Establishment of reference interval for hemoglobin A1C and other hemoglobin subfractions for healthy Saudi adults.

BACKGROUND: The establishment of Reference Intervals (RIs) for Hemoglobin A1C and other hemoglobin subfractions (A1A, A1B, F, LA1C, A0) is of utmost importance in screening, diagnosing, and monitoring diabetes and other hemoglobin abnormalities through the application of high-pressure liquid chromatography (HPLC) technique. Because there are no locally established RIs for these parameters, it is essential to establish RIs specific to the Saudi population to accurately diagnose and monitor diabetic individuals and identify abnormal levels in hemoglobin subfractions. METHODS: As part of the IFCC global multicenter study of laboratory reference values, a cross-sectional study was conducted in Saudi Arabia. The study involved recruiting a total of 381 healthy adult subjects (>18 years, BMI 28.3 ± 6 kg/m2). Blood samples were analyzed for A1C, biochemical and other immunoassay parameters. The need for RIs based on sex, age, and BMI was determined using the standard deviation ratio (SDR) through a 3-level nested ANOVA. RESULTS: Based on the threshold of SDR≥0.4, RIs for A1C and other Hb subfractions were not partitioned by sex or BMI, but partitioned by age (<45 & ≥45 years) for A1C, LA1C, A0 and F. Spearman's correlation between glucose, insulin, and C-peptide showed a positive association with different hemoglobin subtractions of A1B, F, A1C, and LA1C. The RIs were obtained by using the parametric method and the latent abnormal values exclusion (LAVE) principle was applied on A1C. CONCLUSION: This study established RIs for A1C and other Hb subfractions for healthy adult Saudis. Age was found to be an important source of variation for most of the parameters including A1C. These findings will enhance the understanding and clinical decision-making concerning A1C and other hemoglobin subfractions. The elevated upper limit of RIs for A1C reflects the high prevalence of diabetes in the Saudi population specially in those with increased age.

Integrated water quality dynamics in Wadi Hanifah: Physical, chemical, and biological perspectives.

The Wadi Hanifah, a crucial aquatic ecosystem, has unfavorable consequences from natural occurrences and human activities. Recognizing the critical need for sustainable water management, this study provides an in-depth evaluation of wadi water quality. A comprehensive assessment was conducted, analyzing physical properties (temperature, pH, electrical conductivity, turbidity, color, and odor), chemical constituents (nitrogen compounds, ion concentrations, heavy metals), and bacterial diversity. The study found significant temperature fluctuations, particularly in sun-exposed or stagnant water areas. The water exhibited slight alkalinity and variable electrical conductivity and turbidity, indicating differing pollution levels. High ammonia and heavy metal concentrations suggested organic and industrial contamination, respectively. In addition, the prevalent fecal-indicator bacteria pointed to possible sewage or agricultural runoff. The research highlights the complex interplay of natural and anthropogenic factors affecting Wadi Hanifah's water quality. It emphasizes the need for location-specific environmental management strategies focusing on pollution control and conservation to safeguard the wadi's ecological health. This study provides vital insights for effective water resource management in Wadi Hanifah, serving as a model for similar ecosystems.

Correlation Between C-Reactive Protein and Lipid Analytes in Dry Age-Related Macular Degeneration: A Retrospective Study.

INTRODUCTION: To date few studies have investigated the correlation between inflammatory markers and lipoproteins in the serum of age-related macular degeneration (AMD) patients, often reporting conflicting findings. This study aimed to investigate the correlation between lipid analytes and C-reactive protein (CRP) levels in individuals diagnosed with dry AMD. METHODS: A standard clinical lipid panel (total cholesterol, triglycerides, high-density lipoprotein [HDL], and low-density lipoproteins) and CRP laboratory results were retrospectively collected from the medical records of patients with dry AMD and age- and sex-matched controls. RESULTS: The study included 90 patients with dry AMD and 270 patients without AMD. In univariate analysis, CRP showed a higher mean value in cases than in controls. After adjusting for age and sex, CRP and triglyceride levels showed significant differences between cases and controls. Pearson's correlation analysis revealed a significant negative correlation between CRP and HDL levels in the dry AMD group (n=90). Other lipid analytes showed no significant correlations with CRP. CONCLUSION: Our findings add to the growing body of evidence linking inflammation to AMD. Although it is unclear whether changes in serum CRP and triglyceride levels are the causes or effects, monitoring both analytes may be beneficial as an early disease predictor, especially in individuals with a family history of AMD. The negative correlation between CRP and HDL (i.e., inflammation and good cholesterol) may be targeted for future therapies.

Enzyme Production and Inhibitory Potential of Pseudomonas aeruginosa: Contrasting Clinical and Environmental Isolates.

(1) Background: This study summarizes the findings of two studies investigating the inhibitory effects of Pseudomonas aeruginosa strains from clinical and environmental sources against gram-positive and gram-negative bacteria and fungi. The studies also analyzed the correlation between enzyme production and inhibitory effects to gain insights into the antimicrobial capabilities of P. aeruginosa strains; (2) Methods: Both studies employed similar methodologies, including the use of disk diffusion and well diffusion methods to assess the inhibitory effects of P. aeruginosa strains against target pathogens. Enzyme production was analyzed through various biochemical assays to determine the diversity and frequencies of enzyme secretion among the strains; (3) Results: A comparative analysis of enzyme production in P. aeruginosa strains from clinical sources revealed significant variations in enzyme production, with hemolysin and protease being the most commonly produced enzymes. Gelatinase production showed lower rates, whereas chondroitinase and hyaluronidase were absent or occurred less frequently. In contrast, a comparative analysis of enzyme production in environmental isolates showed different patterns, indicating adaptation to environmental conditions. Pyocyanin production was absent in all environmental isolates. The inhibitory effects against gram-positive and gram-negative bacteria varied among different P. aeruginosa strains, with strain-specific variations observed. Limited inhibitory effects were observed against fungi, primarily toward gram-positive bacteria; (4) Conclusions: The findings highlight the strain-specific nature of inhibitory effects and enzyme production in P. aeruginosa strains. The correlation between enzyme production and inhibitory effects against gram-positive bacteria suggest a potential role of specific enzymes, such as hemolysin and protease, in the antimicrobial activity. The complexity of the relationship between enzyme production and the inhibition of different pathogens requires further investigation. The results emphasize the potential of P. aeruginosa strains as sources for antimicrobial strategies, particularly against gram-positive bacteria. Future research should focus on understanding the mechanisms underlying these inhibitory effects and exploring their therapeutic applications.

Assessment of the Knowledge and Opinions of Undergraduate Health Care Students Concerning Influenza Vaccination in Saudi Arabia: A Cross-Sectional Study.

Introduction: Influenza remains a significant global public health challenge, causing substantial morbidity and mortality worldwide. Despite the availability of influenza vaccines, challenges related to vaccine hesitancy and healthcare professionals' attitudes persist. Furthermore, there is a need to understand the knowledge and opinions of undergraduate healthcare students regarding influenza vaccinations. Therefore, we aimed to assess and compare the knowledge and opinions of undergraduate healthcare students about influenza vaccinations, addressing the existing knowledge gap in this area. Methods: We employed a cross-sectional study design to assess the opinions and knowledge of undergraduate healthcare students in Saudi Arabia regarding influenza vaccination. A total of 137 healthcare programs were invited to participate via filled-out the survey online. Data analysis was performed using SPSS, with descriptive statistics for the demographic profile and Chi-Square and independent t-tests for examining associations and differences in opinions and knowledge, respectively. Results: A total of 429 undergraduate students completed the survey and were included. Significant associations were found between the students' major and their beliefs regarding the effectiveness of the vaccine in preventing influenza (p=0.017) and the inclusion of influenza vaccines in medical practice (p=0.016). The majority of students agreed with seven out of nine knowledge statements, with agreement percentages ranging from 42.9% to 44.8%. When comparing knowledge scores, students majoring in medicine had a significantly higher mean knowledge score (3.91) compared to students studying other medical sciences (3.72) (p=0.019). Conclusion and Recommendations: Our study suggests that a comprehensive approach involving education, awareness initiatives, and policy changes is needed to enhance knowledge about influenza vaccination among Saudi Arabian undergraduate students in Medical School allied medical sciences and medical degree programs. By implementing these strategies, we can promote a positive attitude towards flu vaccination and ultimately increase its uptake.

From Hospital to Community: Exploring Antibiotic Resistance and Genes Associated with Virulence Factor Diversity of Coagulase-Positive Staphylococci.

Coagulase-positive staphylococcus (CoPS), including methicillin-resistant Staphylococcus aureus (MRSA), poses a global threat. The increasing prevalence of MRSA in Saudi Arabia emphasizes the need for effective management. This study explores the prevalence of virulence-associated genes and antibiotic resistance patterns in CoPS. Nasal swabs from 200 individuals were collected, and standard protocols were used for the isolation, identification, and characterization of CoPS and coagulase-negative staphylococci (CoNS). Additionally, antimicrobial susceptibility testing and PCR were conducted. Bacterial growth was observed in 58.5% of participants, with 12% positive for CoPS and 30% positive for CoNS. Hospital personnel carriers showed a significantly higher proportion of CoNS compared with non-hospital personnel carriers. Non-hospital personnel CoPS strains displayed higher sensitivity to oxacillin than hospital personnel strains. Cefoxitin exhibited the highest sensitivity among ß-lactam antibiotics. All isolates were sensitive to trimethoprim/sulfamethoxazole, rifampin, and quinupristin. Polymerase chain reaction analysis detected methicillin resistance genes in both non-hospital and hospital personnel MRSA strains. The coa and spa genes were prevalent in MRSA isolates, while the Luk-PV gene was not detected. A high prevalence of CoPS and CoNS was observed in both non-hospital and hospital personnel carriers. Occupational risk factors may contribute to the differences in the strain distribution. Varying antibiotic susceptibility patterns indicate the effectiveness of oxacillin and cefoxitin. Urgent management strategies are needed due to methicillin resistance. Further research is necessary to explore additional virulence-associated genes and develop comprehensive approaches for CoPS infection prevention and treatment in Saudi Arabia.

Immunoglobulin A levels and its correlation with neutrophil-to-lymphocyte ratio as inflammatory biomarkers for dry eye disease in type 2 diabetes: a retrospective study.

Background: The neutrophil-to-lymphocyte ratio (NLR) and immunoglobulin A (IgA) level are commonly used as biomarkers for inflammation. Patients with type 2 diabetes (T2D) may experience an imbalance of tear film and inflammation, which can result in dry eye disease (DED). This study aimed to assess the levels of IgA and explore its correlation with the NLR as potential inflammatory biomarkers for dry eye disease in patients with T2D. Methods: A retrospective study was conducted at the cornea clinic and diabetes centre of King Abdulaziz Medical City (Jeddah, Saudi Arabia). The study included patients with DED and the number of available T2D-DED patients determined the sample size. Neutrophil, lymphocyte, IgA and CRP (C-reactive protein) laboratory values were obtained from medical records and correlational analyses were performed. Results: The study included 85 patients with an average age of 54 ± 14.4 years for the DED group (n=32) and 62 ± 13.9 years for the T2D-DED group (n=53). The age difference between the two groups was statistically significant (p 0.0001). The NLR values of the T2D-DED and DED groups were 3.203 ± 0.66 and 2.406 ± 0.46, respectively, with no significant difference (p<0.285). Similarly, there were no significant differences in neutrophil and lymphocyte values between the two groups. The IgA levels showed no significant variation between T2D-DED and DED groups (p<0.364). Spearman's correlation analysis in the DED group showed a significant negative correlation between IgA and lymphocyte (p=0.011; r= - 0.471) values and significant positive correlations between IgA and neutrophil (p=0.014; r=0.309) and NLR (p=0.052; r= - 0.283) values. In the T2D-DED group, a significant correlation was found between IgA and CRP values (p=0.032; r=0.33). Conclusion: Although diabetic patients may exhibit higher levels of NLR and IgA that correlate with disease severity, our study did not find significant differences in NLR and IgA values between the two groups. These findings may guide future research and enhance understanding of the disease's underlying mechanisms.

Assessment of aggregate index of systemic inflammation and systemic inflammatory response index in dry age-related macular degeneration: a retrospective study.

Introduction: Inflammation is known to contribute to the development of age-related macular degeneration (AMD). Several inflammatory indices derived from routine complete blood counts have been proposed as biomarkers in multiple disorders. Methods: In this study, clinical and laboratory data were retrospectively collected from medical records to assess the aggregate index of systemic inflammation (AISI) and the systemic inflammatory response index (SIRI) as potential biomarkers of systemic inflammation in patients with early diagnosis of dry AMD. Results: The study included 90 patients with dry AMD and 270 age/sex-matched patients with cataracts as a control group. There were no significant differences in the AISI and SIRI results between the cases and controls (p = 0.16 and 0.19, respectively). Conclusion: This suggests that AISI and SIRI may be inadequate metrics for AMD or lack sensitivity in detecting inflammatory changes. Exploring other routine blood markers may help to identify and prevent the early stages of AMD.

The diagnostic yield of CGH and WES in neurodevelopmental disorders.

Background: Neurodevelopmental disorders are a group of conditions characterized by developmental delays leading to abnormal brain functions. The methods of diagnosis and treatment of these conditions are complicated, and their treatment involves a combination of various forms of therapy. In recent years, the development of high-resolution technologies has played an important role in revealing the microdeletions, microduplications, and single-nucleotide variants of the chromosomes and how they are linked to the development of neurodevelopmental disorders. The wide implementation and application of molecular methodologies have started to shed light on the functional importance of using the appropriate methods in detecting these genetic variations that are categorized as either pathogenic or benign. The study aimed to compare the diagnostic yield of comparative hybridization (CGH) and whole exome sequencing (WES) in neurodevelopmental disorders among children attending the King Abdullah Specialist Children Hospital, Riyadh, Saudi Arabia. Methods: A retrospective study was conducted between 2015 and 2018 on 105 patients diagnosed with neurodevelopmental disorders through array-based CGH (Array-CGH) and WES. Results: In a sample of 105 patients, 16% was the hit rate of copy number variations (CNVs). WES was requested for CNV-negative patients (n = 79), of which 30% was the hit rate of pathogenic or likely pathogenic single-nucleotide variants. There was a difference in the diagnostic yield between CGH (16%) and WES (30%). Conclusion: WES was a better approach than Array-CGH to detect various DNA mutations or variants. Our findings could guide clinicians, researchers, and testing laboratories select the most cost-effective and appropriate approach for diagnosing their patients.

Establishment of reference intervals for hematological parameters of adult population in the western region of Saudi Arabia.

BACKGROUND: Most of hematology laboratories in Saudi Arabia utilize the reference intervals (RIs) provided by instrument manufacturers. This study aimed to define RIs of hematological parameters for adult population in the western region of Saudi Arabia and to explore their specific features from an international perspective. METHOD: This study was conducted according to the harmonized protocol of IFCC Committee on RIs and Decision Limits. Blood samples collected from 409 healthy Saudi males and females adults were analyzed for complete blood count (CBC) by using Cell-Dyn Sapphire analyzer and for iron profile by using Architect analyzers. The needs for RIs partitioned by sex and age was based on standard deviation ratio (SDR) and/or bias ratio (BR). RIs were derived parametrically with/without application of the latent abnormal values exclusion method (LAVE). RESULTS: Based on thresholds of SDR≥0.4 and/or BR≥0.57, RIs were partitioned by sex for red-blood cell count, hemoglobin, hematocrit, red cell distribution width, erythrocyte sedimentation rate, iron, transferrin, ferritin, eosinophil, platelet, plateletcrit, etc. Partitioning by age was not necessary for any of the analytes. LAVE procedure caused appreciable changes in RI limits for most erythrocyte and iron parameters but not for leukocyte parameters. Comparable to other non-IFCC studies on CBC RIs, the RBC and hematocrit (Ht) ranges have shifted to a higher side in both genders. After applying the LAVE method, the male and female RIs for Hb were 4.56 to 6.22 ×106/µL and 3.94 to 5.25 ×106/µL respectively while RIs for Ht were 40.2 to 52.0% and 33.6 to 44.5% respectively. CONCLUSION: LAVE method contributed to reducing the influence of latent anemia in deriving RIs for erythrocyte related parameters. Using the up-to-date methods, the RIs of CBC determined specifically for Saudis will help to improve the interpretation of test results in medical decision making.

Investigating Neutrophil-to-Lymphocyte and C-Reactive Protein-to-Albumin Ratios in Type 2 Diabetic Patients with Dry Eye Disease.

BACKGROUND: Patients with Diabetes mellitus (DM) are at risk of developing dry eye disease (DED). We investigated routine laboratory parameters in patients with type 2 DM (T2D) and T2D-DED to identify potential inflammatory markers. METHODS: A retrospective study of 241 randomly selected patients (30 DED non-diabetic, 120 T2D, and 91 with T2D-DED). The neutrophil-to-lymphocyte ratios (NLR), CRP-to-albumin ratios (CAR), and the glycosylated haemoglobin A1c (HbA1c) results were correlated between groups. RESULTS: The NLR and HbA1c were significantly higher in the T2D-DED group (p≤0.001 and 0.0001, respectively) when compared with T2D and DED non-diabetic groups. CAR was insignificantly high in the three groups (p=0.192). A positive correlation was identified between CAR and NLR in T2D-DED patients (p= 0.008). CONCLUSION: In T2D-DED patients, NLR was significantly high and positively correlate with CAR. These results predicate diabetes with dry eye complications, and biomarker-mediated inflammation may have important roles in DED pathogenesis.

Anolis carolinensis as a model to understand the molecular and cellular basis of foveal development.

The fovea is an anatomical specialization of the central retina containing closely packed cone-photoreceptors providing an area of high acuity vision in humans and primates. Despite its key role in the clarity of vision, little is known about the molecular and cellular basis of foveal development, due to the absence of a foveal structure in commonly used laboratory animal models. Of the amniotes the retina in birds of prey and some reptiles do exhibit a typical foveal structure, but they have not been studied in the context of foveal development due to lack of availability of embryonic tissue, lack of captive breeding programs, and limited genomic information. However, the genome for the diurnal bifoveate reptile species Anolis carolinensis (green anole) was recently published and it is possible to collect embryos from this species in captivity. Here, we tested the feasibility of using the anole as a model to study foveal development. Eyes were collected at various stages of development for histological analysis, immunofluorescence, and apoptosis. We show that at embryonic stage (ES) 10 there is peak ganglion cell density at the incipient central foveal region and a single row of cone photoreceptor nuclei. At ES17 the foveal pit begins to form and at this stage there are 3-4 rows of cone nuclei. Post-hatching a further increase in cone density and lengthening of inner and outer segments is observed. A yellowish pigment was seen in the adult central foveal region, but not in the temporal fovea. At ES14 Pax6 was localized across the entire retina, but was more prominent in the ganglion cell layer (GCL) and the part of the inner nuclear layer (INL) containing amacrine cell bodies. However, at ES17 Pax6 expression in the ganglion cells of the central retina was markedly reduced. Bioinformatic analysis revealed that 86% of human candidate foveal hypoplasia genes had an orthologous gene or DNA sequence in the green anole. These findings provide the first insight into foveal morphogenesis in the green anole and suggest that it could be a very useful model for investigating the molecular signals driving foveal development, and thus inform on human foveal development and disease.

Correlation of novel PAX6 gene abnormalities in aniridia and clinical presentation.

OBJECTIVE: To describe the clinical presentation and genotype of subjects with aniridia with a particular focus on foveal hypoplasia. DESIGN: Prospective cohort study. PARTICIPANTS: Thirty-three Canadian participants with aniridia and of various ethnic backgrounds residing in British Columbia. METHODS: Full ophthalmic examinations and posterior segment spectral domain-optical coherence tomography (SD-OCT) imaging were performed. Foveal hypoplasia was graded independently by 2 staff ophthalmologists. PAX6 sequencing was performed and chromosomal 11p anomalies investigated. Candidate gene and single-nucleotide polymorphism sequencing in genes functionally related to PAX6 were also studied. RESULTS: Best corrected visual acuities in the cohort ranged from 0.0 logMAR to no light perception. Total absence of iris tissue was seen in the majority (42 of 66 eyes). In those in whom SD-OCT was possible, foveal hypoplasia was seen in the majority (45 of 56 eyes, 80%). Molecular genetic defects involving PAX6 were identified in 30 participants (91%), including 4 novel PAX6 mutations (Gly18Val; Ser65ProfsX14; Met337ArgfsX18; Ser321CysfsX34) and 4 novel chromosome 11p deletions inclusive of PAX6 or a known PAX6 regulatory region. CONCLUSIONS: The number of PAX6 mutations associated with aniridia continues to increase. Variable foveal architecture despite nearly identical anterior segment disease in 4 participants with an Ex9 ELP4-Ex4 DCDC1 deletion suggested that molecular cues causing variation in disease in the posterior segment differ from those at play in the anterior segment. Results in 3 patients without identifiable PAX6 mutations and a review of the literature suggest that such cases be described as phenocopies rather than actual cases of the syndrome of aniridia.