Follow-Up and Comparative Assessment of SARS-CoV-2 IgA, IgG, Neutralizing, and Total Antibody Responses After BNT162b2 or mRNA-1273 Heterologous Booster Vaccination.

BACKGROUND: Priming with ChAdOx1 followed by heterologous boosting is considered in several countries. Nevertheless, analyses comparing the immunogenicity of heterologous booster to homologous primary vaccination regimens and natural infection are lacking. In this study, we aimed to conduct a comparative assessment of the immunogenicity between homologous primary vaccination regimens and heterologous prime-boost vaccination using BNT162b2 or mRNA-1273. METHODS: We matched vaccinated naïve (VN) individuals (n = 673) with partial vaccination (n = 64), primary vaccination (n = 590), and primary series plus mRNA vaccine heterologous booster (n = 19) with unvaccinated naturally infected (NI) individuals with a documented primary SARS-CoV-2 infection (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 < 0.05) but also showed ~3-fold less anti-S1 IgA response compared to infection-induced immunity (p < 0.001). Nevertheless, a heterologous booster led to an increase of ~12 times in the immune response when compared to two consecutive homologous ChAdOx1 immunizations. Furthermore, correlation analyses revealed that both anti-S-RBD IgG and anti-S1 IgA significantly contributed to virus neutralization among NI individuals, particularly in symptomatic and pauci-symptomatic individuals, whereas among VN individuals, anti-S-RBD IgG was the main contributor to virus neutralization. CONCLUSION: The results emphasize the potential benefit of using heterologous mRNA boosters to increase antibody levels and neutralizing capacity particularly in patients who received primary vaccination with ChAdOx1.

Biochemical and structural impact of two novel missense mutations in cystathionine ß-synthase gene associated with homocystinuria.

Homocystinuria is a rare disease caused by mutations in the CBS gene that results in a deficiency of cystathionine ß-synthase (CBS). CBS is an essential pyridoxal 5'-phosphate (PLP)-dependent enzyme in the transsulfuration pathway, responsible for combining serine with homocysteine to produce cystathionine, whose activity is enhanced by the allosteric regulator S-adenosylmethionine (SAM). CBS also plays a role in generating hydrogen sulfide (H2S), a gaseous signaling molecule with diverse regulatory functions within the vascular, nervous, and immune systems. In this study, we present the clinical and biochemical characterization of two novel CBS missense mutations that do not respond to pyridoxine treatment, namely c.689T > A (L230Q) and 215A > T (K72I), identified in a Chinese patient. We observed that the disease-associated K72I genetic variant had no apparent effects on the spectroscopic and catalytic properties of the full-length enzyme. In contrast, the L230Q variant expressed in Escherichia coli did not fully retain heme and when compared with the wild-type enzyme, it exhibited more significant impairments in both the canonical cystathionine-synthesis and the alternative H2S-producing reactions. This reduced activity is consistent with both in vitro and in silico evidence, which indicates that the L230Q mutation significantly decreases the overall protein's stability, which in turn, may represent the underlying cause of its pathogenicity.

The genetic basis and the diagnostic yield of genetic testing related to nonsyndromic hearing loss in Qatar.

Hearing loss is the most predominant sensory defect occurring in pediatrics, of which, 66% cases are attributed to genetic factors. The prevalence of hereditary hearing loss increases in consanguineous populations, and the prevalence of hearing loss in Qatar is 5.2%. We aimed to investigate the genetic basis of nonsyndromic hearing loss (NSHL) in Qatar and to evaluate the diagnostic yield of different genetic tests available. A retrospective chart review was conducted for 59 pediatric patients with NSHL referred to the Department of Adult and Pediatric Medical Genetics at Hamad Medical Corporation in Qatar, and who underwent at least one genetic test. Out of the 59 patients, 39 were solved cases due to 19 variants in 11 genes and two copy number variants that explained the NSHL phenotype. Of them 2 cases were initially uncertain and were reclassified using familial segregation. Around 36.8% of the single variants were in GJB2 gene and c.35delG was the most common recurrent variant seen in solved cases. We detected the c.283C > T variant in FGF3 that was seen in a Qatari patient and found to be associated with NSHL for the first time. The overall diagnostic yield was 30.7%, and the diagnostic yield was significantly associated with genetic testing using GJB2 sequencing and using the hearing loss (HL) gene panel. The diagnostic yield for targeted familial testing was 60% (n = 3 patients) and for gene panel was 50% (n = 5). Thus, we recommend using GJB2 gene sequencing as a first-tier genetic test and HL gene panel as a second-tier genetic test for NSHL. Our work provided new insights into the genetic pool of NSHL among Arabs and highlights its unique diversity, this is believed to help further in the diagnostic and management options for NSHL Arab patients.

Perinatal outcomes in women with class IV obesity compared to women in the normal or overweight body mass index categories: A population-based cohort study in Qatar.

Background: The prevalence of childhood and adult obesity is rising exponentially worldwide. Class IV obesity (body mass index, BMI ≥50 kg/m2) is associated with a higher risk of adverse perinatal outcomes. This study compared these outcomes between women with class IV obesity and women in the normal or overweight categories during pregnancy. Methods: A retrospective cohort study was performed in Qatar, including women having singleton live births beyond 24 weeks of gestation, classified into two class IV obesity and normal/overweight (BMI between 18.5 and 30.0 kg/m2). The outcome measures included the mode of delivery, development of gestational diabetes and hypertension, fetal macrosomia, small for date baby, preterm birth and neonatal morbidity. Adjusted odds ratios (aOR) with 95% confidence intervals (95% CI) were determined using multivariable logistic regression models. Results: A total of 247 women with class IV obesity were compared with 6797 normal/overweight women. Adjusted analysis showed that women with class IV obesity had 3.2 times higher odds of cesarean delivery (aOR: 3.19, CI: 2.26-4.50), 3.4 times higher odds of gestational diabetes (aOR: 3.39, CI: 2.55-4.50), 4.2 times higher odds of gestational hypertension (aOR: 4.18, CI: 2.45-7.13) and neonatal morbidity (aOR: 4.27, CI: 3.01-6.05), and 6.5 times higher odds of macrosomia (aOR 6.48, CI 4.22-9.99). Conclusions: Class IV obesity is associated with more adverse perinatal outcomes compared with the normal or overweight BMI categories. The study results emphasized the need for specialized antenatal obesity clinics to address the associated risks and reduce complications.

Impact of bariatric surgery on maternal gestational weight gain and pregnancy outcomes in women with obesity: A population-based cohort study from Qatar.

BACKGROUND: Bariatric surgery is performed in obese women of reproductive age to help achieve a healthy prepregnancy weight to reduce the complications associated with obesity in pregnancy. However, these procedures can impact maternal nutrition and gestational weight gain (GWG). This study evaluates the maternal and neonatal outcomes in women with prepregnancy bariatric surgery and determines the impact on GWG. METHODS: This study included 24 weeks gestation or more pregnancies, with a maternal BMI at delivery of 30 kg/m2 or more. It was categorized into two groups based on whether they had prepregnancy bariatric surgery (exposed) or not (unexposed). The outcomes included gestational diabetes (GDM), gestational hypertension (GHT), mode of delivery, preterm birth (PTB), GWG, birthweight (BW) and customized BW centiles, low birthweight (LBW), congenital anomalies, and admission to the neonatal intensive unit (NICU). Categorization was also done based on the adequacy of GWG (low, adequate, and excess). RESULTS: A total of 8,323 women were included in the study, 194 of whom had prepregnancy bariatric surgery. After adjusting for confounders, the exposed group had a mean GWG 1.33 kg higher than the unexposed group (95% CI 0.55-2.13, p = 0.001). The exposed group had higher odds of PTB (aOR 1.78, 95% CI 1.16-2.74, p = 0.008), CD (aOR 6.52, 95% CI 4.28-9.93, p < 0.001), LBW in term babies (aOR 2.60, 95% CI 1.34-5.03, p = 0.005), congenital anomalies (aOR 2.64, 95% CI 1.21-5.77, p = 0.015), low APGAR score (aOR 3.75, 95% CI 1.12-12.5, p = 0.032) and 80.4g lesser birthweight (95% CI -153.0, -5.8; p = 0.034). More women in the low GWG category had LBW babies (28.6% versus 6.7% in the high GWG group, p = 0.033), lowest mean BW and median BW centiles (2775 grams versus 3289 grams in the high GWG group, p = 0.004 and 57.5% versus 74.5% in the high GWG group, p = 0.040, respectively). CONCLUSION: The findings of this study highlight differences in perinatal outcomes such as preterm birth, low birth weight, congenital anomalies, cesarean deliveries, and gestational weight gain between post-bariatric women and controls. These insights can help inform the planning and provision of appropriate maternity care to enhance patient safety and outcomes. The results of this study can also guide the counseling of reproductive age-group women who are planning to undergo bariatric surgery.

Maternal and neonatal outcomes associated with multiple repeat cesarean deliveries: A registry-based study from Qatar.

BACKGROUND: Cesarean delivery (CD) is associated with increased maternal and neonatal morbidity compared to vaginal delivery, particularly in cases classified as emergency procedures or when there are multiple CDs. This retrospective cohort study aims to examine the incidence of maternal and neonatal complications in women with multiple CDs. METHODS: This study used data from a national perinatal database obtained from a single tertiary maternity care hospital. Women who delivered a singleton live birth after 24 weeks of gestation by CD were stratified into five groups based on the number of CDs, with the last group having five or more CDs. The women were divided into those with five or more CDs (Group 5) versus those with fewer than five (Groups 1 to 4). The maternal outcomes included intra-operative surgical complications, blood loss, and intensive care unit (ICU) admission. The neonatal outcomes included preterm birth, neonatal ICU (NICU) admission, respiratory distress syndrome (RDS), and perinatal death. RESULTS: Of the 6,316 women in the study, 2,608 (41.3%) had a primary CD. 30.3%, 17.5%, and 7.3% of the cohort had their second, third, and fourth CDs, respectively. Women undergoing the 5th CD and above formed the remaining 3.5% (227). Women in Group 5 had the highest risk of suffering a surgical complication (3.1%, p = 0.015) and postpartum hemorrhage (7.5%, p = 0.010). 24% of babies in Group 5 were born preterm (p < 0.001). They also had a 3.5 times higher risk of having a surgical complication (RR = 3.5, 95% CI 1.6-7.6, p = 0.002), a 1.8 times higher risk of developing postpartum hemorrhage (RR = 1.8, 95% CI 1.1-2.9, p = 0.014), a 1.7 times higher risk of delivering between 32-37 weeks of gestation (RR = 1.7, 95% CI 1.3-2.2, p < 0.001), a higher risk of the baby getting admitted to NICU (RR = 1.3, 95% CI 1.0-1.6, p = 0.038), and developing RDS (RR = 1.5, 95% CI 1.2-2.0, p = 0.002) compared to Groups 1-4. The risks of neonatal outcomes such as NICU admission (RR 2.9, 95% CI 2.1-4.0) and RDS (RR 3.5, 95% CI 2.3-5.5) were much higher in elective CDs performed at term compared to preterm births (p < 0.001 for both). CONCLUSION: Maternal morbidity significantly increases with the increasing number of CD. The increased risk of RDS and NICU admissions in the neonate with multiple CDs reflects lower gestational age and birthweight in these groups-consideration of preoperative steroids for lung maturation in these women to reduce neonatal morbidity warrants further discussion.

Current Technologies and Future Perspectives in Immunotherapy towards a Clinical Oncology Approach.

Immunotherapy is now established as a potent therapeutic paradigm engendering antitumor immune response against a wide range of malignancies and other diseases by modulating the immune system either through the stimulation or suppression of immune components such as CD4+ T cells, CD8+ T cells, B cells, monocytes, macrophages, dendritic cells, and natural killer cells. By targeting several immune checkpoint inhibitors or blockers (e.g., PD-1, PD-L1, PD-L2, CTLA-4, LAG3, and TIM-3) expressed on the surface of immune cells, several monoclonal antibodies and polyclonal antibodies have been developed and already translated clinically. In addition, natural killer cell-based, dendritic cell-based, and CAR T cell therapies have been also shown to be promising and effective immunotherapeutic approaches. In particular, CAR T cell therapy has benefited from advancements in CRISPR-Cas9 genome editing technology, allowing the generation of several modified CAR T cells with enhanced antitumor immunity. However, the emerging SARS-CoV-2 infection could hijack a patient's immune system by releasing pro-inflammatory interleukins and cytokines such as IL-1ß, IL-2, IL-6, and IL-10, and IFN-γ and TNF-α, respectively, which can further promote neutrophil extravasation and the vasodilation of blood vessels. Despite the significant development of advanced immunotherapeutic technologies, after a certain period of treatment, cancer relapses due to the development of resistance to immunotherapy. Resistance may be primary (where tumor cells do not respond to the treatment), or secondary or acquired immune resistance (where tumor cells develop resistance gradually to ICIs therapy). In this context, this review aims to address the existing immunotherapeutic technologies against cancer and the resistance mechanisms against immunotherapeutic drugs, and explain the impact of COVID-19 on cancer treatment. In addition, we will discuss what will be the future implementation of these strategies against cancer drug resistance. Finally, we will emphasize the practical steps to lay the groundwork for enlightened policy for intervention and resource allocation to care for cancer patients.

Genomic insights and advanced machine learning: characterizing autism spectrum disorder biomarkers and genetic interactions.

Autism Spectrum Disorder (ASD) is a complex neurodevelopmental condition characterized by altered brain connectivity and function. In this study, we employed advanced bioinformatics and explainable AI to analyze gene expression associated with ASD, using data from five GEO datasets. Among 351 neurotypical controls and 358 individuals with autism, we identified 3,339 Differentially Expressed Genes (DEGs) with an adjusted p-value (≤ 0.05). A subsequent meta-analysis pinpointed 342 DEGs (adjusted p-value ≤ 0.001), including 19 upregulated and 10 down-regulated genes across all datasets. Shared genes, pathogenic single nucleotide polymorphisms (SNPs), chromosomal positions, and their impact on biological pathways were examined. We identified potential biomarkers (HOXB3, NR2F2, MAPK8IP3, PIGT, SEMA4D, and SSH1) through text mining, meriting further investigation. Additionally, we shed light on the roles of RPS4Y1 and KDM5D genes in neurogenesis and neurodevelopment. Our analysis detected 1,286 SNPs linked to ASD-related conditions, of which 14 high-risk SNPs were located on chromosomes 10 and X. We highlighted potential missense SNPs associated with FGFR inhibitors, suggesting that it may serve as a promising biomarker for responsiveness to targeted therapies. Our explainable AI model identified the MID2 gene as a potential ASD biomarker. This research unveils vital genes and potential biomarkers, providing a foundation for novel gene discovery in complex diseases.

Studying carrier frequency of spinal muscular atrophy in the State of Qatar and comparison to other ethnic groups: Pilot study.

BACKGROUND: Spinal muscular atrophy (SMA) is an autosomal recessive disease caused by mutations and deletions in SMN1 at exon 7. The carrier frequency for SMN1 mutations ranges from 2 to 4% in the general population. METHODS: We examined allelic, genotypic relatedness and copy number (CN) variations and frequencies of SMN1 and SMN2, in 13,426 samples from Qatar biobank (QBB) to provide a precise estimation of SMA carrier frequency in Qatar in comparison to other populations. RESULTS: The SMA carrier frequency was found to be (2.8%) and the rs143838139 was found in 491/13426 (3.66%) of individuals. The SNP rs121909192, which is a pathogenic risk factor, was found in 321/13500 (2.38%). In Addition 242/11379 (2.13%) had two copies of SMN1 and the rs143838139, which may explain the (2 + 0) silent carrier. Additionally, two participants were found to be SMA type 4 with 0 and 4 copy numbers in SMN1 and SMN2, respectively. CONCLUSION: The SMA carrier frequency in Qatar was found to be comparable to Saudi Arabia and Caucasians. The likely pathogenic variant, rs121909192, was found to be significantly higher when compering with other in our study. The rs143838139 variant, which has a strong association with the silent carrier genotype, has been found. Consequently, testing for this SNP may enhance the precision of evaluating the likelihood of a patient having an affected child. We conclude that the frequency of SMA carriers varies within the Qatar population and other ethnic groups.

High-sensitive detection and quantitation of thyroid-stimulating hormone (TSH) from capillary/fingerstick and venepuncture whole-blood using fluorescence-based rapid lateral flow immunoassay (LFIA).

Background: In the last decade, point of care testing (POCT) such as lateral flow immunoassays (LFIA) were developed for rapid TSH measurement. Most of these TSH-LFIAs are designed for qualitative measurements (i.e., if TSH values > 5, or >15 IU/L) and as screening tests for primary hypothyroidism in children and adults. Serum or plasma, but not venepuncture whole-blood or fingerstick/capillary, are usually used to quantify TSH accurately. Studies on performance evaluation of TSH-LFIAs POCT using venepuncture or fingerstick whole-blood are limited. Additionally, limited studies evaluated the performance and validity of TSH-LFIAs POCT compared to valid and reliable reference methods. To our knowledge, this is the first study to evaluate three different blood withdrawal techniques for evaluating POCT of TSH. Aim: We aim to evaluate the performance of a new fluorescence-based LFIA and its Finecare™ fluorescent reader for quantitative measurement of TSH from a fingerstick, venepuncture whole-blood, and serum. Methods: 102 fingerstick, venepuncture whole-blood, and serum samples (with normal and abnormal TSH values) were analyzed by Finecare™ Rapid Quantitative LFIA test and Roche CobasPro-c503 as a reference test. Results: Using serum, when compared to CobasPro-c503 reference method, Finecare™ showed high sensitivity [90.5 % (69.6-98.8)] and specificity [96.3 % (89.6-99.2)] for diagnosis of thyroid abnormalities (<0.35 or >4.5 mIU/L). The actual test values (mIU/L) of Finecare™ showed excellent agreement (Cohen's Kappa = 0.85) and strong correlation (r = 0.93, p < 0.0001) with CobasPro-c503. Using venepuncture whole-blood samples, Finecare™ showed similar results to serum with high sensitivity [95.2 % (76.2-99.9)], specificity [97.5 % (91.4-99.7)], excellent agreement (Cohen's Kappa = 0.91), and very strong correlation (r = 0.95, p < 0.0001) with CobasPro-c503. These results suggest that Finecare™ can be used for quantitative measurement of TSH using serum or venepuncture whole-blood. These key performance indicators were slightly decreased when fingerstick whole-blood samples were used: sensitivity [85.7 %(63.7-97)], specificity [90.0 %,(81.5-96)], good agreement (Cohen's Kappa = 0.7) and very strong correlation (r = 0.9, p < 0.0001) with CobasPro-c503. A subgroup analysis of abnormal TSH samples revealed a strong and significant correlation between the reference, Finecare™ whole-blood (r = 0.692; p = 0.0015), and fingerstick test Finecare™ (r = 0.66; p = 0.0025). A very strong correlation was also observed between Cobaspro-c508 serum and Finecare™ serum (r = 0.88; p < 0.0001). Conclusion: In comparison to the reference assay, our study demonstrates that Finecare™ exhibits high sensitivity, specificity, agreement, and a strong correlation. These findings provide evidence that Finecare™ is a reliable, valid, and accurate point-of-care test for TSH screening and quantitative measurement, especially in non- or small laboratory settings.

Follow up and comparative assessment of IgG, IgA, and neutralizing antibody responses to SARS-CoV-2 between mRNA-vaccinated naïve and unvaccinated naturally infected individuals over 10 months.

BACKGROUND: Evidence on the effectiveness of vaccination-induced immunity compared to SARS-CoV-2 natural immunity is warranted to inform vaccination recommendations. AIM: In this study, we aimed to conduct a comparative assessment of antibody responses between vaccinated naïve (VN) and unvaccinated naturally infected individuals (NI) over 10 Months. METHOD: The study comprised fully-vaccinated naïve individuals (VN; n = 596) who had no history of SARS-CoV-2 infection, and received two doses of either BNT162b2 or mRNA-1273, and naturally infected individuals who had a documented history of SARS-CoV-2 infection and no vaccination record (NI cohort; n = 218). We measured the levels of neutralizing total antibodies (NtAbs), anti-S-RBD IgG, and anti-S1 IgA titers among VN and NI up to ∼10 months from administration of the first dose, and up to ∼7 months from SARS-CoV-2 infection, respectively. To explore the relationship between the antibody responses and time, Spearman's correlation coefficient was computed. Furthermore, correlations between the levels of NtAbs/anti-S-RBD IgG and NtAbs/anti-S1 IgA were examined through pairwise correlation analysis. RESULTS: Up to six months, VN individuals had a significantly higher NtAb and anti-S-RBD IgG antibody responses compared to NI individuals. At the 7th month, there was a significant decline in antibody responses among VN individuals, but not NI individuals, with a minimum decrease of 3.7-fold (p < 0.001). Among VN individuals, anti-S1 IgA levels began to decrease significantly (1.4-fold; p = 0.007) after two months, and both NtAb and S-RBD IgG levels began to decline significantly (NtAb: 2.0-fold; p = 0.042, S-RBD IgG: 2.4-fold; p = 0.035) after three months. After 10 months, the most significant decline among VN individuals was observed for S-RBD-IgG (30.0-fold; P < 0.001), followed by NtAb (15.7-fold; P < 0.001) and S-IgA (3.7-fold; P < 0.001) (most stable). Moreover, after 5 months, there was no significant difference in the IgA response between the two groups. CONCLUSION: These findings have important implications for policymakers in the development of vaccination strategies, particularly in the consideration of booster doses to sustain long-lasting protection against COVID-19.

The impact of abnormal maternal body mass index during pregnancy on perinatal outcomes: a registry-based study from Qatar.

OBJECTIVES: Abnormal body mass index (BMI) during pregnancy, a growing public health concern, increases maternal and neonatal complications. This study aimed to investigate the impact of abnormal BMI on perinatal outcomes compared to normal BMI. METHODS: A total of 14,624 women having singleton births were categorized as underweight (BMI<18.5 kg/m2), overweight (25.0-29.9 kg/m2), obesity class I (30.0-34.9 kg/m2), obesity class II (35.0-39.9 kg/m2), and obesity class III (≥40.0 kg/m2) and compared to those with normal BMI (18.5-24.9 kg/m2). Outcomes included gestational diabetes (GDM), gestational hypertension (GHT), postpartum haemorrhage (PPH), cesarean delivery (CD), preterm birth (PTB), low birth weight (LBW), congenital anomalies and neonatal intensive care unit admission. RESULTS: Women with increasing BMI had increasingly higher odds of developing specific adverse outcomes, the highest being in the class III obesity group (GDM-aOR 2.71, 95 % CI 2.25-3.27, p<0.001, GHT-aOR 5.32 95 % CI 3.49-8.11, p<0.001, CD-aOR 2.33 95 % CI 1.85-2.94, p<0.001, PPH-aOR 1.77 95 % CI 1.35-2.33, p<0.001). On the other hand, being underweight during pregnancy was associated with increased odds of PTB (aOR 2.09, 95 % CI 1.37-3.20, p=0.001), LBW (OR 1.88, 95 % CI 1.27-2.79, p=0.002) and congenital anomalies (aOR 2.52 95 % CI 1.12-5.64, p=0.025). Majority in the underweight category gained less than expected gestational weight gain during the pregnancy. CONCLUSIONS: The findings of this study have important implications for the clinical management of pregnant women with abnormal BMI. Interventions to improve maternal and neonatal outcomes must focus on enhancing pre-pregnancy BMI and maintaining adequate gestational weight gain.

Impact of timing and severity of COVID-19 infection in pregnancy on intrauterine fetal growth- a registry-based study from Qatar.

BACKGROUND: The novel coronavirus disease (COVID-19) pandemic has impacted pregnant women, increasing maternal and neonatal morbidity. The placenta is a potential target for the pathophysiological processes due to the increased thrombotic inflammatory activation and inadequate uteroplacental perfusion and oxygenation, potentially causing intrauterine growth restriction. This study investigates the impact of gestational age at diagnosis of COVID-19 and the presence of symptoms on intrauterine fetal growth in pregnant women. METHODS: A retrospective review of COVID-19 positive pregnant women in Qatar from March 2020 to March 2021 was conducted. They were divided based on trimester of pregnancy in which they were infected. The outcomes included birthweight, customised fetal birthweight centiles, small for gestational age (SGA) baby and daily growth increments, compared between the trimesters and between symptomatic and asymptomatic women. RESULTS: In our cohort, 218 women (20.5%) were infected in the first trimester, 399 (37.5%) in the second and 446 (42%) in the third. Women in the second trimester were significantly younger and symptomatic. Women infected in the first trimester were least likely to have diabetes. The mean birthweight, risk of SGA (11.5% vs 10% vs 14.6%, p = 0.302), and median customized growth centiles (47.6% vs 45.9% vs 46.1%)were similar between the groups. Symptomatic women had significantly lower mean birthweight (3147 gms vs 3222 gms) and median birthweight centiles (43.9% vs 54.0%)compared to the asymptomatic (p<0.05 for both). In women infected within 20 weeks of gestation, a delay in daily fetal growth increments was noted with symptomatic disease, although not statistically significant. CONCLUSION: This study shows that women with symptomatic disease had lower birth centiles and birth weights. This was regardless of the gestational age at which they were infected. Early symptomatic disease seems to have an impact on fetal growth velocity; however, larger studies are needed to corroborate these findings.

Association of single nucleotide polymorphisms with dyslipidemia and risk of metabolic disorders in the State of Qatar.

BACKGROUND: Dyslipidemia is recognized as one of the risk factors of cardiovascular diseases (CVDs), type 2 diabetes mellitus (T2DM), and non-alcoholic fatty liver disease (NAFLD). OBJECTIVE: The study aimed to investigate the association between selected single nucleotide polymorphisms (SNPs) with dyslipidemia and increased susceptibility risks of CVD, NAFLD, and/or T2DM in dyslipidemia patients in comparison with healthy control individuals from the Qatar genome project. METHODS: A community-based cross-sectional study was conducted among 2933 adults (859 dyslipidemia patients and 2074 healthy control individuals) from April to December 2021 to investigate the association between 331 selected SNPs with dyslipidemia and increased susceptibility risks of CVD, NAFLD and/or T2DM, and covariates. RESULTS: The genotypic frequencies of six SNPs were found to be significantly different in dyslipidemia patients subjects compared to the control group among males and females. In males, three SNPs were found to be significant, the rs11172113 in over-dominant model, the rs646776 in recessive and over-dominant models, and the rs1111875 in dominant model. On the other hand, two SNPs were found to be significant in females, including rs2954029 in recessive model, and rs1801251 in dominant and recessive models. The rs17514846 SNP was found for dominant and over-dominant models among males and only the dominant model for females. We found that the six SNPs linked to gender type had an influence in relation to disease susceptibility. When controlling for the four covariates (gender, obesity, hypertension, and diabetes), the difference between dyslipidemia and the control group remained significant for the six variants. Finally, males were three times more likely to have dyslipidemia in comparison with females, hypertension was two times more likely to be present in the dyslipidemia group, and diabetes was six times more likely to be in the dyslipidemia group. CONCLUSION: The current investigation provides evidence of association for a common SNP to coronary heart disease and suggests a sex-dependent effect and encourage potential therapeutic applications.

Performance Evaluation of a New Fluorescent-Based Lateral Flow Immunoassay for Quantification of Hemoglobin A1c (HBA1c) in Diabetic Patients.

BACKGROUND: Rapid hemoglobin A1C (HbA1c) level monitoring is essential in slowing the progression of diabetes. This need becomes challenging in low resources countries where the social burden of the disease is overwhelming. Recently, fluorescent-based lateral flow immunoassays (LFIAs) gained wide attention for small laboratories and population surveillance. AIM: We aim to evaluate the performance of Finecare™ HbA1c Rapid Test, certified by CE, NGSP, and IFCC, for the quantitative measurement of hemoglobin A1C (HbA1c) along with its reader. METHODS: A total of 100 (fingerstick and venepuncture whole blood) samples were analyzed by Wondfo Finecare™ HbA1c Rapid Quantitative Test and the results were compared with the reference assay Cobas Pro c503. RESULTS: A strong correlation was observed between Finecare™/Cobas Pro c503 with fingerstick (r > 0.93, p < 0.0001) and venous (r > 0.97, p < 0.0001) blood samples. Finecare™ measurements showed excellent agreement and compliance with Roche Cobas Pro c503 as the mean bias was negligible; 0.05 (Limits-of-agreement: -0.58-0.68) with fingerstick and 0.003 (Limits-of-agreement: -0.49-0.50) with venous blood. Interestingly, a very small mean bias (0.047) was also shown between the fingerstick and the venepuncture data, indicating that the type of sample used does not affect the results and the high reproducibility of the assay. Finecare™ showed 92.0% (95% CI: 74.0-99.0) sensitivity and 94.7% (95% CI: 86.9-98.5) specificity compared to the Roche Cobas Pro c503 using fingerstick whole blood samples. Finecare™ showed 100% (95% CI: 86.3-100) sensitivity and 98.7% (95% CI: 92.8-100) specificity compared to the Cobas Pro c503 using venepuncture samples. Cohen's Kappa denoted excellent agreement with Cobas Pro c503; 0.84 (95% CI: 0.72-0.97) and 0.97 (95% CI: 0.92-1.00) using fingerstick and venous blood samples, respectively. Most importantly, Finecare™ showed a significant difference between normal, pre-diabetic, and diabetic samples (p < 0.0001). Similar results were obtained when an additional 47 samples (from different participants; mainly diabetic) were analyzed in a different lab using different Finecare™ analyzer and different kit lot number. CONCLUSIONS: Finecare™ is a reliable and rapid assay (5 min) which can be easily implemented for long-term monitoring of HbA1c in diabetic patients, particularly in small laboratory settings.

Management of chronic myeloid leukaemia: current treatment options, challenges, and future strategies.

ABSTRACTSmall molecule therapy is a critical component of targeted anticancer treatment, with tyrosine kinase inhibitors (TKIs) being the first compounds to treat the clonal Chronic Myelogenous Leukaemia (CML) translocation t (9;22) (q34; q11) effectively since 2001. TKIs, such as imatinib, have improved the 10-year survival rate of CML patients to 80%. They bind the BCR::ABL1 kinase and inhibit downstream signaling pathways. However, therapy failure may be seen in 20-25% of CML patients due to intolerance or inadequacy related to BCR::ABL1 dependent or independent mechanisms. This review aimed to summarize current treatment options involving TKIs, resistance mechanisms and the prospective approaches to overcome TKI resistance. We highlight BCR::ABL1-dependent mechanisms of TKI resistance by reviewing clinically-documented BCR::ABL1 mutations and their consequences for TKI binding. In addition, we summarize BCR::ABL1 independent pathways, including the relevance of drug efflux, dysregulation of microRNA, and the involvement of alternative signaling pathways. We also discuss future approaches, such as gene-editing techniques in the context of CML, as potential therapeutic strategies.

Prevalence, predictors, and outcomes of major congenital anomalies: A population-based register study.

Congenital anomalies (CAs) are a leading cause of morbidity and mortality in early life. We aimed to assess the incidence, risk factors, and outcomes of major CAs in the State of Qatar. A population-based retrospective data analysis of registry data retrieved from the Perinatal Neonatal Outcomes Research Study in the Arabian Gulf (PEARL-Peristat Study) between April 2017 and March 2018. The sample included 25,204 newborn records, which were audited between April 2017 and March 2018, of which 25,073 live births were identified and included in the study. Maternal risk factors and neonatal outcomes were assessed for association with specific CAs, including chromosomal/genetic, central nervous system (CNS), cardiovascular system (CVS), facial, renal, multiple congenital anomalies (MCAs) using univariate and multivariate analyses. The incidence of any CA among live births was 1.3% (n = 332). The most common CAs were CVS (n = 117; 35%), MCAs (n = 69, 21%), chromosomal/genetic (51; 15%), renal (n = 39; 12%), CNS (n = 20; 6%), facial (14, 4%), and other (GIT, Resp, Urogenital, Skeletal) (n = 22, 7%) anomalies. Multivariable regression analysis showed that multiple pregnancies, parity ≥ 1, maternal BMI, and demographic factors (mother's age and ethnicity, and infant's gender) were associated with various specific CAs. In-hospital mortality rate due to CAs was estimated to be 15.4%. CAs were significantly associated with high rates of caesarean deliveries (aOR 1.51; 95% CI 1.04-2.19), Apgar < 7 at 1 min (aOR 5.44; 95% CI 3.10-9.55), Apgar < 7 at 5 min (aOR 17.26; 95% CI 6.31-47.18), in-hospital mortality (aOR 76.16; 37.96-152.8), admission to neonatal intensive care unit (NICU) or perinatal death of neonate in labor room (LR)/operation theatre (OT) (aOR 34.03; 95% CI 20.51-56.46), prematurity (aOR 4.17; 95% CI 2.75-6.32), and low birth weight (aOR 5.88; 95% CI 3.92-8.82) before and after adjustment for the significant risk factors. This is the first study to assess the incidence, maternal risk factors, and neonatal outcomes associated with CAs in the state of Qatar. Therefore, a specialized congenital anomaly data registry is needed to identify risk factors and outcomes. In addition, counselling of mothers and their families may help to identify specific needs for pregnant women and their babies.

Protein Tyrosine Phosphatase Receptor Gamma as Potential Therapeutic Target for Chronic Myeloid Leukemia Patients.

The worldwide CML incidence expects 100,000 patients every year thus representing a substantial health burden. A year 2000 is notable year, where Tyrosine kinase inhibitors (TKIs) had been introduced to the CML treatment plan. However, despite the dramatically reduce in mortality rate of CML patients due to TKIs, still over 25% of CML patients need to switch TKIs at least once during treatment timeline for many reasons. On the other hand, PTPRG behave as a tumor suppressor gene in different neoplasms and is strongly down-regulated in CML patients. We discussed briefly in series of articles the possible reasons of it is down regulation. Here, we discuss its role as potential therapeutic target in treatment plan.

Neutralizing antibodies against SARS-CoV-2 are higher but decline faster in mRNA vaccinees compared to individuals with natural infection.

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 < 0.001) than the NI group at P-I, except for IgM. In the VN group, a significant waning in antibody response was observed in all isotypes. There was about an ~ 4-fold decline in NTAb levels (P < 0.001), anti-S-RBD-IgG (~5-fold, P < 0.001), anti-S-RBD-IgM (~6-fold, P < 0.001) and anti-S1-IgA (2-fold, P < 0.001). In the NI group, a significant but less steady decline was notable in S-RBD-IgM (~2-fold, P < 0.001), and a much smaller but significant difference in NTAb (<2-fold, P < 0.001) anti-S-RBD IgG (<2-fold, P = 0.005). Unlike the VN group, the NI group mounted a lasting anti-S1-IgA response with no significant decline. Anti-S1-IgA, which were ~ 3-fold higher in VN subjects compared with NI in P-1 (P < 0.001), dropped to almost the same levels, with no significant difference observed between the two groups in P-II. CONCLUSION: Whereas double-dose mRNA vaccination boosted antibody levels, vaccinated individuals' 'boost' was relatively short-lived.