Search results for: disease severity

Authors: Ntokozo Dambuza, Maryna Van De Venter, Trevor Koekemoer

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Oxidative stress contributes to the pathogenesis of many diseases and consequently antioxidant therapy has attracted much attention as a potential therapeutic strategy. Regardless of the quantities ingested, antioxidants need to reach the diseased tissues at concentrations sufficient to combat oxidative stress. Bioavailability is thus a defining criterion for the therapeutic efficacy of antioxidants. In addition, therapeutic antioxidants must possess biologically relevant characteristics which can target the specific molecular mechanisms responsible for disease related oxidative stress. While many chemical antioxidant assays are available to quantify antioxidant capacity, they relate poorly to the biological environment and provide no information as to the bioavailability. The present comparative study thus aims to characterise green and fermented rooibos extracts, well recognized for their exceptional antioxidant capacity, in terms of antioxidant bioavailability and efficacy in a disease relevant cellular setting. Chinese green tea antioxidant activity was also evaluated. Chemical antioxidant assays (FRAP, DPPH and ORAC) confirmed the potent antioxidant capacity of both green and fermented rooibos, with green rooibos possessing antioxidant activity superior to that of fermented rooibos and Chinese green tea. Bioavailability was assessed using the PAMPA assay and the results indicate that green and fermented rooibos have a permeation coefficient of 5.7 x 10-6 and 6.9 x 10-6 cm/s, respectively. Chinese green tea permeability coefficient was 8.5 x 10-6 cm/s. These values were comparable to those of rifampicin, which is known to have a high permeability across intestinal epithelium with a permeability coefficient of 5 x 10 -6 cm/s. To assess the antioxidant efficacy in a cellular context, U937 and red blood cells were pre-treated with rooibos and Chinese green tea extracts in the presence of a dye DCFH-DA and then exposed to oxidative stress. Green rooibos exhibited highest activity with an IC50 value of 29 μg/ml and 70 μg/ml, when U937 and red blood cells were exposed oxidative stress, respectively. Fermented rooibos and Chinese green tea had IC50 values of 61 μg/ml and 57 μg/ml for U937, respectively, and 221 μg/ml and 405 μg/ml for red blood cells, respectively. These results indicate that fermented and green rooibos extracts were able to permeate the U937 cells and red blood cell membrane and inhibited oxidation of DCFH-DA to a fluorescent DCF within the cells.

Keywords: rooibos, antioxidants, permeability, bioavailability

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Authors: Elisangela Sobreira, Denise Teixeira

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Visceral leishmaniasis is a public health problem in Brazil, it is the main reservoir dog. In the period 2012-2016 78 diagnoses were performed in dogs suspected. Blood samples were collected from the cephalic vein obtaining serum used for the indirect immunofluorescence test and enzyme-linked immunosorbent assay, while it collected a drop of blood for the rapid chromatographic immunoassay. Obtained in 32 dogs positive. The test is important for the control of this disease and is used routinely in the Zoonoses Control Center.

Keywords: Brazil, dogs, Leismaniasis, Zoonoses center

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Authors: Maha Salah, Hanaa Hashem, Mahmoud M. Alsagheir, Mohammed Salah

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Acute respiratory distress syndrome (ARDS) represents a complex clinical syndrome and carries a high risk for mortality. The severity of the clinical course, the uncertainty of the outcome, and the reliance on the full spectrum of critical care resources for treatment mean that the entire health care team is challenged. Researchers and clinicians have investigated the nature of the pathological process and explored treatment options with the goal of improving outcome. Through this application of research to practice, we know that some previous strategies have been ineffective, and innovations in mechanical ventilation, sedation, nutrition, and pharmacological intervention remain important research initiatives. Developed Clinical pathway is multidisciplinary plans of best clinical practice for this specified groups of patients that aid in the coordination and delivery of high quality care. They are a documented sequence of clinical interventions that help a patient to move, progressively through a clinical experience to a desired outcome. Although there is a lot of heterogeneity in patients with ARDS, this suggested developed clinical pathway with alternatives was built depended on a lot of researches and evidence based medicine and nursing practices which may be helping these patients to improve outcomes, quality of life and decrease mortality.

Keywords: acute respiratory distress syndrome (ARDS), clinical pathway, clinical syndrome

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Authors: Maria Angelica Trak-Fellermeier, Alison K. Macchi, Rodolfo Galvan, Yolangel Hernandez, Thresia Gambon, Rebeca Martinez, Cristina Palacios

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Poor lifestyle habits, vitamin D deficiency, and inadequate calcium intake, particularly during the COVID-19 pandemic, may contribute to severe osteopenia in childhood, increasing future fractures and osteoporosis risk. We here present a case of osteopenia in a 13-year-old white, Hispanic, premenarchal girl who completed the baseline visit of the MetA-Bone Trial during the COVID-19 pandemic. The premenarchal girl has a family history of osteoporosis (maternal grandfather) but no previous fractures; moderate outdoor activity was <1 hour/day 3 times/week with 8 hours/day of sleep. Consumption of dairy products and vegetables was <1 serving/day. Lab blood tests confirmed vitamin D deficiency (serum 25(OH)D: 9 ng/L) and hyperphosphatemia (5.2 mg/dL); other tests were normal. DXA scan Z‐score was ‐2.2 SD (indicative of osteopenia by age and sex). The premenarchal girl was referred to a pediatrician, who confirmed the results, and prescribed a daily supplement with 2000 IU of vitamin D and 1000 mg of calcium. Seclusion during the COVID-19 pandemic may have contributed to the severity of the findings. Therefore, we recommend screening children undergoing growth spurts for vitamin D, calcium, and poor lifestyle habits during and after the pandemic.

Keywords: bone mass, vitamin D, puberty, Hispanic

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Authors: Szu-Yin Chu

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Self-determination has been particularly influential in obtaining a better quality of life through successful transition processes for students with disabilities. The development of self-determination through learning has raised attention at an early age. This study used a survey questionnaire to construct the understanding of the self-determination in Taiwan, learn the perspectives about the environmental and situational contexts where the respondents expect children to display self-determination skills in different cultures. Specifically, the research questions are: (a) What are Taiwanese families’ general perspectives about the development of foundations of self-determination for young children with special needs? and (b) how does families’ demographic background (i.e., income level, educational background) and child characteristics (i.e., age, emotional or behavior problems) impact Taiwanese families’ perspectives on the foundations of self-determination across three critical components (i.e., choice-making and problem-solving, self-regulation, and engagement) for young children with special needs? Data from 125 participants were gathered and analyzed. The findings suggested that Taiwanese families showed very positive attitudes toward promoting a foundation of self-determination for young children with special needs. Families’ income level and child’s severity of emotional/behavioral problems were two variables that were found to impact families’ views on their child’s foundational self-determination skills. Implications for future research and practice in supporting families to promote foundations of self-determination for young children with special needs will be provided.

Keywords: disabilities, self-determination, Taiwan, young children

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Authors: S. A. Hashemvarzi, A. Heidarianpour, Z. Fallahmohammadi, M. Pourghasem, M. Kaviani

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Introduction: Parkinson’s disease (PD) is a progressive neurodegenerative in the central nervous system characterized by the loss of dopaminergic neurons in the substantia nigra resulting in loss of dopamine release in the striatum. Non-drug treatment options such as Stem cell transplantation and exercise have been considered for treatment of Parkinson's disease. Purpose: The purpose of this study was to evaluate the effect of aerobic exercise after bone marrow stem cells transplantation on recovery of dopaminergic neurons and promotion of angiogenesis markers in the striatum of parkinsonian rats. Materials and Methods: 42 male Wistar rats were divided randomly into six groups: Normal (N), Sham (S), Parkinson’s (P), Stem cells transplanted Parkinson’s (SP), Exercised Parkinson’s (EP) and Stem cells transplanted + Exercised Parkinson’s (SEP). To create a model of Parkinson's, the striatum was destroyed by injection of 6-hydroxy-dopamine into the striatum through stereotaxic apparatus. Stem cells were derived from the bone marrow of femur and tibia of male rats with 6-8 weeks old. After cultivation, approximately 5×105 cells in 5 microliter of medium were injected into the striatum of rats through the channel. Aerobic exercise was included 8 weeks of running on the treadmill with a speed of 15 meters per minute. At the end, all subjects were decapitated and striatum tissues were separately isolated for measurement of vascular endothelial growth factor (VEGF), dopamine (DA) and tyrosine hydroxylase (TH) levels. Results: VEGF, DA and TH levels in the striatum of parkinsonian rats significantly increased in treatment groups (SP, EP and SEP), especially in SEP group compared to P group after treatment (P<0.05). Conclusion: The findings implicate that the BMSCs transplantation in combination with exercise would have synergistic effects leading to functional recovery, dopaminergic neurons recovery and promotion of angiogenesis marker in the striatum of parkinsonian rats.

Keywords: stem cells, treadmill training, neurotrophic factors, Parkinson

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Authors: Yasar Samet Gokceoglu, Ayse Nur Incesu, Furkan Okatar, Berk Nimetoglu, Serkan Bayram, Turgut Akgul

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Ankle syndesmosis injuries pose a significant challenge in orthopedic practice due to their potential for prolonged recovery and chronic ankle dysfunction. Accurate diagnosis and management of these injuries are essential for achieving optimal patient outcomes. The use of radiological methods, such as X-ray, computed tomography (CT), and magnetic resonance imaging (MRI), plays a vital role in the accurate diagnosis of syndesmosis injuries in the context of ankle fractures. Treatment options for ankle syndesmosis injuries vary, with surgical interventions such as screw fixation and suture-button implantation being commonly employed. The choice of treatment is influenced by the severity of the injury and the presence of associated fractures. Additionally, the mechanism of injury, such as pure syndesmosis injury or specific fracture types, can impact the stability and management of syndesmosis injuries. Ankle fractures with syndesmosis injury present a complex clinical scenario, requiring accurate diagnosis, appropriate reduction, and tailored management strategies. The interplay between the mechanism of injury, associated fractures, and treatment modalities significantly influences the outcomes of these challenging injuries. The long-term outcomes and patient satisfaction following ankle fractures with syndesmosis injury are crucial considerations in the field of orthopedics. Patient-reported outcome measures, such as the Foot and Ankle Outcome Score (FAOS), provide essential information about functional recovery and quality of life after these injuries. When diagnosing syndesmosis injuries, standard measurements, such as the medial clear space, tibiofibular overlap, tibiofibular clear space, anterior tibiofibular ratio (ATFR), and the anterior-posterior tibiofibular ratio (APTF), are assessed through radiographs and computed tomography (CT) scans. These parameters are critical in evaluating the presence and severity of syndesmosis injuries, enabling clinicians to choose the most appropriate treatment approach. Despite advancements in diagnostic imaging, challenges remain in accurately diagnosing and treating ankle syndesmosis injuries. Traditional diagnostic parameters, while beneficial, may not capture the full extent of the injury or provide sufficient information to guide therapeutic decisions. This gap highlights the need for exploring additional diagnostic parameters that could enhance the accuracy of syndesmosis injury diagnoses and inform treatment strategies more effectively. The primary goal of this research is to evaluate the usefulness of traditional radiographic measurements in comparison to new CT-based measurements for diagnosing ankle syndesmosis injuries. Specifically, this study aims to assess the accuracy of conventional parameters, including medial clear space, tibiofibular overlap, tibiofibular clear space, ATFR, and APTF, in contrast with the recently proposed CT-based measurements such as the delta and gamma angles. Moreover, the study intends to explore the relationship between these diagnostic parameters and functional outcomes, as measured by the Foot and Ankle Outcome Score (FAOS). Establishing a correlation between specific diagnostic measurements and FAOS scores will enable us to identify the most reliable predictors of functional recovery following syndesmosis injuries. This comparative analysis will provide valuable insights into the accuracy and dependability of CT-based measurements in diagnosing ankle syndesmosis injuries and their potential impact on predicting patient outcomes. The results of this study could greatly influence clinical practices by refining diagnostic criteria and optimizing treatment planning for patients with ankle syndesmosis injuries.

Keywords: ankle syndesmosis injury, diagnostic accuracy, computed tomography, radiographic measurements, Tibiofibular syndesmosis distance

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Authors: Rita Alfattal, Maryam Alfarhan, Adeeb M. Algaith, Buthaina Albash, Reem M. Elshafie, Asma Alshammari, Ahmad Alahmad, Fatima Dashti, Rasha Alsafi, Hind Alsharhan

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Defects of respiratory chain complex III (CIII) result in characteristic but rare mitochondrial disorders associated with distinct neuroradiological findings. The underlying molecular defects affecting mitochondrial CIII assembly factors are few and yet to be identified. LYRM7 assembly factor is required for proper CIII assembly where it acts as a chaperone for the Rieske iron‐sulfur (UQCRFS1) protein in the mitochondrial matrix and stabilizing it. We present here the seventeenth individual with LYRM7-associated mitochondrial leukoencephalopathy harboring a previously reported rare pathogenic homozygous LYRM 7 variant, c.2T>C, (p.Met1?). Like previously reported individuals, our 4-year-old male proband presented with recurrent metabolic and lactic acidosis, encephalopathy, and myopathy. Further, he has additional, previously unreported features, including an acute stroke like episode with bilateral central blindness and optic neuropathy, recurrent hyperglycemia and hypertension associated with metabolic crisis. However, he has no signs of psychomotor regression. He has been stable clinically with residual left-sided reduced visual acuity and amblyopia, and no more metabolic crises for 2-year-period while on the mitochondrial cocktail. Although the reported brain MRI findings in other affected individuals are homogenous, it is slightly different in our index, revealing evidence of bilateral almost symmetric multifocal periventricular T2 hyperintensities with hyperintensities of the optic nerves, optic chiasm, and corona radiata but with no cavitation or cystic changes. This report describes new clinical and radiological findings of LYRM7-associated disease. The report also summarizes the clinical and molecular data of previously reported individuals describing the full phenotypic spectrum.

Keywords: LYRM7 gene defect, mitochondrial disease, , lactic acidosis, , genetic disorder

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Authors: Mythri G., Manjunath ML, Girish Babu M., Shireen Swaliha Quadri

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Background: The increase in diabetes among the elderly is of concern because in addition to the wide range of traditional diabetes complications, evidence has been growing that diabetes is associated with increased risk of cognitive decline. Aims and Objectives: To find out if there is any association between blood sugar levels and short-term and working memory status in patients of type 2 diabetes. Materials and Methods: The study was carried out in 200 individuals aged between 40-65 years consisting of 100 diagnosed cases of Type 2 Diabetes Mellitus and 100 non-diabetics from OPD of Mc Gann Hospital, Shivamogga. Rye’s Auditory Verbal Learning Test, Verbal Fluency Test and Visual Reproduction Test, Working Digit Span Test and Validation Span Test were used to assess short-term and working memory. Fasting and Post Prandial blood sugar levels were estimated. Statistical analysis was done using SPSS 21. Results: Memory test scores of type 2 diabetics were significantly reduced (p < 0.001) when compared to the memory scores of age and gender matched non-diabetics. Fasting blood sugar levels were found to have a negative correlation with memory scores for all 5 tests: AVLT (r=-0.837), VFT (r=-0.888), VRT(r=-0.787), WDST (r=-0.795) and VST (r=-0.943). Post- Prandial blood sugar levels were found to have a negative correlation with memory scores for all 5 tests: AVLT (r=-0.922), VFT (r=-0.848), VRT(r=-0.707),WDST (r=-0.729) and VST (r=-0.880) Memory scores in all 5 tests were found to be negatively correlated with the FBS and PPBS levels in diabetic patients (p < 0.001). Conclusion: The decreased memory status in diabetic patients may be due to many factors like hyperglycemia, vascular disease, insulin resistance, amyloid deposition and also some of the factor combine to produce additive effects like, type of diabetes, co-morbidities, age of onset, duration of the disease and type of therapy. These observed effects of blood sugar levels of diabetics on memory status are of potential clinical importance because even mild cognitive impairment could interfere with todays’ activities.

Keywords: diabetes, cognition, diabetes, HRV, respiratory medicine

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Authors: Dhananjay W. Bansod, Santosh Phad

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Non-Communicable Diseases (NCD) are major contributing factors to the disease burden in the world as well as in India. With a growing proportion of older persons in India gives rise to several challenges. With the advancement of age, elderly is exposed to various kinds of health problems more specifically NCDs. Therefore, an effort has been made to examine the prevalence of NCDs among older persons and its treatment-seeking behaviour, also it is tried to explore the association between the NCDs and its effect on the overall wellbeing of older persons. Data used from “Building Knowledge Base of Population Ageing Survey” conducted in 2011 in seven states of India. Six chronic diseases used (non-communicable diseases) namely Arthritis, Hypertension, Cataract, Diabetes, Asthma and Heart diseases to understand the issues related to NCDs. Also seen the effect of NCDs on the wellbeing of the elderly, the subjective well-being consists of nine questions from which SUBI score generated for mental health status, which ranges from 9 to 27. This Index indicates that lower the score better is the mental health status. Further, this index modified and generated three categories of Better (9-15), Average (16-20) and Worse (21-27). The reliability analysis is carried out with the coefficient (Cronbach’s alpha) of the scale was 0.8884. The result shows that Orthopedic / musculoskeletal ailments involving arthritis, rheumatism and osteoarthritis are the most common type of ailment followed by hypertension. Two-thirds of the elderly reported suffering from at least one chronic ailment. Most chronic illness conditions received some form of treatment and mainly depend on public health facilities. Financial insecurity is the primary obstruction in seeking treatment for most of the chronic ailments which typically require a longer duration of medication and repeated medical consultations, both having significant economic implications. According to SUBI index, only 15 per cent of the elderly are in Better mental health status, and one-third of the elderly are with the worse score. Elderly with the ailments like Cataract, Asthma and Arthritis have worse mental health. It depicts that the burden of disease is more among the elderly and it is directly affecting the overall wellbeing of older persons.

Keywords: NCD, well-being, older person, India

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Authors: Seyed Abbas Tabatabaei, Saeid Amini, Hamid Reza Ghafouri

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One of the most important factors in flexible pavement failure is the lack of proper drainage along the roads. Water on the Paving Systems is one of the main parameters of pavement failure. Though, if water is discharged without delay and prior to discharge in order to prevent damaging the pavement the lifetime of the pavement will be considerably increased. In this study, duration of water stay and materials properties in pavement systems and the effects of aggregate gradation, and hydraulic conductivity of the drainage rate and Effects of subsurface drainage systems, drainage and reduction in the lifetime of the pavement have been studied. The study conducted in accordance with the terms offered can be concluded as under. The more hydraulic conductivity the less drainage time and the use of sub-surface drainage system causes two to three times of the pavement lifetime. In this research it has been tried by study and calculate the drained and undrained pavements lifetime by considering the effectiveness of water and drainage coefficient on flexible materials modulus and by using KENLAYER software to compare the present value cost of these pavements has been paid for a 20 year lifetime design. In this study, 14 pavement sections have been considered, of which 7 sections have been drained and 7 other not. Results show that drained pavements have more initial costs but the failure severity is so little in them and have longer lifetime for a 20 year lifetime design, the drained pavements seem so economic.

Keywords: drainage, base and sub-base, elasticity modulus, aggregation

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Authors: Ahmed Elbeheri, Tarek Zayed

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Steel bridges deterioration has been one of the problems in North America for the last years. Steel bridges deterioration mainly attributed to the difficult weather conditions. Steel bridges suffer fatigue cracks and corrosion, which necessitate immediate inspection. Visual inspection is the most common technique for steel bridges inspection, but it depends on the inspector experience, conditions, and work environment. So many Non-destructive Evaluation (NDE) models have been developed use Non-destructive technologies to be more accurate, reliable and non-human dependent. Non-destructive techniques such as The Eddy Current Method, The Radiographic Method (RT), Ultra-Sonic Method (UT), Infra-red thermography and Laser technology have been used. Digital Image processing will be used for Corrosion detection as an Alternative for visual inspection. Different models had used grey-level and colored digital image for processing. However, color image proved to be better as it uses the color of the rust to distinguish it from the different backgrounds. The detection of the rust is an important process as it’s the first warning for the corrosion and a sign of coating erosion. To decide which is the steel element to be repainted and how urgent it is the percentage of rust should be calculated. In this paper, an image processing approach will be developed to detect corrosion and its severity. Two models were developed 1st to detect rust and 2nd to detect rust percentage.

Keywords: steel bridge, bridge inspection, steel corrosion, image processing

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Authors: Amir Hamed Abd-Elrahman, Mohamed Bessat

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450 fattening cattle and buffaloes aged from 6 to 30 months old were examined clinically to determine patterns of occurrence of hemoparasitic diseases and the efficacy of different anti theilerial drugs. 420 animals examined clinically to determine relation between different outbreak of FMD and LSD in Egypt 2012- 2013 and haemoprotozoal diseases. The clinical pictures of haemoprotozoal diseases are variable, from sever to mild, depending on the endemic situation which governed by frequent previous exposure and tick infestation. B. bigemina is the most common haemoprotozoal diseases in the area of study and the infection rate in a descending manner for B. bigemina, A. marginale and T. annulata were 20%, 9.7% and 6.6% respectively. The species susceptibility of B. bigemina and T. annulata showed a higher incidence in cattle than buffaloes while in A. marginale showed a little difference in cattle and buffaloes susceptibility by 10% and 9.2% respectively. The breed susceptibility of B. bigemina and T. annulata showed a higher incidence in crossbred cattle than native baladi cattle while A. marginale showed a higher incidence in native baladi cattle than crossbred cattle. The maximal infection rates were recorded during summer months. The infection rates of B. bigemina and A. marginale were higher among young animals over 6 months and declined above 2 year old while in T. annulata the infection rates were lower among young animals and increased above 2 year old. The case fatality of T. annulata was higher than A. marginale and B. bigemina. Efficacy of different anti theilerial drugs were studied, cure rate of chlouroquine group and Butalex group were 60% disappearance of schizont in lymph node smear after 9 days and 5 days respectively while cure rate of Oxytetracycline Dihydrate (Alamycine) group 20% with disappearance of schizont in lymph node smear after 14 days. FMD and LSD infection enhancement the occurrence of bovine haemoprotozoal diseases.

Keywords: Babesia bigemina, Anaplasma marginale, Theileria annulata, FMD, LSD, ephemeral fever

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Authors: Hala Raslan, Noha Eltaweel, Hanaa Rasmi, Solaf Kamel, May Magdy, Sherif Ismail, Khalda Amr

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Introduction: Rheumatoid arthritis (RA) is an inflammatory, autoimmune disorder with progressive joint damage. Osteoarthritis (OA) is a degenerative disease of the articular cartilage that shows multiple clinical manifestations or symptoms resembling those of RA. Genetic predisposition is believed to be a principal etiological factor for RA and OA. In this study, we aimed to measure the expression of the top deregulated miRNAs that might be the cause of pathogenesis in both diseases, according to our latest NGS analysis. Six of the deregulated miRNAs were selected as they had multiple target genes in the RA pathway, so they are more likely to affect the RA pathogenesis.Methods: Eighty cases were recruited in this study; 45 rheumatoid arthiritis (RA), 30 osteoarthiritis (OA) patients, as well as 20 healthy controls. The selection of the miRNAs from our latest NGS study was done using miRwalk according to the number of their target genes that are members in the KEGG RA pathway. Total RNA was isolated from plasma of all recruited cases. The cDNA was generated by the miRcury RT Kit then used as a template for real-time PCR with miRcury Primer Assays and the miRcury SYBR Green PCR Kit. Fold changes were calculated from CT values using the ΔΔCT method of relative quantification. Results were compared RA vs Controls and OA vs Controls. Target gene prediction and functional annotation of the deregulated miRNAs was done using Mienturnet. Results: Six miRNAs were selected. They were miR-15b-3p, -128-3p, -194-3p, -328-3p, -542-3p and -3180-5p. In RA samples, three of the measured miRNAs were upregulated (miR-194, -542, and -3180; mean Rq= 2.6, 3.8 and 8.05; P-value= 0.07, 0.05 and 0.01; respectively) while the remaining 3 were downregulated (miR-15b, -128 and -328; mean Rq= 0.21, 0.39 and 0.6; P-value= <0.0001, <0.0001 and 0.02; respectively) all with high statistical significance except miR-194. While in OA samples, two of the measured miRNAs were upregulated (miR-194 and -3180; mean Rq= 2.6 and 7.7; P-value= 0.1 and 0.03; respectively) while the remaining 4 were downregulated (miR-15b, -128, -328 and -542; mean Rq= 0.5, 0.03, 0.08 and 0.5; P-value= 0.0008, 0.003, 0.006 and 0.4; respectively) with statistical significance compared to controls except miR-194 and miR-542. The functional enrichment of the selected top deregulated miRNAs revealed the highly enriched KEGG pathways and GO terms. Conclusion: Five of the studied miRNAs were greatly deregulated in RA and OA, they might be highly involved in the disease pathogenesis and so might be future therapeutic targets. Further functional studies are crucial to assess their roles and actual target genes.

Keywords: MiRNAs, expression, rheumatoid arthritis, osteoarthritis

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Authors: Mostafa Elbaba

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Because childhood renal diseases are grossly different compared to adult diseases, pediatric nephrology was founded as a specialty in 1965. Renal pathology specialty was introduced at the London Ciba Symposium in 1961. The history of renal pathology can be divided into two eras: one starting in the 1650s with the invention of the microscope, the second in the 1950s with the implementation of renal biopsy, and the presence of electron microscopy and immunofluorescence study. Prior to the 1950s, the study of diseased human kidneys was restricted to postmortem examination by gross pathology. In 1827, Richard Bright first described his triad of kidney disease, which was confirmed by morbid kidney changes at autopsy. In 1905 Friedrich Mueller coined the term “nephrosis” describing the inflammatory form of “degenerative” diseases, and later F. Munk added the term “lipoid nephrosis”. The most profound influence on renal diseases’ classification came from the publication of Volhard and Fahr in 1914. In 1899, Carl Max Wilhelm Wilms described Wilms' tumor of the kidneys in children. Chronic pyelonephritis was a popular renal diagnosis and the most common cause of uremia until the 1960s. Although kidney biopsy had been used early in the 1930s for renal tumors, the earliest reports of its use in the diagnosis of medical kidney disease were by Iversen and Brun in 1951, followed by Alwall in 1952, then by Pardo in 1953. The earliest intentional renal biopsies were done in 1944 by Nils Alwall, while the procedure was abandoned after the death of one of his 13 patients who biopsied. In 1950, Antonino Perez-Ara attempted renal biopsies, but his results were missed because of an unpopular journal publication. In the year 1951, Claus Brun and Poul Iverson developed the biopsy procedure using an aspiration technique. Popularizing renal biopsy practice is accredited to Robert Kark, who published his distinct work in 1954. He perfected the technique of renal biopsy in the prone position using the Vim-Silverman needle and used intravenous pyelography to improve the localization of the kidney.

Keywords: history, medicine, nephrology, pediatrics, pathology

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Authors: Aliseydi Bozkurt

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Objectives: Benign prostatic hyperplasia (BPH) is the most common benign disease, and prostate cancer (PC) is malign disease of the prostate gland. Transrectal ultrasound-guided biopsy (TRUS-bx) is one of the most important diagnostic tools in PC diagnosis. Identifying men at increased risk for having a biopsy detectable prostate cancer should consider prostate specific antigen density (PSAD), f/t PSA Ratio, an estimate of prostate volume. Method: We retrospectively studied 269 patients who had a prostate specific antigen (PSA) score of 4 or who had suspected rectal examination at any PSA level and received TRUS-bx between January 2015 and June 2018 in our clinic. TRUS-bx was received by 12 experienced urologists with 12 quadrants. Prostate volume was calculated prior to biopsy together with TRUS. Patients were classified as malignant and benign at the end of pathology. Age, PSA value, prostate volume in transrectal ultrasonography, corpuscle biopsy, biopsy pathology result, the number of cancer core and Gleason score were evaluated in the study. The success rates of PV, PSAD, and f/tPSA were compared in all patients and those with PSA 2.5-10 ng/mL and 10.1-30 ng/mL tp foresee prostate cancer. Result: In the present study, in patients with PSA 2.5-10 ng/ml, PV cut-off value was 43,5 mL (n=42 < 43,5 mL and n=102 > 43,5 mL) while in those with PSA 10.1-30 ng/mL prostate volüme (PV) cut-off value was found 61,5 mL (n=31 < 61,5 mL and n=36 > 61,5 mL). Total PSA values in the group with PSA 2.5-10 ng/ml were found lower (6.0 ± 1.3 vs 6.7 ± 1.7) than that with PV < 43,5 mL, this value was nearly significant (p=0,043). In the group with PSA value 10.1-30 ng/mL, no significant difference was found (p=0,117) in terms of total PSA values between the group with PV < 61,5 mL and that with PV > 61,5 mL. In the group with PSA 2.5-10 ng/ml, in patients with PV < 43,5 mL, f/t PSA value was found significantly lower compared to the group with PV > 43,5 mL (0.21 ± 0.09 vs 0.26 ± 0.09 p < 0.001 ). Similarly, in the group with PSA value of 10.1-30 ng/mL, f/t PSA value was found significantly lower in patients with PV < 61,5 mL (0.16 ± 0.08 vs 0.23 ± 0.10 p=0,003). In the group with PSA 2.5-10 ng/ml, PSAD value in patients with PV < 43,5 mL was found significantly higher compared to those with PV > 43,5 mL (0.17 ± 0.06 vs 0.10 ± 0.03 p < 0.001). Similarly, in the group with PSA value 10.1-30 ng/mL PSAD value was found significantly higher in patients with PV < 61,5 mL (0.47 ± 0.23 vs 0.17 ± 0.08 p < 0.001 ). The biopsy results suggest that in the group with PSA 2.5-10 ng/ml, in 29 of the patients with PV < 43,5 mL (69%) cancer was detected while in 13 patients (31%) no cancer was detected. While in 19 patients with PV > 43,5 mL (18,6%) cancer was found, in 83 patients (81,4%) no cancer was detected (p < 0.001). In the group with PSA value 10.1-30 ng/mL, in 21 patients with PV < 61,5 mL (67.7%) cancer was observed while only in10 patients (32.3%) no cancer was seen. In 5 patients with PV > 61,5 mL (13.9%) cancer was found while in 31 patients (86.1%) no cancer was observed (p < 0.001). Conclusions: Identifying men at increased risk for having a biopsy detectable prostate cancer should consider PSA, f/t PSA Ratio, an estimate of prostate volume. Prostate volume in PC was found lower.

Keywords: prostate cancer, prostate volume, prostate specific antigen, free/total PSA ratio

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Authors: S. Boonlertnirun, R. Suvannasara, K. Boonlertnirun

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Hypoxia has negative effects on growth and crop yield, its severity is so varied depending on crop growth stages, duration of hypoxia and crop species. The objective was to evaluate the sensitive growth stage and the duration of hypoxia negatively affecting growth and yield of waxy corn. Pot experiment was conducted using a split plot in randomized complete block with 3 growth stages: V3 (3-4 true leaves), V7 (7-8 true leaves), and R1 (silking stage), and three hypoxic durations: 6, 9, and 12 days, in an open–ended outdoor greenhouse during January to March 2013. The results revealed that different growth stages had significantly (p < 0.5) different responses to hypoxia, seeing that the sensitive growth stage affecting plant height, yield and yield components was mostly detected in V7 growth stage whereas leaf greenness and days to silking were sensitive to hypoxia at R1 growth stage. Different hypoxic durations significantly affected the yield and yield components, hypoxic duration of twelve days showed the most negative effect greater than the others. In this present study, it can be concluded that waxy corn plants were waterlogged at V7 growth stage for twelve days had the most negative effect on yield and yield components.

Keywords: hypoxia duration, waxy corn, growth stage, Zea mays L.

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Authors: Elena Pello, Martin Bobak, Yuri Nikitin

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In current issue we evaluated integration of magnesium with lipids; the attractive findings were obtained in men and women; the crucial ties of magnesium with total cholesterol in hypertensive men, with total cholesterol in concordance with low-density lipoprotein cholesterol in hypertensive women were disclosed; unanswered questions were trapped, difficulties were surmounted, and magnesium deficiency perseverance in pathogenesis of cardiovascular disease development was expressed; nutrients as well as risk factors may contribute to cardiovascular complications.

Keywords: dietary, magnesium, hypertension, lipids

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Authors: Iulia Crisan

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Objective: The present study investigates the cross-cultural validity of three North-American performance validity indicators (PVTs) by comparing base rates of failure (BRF) in Romanian and Canadian disability applicants. Methods: Three PVTs (Test of Memory Malingering Trial 1 [TOMM-1], Rey Fifteen Item Test free recall [Rey-15 FR], and Rey FR+Recognition [Rey COMB]) were administered to a heterogeneous Romanian clinical sample (N Ro =54) and a similar Canadian sample (N Can = 52). Patients were referred for assessment to determine the severity of their cognitive deficits. Results: We compared the BRF in both samples at various cutoffs. BRF on TOMM-1 at ≤ 43 was similar (Ro = 33.3% vs. Can = 40.4%); at ≤40, Ro = 22.2% vs. Can = 25.0%. Likewise, comparable BRF were observed on Rey-15 FR at ≤ 8 (Ro = 7.4% vs. Can = 11.5%) and ≤ 11 (Ro = 27.8% vs. Can = 23.1%). However, the Romanian sample produced significantly higher failure rates on the Rey COMB at variable cutoffs (p <.05), possibly because Romanian patients were significantly older than the Canadian sample. Conclusion: Our findings offer proof of concept for the cross-cultural validity of the TOMM and Rey-15 FR. At the same time, they serve as a reminder that the generalizability of PVT cutoffs to different populations should not be assumed but verified empirically. Employing the TOMM as a criterion measure for newly developed PVTs is discussed.

Keywords: performance validity indicators, cross-cultural validity, failure base rates, clinical samples, cognitive dysfunction, TOMM-1, Rey-15, Rey COMB

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Authors: Mansi Srivastava, Uzma Saqib, Adnan Naim, Anjali Roy, Dongfang Liu, Deepak Bhatnagar, Ravinder Ravinder, Mirza S. Baig

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Macrophages polarize to proinflammatory M1 or anti-inflammatory M2 states with distinct physiological functions. This transition within the M1 to M2 phenotypes decides the nature, duration, and severity of an inflammatory response. However, inspite of a substantial understanding of the fate of these phenotypes, the underlying molecular mechanisms are not well understood. We have investigated the role of Neuronal nitric oxide synthase (NOS1) mediated regulation of Activator protein 1 (AP-1) transcription factor in macrophages as a critical effector of macrophage phenotypic change. Activator protein 1 (AP-1) is a group of dimeric transcription factors composed of jun, Fos, and ATF family proteins. We determined that NOS1-derived nitric oxide (NO) facilitate Fos and jun interaction which induces IL12 & IL23 expression. Pharmacological inhibition of NOS1 inhibits Fos and jun interaction but increases ATF2 and Fos dimerization. Switching of Fos and jun dimer to ATF2 and jun dimerization switches phenotype from IL–12high IL-23high IL-10low to IL–12low IL-23lowIL-10high phenotype, respectively. Together, these findings highlight a key role of the TLR4-NOS1-AP1 signaling axis in regulating macrophage polarization.

Keywords: inflammation, macrophage, lipopolysaccharide (LPS), proinflammatory cytokines, activator protein 1 (AP-1), neuronal nitric oxide synthase (NOS1)

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Authors: R. Alramyan, S. Alsalamah, R. Alrashed, R. Alakel, F. Altheyeb, M. Alessa

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Background: Nutritional support with total parenteral nutrition (TPN) is usually commenced with hematopoietic stem cell transplantation (HSCT) patients. However, it has its benefits and risks. Complications related to central venous catheter such as infections, and metabolic disturbances, including abnormal liver function, is usually of concern in such patients. Methods: A retrospective charts review of all pediatric patients who underwent HSCT between the period 2015-2018 in a tertiary hospital in Riyadh, Saudi Arabia. Patients' demographics, types of conditioning, type of nutrition, and patients' outcomes were collected. Statistical analysis was conducted using SPSS version 22. Frequencies and percentages were used to describe categorical variables. Mean, and standard deviation were used for continuous variables. A P value of less than 0.05 was considered as statically significant. Results: a total of 162 HSCTs were identified during the period mentioned. Indication of allogenic transplant included hemoglobinopathy in 50 patients (31%), acute lymphoblastic leukemia in 21 patients (13%). TPN was used in 96 patients (59.30%) for a median of 14 days, nasogastric tube feeding (NGT) in 16 (9.90%) patients for a median of 11 days, and 71 of patients (43.80%) were able to tolerate oral feeding. Out of the 96 patients (59.30%) who were dependent on TPN, 64 patients (66.7%) had severe mucositis in comparison to 17 patients (25.8%) who were either on NGT or tolerated oral intake. (P-value= 0.00). Sinusoidal obstruction syndrome (SOS) was seen in 14 patients (14.6%) who were receiving TPN compared to none in non-TPN patients (P=value 0.001). Moreover, majority of patients who had SOS received myeloablative conditioning therapy for non-malignant disease (hemoglobinopathy). However, there were no statistically significant differences in Graft-vs-Host Disease (both acute and chronic), bacteremia, and patient outcome between both groups. Conclusions: Nutritional support using TPN is used in majority of patients, especially post-myeloablative conditioning associated with severe mucositis. TPN was associated with VOD, especially in hemoglobinopathy patients who received myeloablative therapy. This may emphasize on use of preventative measures such as fluid restriction, use of diuretics, or defibrotide in high-risk patients.

Keywords: hematopoeitic stem cell transplant, HSCT, stem cell transplant, sinusoidal obstruction syndrome, total parenteral nutrition

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Authors: Antonia Egli, Theo Lynn, Pierangelo Rosati, Gary Sinclair

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The World Health Organization (WHO) defines vaccine hesitancy as the postponement or complete denial of vaccines and estimates a direct linkage to approximately 1.5 million avoidable deaths annually. This figure is not immune to public health developments, as has become evident since the global spread of COVID-19 from Wuhan, China in early 2020. Since then, the proliferation of influential, but oftentimes inaccurate, outdated, incomplete, or false vaccine-related information on social media has impacted hesitancy levels to a degree described by the WHO as an infodemic. The COVID-19 pandemic and related vaccine hesitancy levels have in 2022 resulted in the largest drop in childhood vaccinations of the 21st century, while the prevalence of online stigma towards vaccine hesitant consumers continues to grow. Simultaneously, a second disease has risen to global importance: Monkeypox is an infection originating from west and central Africa and, due to racially motivated online hate, was in August 2022 set to be renamed by the WHO. To better understand public reactions towards two viral infections that became global threats to public health no two years apart, this research examines user replies to threads published by the WHO on Twitter. Replies to two Tweets from the @WHO account declaring COVID-19 and Monkeypox as ‘public health emergencies of international concern’ on January 30, 2020, and July 23, 2022, are gathered using the Twitter application programming interface and user mention timeline endpoint. Research methodology is unique in its analysis of stigmatizing, racist, and hateful content shared on social media within the vaccine discourse over the course of two disease outbreaks. Three distinct analyses are conducted to provide insight into (i) the most prevalent topics and sub-topics among user reactions, (ii) changes in sentiment towards the spread of the two diseases, and (iii) the presence of stigma, racism, and online hate. Findings indicate an increase in hesitancy to accept further vaccines and social distancing measures, the presence of stigmatizing content aimed primarily at anti-vaccine cohorts and racially motivated abusive messages, and a prevalent fatigue towards disease-related news overall. This research provides value to non-profit organizations or government agencies associated with vaccines and vaccination programs in emphasizing the need for public health communication fitted to consumers' vaccine sentiments, levels of health information literacy, and degrees of trust towards public health institutions. Considering the importance of addressing fears among the vaccine hesitant, findings also illustrate the risk of alienation through stigmatization, lead future research in probing the relatively underexamined field of online, vaccine-related stigma, and discuss the potential effects of stigma towards vaccine hesitant Twitter users in their decisions to vaccinate.

Keywords: social marketing, social media, public health communication, vaccines

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Authors: Li-Ju Chen, Hsiang-Lin Chan, Hsin-Yi Kathy Cheng, Hui-Ju Chen

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Stereotype behavior is one of the maladaptive syndromes of the individuals with autism. Most of the previous researches focused on the stereotype behavior with stimulating type, while less on the stereotype behavior about cognition (This research names it cognitive stereotype behavior; CSB). This research explored CSB and the rationality to explain CSB with imprinting phenomenon. After excluding the samples without CSB described, the data that came from 271 individuals with autism were recruited and analyzed with quantitative and qualitative analyses. This research discovers that : (1) Most of the individuals with autism originally came out CSB at 3 years old and more than a half of them appeared before 4 years old; The average age which firstly came out CSB was 6.10 years old, the average time insisting or ossifying CSB was 31.71 minutes each time and the average longest time which they last was 358.35 minutes (5.97 hours). (2) CSB demonstrates various aspects, this research classified them into 4 fields with 26 categories. They were categorized into sudden CSB or habitual CSB by imprinting performance. (3) Most of the autism commented that their CSBs were not necessary but they could not control them well. One-third of them appeared CSB suddenly and the first occurrence accompanied a strong emotional or behavioral response. (4) Whether respondent is the person with autism himself/herself or not was the critical element: on the awareness of the severity degree, disturbance degree, and the emotional /behavioral intensity at the first-time CSB happened. This study concludes imprinting could reasonably explain the phenomenon CSB forms. There are implications leading the individuals with autism and their family to develop coping strategies to promote individuals with autism having a better learning accomplishment and life quality in their future.

Keywords: autism, cognitive stereotype behavior, constructivism, imprinting, stereotype

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Authors: Seyed Abbas Tabatabaei, Afshin Ghanbarzadeh, Mehdi Abidizadeh

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Nowadays the subject of road traffic accidents and the high social and economic costs due to them is the most fundamental problem that experts and providers of transport and traffic brought to a challenge. One of the most effective measures is to enhance the skid resistance of road surface. This research aims to study the intersection of one case in Ahwaz and the effect of increasing the skid resistance in reducing pedestrian injuries in accidents at intersections. In this research the device was developed to measure the coefficient of friction and tried the rules and practices of it have a high similarity with the Locked Wheel Trailer. This device includes a steel frame, wheels, hydration systems, and force gauge. The output of the device is that the force gauge registers. By investigate this data and applying the relationships relative surface coefficient of friction is obtained. Friction coefficient data for the current state and the state of the new pavement are obtained and plotted on the graphs based on the graphs we can compare the two situations and speed at the moment of collision between the two modes are compared. The results show that increasing the coefficient of friction to what extent can be effective on the severity and number of accidents.

Keywords: intersection, coefficient of friction, skid resistance, locked wheels, accident, pedestrian

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Authors: Kenichi Yamahara, Makiko Ohshima, Shunsuke Ohnishi, Hidetoshi Tsuda, Akihiko Taguchi, Toshihiro Soma, Hiroyasu Ogawa, Jun Yoshimatsu, Tomoaki Ikeda

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We have previously reported the therapeutic potential of rat fetal membrane(FM)-derived mesenchymal stem cells (MSCs) using various rat models including hindlimb ischemia, autoimmune myocarditis, glomerulonephritis, renal ischemia-reperfusion injury, and myocardial infarction. In this study, 1) we isolated and characterized MSCs from human amnion and chorion; 2) we examined their differences in the expression profile of growth factors and cytokines; and 3) we investigated the therapeutic potential and difference of these MSCs using murine hindlimb ischemia and acute graft-versus-host disease (GVHD) models. Isolated MSCs from both amnion and chorion layers of FM showed similar morphological appearance, multipotency, and cell-surface antigen expression. Conditioned media obtained from amnion- and chorion-derived MSCs inhibited cell death caused by serum starvation or hypoxia in endothelial cells and cardiomyocytes. Amnion and chorion MSCs secreted significant amounts of angiogenic factors including HGF, IGF-1, VEGF, and bFGF, although differences in the cellular expression profile of these soluble factors were observed. Transplantation of human amnion or chorion MSCs significantly increased blood flow and capillary density in a murine hindlimb ischemia model. In addition, compared to human chorion MSCs, human amnion MSCs markedly reduced T-lymphocyte proliferation with the enhanced secretion of PGE2, and improved the pathological situation of a mouse model of GVHD disease. Our results highlight that human amnionand chorion-derived MSCs, which showed differences in their soluble factor secretion and angiogenic/immuno-suppressive function, could be ideal cell sources for regenerative medicine.

Keywords: amnion, chorion, fetal membrane, mesenchymal stem cells

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Authors: Gehan Hussein, Hala Agha, Rasha Abdelraof, Marina George, Antoine Fakhri

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Background: β-Thalassemia major (TM) and sickle cell disease (SCD) are inherited hemoglobin disorders resulting in chronic hemolytic anemia. Cardiovascular involvement is an important cause of morbidity and mortality in these groups of patients. The narrow border is between overt myocardial dysfunction and clinically silent left ventricular (LV) and / or right ventricular (RV) dysfunction in those patients. 3 D Speckle tracking echocardiography (3D STE) is a novel method for the detection of subclinical myocardial involvement. We aimed to study myocardial affection in SCD and TM using 3D STE, comparing it with conventional echocardiography, correlate it with serum ferritin level and lactate dehydrogenase (LDH). Methodology: Thirty SCD and thirty β TM patients, age range 4-18 years, were compared to 30 healthy age and sex matched control group. Cases were subjected to clinical examination, laboratory measurement of hemoglobin level, serum ferritin, and LDH. Transthoracic color Doppler echocardiography, 3D STE, tissue Doppler echocardiography, and aortic speckle tracking were performed. Results: significant reduction in global longitudinal strain (GLS), global circumferential strain (GCS), and global area strain (GAS) in SCD and TM than control (P value <0.001) there was significantly lower aortic speckle tracking in patients with TM and SCD than control (P value< 0.001). LDH was significantly higher in SCD than both TM and control and it correlated significantly positive mitral inflow E, (p value:0.022 and 0.072. r: 0.416 and -0.333 respectively) lateral E/E’ (p value.<0.001and 0.818. r. 0.618 and -0. 044.respectively) and septal E/E’ (p value 0.007 and 0.753& r value 0.485 and -0.060 respectively) in SCD but not TM and significant negative correlation between LDH and aortic root speckle tracking (value 0.681& r. -0.078.). The potential diagnostic accuracy of LDH in predicting vascular dysfunction as represented by aortic root GCS with a sensitivity 74% and aortic root GCS was predictive of LV dysfunction in SCD patients with sensitivity 100% Conclusion: 3D STE LV and RV systolic dysfunction in spite of their normal values by conventional echocardiography. SCD showed significantly lower right ventricular dysfunction and aortic root GCS than TM and control. LDH can be used to screen patients for cardiac dysfunction in SCD, not in TM

Keywords: thalassemia major, sickle cell disease, 3d speckle tracking echocardiography, LDH

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Authors: Izabela P. Vatanabe, Rafaela Peron, Patricia Manzine, Marcia R. Cominetti

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Introduction: Considering the increase in life expectancy of world population, there is an emerging concern in health services to allocate better care and care to elderly, through promotion, prevention and treatment of health. It has been observed that frailty syndrome is prevalent in elderly people worldwide and this complex and heterogeneous clinical syndrome consist of the presence of physical frailty associated with cognitive dysfunction, though in absence of dementia. This can be characterized by exhaustion, unintentional weight loss, decreased walking speed, weakness and low level of physical activity, in addition, each of these symptoms may be a predictor of adverse outcomes such as hospitalization, falls, functional decline, institutionalization, and death. Cognitive frailty is a recent concept in literature, which is defined as the presence of physical frailty associated with mild cognitive impairment (MCI) however in absence of dementia. This new concept has been considered as a subtype of frailty, which along with aging process and its interaction with physical frailty, accelerates functional declines and can result in poor quality of life of the elderly. MCI represents a risk factor for Alzheimer's disease (AD) in view of high conversion rate for this disease. Comorbidities and physical frailty are frequently found in AD patients and are closely related to heterogeneity and clinical manifestations of the disease. The decreased platelets ADAM10 levels in AD patients, compared to cognitively healthy subjects, matched by sex, age and education. Objective: Based on these previous results, this study aims to evaluate whether ADAM10 platelet levels of could act as a biomarker of cognitive frailty. Methods: The study was approved by Ethics Committee of Federal University of São Carlos (UFSCar) and conducted in the municipality of São Carlos, headquarters of Federal University of São Carlos (UFSCar). Biological samples of subjects were collected, analyzed and then stored in a biorepository. ADAM10 platelet levels were analyzed by western blotting technique in subjects with MCI and compared to subjects without cognitive impairment, both with and without presence of frailty. Statistical tests of association, regression and diagnostic accuracy were performed. Results: The results have shown that ADAM10/β-actin ratio is decreased in elderly individuals with cognitive frailty compared to non-frail and cognitively healthy controls. Previous studies performed by this research group, already mentioned above, demonstrated that this reduction is still higher in AD patients. Therefore, the ADAM10/β-actin ratio appears to be a potential biomarker for cognitive frailty. The results bring important contributions to an accurate diagnosis of cognitive frailty from the perspective of ADAM10 as a biomarker for this condition, however, more experiments are being conducted, using a high number of subjects, and will help to understand the role of ADAM10 as biomarker of cognitive frailty and contribute to the implementation of tools that work in the diagnosis of cognitive frailty. Such tools can be used in public policies for the diagnosis of cognitive frailty in the elderly, resulting in a more adequate planning for health teams and better quality of life for the elderly.

Keywords: ADAM10, biomarkers, cognitive frailty, elderly

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Authors: Muhammad Fayyaz Nazir, Ellen Wayenberg, Shahzadaah Faahed Qureshi

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Introduction: The study is based on the Contextual Interaction Theory (CIT) constructs to explore the role of policy actors in implementing the COVID-19 Disease Prevention and Control (DP&C) Policy. The study analyzes the role of healthcare workers' contextual factors, such as cognition, motives, and resources, and their interactions in implementing Social Distancing (SD). In this way, we test a two actors policy implementation theory, i.e., the CIT in a three-actor context. Methods: Data was collected through document analysis and semi-structured interviews. For a qualitative study design, interviews were conducted with questions on cognition, motives, and resources from the healthcare workers involved in implementing SD in the local context in Multan – Pakistan. The possible interactions resulting from contextual factors of the policy actors – healthcare workers were identified through framework analysis protocol guided by CIT and supported by trustworthiness criterion and data saturation. Results: This inquiry resulted in theory application, addition, and enrichment. The theoretical application in the three actor's contexts illustrates the different levels of motives, cognition, and resources of healthcare workers – senior administrators, managers, and healthcare professionals. The senior administrators working in National Command and Operations Center (NCOC), Provincial Technical Committees (PTCs), and Districts Covid Teams (DCTs) were playing their role with high motivation. They were fully informed about the policy and moderately resourceful. The policy implementors: healthcare managers working on implementing the SD within their respective hospitals were playing their role with high motivation and were fully informed about the policy. However, they lacked the required resources to implement SD. The target medical and allied healthcare professionals were moderately motivated but lack of resources and information. The interaction resulted in cooperation and the need for learning to manage the future healthcare crisis. However, the lack of resources created opposition to the implementation of SD. Objectives of the Study: The study aimed to apply a two actors theory in a multi actors context. We take this as an opportunity to qualitatively test the theory in a novel situation of the Covid-19 pandemic and make way for its quantitative application by designing a survey instrument so that implementation researchers can apply CIT through multivariate analyses or higher-order statistical modeling. Conclusion: Applying two actors' implementation theory in exploring a complex case of healthcare intervention in three actors context is a unique work that has never been done before, up to the best of our knowledge. So, the work will contribute to the policy implementation studies by applying, extending, and enriching an implementation theory in a novel case of the Covi-19 pandemic, ultimately fulfilling the gap in implementation literature. Policy institutions and other low or middle-income countries can learn from this research and improve SD implementation by working on the variables with weak significance levels.

Keywords: COVID-19, disease prevention and control policy, implementation, policy actors, social distancing

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Authors: Kaycee Bills

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Studies have demonstrated that middle and high school students with disabilities are more likely to experience bullying than other student groups. The high rates of bullying victimization observed among youth with disabilities can result in severe socio-emotional consequences. These socio-emotional consequences often manifest in detrimental impacts on the students’ personal relationships. Past studies have indicated that participating in extracurricular athletic activities can have several socio-emotional benefits for students with disabilities. Given the findings of past studies demonstrating the positive relationship between mental health and participation in sports among students with disabilities, it is possible that participating in athletics could have a moderating relationship on the severity of the impact that bullying has on a student’s relationships with family and friends. Using the National Crime Victimization Survey/School Crime Supplement (NCVS/SCS), this study employs an ordinal logistic regression to determine if participation in extracurricular athletic activities mitigates the damaging impact bullying has on the personal relationships with friends and family among students who have disabilities. This study identified statistically significant results suggesting that students with disabilities who participate in athletics reported reduced levels of negative personal relationships resulting from bullying compared to their peers who did not participate in athletics.

Keywords: disability, inclusion, bullying, relationships

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Authors: Daniel Aberdam

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Haploinsufficiency of PAX6 in humans is the main cause of congenital aniridia, a rare eye disease characterized by reduced visual acuity. Patients have also progressive disorders including cataract, glaucoma and corneal abnormalities making their condition very challenging to manage. Aniridia-related keratopathy (ARK), caused by a combination of factors including limbal stem-cell deficiency, impaired healing response, abnormal differentiation, and infiltration of conjunctival cells onto the corneal surface, affects up to 95% of patients. It usually begins in the first decade of life resulting in recurrent corneal erosions, sub-epithelial fibrosis with corneal decompensation and opacification. Unfortunately, current treatment options for aniridia patients are currently limited. Although animal models partially recapitulate this disease, there is no in vitro cellular model of AKT needed for drug/therapeutic tools screening and validation. We used genome editing (CRISPR/Cas9 technology) to introduce a nonsense mutation found in patients into one allele of the PAX6 gene into limbal stem cells. Resulting mutated clones, expressing half of the amount of PAX6 protein and thus representative of haploinsufficiency were further characterized. Sequencing analysis showed that no off-target mutations were induced. The mutated cells displayed reduced cell proliferation and cell migration but enhanced cell adhesion. Known PAX6 targets expression was also reduced. Remarkably, addition of soluble recombinant PAX6 protein into the culture medium was sufficient to activate endogenous PAX6 gene and, as a consequence, rescue the phenotype. It strongly suggests that our in vitro model recapitulates well the epithelial defect and becomes a powerful tool to identify drugs that could rescue the corneal defect in patients. Furthermore, we demonstrate that the homeotic transcription factor Pax6 is able to be uptake naturally by recipient cells to function into the nucleus.

Keywords: Pax6, crispr/cas9, limbal stem cells, aniridia, gene therapy

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