Challenging Issues Facing STEM Advancement In The UAE Society – A Report On Down Syndrome

Understanding Current Challenges in STEM Advancement in Science, Health and Medicine

U.A.E. is one of the new countries, which was developed in 1971. It has a vast population with dynamic societies. Cases of Down Syndrome are increasing rapidly in U.A.E. as compared to the other countries in the world. There are several diseases in adults which are causing worries (Cancer, Diabetes, Heart attack) but, unfortunately, diseases in fetus or child (Down Syndrome) has also caused worries among all. The government and health ministry face challenges due to this disease and are working on it.

What Is Down Syndrome?

Down Syndrome is a genetic disorder. It occurs mainly in newborns and lasts throughout the entire life. It is a genetic disorder which happens in chromosome 21 in humans (mainly due to trisomy in chromosome 21). It was termed ‘Down’ after Dr. Langdon Down discovered it in 1862. The ratio in U.A.E. is 1:319 (Aburawi et. al., 2015) live births as compared to the entire world, which is 1:700 (Zemel et. al. , 2015).

Instead of creating two copies of chromosome 21, three copies gets created in fetus. The number of chromosomes increases from 46 to 47 in each cell. It represents 95% of total cases of Down Syndrome.

Chromosome number 21 is dislocated and moves to another chromosome (usually chromosome 14), but the number of chromosomes remains 46. It represents 4% of total cases of Down Syndrome out of which one half is hereditary and the other half is sporadic.

It has two types of cells. One which contains 46 chromosomes while other contains 47 chromosomes. It represents 1% of total cases of Down Syndrome.

From the past decade, STEM has evolved widely throughout the world and has provided treatment on many kinds of diseases but still faces challenges in many cases. Down Syndrome has been one of the main challenges in STEM advancement.

Scientists did research in Down Syndrome (Murthy et. al. , 2006) and in a period of 5 years, a total of 63,398 babies were newly born in Dubai among which 24,250 were UAE nationals and 39,148 were non-UAE nationals. Among these newborn 141 of them were confirmed with Down Syndrome (139 trisomy 21, 1 translocation and 1 mosaicism). The overall incidence of Down syndrome in Dubai was 1/449 live births, 1/319 live births for UAE nationals and 1/602 live births for non-UAE nationals.

This research indicated that in order to solve or minimize the problems related to Down Syndrome, genetic counselling is needed and antenatal screening program was introduced prenatal diagnosis could reduce the burden (psychological and genetic) on families and community (Kazemi et. al., 2016). It is actually very difficult to rectify the abnormality of genes in case of Down Syndrome but, still with the help of STEM technologies, scientists have shown some advancement in treatment of patients with Down Syndrome. There are a few conditions which occur often among patients with Down Syndrome and scientists have an answer to these

n Problem in heart	n Problem in vision	n Loos in hearing
n Hypothyroidism	n Blood disorders	n Hypotonia
n Problems with the upper part of the spine	n Disrupted sleep patterns and sleep disorders	n Epilepsy
n Digestive problems	n Celiac disease	n Mental health and emotional problems

Examples of change on two of the Current Challenges

Children who have Down Syndrome develop many disabilities and also increase risks of many health diseases. One of the main problems among these is problem in heart and also the most serious among all health problems. Almost 50% of children who have Down Syndrome have congenital heart disease (CHD). CHD is the most common type of congenital disability. It leads to high blood pressure in lungs and the heart cannot work effectively leading to cyanosis (a condition in which skin shows blue tint due to reduced oxygen level in blood).

American Academy of Pediatrics (AAP) Committee on Genetics suggests that infants should receive the facility of echocardiogram (ECG) and a pediatric cardiologist for evaluation. In some cases, heart problems can be detected before birth, but the more accurate result could be detected to test after birth. Some heart problems are minor and could be treated by medication while others could require surgery.

Multiplexed Immunoassay Biosensors

Advancement in POC (point-of-care) diagnostics are evident with the development of multiplexed immunoassay biosensor. Detection of serum biomarkers is now uncomplicated with the help of this sensor. The sensor is developed with the use of aqueous CdSe/Zns quantum dots, which are photoluminescent. The matrix is composed of microporous nylon membrane, which is carboxyl functionalized, along with fluorescent labels, resulting in high stability and efficiency of the multiplexed immunoassay biosensor (Liu et al., 2013). In Down Syndrome, the two primary biomarkers are:

• β-HCG (β-Human Chorionic Gonadotrophin) and,
• α-FP (α-Fetal Protein)

For multiplexed bioassay sensor, the two aforementioned biomarkers are used for detection of Down Syndrome. Targeted antigens are first captured by the microporous nylon membrane, which is antibody immobilized. These antigens are from the physiological samples and on the membrane surface, forms antibody-antigen complexes, that is, immunocomplexes. These complexes continue to react with the CdSe/ZnS quantum dots conjugated labelled antibodies. Confocal and Atomic Force Microscopy confirms the formation of ‘sandwich’ or triplex structure. Quantitative detection of α-Fetal Protein and β-Human Chorionic Gonadotrophin was realized, as the detectable level of the advanced multiplexed immunoassay biosensor was as low as 1 ng/ml for α-Fetal Protein and 1×10^-6 IU/L for β-Human Chorionic Gonadotrophin. This result was obtained without any enrichment and in very short assay time.

Sonic Hedgehog Signalling Pathway

One of the major trafficking networks is Sonic Hedgehog signally pathway. This network helps to regulate the major events of the developmental processes, which are patterning and growth of multicellular embryos. To establish multiple structure formation and gastrulation’s left-right axes to suitable patterning, it is crucial that the maintenance and regulation of every tissue and stem cell population are ensured. Growth factors triggering the differentiation and proliferation of target cells are regulated by sonic hedgehog in specific populations. This causes to the morphogen causing cells to respond differently. The sonic hedgehog has a broad range of impacts on the development, and thus, many structures are affected by the disruption in the network, which also affects Down Syndrome (Choudhry et al., 2014).

However, latest studies report a deficit in the precursors of trisomic cerebellar granule cell in response to sonic hedgehog’s mitogenic effect, in comparison to euploid counterparts. In mouse models, such deficiency assists in hypocellular cerebellum. This is parallel to the Down Syndrome Phenotype in humans and can be corrected by small-molecule exposure method in the early developmental stages.

Conclusion 

For the past decade U.A.E. sees high rates of Down Syndrome. The government has been working on it and has found a solution. U.A.E. has been successful to open first Down Syndrome in Dubai and are working on infants suffering from it. Since treatment of Down Syndrome is very costly, the government is helping the family by treating these infants.

References

Aburawi, E. H., Nagelkerke, N., Deeb, A., Abdulla, S., & Abdulrazzaq, Y. M. (2015). National growth charts for United Arab Emirates children with Down syndrome from birth to 15 years of age. Journal of epidemiology, 25(1), 20-29.

Choudhry, Z., Rikani, A. A., Choudhry, A. M., Tariq, S., Zakaria, F., Asghar, M. W., … & Mobassarah, N. J. (2014). Sonic hedgehog signalling pathway: a complex network. Annals of neurosciences, 21(1), 28.

Das, I., Park, J. M., Shin, J. H., Jeon, S. K., Lorenzi, H., Linden, D. J., … & Reeves, R. H. (2013). Hedgehog agonist therapy corrects structural and cognitive deficits in a Down syndrome mouse model. Science translational medicine, 5(201), 201ra120-201ra120.

Karmiloff-Smith, A., Al-Janabi, T., D’Souza, H., Groet, J., Massand, E., Mok, K., … & Tybulewicz, V. (2016). The importance of understanding individual differences in Down syndrome. F1000Research, 5.

Kazemi, M., Salehi, M., & Kheirollahi, M. (2016). Down syndrome: current status, challenges and future perspectives. International journal of molecular and cellular medicine, 5(3), 125.

Liu, D., Wu, F., Zhou, C., Shen, H., Yuan, H., Du, Z., … & Li, L. S. (2013). Multiplexed immunoassay biosensor for the detection of serum biomarkers—β-HCG and AFP of Down Syndrome based on photoluminescent water-soluble CdSe/ZnS quantum dots. Sensors and Actuators B: Chemical, 186, 235-243.

Murthy, S., Malhotra, A., Mani, S., Shara, M., Al-Rowaished, E., & Naveed, S. et al. (2006). Incidence of Down Syndrome in Dubai, UAE. Medical Principles And Practice, 16(1), 25-28. doi: 10.1159/000096136

Zemel, B. S., Pipan, M., Stallings, V. A., Hall, W., Schadt, K., Freedman, D. S., & Thorpe, P. (2015). Growth charts for children with Down syndrome in the United States. Pediatrics, 136(5), e1204-e1211.