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Background: Priming with ChAdOx1 followed by heterologous boosting have been considered in several countries. Nevertheless, analyses that provide a comparison of the immunogenicity of heterologous booster in comparison to homologous primary vaccination regimens and natural infection are lacking. In this study, we aimed to conduct a comparative assessment of the immunogenicity between heterologous prime-boost vaccination using BNT162b2 or mRNA-1273 and homologous primary vaccination regimens. Methods: We matched vaccinated naïve individuals (VN; n=673) who had received partial vaccination (n=64), primary vaccination (n=590), or primary series plus one mRNA vaccine heterologous booster (n=19) with individuals with a documented primary SARS-CoV-2 infection and no vaccination record (natural infection; NI cohort; n=206). We measured the levels of neutralizing total antibodies (NTAbs), total antibodies (TAbs), anti-S-RBD IgG, and anti-S1 IgA titers. Results: Homologous primary vaccination with ChAdOx1 not only showed less potent NTAb, TAb, anti-S-RBD IgG, and anti-S1 IgA immune responses compared to primary-BNT162b2 or mRNA-1273 vaccination regimens (P 0.90, P < 0.001). Conclusion: The results emphasize the potential benefit of using heterologous mRNA boosters to increase antibody levels and neutralizing capacity.

Background Waning protection against emerging SARS-CoV-2 variants by pre-existing antibodies elicited because of current vaccination or natural infection is a global concern. Whether this is due to the waning of immunity to SARS-COV-2 remains unclear. Aim We aimed to investigate the dynamics of antibody isotype responses amongst vaccinated naïve (VN) and naturally infected (NI) individuals. Methods We followed up antibody levels in COVID-19 messenger RNA (mRNA)-vaccinated subjects without prior infection (VN, n = 100) in two phases: phase-I (P-I) at ~ 1.4 and phase-II (P-II) at ~ 5.3 months. Antibody levels were compared with those of unvaccinated and naturally infected subjects (NI, n = 40) at ~ 1.7 (P-1) and 5.2 (P-II) months post-infection. Neutralizing antibodies (NTAb), anti-S-RBD-IgG, -IgM and anti-S-IgA isotypes were measured. Results The VN group elicited significantly greater antibody responses (P Conclusion Whereas double-dose mRNA vaccination boosted antibody levels, vaccinated individuals’ ‘boost’ was relatively short-lived.

This study concerns the analysis of the modulation of Chronic Myeloid Leukemia (CML) cell model K562 transcriptome following transfection with the tumor suppressor gene encoding for Protein Tyrosine Phosphatase Receptor Type G (PTPRG) and treatment with the tyrosine kinase inhibitor (TKI) Imatinib. Specifically, we aimed at identifying genes whose level of expression is altered by PTPRG modulation and Imatinib concentration. Statistical tests as differential expression analysis (DEA) supported by gene set enrichment analysis (GSEA) and modern methods of ontological term analysis are presented along with some results of current interest for forthcoming experimental research in the field of the transcriptomic landscape of CML. In particular, we present two methods that differ in the order of the analysis steps. After a gene selection based on fold-change value thresholding, we applied statistical tests to select differentially expressed genes. Therefore, we applied two different methods on the set of differentially expressed genes. With the first method (Method 1), we implemented GSEA, followed by the identification of transcription factors. With the second method (Method 2), we first selected the transcription factors from the set of differentially expressed genes and implemented GSEA on this set. Method 1 is a standard method commonly used in this type of analysis, while Method 2 is unconventional and is motivated by the intention to identify transcription factors more specifically involved in biological processes relevant to the CML condition. Both methods have been equipped in ontological knowledge mining and word cloud analysis, as elements of novelty in our analytical procedure. Data analysis identified RARG and CD36 as a potential PTPRG up-regulated genes, suggesting a possible induction of cell differentiation toward an erithromyeloid phenotype. The prediction was confirmed at the mRNA and protein level, further validating the approach and identifying a new molecular mechanism of tumor suppression governed by PTPRG in a CML context.

1.AbstractBackgroundWaning of protection against emerging SARS-CoV-2 variants by pre-existing antibodies elicited due to current vaccination or natural infection is a global concern. Whether this is due to waning of immunity to SARS-COV-2 remains unclear.AimWe aimed to investigate dynamics of antibody isotype responses among vaccinated naïve (VN) and naturally infected (NI) individuals.MethodsWe followed up antibody levels in COVID-19 mRNA-vaccinated subjects without prior infection (VN, n=100) at two phases: phase-I (P-I) at ∼1.4 and phase-II (P-II) at ∼5.3 months. Antibody levels were compared to those of unvaccinated and naturally infected subjects (NI, n=40) at ∼1.7 (P-1) and 5.2 (P-II) months post-infection. Neutralizing antibodies (NTAb), anti-S-RBD-IgG, -IgM, and anti-S-IgA isotypes were measured.ResultsVN group produced significantly greater antibody responses (ppppppp=0.005), and S-RBD-IgM (∼2-folds, ppConclusionWhile double dose mRNA vaccination boosted antibody levels, this “boost” was relatively short-lived in vaccinated individuals.

The prevalence of homocystinuria in Qatar is 1:1800, mainly due to a founder missense mutation p.R336C. • The cystathionine beta-synthase (CBS) R336C mutant was bacterially expressed, purified and its molecular properties were compared to CBS wild type (WT) recombinant protein. • Our data revealed that p.R336C mutation results in a dramatic reduction (∼86%) of CBS enzymatic activity. • Circular Dichroism experiments suggested that the p.R336C mutation does not significantly alter the secondary structure of the CBS protein. • CD spectra also revealed distinct differences in the thermal unfolding mechanisms of CBS WT and R336C mutant protein species. • Chemical denaturation experiments indicated that the WT CBS protein is thermodynamically more stable than the R336C mutant, suggesting a destabilizing effect of the p.R336C mutation. • This study provides mechanistic insight into the pathogenicity of the p.R336C mutation that leads to a severe homocystinuria phenotype. This publication was made possible by GSRA grant, GSRA6-1-0413-19013, from the Qatar National Research Fund (a member of Qatar Foundation). In addition, NA would like to thank fund from The Medical Research Center at Hamad Medical Corporation for IRGC-06-SI-19-167 grant. The statements made herein are solely the responsibility of the authors. Open Access funding provided by the Qatar National Library.

This study concerns the analysis of the modulation of Chronic Myeloid Leukemia (CML) cell model K562 transcriptome following transfection with the tumor suppressor gene encoding for Protein Tyrosine Phosphatase Receptor Type G (PTPRG) and treatment with the tyrosine kinase inhibitor (TKI) Imatinib. Specifically, we aimed at identifying genes whose level of expression is altered by PTPRG modulation and Imatinib concentration. Statistical tests as differential expression analysis (DEA) supported by gene set enrichment analysis (GSEA) and modern methods of ontological term analysis are presented along with some results of current interest for forthcoming experimental research in the field of the transcriptomic landscape of CML. In particular, we present two methods that differ in the order of the analysis steps. After a gene selection based on fold-change value thresholding, we applied statistical tests to select differentially expressed genes. Therefore, we applied two different methods on the set of differentially expressed genes. With the first method (Method 1), we implemented GSEA, followed by the identification of transcription factors. With the second method (Method 2), we first selected the transcription factors from the set of differentially expressed genes and implemented GSEA on this set. Method 1 is a standard method commonly used in this type of analysis, while Method 2 is unconventional and is motivated by the intention to identify transcription factors more specifically involved in biological processes relevant to the CML condition. Both methods have been equipped in ontological knowledge mining and word cloud analysis, as elements of novelty in our analytical procedure. Data analysis identified RARG and CD36 as a potential PTPRG up-regulated genes, suggesting a possible induction of cell differentiation toward an erithromyeloid phenotype. The prediction was confirmed at the mRNA and protein level, further validating the approach and identifying a new molecular mechanism of tumor suppression governed by PTPRG in a CML context.

Two mRNA vaccines, Pfizer-BNT162b2 and Moderna-mRNA-1273, were granted the US Food and Drug Administration Emergency Use Authorization for preventing COVID-19. However, little is known about the difference in antibody responses induced by the two mRNA vaccines in naïve and individuals with a previous history of infections (PI group). Therefore, we investigated the levels of anti-S-RBD total antibodies (IgM, IgA, and IgG), anti-S-RBD IgG, and anti-S-RBD IgA in these two groups 1-13 (median=6) weeks following administration of two doses of mRNA-1273 or BNT162b2 vaccines. Results showed that in naïve-vaccinated group, the mRNA-1327 vaccine induces significantly higher levels of S-RBD total antibodies (3.5-fold; p

Woodhouse-Sakati syndrome (WSS) is a rare autosomal recessive neuroendocrine and ectodermal disorder caused by variants in the DCAF17 gene. In Qatar, the c.436delC variant has been reported as a possible founder pathogenic variant with striking phenotypic heterogeneity. In this retrospective study, we report on the clinical and molecular characteristics of additional 58 additional Qatari patients with WSS and compare them to international counterparts' findings. A total of 58 patients with WSS from 32 consanguineous families were identified. Ectodermal and endocrine (primary hypogonadism) manifestations were the most common presentations (100%), followed by diabetes mellitus (46%) and hypothyroidism (36%). Neurological manifestations were overlapping among patients with intellectual disability (ID) being the most common (75%), followed by sensorineural hearing loss (43%) and both ID and aggressive behavior (10%). Distinctive facial features were noted in all patients and extrapyramidal manifestations were uncommon (8.6%). This study is the largest to date on Qatari patients with WSS and highlights the high incidence and clinical heterogeneity of WSS in Qatar due to a founder variant c.436delC in the DCAF17 gene. Early suspicion of WSS among Qatari patients with hypogonadism and ID, even in the absence of other manifestations, would shorten the diagnostic odyssey, guide early and appropriate management, and avoid potential complications.

Background The rapid growth of Qatar in the last two decades has attracted a large influx of immigrant workers who mostly come from HEV-hyperendemic countries. Thus, we aim to investigate the prevalence of HEV among acute non-A-C hepatitis patients in Qatar; and to evaluate the performance of four dominant commercial serological assays for HEV diagnosis. Methods 259 patients with non-A-C hepatitis were tested using the Wantai HEV-IgM, HEV-IgG, HEV-Ag ELISA kits, and the MP Biomedical HEV-Total Ab ELISA kit. ALT levels were tested and HEV RNA (viral loads) was performed using Taqman AmpliCube HEV RT-PCR kit (Mikrogen, Neuried, Germany). The performance of each kit was assessed according to the RT-PCR results. Results HEV-RNA was detected in 23.1% of the samples. Most of these HEV-RNA-positive cases belonged to non-Qatari residents from the Indian subcontinent; India, Pakistan, etc. HEV-Ag, HEV-IgM, HEV-IgG, HEV-Total Ab were detected in 5.56%, 8.65%, 32.1%, and 34.2% of all tested samples, respectively. Elevated ALT levels were highly correlated with the HEV-Ag, HEV-IgM, HEV-RNA but not with the HEV-IgG and HEV-Total Ab. Although HEV-Ag was very specific (100%), yet its sensitivity was poor (36.7%). HEV-IgM demonstrated the best second marker for diagnosis of acute HEV after RT-PCR as jugged by the overall performance parameters: specificity (96.2%), sensitivity (71.4%), PPV (83.3%), NPP (92.7%), agreement with RT-PCR (91.0%), and Kappa-value (0.71). Conclusion Our study demonstrated a high prevalence of HEV virus in Qatar, mostly among immigrants from the Indian subcontinent. The HEV-IgM represents the best marker for detecting the acute HEV infection, where RT-PCR cannot be performed.

Preterm birth (PTB) and early term birth (ETB) are associated with high risks of perinatal mortality and morbidity. While extreme to very PTBs have been extensively studied, studies on infants born at later stages of pregnancy, particularly late PTBs and ETBs, are lacking. In this study, we aimed to assess the incidence, risk factors, and feto-maternal outcomes of PTB and ETB births in Qatar. We examined 15,865 singleton live births using 12-month retrospective registry data from the PEARL-Peristat Study. PTB and ETB incidence rates were 8.8% and 33.7%, respectively. PTB and ETB in-hospital mortality rates were 16.9% and 0.2%, respectively. Advanced maternal age, pre-gestational diabetes mellitus (PGDM), assisted pregnancies, and preterm history independently predicted both PTB and ETB, whereas chromosomal and congenital abnormalities were found to be independent predictors of PTB but not ETB. All groups of PTB and ETB were significantly associated with low birth weight (LBW), large for gestational age (LGA) births, caesarean delivery, and neonatal intensive care unit (NICU)/or death of neonate in labor room (LR)/operation theatre (OT). On the other hand, all or some groups of PTB were significantly associated with small for gestational age (SGA) births, Apgar &lt, 7 at 1 and 5 minutes and in-hospital mortality. The findings of this study may serve as a basis for taking better clinical decisions with accurate assessment of risk factors, complications, and predictions of PTB and ETB.

Background:Diabetes Mellitus (DM) is a multisystemic disease involving the homeostasis of insulin secretion by the pancreatic islet beta cells (β-cells). It is associated with hypertension, renal disease, and arterial and arteriolar vascular diseases.Discussion:The classification of diabetes is identified as type 1 (gene linked β-cell destruction in childhood) and type 2 (late onset associated with β-cell overload and insulin resistance in peripheral tissues. Type 1 diabetes is characterized by insulin deficiency, type 2 diabetes by both insulin deficiency and insulin resistance. The former is a genetically programmed loss of insulin secretion whereas the latter constitutes a disruption of the homeostatic relationship between the opposing activity of β- cell insulin and alpha cell (α-cell) glucagon of the Islets of Langerhans. The condition could also occur in pregnancy, as a prenatal occurring event, possibly triggered by the hormonal changes of pregnancy combined with β-cell overload. This review discusses the molecular basis of the biomolecular changes that occur with respect to glucose homeostasis and related diseases in DM. The underlying link between pancreatic, renal, and microvascular diseases in DM is based on oxidative stress and the Unfolded Protein Response (UPR).Conclusion:Studying proteome changes in diabetes can deepen our understanding of the biomolecular basis of disease and help us acquire more efficient therapies.

Classical homocystinuria is a recessive inborn error of metabolism caused by mutations in the cystathionine beta-synthase (CBS) gene. The highest incidence of CBS deficiency in the world is found in the country of Qatar due to the combination of high rates of consanguinity and the presence of a founder mutation, c.1006C>T (p.R336C). This mutation does not respond to pyridoxine and is considered severe. Here we describe the creation of a mouse that is null for the mouse Cbs gene and expresses human p.R336C CBS from a zinc-inducible transgene (Tg-R336C Cbs ). Zinc treated Tg-R336C Cbs mice have extreme elevation in both serum tHcy and liver tHcy compared to control transgenic mice. Both the steady-state protein levels and CBS enzyme activity levels in liver lysates from Tg-R336C Cbs mice are significantly reduced compared to that found in Tg-hCBS Cbs mice expressing wild-type human CBS. Treatment of Tg-R336C Cbs mice with the proteasome inhibitor bortezomib results in stabilization of liver CBS protein and an increase in activity to levels found in corresponding Tg-hCBS Cbs wild type mice. Surprisingly, serum tHcy did not fully correct even though liver enzyme activity was as high as control animals. This discrepancy is explained by in vitro enzymatic studies of mouse liver extracts showing that p.R336C causes reduced binding affinity for the substrate serine by almost seven-fold and significantly increased dependence on pyridoxal phosphate in the reaction buffer. These studies demonstrate that the p.R336C alteration effects both protein stability and substrate/cofactor binding. National Institute of Diabetes and Digestive and Kidney Diseases, Grant/Award Number: DK101404; Qatar Foundation, Grant/Award Number: NPR7‐355‐3‐088; NPRP grant, Grant/Award Number: NPR7‐355‐3‐088; National Institutes of Health, Grant/Award Numbers: P30 CA006927, R01 DK101404

Background Clinical exome sequencing (CES) is rapidly becoming the diagnostic test of choice in patients with suspected Mendelian diseases especially those that are heterogeneous in etiology and clinical presentation. Reporting large CES series can inform guidelines on best practices for test utilization, and improves accuracy of variant interpretation through clinically‐oriented data sharing. Methods This is a retrospective series of 509 probands from Qatar who underwent singleton or trio CES either as a reflex or naïve (first‐tier) test from April 2014 to December 2016 for various clinical indications. Results The CES diagnostic yield for the overall cohort was 48.3% (n = 246). Dual molecular diagnoses were observed in 2.1% of cases; nearly all of whom (91%) were consanguineous. We report compelling variants in 11 genes with no established Mendelian phenotypes. Unlike reflex‐WES, naïve WES was associated with a significantly shorter diagnostic time (3 months vs. 18 months, p

Clinical Exome Sequencing (CES) has increasingly become a popular diagnostic tool in patients suffering from genetic disorders that are clinically and genetically complicated. Myeloproliferative Neoplasms (MPNs) is an example of a heterogeneous disorder. In Qatar, familial cases of MPNs are more frequently seen than described in the literature. In this study, we aimed to use CES to classify six Qatari subjects that were suspected of clinical diagnosis of MPNs, according to the WHO 2008 diagnostic criteria for hematologic malignancies, and identify variants that can potentially explain the phenotypic diversity of MPNs. We sequenced six Qatari subjects using CES, of whom, three probands were unrelated families and three members were from the same family, all probands come from consanguineous families, and had a positive family history of MPNs. CES identified 61 variants in 50 genes; of which, 13 were recurrently mutated in our patients. Ten novel variants were identified in ten known genes related to MPNs and seven variants were identified in seven novel candidate genes. The genotype of the six subjects was due to a combination of different variants in different genes. This study serves as a pilot study to investigate the complexity of the genotype of patients with MPNS in Qatar, and serves as a guide for further well-controlled genetic epidemiological studies for patients with MPNs. CES is a powerful tool to be used in the genetic clinics for differential and definitive diagnosis of patients with MPNs.

Human parvovirus (B19V) is the causative agent of erythema infectiosum in children and is linked to a wide range of clinical manifestations. Studies related to B19V prevalence in the Middle East and North Africa (MENA) region and other parts of Asia are very scarce. The objectives of this study were to estimate the seroprevalence (anti-B19V IgM and IgG), the viremia rate (B19V DNA), and the circulating genotypes of B19V among blood donors in Qatar. Methods: Donors’ blood samples (n = 5026) from different nationalities, mainly from the MENA region and South East Asia, were collected from 2014–2016. Samples were tested for the B19V DNA using RT-PCR. Furthermore, 1000 selected samples were tested to determine the seroprevalence of B19V antibodies using enzyme-linked immunosorbent assay (ELISA). Genotyping was performed on 65 DNA positive samples by sequencing of nested PCR fragments (NS1-VP1u region, 927 nt). Results: Only 1.4% (70/5026) of the samples had detectible B19V DNA in their blood. B19V DNA prevalence statistically decreased with age (p = 0.03). Anti-B19V IgG was detected in 60.3% (561/930) of the tested samples, while only 2.1% (20/930) were IgM-positive and 1.2% (11/930) were both IgM- and IgG-positive. B19V genotyping showed a predominance of Genotype 1 (100%). Sequence analysis of the NS1-VP1u region revealed 139 mutation sites, some of which were amino acid substitutions. Conclusion: Our results indicated a relatively high seroprevalence of B19V in Qatar. Most importantly, B19 DNA was detected among Qatari and non-Qatari blood donors. Therefore, blood banks in Qatar might need to consider screening for B19V, especially when transfusion is intended for high-risk populations, including immunocompromised patients.

The prevalence rate of Autism Spectrum Disorder (ASD) has reached over 1% world-wide prompting governments, health providers and schools to develop programs and policies to address this challenging disorder. Here, we review the cause(s), as well as environmental factors, genetic mutations, and neural pathways that are implicated in ASD. We also discuss the criteria that are commonly used for the diagnosis of ASD and future clinical genetic testing that can aid in the diagnosis of this disorder. Finally, we provide practical steps that can be used to reduce the incidence and severity of ASD, as well as prognosis and treatment of autism.

Protein tyrosine phosphatase receptor type &gamma, (PTPRG) is a tumor suppressor gene, down-regulated in Chronic Myeloid Leukemia (CML) cells by the hypermethylation of its promoter region. &beta, catenin (CTNNB1) is a critical regulator of Leukemic Stem Cells (LSC) maintenance and CML proliferation. This study aims to demonstrate the antagonistic regulation between &beta, catenin and PTPRG in CML cells. The specific inhibition of PTPRG increases the activation state of BCR-ABL1 and modulates the expression of the BCR-ABL1- downstream gene &beta, Catenin. PTPRG was found to be capable of dephosphorylating &beta, catenin, eventually causing its cytosolic destabilization and degradation in cells expressing PTPRG. Furthermore, we demonstrated that the increased expression of &beta, catenin in PTPRG-negative CML cell lines correlates with DNA (cytosine-5)-methyl transferase 1 (DNMT1) over-expression, which is responsible for PTPRG promoter hypermethylation, while its inhibition or down-regulation correlates with PTPRG re-expression. We finally confirmed the role of PTPRG in regulating BCR-ABL1 and &beta, catenin phosphorylation in primary human CML samples. We describe here, for the first time, the existence of a regulative loop occurring between PTPRG and &beta, catenin, whose reciprocal imbalance affects the proliferation kinetics of CML cells.

Background: Several studies showed that the aberrant DNA methylations are involved in leukemia and cancer pathogenesis. PTPRG is a natural inhibitory mechanism that is found to be down-regulated in Chronic Myeloid Leukemia (CML) disease. The mechanism behind its down-regulation has not been fully elucidated. Aim: The study investigates the role of methylation as a possible mechanism of PTPRG under-expression in CML patients. Method: Peripheral blood samples from CML patients treated with tyrosine kinase inhibitors (TKIs) and healthy controls were collected. DNA was extracted and treated with bisulfite treatment, followed by PCR and sequencing of 25 of CpG in Promoter and 26 of CpG in the Intronic regions of PTPRG. Bisulfite-sequencing technique as a high-resolution method was employed. Results : CML groups (New Diagnosed and Failed treatment) have significantly higher methylation levels in the Promoter and Intron regions compared to the healthy group. There were also significant differences in methylation levels of CpG sites in the Promoter and Intronic regions amongst the groups. Conclusion: Aberrant methylation of PTPRG is documented and potentially is one of the possible mechanisms of PTPRG down-regulation in CML.

Autism spectrum disorder (ASD) is characterized by impairment in behavior, communication, and social interaction. Thus, accurate identification, regular behavioral and other nonmedical interventions would improve the diagnosis, management, and treatment of this condition.In this chapter, we investigate the importance of diagnosing and identifying comorbid psychiatric disorders that occur with ASD as these conditions can often complicate treatment, and failure to recognize them can result in deficits that can persist into adolescence and adulthood. In addition, we explore the impact of comprehensive psychological intervention in ASD patients with comorbid psychiatric disorders with the ultimate goal of improving overall quality of life.

Autism spectrum disorder (ASD) is a highly heritable, heterogeneous, and complex pervasive neurodevelopmental disorder (PND) characterized by distinctive abnormalities of human cognitive functions, social interaction, and speech development.Nowadays, several genetic changes including chromosome abnormalities, genetic variations, transcriptional epigenetics, and noncoding RNA have been identified in ASD. However, the association between these genetic modifications and ASDs has not been confirmed yet.The aim of this review is to summarize the key findings in ASD from genetic viewpoint that have been identified from the last few decades of genetic and molecular research.

To support the deployment of serology assays for population screening during the COVID-19 pandemic, we compared the performance of three fully automated SARS-CoV-2 IgG assays: Mindray CL-900i&reg, (target: spike [S] and nucleocapsid [N]), BioM&eacute, rieux VIDAS&reg, 3 (target: receptor-binding domain [RBD]) and Diasorin LIAISON&reg, XL (target: S1 and S2 subunits). A total of 111 SARS-CoV-2 RT-PCR- positive samples collected at &ge, 21 days post symptom onset, and 127 pre-pandemic control samples were included. Diagnostic performance was assessed in correlation to RT-PCR and a surrogate virus-neutralizing test (sVNT). Moreover, cross-reactivity with other viral antibodies was investigated. Compared to RT-PCR, LIAISON&reg, XL showed the highest overall specificity (100%), followed by VIDAS&reg, 3 (98.4%) and CL-900i&reg, (95.3%). The highest sensitivity was demonstrated by CL-900i&reg, (90.1%), followed by VIDAS&reg, 3 (88.3%) and LIAISON&reg, XL (85.6%). The sensitivity of all assays was higher in symptomatic patients (91.1&ndash, 98.2%) compared to asymptomatic patients (78.4&ndash, 80.4%). In correlation to sVNT, all assays showed excellent sensitivities (92.2&ndash, 96.1%). In addition, VIDAS&reg, 3 demonstrated the best correlation (r = 0.75) with the sVNT. The present study provides insights on the performance of three fully automated assays, which could help diagnostic laboratories in the choice of a particular assay according to the intended use.

Conflict leads to toxic stress and health problems in childhood and beyond. Long term investment in evidence-informed mitigation strategies is needed to end the devastating cycles of violence. يؤدي الصراع إلى إجهاد سام ومشاكل صحية في مرحلة الطفولة وما بعدها. هناك حاجة إلى استثمار طويل الأجل في استراتيجيات التخفيف المدعومة بالأدلة لإنهاء دورات العنف المدمرة.

Autism spectrum disorder (ASD) is a highly heritable, heterogeneous, and complex pervasive neurodevelopmental disorder (PND) characterized by distinctive abnormalities of human cognitive functions, social interaction, and speech development.

Background: Complement system is one of ancient innate immune systems in our body fighting against pathogens and foreign bodies. Either one of its three pathways, classical, alternative or lectin activates it. Because of its role and importance in combating against different pathological conditions, it works through defined proteins including regulators and inhibitors. However, over or under stimulation of complement system can lead to various diseases. A number of analytical assays are used to measure complement proteins and its activation states considering complement 3 (C3), complement 4 (C4) as the most common test used. Objectives: Our aims are to study the clinical utility and cost effectiveness of C3 and C4 among different clinical subspecialties in Hamad Medical Corporation (HMC), Doha-Qatar. Design and methods: A retrospective study was conducted using electronic medical records to generate patient’s list from clinical immunology laboratory at HMC. Data on 326 patients were collected from 1st January till 31st March, 2017 and used as pilot study after omitting duplications. The data was studied for its demographical, disease categories, C3 and C4 test results. C3 and C4 test cost were calculated inside HMC and compared to other healthcare providers in country and abroad. Results: A total of 326 patients, 148 males and 178 females (M/F ratio:0.8:1), of age (mean age ±SD) of 36 ± 17.6 years. 289(86%) were >15 years and 47(14%) were 15 or less. Kidney diseases (34%), autoimmune diseases (25%), and allergic diseases (18%) were the top 3 diseases, and constituted 77% of all diseases. 45/336 (13.4%) showed low C3, C4, or both. Mean levels of C3 (±SD) was 120.8 ±36.3 mg/dl, and C4 was27.85±11.9 mg/dl. High C3 and C4 levels were observed in 53 (15.7%) of patients. The cost of performing one test either C3 or C4 in HMC is 22 QR ($6), while other healthcare providers inside the country costed 150-300 QR ($41.2-$82.4). Conclusion: Autoimmune diseases, renal diseases and joist diseases were the most common diseases with low C3 and C4 levels. Although the cost of a single test of C3 or C4 is low, the total annual cost is huge. The treating physician is recommended to exercise judicious clinical wisdom when ordering C3 or C4 tests as diagnostic tools

Autism spectrum disorder (ASD) is a complex neurodevelopmental disorder generally manifesting in the first few years of life and tending to persist into adolescence and adulthood. It is characterized by deficits in communication and social interaction and restricted, repetitive patterns of behavior, interests, and activities. It is a disorder with multifactorial etiology. In this chapter, we will focus on the most important and common epidemiological studies, pathogenesis, screening, and diagnostic tools along with an explication of genetic testing in ASD.

Background: In two years from now, Qatar will host the 2022 World Cup competition, which requires high level of preparedness and readiness in different sectors including healthcare. Among different subsections of health, the blood bank and the Blood Donor Center will have a major role in this event especially in case of unforeseen incidences. Accordingly, a proper assessment of the current blood resource availability and a prediction of future blood needs helps in overcoming any obstacle that could be faced during the event. Objectives: (1) Highlight the process of the blood supply chain, with a detailed delineation of the needed amount of blood components for both routine and emergency situations services, and outline the proper measures taken to deliver the safest and most appropriate blood units and reduce wastage of blood component. (2) Assess the current standing of the Blood Donor Center and corresponding units in Qatar. (3) Develop a forecast model that predicts the number of blood donors in the next four years as a method to evaluate the readiness of the Blood Donor facility to host the world cup event. (4) Explore the potential challenges that could be faced when meeting the benchmark of donation and established an action plan to overcome these anticipated challenges. Materials and methods: Both qualitative (interviews) and a quantitative (data collection and analysis) approaches have been implemented in our study. We also established a time series forecast model using Autoregressive Integrated Moving Average (ARIMA). Results: The number of donors in the next four years, which is predicted to increase by 26%, will not be able to be accommodated in the current Blood Donor Center facility. Therefore, the established blood stock benchmark will not be met despite that the Center and its corresponding units are fully equipped with high standard equipment and follow international guidelines in the process of blood withdrawal. Conclusion: Infrastructure improvements and logistics support for Hamad Medical Corporation Blood Donor Center are required to support the continuously increasing numbers of blood donors for daily demand and during mega events.

Background Abnormal fetal growth can be associated with factors during pregnancy and at postpartum. Objective In this study, we aimed to assess the incidence, risk factors, and feto-maternal outcomes associated with small-for-gestational age (SGA) and large-for-gestational age (LGA) infants. Methods We performed a population-based retrospective study on 14,641 singleton live births registered in the PEARL-Peristat Study between April 2017 and March 2018 in Qatar. We estimated the incidence and examined the risk factors and outcomes using univariate and multivariate analysis. Results SGA and LGA incidence rates were 6.0% and 15.6%, respectively. In-hospital mortality among SGA and LGA infants was 2.5% and 0.3%, respectively, while for NICU admission or death in labor room and operation theatre was 28.9% and 14.9% respectively. Preterm babies were more likely to be born SGA (aRR, 2.31; 95% CI, 1.45–3.57) but male infants (aRR, 0.57; 95% CI, 0.4–0.81), those born to parous (aRR 0.66; 95% CI, 0.45–0.93), or overweight (aRR, 0.64; 95% CI, 0.42–0.97) mothers were less likely to be born SGA. On the other hand, males (aRR, 1.82; 95% CI, 1.49–2.19), infants born to parous mothers (aRR 2.16; 95% CI, 1.63–2.82), or to mothers with gestational diabetes mellitus (aRR 1.36; 95% CI, 1.11–1.66), or pre-gestational diabetes mellitus (aRR 2.58; 95% CI, 1.8–3.47) were significantly more likely to be LGA. SGA infants were at high risk of in-hospital mortality (aRR, 226.56; 95% CI, 3.47–318.22), neonatal intensive care unit admission or death in labor room or operation theatre (aRR, 2.14 (1.36–3.22). Conclusion Monitoring should be coordinated to alleviate the risks of inappropriate fetal growth and the associated adverse consequences.

Background Protein tyrosine phosphatase receptor gamma (PTPRG) is a ubiquitously expressed member of the protein tyrosine phosphatase family known to act as a tumor suppressor gene in many different neoplasms with mechanisms of inactivation including mutations and methylation of CpG islands in the promoter region. Although a critical role in human hematopoiesis and an oncosuppressor role in chronic myeloid leukemia (CML) have been reported, only one polyclonal antibody (named chPTPRG) has been described as capable of recognizing the native antigen of this phosphatase by flow cytometry. Protein biomarkers of CML have not yet found applications in the clinic, and in this study, we have analyzed a group of newly diagnosed CML patients before and after treatment. The aim of this work was to characterize and exploit a newly developed murine monoclonal antibody specific for the PTPRG extracellular domain (named TPγ B9-2) to better define PTPRG protein downregulation in CML patients. Methods TPγ B9-2 specifically recognizes PTPRG (both human and murine) by flow cytometry, western blotting, immunoprecipitation, and immunohistochemistry. Results Co-localization experiments performed with both anti-PTPRG antibodies identified the presence of isoforms and confirmed protein downregulation at diagnosis in the Philadelphia-positive myeloid lineage (including CD34+/CD38bright/dim cells). After effective tyrosine kinase inhibitor (TKI) treatment, its expression recovered in tandem with the return of Philadelphia-negative hematopoiesis. Of note, PTPRG mRNA levels remain unchanged in tyrosine kinase inhibitors (TKI) non-responder patients, confirming that downregulation selectively occurs in primary CML cells. Conclusions The availability of this unique antibody permits its evaluation for clinical application including the support for diagnosis and follow-up of these disorders. Evaluation of PTPRG as a potential therapeutic target is also facilitated by the availability of a specific reagent capable to specifically detect its target in various experimental conditions. Electronic supplementary material The online version of this article (doi:10.1186/s13045-017-0494-z) contains supplementary material, which is available to authorized users.

Background Consanguineous marriages are common in the Middle East including the Gulf countries. The rate of consanguinity in Qatar is approximately 54%, which are mainly first cousins’ marriages. Previous studies showed that consanguinity increases the prevalence of birth defects and other genetic disorders. Thus, we studied the effects of consanguinity in a cohort of subjects with certain genetic disorders in Qatar. Methods This cross‐sectional study was conducted at two centers in Qatar (Hamad Medical Corporation “HMC” and Shafallah “SC”) including 599 Qatari families with certain types of genetic and nongenetic anomalies. Results Consanguineous marriages were seen in 397 of 599 (66.2%) Qatari families and first cousin group counts for 65% in Qatari population. In the total cohort and at HMC, all consanguineous marriages had a significantly higher risk of Autosomal Recessive disorders than nonconsanguineous marriages (total cohort: odds ratio (OR) = 1.72; 95% CI: 1.10, 2.71; p = .02; HMC: OR = 2.98; 95% CI: 1.37, 6.09; p = .005). On the other hand, at HMC, nonconsanguinity was significantly related to chromosomal abnormality (OR = 6.36; 95% CI: 1.13, 35.85; p = .036). Conclusion Our data suggest a significant role of parental consanguinity in increasing the prevalence of genetic disorders; mainly Autosomal Recessive disorders. Chromosomal abnormality disorders were significantly higher among nonconsanguineous marriages. These results help better inform policy makers on social, educational, and public health initiatives that might mitigate the impact of genetic disease in the Qatari society., The study highlights the significant role of parental consanguinity and specific relatedness (first cousin) in increasing the risk of developing genetic disorders, in particular Autosomal Recessive.