent, mediation, moderation, conflict, couple, well-being

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Authors: Mohammad Abdullah Almalki

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Background: Despite the frequent usage of ankle arthroscopy, there is limited medical literature regarding its indications, patterns of admissions, surgical outcomes, and associated complicated at Saudi Arabia. Hence, this study would highlight the surgical outcomes of such surgical approach that will assist orthopedic surgeons to detect which surgical procedure needs to be done as well as to help them regarding their diagnostic workups. Methods: At the Orthopedic Division of King Abdul‑Aziz Medical City in Riyadh and through a cross‑sectional design and convenient sampling techniques, the present study had recruited 20 subjects who fulfill the inclusion and exclusion criteria between 2016 and 2018. Data collection was carried out by a questionnaire designed and revised by an expert panel of health professionals. Results: Twenty patients were reviewed (11M and 9F) with an average age of 40.1 ± 12.2. Only 30% of the patients (5M, 1F) have no comorbidity, but 70% of patients (7M, 8F) were having at least one comorbidity. The most common indications were osteochondritis dissecans (n = 7, 35%), ankle fracture without dislocation (n = 4, 20%), and tibiotalar impingement (n = 3, 15%). Patients recorded pain in all cases (100%). The top four symptoms after pain were instability (30%, n = 6), muscle weakness (15%, n = 3) swelling (15%, n = 3), and stiffness (5%, n = 1). Two‑third of cases reached to their full healthy status and toe‑touch weight‑bearing was seen in two patients (10%). Conclusion: Ankle arthroscopy improved the rehabilitation rates in our tertiary care center. In addition, the surgical outcomes are favorable in our hospital since it has a very short length of stay, unexpended surgery, and fewest physiotherapy sessions.

Keywords: ankle, arthroscopy, indications, patterns

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Authors: Joseph Salim

Abstract:

This paper proposes the development of a supervised machine learning system to predict the consequences of untreated bruxism (teeth grinding) on gingival (gum) recession and jaw pain (most often bilateral jaw pain with possible headaches and limited ability to open the mouth). As a general dentist in a multi-specialty practice, the author has encountered many patients suffering from these issues due to uncontrolled bruxism (teeth grinding) at night. The most effective treatment for managing this problem involves wearing a nightguard during sleep and receiving therapeutic Botox injections to relax the muscles (the masseter muscle) responsible for grinding. However, some patients choose to postpone these treatments, leading to potentially irreversible and costlier consequences in the future. The proposed machine learning model aims to track patients who forgo the recommended treatments and assess the percentage of individuals who will experience worsening jaw pain, gingival (gum) recession, or both within a 3-to-5-year timeframe. By accurately predicting these outcomes, the model seeks to motivate patients to address the root cause proactively, ultimately saving time and pain while improving quality of life and avoiding much costlier treatments such as full-mouth rehabilitation to help recover the loss of vertical dimension of occlusion due to shortened clinical crowns because of bruxism, gingival grafts, etc.

Keywords: artificial intelligence, machine learning, predictive insights, bruxism, teeth grinding, therapeutic botox, nightguard, gingival recession, gum recession, jaw pain

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Authors: Qin Yang, Fan Zhang, Juan Du, Chongkui Sun, Krishna Kota, Yun-Ling Zheng

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Telomeres are specialized structures at chromosome ends consisting of tandem repetitive DNA sequences [(TTAGGG)n in humans] and associated proteins, which are necessary for telomere function. Telomere lengths are tightly regulated within a narrow range in normal human somatic cells, the basis of cellular senescence and aging. Previous studies have extensively focused on how short telomeres are extended and have demonstrated that telomerase plays a central role in telomere maintenance through elongating the short telomeres. However, the molecular mechanisms of regulating excessively long telomeres are unknown. Here, we found that telomerase enzymatic component hTERT plays a dual role in the regulation of telomeres length. We analyzed single telomere alterations at each chromosomal end led to the discoveries that hTERT shortens excessively long telomeres and elongates short telomeres simultaneously, thus maintaining the optimal telomere length at each chromosomal end for an efficient protection. The hTERT-mediated telomere shortening removes large segments of telomere DNA rapidly without inducing telomere dysfunction foci or affecting cell proliferation, thus it is mechanistically distinct from rapid telomere deletion. We found that expression of hTERT generates telomeric circular DNA, suggesting that telomere homologous recombination may be involved in this telomere shortening process. Moreover, the hTERT-mediated telomere shortening is required its enzymatic activity, but telomerase RNA component hTR is not involved in it. Furthermore, shelterin protein TPP1 interacts with hTERT and recruits it on telomeres to mediate telomere shortening. In addition, telomere-associated proteins, DKC1 and TCAB1 also play roles in this process. This novel hTERT-mediated telomere shortening mechanism not only exists in cancer cells, but also in primary human cells. Thus, the hTERT-mediated telomere shortening is expected to shift the paradigm on current molecular models of telomere length maintenance, with wide-reaching consequences in cancer and aging fields.

Keywords: aging, hTERT, telomerase, telomeres, human cells

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