PDE4B Proposed as a High Myopia Susceptibility Gene in Chinese Population

Myopia is the most common cause of refractive error worldwide. High myopia is a severe type of myopia, which usually accompanies pathological changes in the fundus. To identify high myopia susceptibility genes, DNA-pooling based genome-wide association analysis was used to search for a correlation between single nucleotide polymorphisms and high myopia in a Han Chinese cohort (cases vs. controls in discovery stage: 507 vs. 294; replication stage 1: 991 vs. 1,025; replication stage 2: 1,021 vs. 52,708). Three variants (rs10889602T/G, rs2193015T/C, rs9676191A/C) were identified as being significantly associated with high myopia in the discovery, and replication stage. rs10889602T/G is located at the third intron of phosphodiesterase 4B (PDE4B), whose functional assays were performed by comparing the effects of rs10889602T/T deletion of this risk allele on PDE4B and COL1A1 gene and protein expression levels in the rs10889602T/Tdel/del, rs10889602T/Tdel/wt, and normal control A549 cell lines. The declines in the PDE4B and COL1A1 gene expression levels were larger in the rs10889602T/T deleted A549 cells than in the normal control A549 cells (one-way ANOVA, p < 0.001). The knockdown of PDE4B by siRNA in human scleral fibroblasts led to downregulation of COL1A1. This correspondence between the declines in rs10889602 of the PDE4B gene, PDE4B knockdown, and COL1A1 protein expression levels suggest that PDE4B may be a novel high myopia susceptibility gene, which regulates myopia progression through controlling scleral collagen I expression levels. More studies are needed to determine if there is a correlation between PDE4B and high myopia in other larger sample sized cohorts.

Association Between IL-23 And Coronary Arterial Lesions In Children With Kawasaki Disease

The pathogenesis of coronary artery lesions (CALs) in KD patients has been thought of as an unknown stimulus that triggers an inflammatory cascade with activation of the immune system. However, interleukin-23 (IL-23) is supposed as a key cytokine in inflammatory and autoimmunity diseases. The role of IL-23 in the pathogenesis of CALs has not been fully elucidated. This study explored the relationship between the serum IL-23 levels and CALs in patients with KD. We collected blood specimens from 90 children with KD before intravenous immunoglobulin (IVIG) therapy. Levels of IL-23, IL-6, IL-17A, IL-10, MCP-1 and VEGF were measured in 190 cases, including 4 groups: KD with CALs (n = 46), KD without CALs (n = 44), febrile control group, (FC, n = 40) and normal control group, (NC, n = 60). Clinical parameters were tested in all subjects. IL-23 was significantly elevated in the KD group compared with the febrile and normal control groups, especially increased in the KD patients with CALs. Serum levels of IL-23 in KD patients were positively associated with WBC, CRP, IL-6, IL-17A, IL-10, MCP-1, and VEGF in children with KD. IL-23 may be involved in the pro-inflammatory process and the pathogenesis of CALs in KD patients.

Formulation of Cinchona Extract (Cinchona succirubra) Cream and The Safety as Hair Fertilizer

Background: cinchona extract contains quinoline alkaloids, has telangiectatic activity, is practically insoluble in water so penetration into hair follicles is low and requires a delivery system, namely cream. Objective: to determine the formula of cinchona extract cream with good activity, physical stability and safety. Methodology: cinchona bark extraction (soxhletation method), phytochemical screening, cinchona extract dosage determination, optimization of cream formula using Design Expert software version 11. Evaluation: pH, adhesion, spreadability, viscosity and cycling test stability. Activity test using guinea pigs (Cavia porcellus) for 14 days, parameters of hair length/2 days, hair mass (14th day). Acute dermal irritation test using rabbit (Orycogalus cuniculus) by erythema and edema index parameters. Results: cinchona extract (13.32% yield) contained quinoline alkaloids, cinchona extract dosage was 20% (p<0.05). The optimum formula is F2 with characteristics: pH 6.48±0.07, adhesion 1.16±0.07, spreadability 4.99±0.85 and viscosity 3067±416.45, has good physical stability. Activity test: test area hair length 13.54 – 62.14% longer than normal control and 10.10 – 49.17% than negative control. The hair mass of test area was 122.91% heavier than normal control and 104.48% of negative control (p<0.05). Cinchona extract and excipients were non-irritant. Conclusion: Cinchona extract cream (20%) has hair fertilizer activity, good physical stability and safety.

Inter-eye Differences in Ocular Biometric Parameters of Concomitant Exotropia

Purpose: To evaluate the ocular biometric parameters in patients with constant and intermittent exotropia by the measurement of swept-source optical coherence tomography (SS-OCT) optical biometer OA-2000 and comparing it with the normal control subjects.Design: Cross-sectional case-control study.Participants: Fifty-five constant and 24 intermittent patients with exotropia with central fixation and 77 orthotropic normal control participants aged 4–18 years old.Methods: Non-contact and high-resolution optical biometric OA-2000 measurements were conducted under uniform ambient light conditions. The statistical analysis included intraclass correlation coefficient (ICC), Bland-Altman plot, and independent t-tests.Main Outcome Measures: Spherical equivalent (SE), ocular biological parameters such as pupil diameter (PD), anterior chamber depth (ACD), lens thickness (LT), and axial lengths (AL). The absolute values of inter-eye differences for SE, PD, ACD, LT, and AL were recorded as AnisoSE, AnisoPD, AnisoACD, AnisoLT, and AnisoAL, respectively.Results: AnisoSE (0.878 vs. 0.577, P = 0.019), AnisoAL (0.395 vs. 0.208, P = 0.001), AnisoACD (0.060 vs. 0.032, P &lt; 0.001), AnisoLT (0.060 vs. 0.031, P = 0.002), and AnisoPD (0.557 vs. 0.340, P = 0.002) were significantly larger in concomitant patients with exotropia. The SE, AL, ACD, LT, and PD showed excellent binocular correlation with ICC values that ranged from 0.943 to 0.987 in control participants and from 0.767 to 0.955 in concomitant exotropia patients. Bland-Altman plots showed the wider range of agreement in patients with concomitant exotropia than the control participants (SE: 5.0288 vs. 3.3258; AL: 2.2146 vs. 1.3172; ACD:0.3243 vs. 0.1682; PD: 2.4691 vs. 1.9241; and LT:0.3723 vs 0.1858).Conclusion: Patients with concomitant exotropia showed larger inter-eye differences in SE, ACD, LT, PD, and AL. Advice should be given to suspicious children to avoid or delay the development of concomitant exotropia.

The quantitative measurements of choroidal thickness and volume in diabetic retinopathy using optical coherence tomography and optical coherence tomography angiography; correlation with vision and foveal avascular zone

Background To represent choroidal thickness (CT) and choroidal volume (CV) databases in diabetic retinopathy (DR) patients and healthy control participants using optical coherence tomography (OCT) and enhanced depth imaging OCT (EDI-OCT). No study had evaluated CT at all main stages of diabetic retinopathy in a single study. Methods The study included 176 eyes from 93 patients (39–80 years old; 42% females) who were divided into three groups based on DR severity and normal control group: 39 eyes no DR, 64 eyes NPDR, 33 eyes PDR, and 40 eyes normal control. The CT and CV were measured and statistically analyzed. Intra-observer and inter-observer coefficients of repeatability were calculated. Results Subfoveal CT showed persistent thinning from normal group (322.50 ± 69.24) to no-diabetic retinopathy (NDR, 308.33 ± 74.45) to nonproliferative diabetic retinopathy (NPDR, 283.45 ± 56.50) group and then thickening as the patient progressed to proliferative diabetic retinopathy (PDR, 295.17 ± 95.69) (P = 0.087). A significant difference was found between the control group and the NDR, NPDR, and PDR groups in nearly all CT and CV of Early Treatment Diabetic Retinopathy Study macular subfields. Fasting blood sugar (FBS = 189.08 ± 51.3 mg/dl) and diabetes mellitus (DM) duration (13.6 ± 6.5 years) had no noticeable effect on CT. In patients with diabetes, the best-corrected visual acuity (BCVA), diabetic macular edema (DME), and foveal avascular zone (FAZ) were not affected by CT and CV. Conclusions The choroidal thickness decreases from the early stages of diabetic retinopathy up to the NPDR stage, with a subsequent modest rise in CT during the PDR stage. There was no correlation between FBS, diabetes duration, BCVA, DME, and FAZ, and CT.

Role of Transcription Factor 7 like 2 and Silent Information Regulator 1 Genes in the Development of Cardiovascular Complications in a Group of Egyptian Patients with Chronic Kidney Disease

BACKGROUND: Sirtuins silent information regulator 1 (SIRT) is histone deacetylases that act as antioxidants and involved in the pathogenesis of cardiovascular diseases (CVD) which are the major complications of chronic kidney disease (CKD). Transcription factor 7-like 2 (TCF7L2) genetic polymorphisms could contribute to the risk of CVD as TCF7L2 proteins regulate vascular remodeling. AIM: We tried to demonstrate the role of genetic polymorphisms: rs7069102 and rs10823108 in SIRT1 gene and rs7903146 in TCF7L2 gene in the development of CVD in CKD Egyptian patients. METHODS: This study included 120 CKD patients (60 with CVD and 60 without CVD) and 60 age and sex-matched healthy subjects as a control group. Routine laboratory investigations were performed and genotyping for candidate single nucleotide polymorphisms was done by Taqman-real-time polymerase chain reaction. RESULTS: The frequency of the C allele of rs7069102 was significantly higher in CKD patients with CVD as compared to the normal control group (p < 0.001) and as compared to CKD patients without CVD (p < 0.001). Percentages of AG and GG genotypes of rs10823108 were significantly higher in CKD patients with CVD as compared to the normal control group (p = 0.002, 0.035, respectively). The frequency of the T allele of rs7903146 was significantly higher in CKD patients with CVD as compared to the normal control group (p < 0.001). CONCLUSION: We found that C allele of rs7069102, GG and AG genotypes of rs10823108 in the SIRT1 gene and T allele of rs7903146 in TCF7L2 gene have a potential role in the pathogenesis and the risk of CVD development in CKD Egyptian patients.

Comparison of the Efficiency of Lepidium sativum, Ficus carica, and Punica granatum Methanolic Extracts in Relieving Hyperglycemia and Hyperlipidemia of Streptozotocin-Induced Diabetic Rats

Background. Diabetes mellitus (DM) is a metabolic disorder characterized by high blood glucose levels that occurs either due to insufficient insulin production or mounting resistance to its action. The purpose of this study was to investigate if methanolic extracts of Lepidium sativum seeds, Ficus carica, and Punica granatum leaves had any effect on blood sugar levels in normal and streptozotocin (STZ) diabetic rats, as well as to explore the most effective extract. Method. Healthy male albino rats weighing 185-266 g were divided into nine groups of eight rats each: normal control, diabetic control, diabetic rats with dietary supplements of L. sativum, F. carica, and P. granatum methanolic extracts, and diabetics treated with insulin. All of the rats were fed on ordinary diet with nutritional pellets and were given water ad libitum. To induce diabetes, all animals were administered with STZ intraperitoneal injection at a dose of 60 mg/kg body weight. For five weeks, the crude plant extracts were given orally to various groups of rats at doses of one hundred and two hundred mg/kg body weight. After that, animal groups were sacrificed and blood samples were taken. Results. Phytochemical analysis revealed that the highest amounts of polyphenolic compounds were present in L. sativum seeds and P. granatum leaves, while leaves of F. carica showed the highest amounts of alkaloid and flavonoid content compared to other extracts. Oral administration of F. carica and L. sativum extracts at the dosage of 100 and 200 mg/kg significantly reduced glucose, lipid profile, kidney, and liver enzyme levels. A significant increase in HbAlc levels was also observed with L. sativum extract at a dose of 200 mg/kg compared to diabetic controls. Mellitus rats supplemented with 100 and 200 mg/kg methanolic extracts of P. granatum had higher serum triglycerides and lower serum low-density lipoprotein cholesterol (LDL-C) than normal control rats. F. carica extract is more effective than L. sativum and P. granatum extracts in the prevention and control of type 2 diabetes mellitus (T2DM) and its consequences.

Comparison of the Human Gut Microbiota between Normal Control Subjects and Patients with Colonic Polyps and Colorectal Cancer

Background: The human gut microbiota has been related to numerous colonic diseases. To identify colorectal cancer (CRC)-associated microbiota, the gut microbiomes of patients with colonic polyps and CRC compared to normal controls were analyzed.Methods: Between July and December 2020, forty-four stool samples were obtained from participants older than 50 years who were scheduled for elective colonoscopies at the Surgery Clinic, Songklanagarind Hospital. The samples were divided into 3 groups (17 normal control, 17 colonic polyps, and 10 CRC) and were collected for analysis with a 16s metagenomic sequencing library preparation with MiSeq Reporter software (MSR) following the protocol of the 16s metagenomics workflow. The microbiome data were analyzed with Kruskal–Wallis test with the Dunn-Bonferroni post hoc method.Results: The relative proportions of beneficial butyrate-producers Kineothrix alysoides, Eubacterium rectale, and Roseburia inulinsivorans were significantly higher in healthy control and colonic polyp groups compared with the CRC group at the top three lowest p-values. The recommended CRC biomarker Clostridium symbiosum was shown in a significantly higher proportion in the CRC group than in the normal control group. The prevalences and relative proportion of the novel CRC-associated species Acutalibacter muris and the familiar CRC-associated species Christensenella massiliensis and lntestinimonas butyriciproducens were significantly higher in the CRC group than in the normal control and colonic polyp groups at the top three lowest p-values.Conclusions: A correlation between specific bacteria and clinical outcomes was found in this pilot study. The microbiome data revealed possible microbial biomarkers associated with CRC. Studies with larger numbers of stool samples are required to substantiate our findings.

Effect of Tamarindus indica juice intake on some oxidative stress markers in carbon tetrachloride induced rats

Tamarind tree is a multipurpose tree of which almost every part finds at least some use, either nutritional or medicinal. Due to its pleasant acidic taste and rich aroma, the pulp is widely used for domestic and industrial purpose. A study was carried out to evaluate the effect of Tamarind juice intake in CCl4 induced oxidative stress albino rats. The Proximate, antinutrient, and Phytochemical contents of tamarind juice were analyzed using standard AOAC methods while mineral contents were determined using atomic absorption spectrometry. Oxidative stress markers were also analyzed using colorimetric assay kit. The serum levels of oxidative stress markers were compared between the normal and test groups. Experimental rats were divided into five groups: Normal control group, negative control (CCl4) group, standard drug (Vitamin C) group, tamarind low and high dose group. At the end of the experiment, significant increase in malondialdehyde level and decrease in superoxide dismutase, catalase, reduced glutathione and glutathione Peroxidase activities were recorded in CCl4-exposed rats as compared to normal control group. In the tamarind supplemented groups, the level of MDA along with the activities of SOD, CAT, GSH and GPx were comparable with the normal control rats (p>0.05). Thus, it appears that tamarind juice ameliorate the effect of CCl4; suggesting that consumption of natural compounds with an antioxidant profile may be a preventive alternative to those diseases associated with oxidative stress.

Comparison of the Mini-Mental State Examination and Computerized Brief Cognitive Screening Test as Cognitive Screening Tools in Patients with Mild Cognitive Impairment

Background: The aim of this study was to establish the validity and reliability of the Computerized Brief Cognitive Screening Test (CBCog) for early detection of cognitive impairment. Method: One hundred and sixty participants, including community-dwelling and out-patient volunteers (both men and women) aged ≥ 65 years, were enrolled in the study. All participants were screened using the CBCog and Mini-Mental State Examination (MMSE). The internal consistency of the CBCog was analyzed using Cronbach’s α test. Areas under the curves (AUCs) of receiver operating characteristic analyses were used to test the predictive accuracy of the CBCog in detecting mild cognitive impairment (MCI) in order to set an appropriate cutoff point. Results: The CBCog scores were positively correlated with the MMSE scores of patients with MCI-related dementia (r = 0.678, P < .001). The internal consistency of the CBCog (Cronbach’s α) was 0.706. It was found that the CBCog with a cutoff point of 19/20 had a sensitivity of 97.5% and a specificity of 53.7% for the diagnosis of MCI with education level ≥ 6 years. The AUC of the CBCog for discriminating the normal control elderly from patients with MCI (AUC = 0.827, P < 0.001) was larger than that of the MMSE for discriminating the normal control elderly from patients with MCI (AUC= 0.819, P < .001). Conclusion: The CBCog demonstrated to have sufficient validity and reliability to evaluate mild cognitive impairment, especially in highly educated elderly people.