CAUSES AND MANAGEMENT OF VIRAL EYE INFECTION

Introduction: The eye is a fascinating organ for several reasons. It is not only have a composite structure, however it is considered an immune-privileged organ. The anatomy of the eye is composed of the anterior and posterior parts, the line of division is posterior to the lens. The anterior chamber lies within the anterior segment and is an immuneprivileged anatomical location, this is due to the fact that the T-cell response in this area is suppressed This protects the eye from potentially destructive immune attacks however it also makes defence against infectious agents challenging, particularly where T-cell responses are critical for immunological defence. Viruses could get into the eye by direct inoculation, or through haematogenous or neuronal spread. The diagnoses of viral eye infections are usually clinical one, helped by taking a thorough history and performing ophthalmic examination. But in challenging cases the lab tests are essential. In this review, we will discuss the most recent evidence regarding Causes and management of viral eye infection Aim of work: In this review, we will discuss the most recent evidence regarding Causes and management of viral eye infection Methodology: We did a systematic search for Causes and management of viral eye infection using PubMed search engine (http://www.ncbi.nlm.nih.gov/) and Google Scholar search engine (https://scholar.google.com). All relevant studies were retrieved and discussed. We only included full articles. Conclusions: A wide range of of viruses can affect the eye and cause viral eye infections, either as a primary infection or reactivation. Some affect the eye directly while the others indirectly but may still manifest with eye disease. One virus may affect several parts of the eye, while different viruses may cause the same eye disease. This could complicate the clinical diagnosis of viral eye disease, but the lab tests like PCR and antibody tests could assist in challenging cases where there may be diagnostic dilemma. The HIV epidemic has had an huge impact on ophthalmology clinics, this is because the virus can cause different eye diseases, and the associated decrease in cell-mediated immunity makes the person highly susceptible to opportunistic viral eye infections, sometimes with severe morbidity. There could be other viruses that may affect the eye that we did not discuss. Key words: Causes, management, viral eye infection

Strategies for the identification and cloning of genes encoding pyrimidine transporters of Leishmania and Trypanosoma species

In recent years, it has become clear that pyrimidine metabolism is an excellent target for anti-protozoan drug development, with multiple enzymes genetically validated as essential. Pyrimidine nucleobase and nucleoside analogues with promising activity against Leishmania and Trypanosoma species can be readily identified. Well-known drugs like 5-fluorouracil and 5-fluoro-2’deoxyuridine are rapidly metabolised by the parasites and incorporated into RNA and metabolic intermediates such as 5F-2’dUMP and UDP-glucose. We thus see that pyrimidine salvage is a major vulnerability in protozoa, with non-redundant pathways sensitive to inhibition by small pyrimidine analogues. Currently, the main factor slowing down progress towards actual therapeutic exploitation of this weakness is the lack of information on the transport proteins for pyrimidines that need to efficiently internalise the pyrimidine analogues into the parasites. The De Koning laboratory cloned the first protozoan purine nucleobase transporter in 2003 and here we report strategies to similarly identify the pyrimidine transporter family. We characterized thymidine transport in L. major promastigotes in order to establish which transporter is responsible for its uptake. We found two separate thymidine transport activities represent LmajNT1.1 and LmajNT1.2, with Km values of 4.2 mM and 26.9 mM, respectively. In addition, to verify the reported L. donovani model of two NT1-like genes encoding uridine/adenosine transporters, and an NT2 gene encoding an inosine transporter, we cloned the L. major and L. mexicana ENT-family genes that are syntenic with the L. donovani nucleoside transporters, expressing each in T. brucei for individual characterisation. Consistent with the L. donovani reports, the NT1-like genes of either species mediated the adenosine-sensitive uptake of [3H]-uridine but not of [3H]-inosine. Conversely, the NT2-like genes mediated the uptake of [3H]-inosine but not [3H]-uridine. These results showed that the organisation of nucleoside transport is strictly conserved among Leishmania species - a conclusion that has important implications for the development of a nucleoside-based chemotherapy. Comparative sequencing of wild-type strains and 5-fluorouracil-resistant lines of T. b. brucei and L. mexicana using RNA-seq was performed in order to identify the candidate pyrimidine transporter genes downregulated in the resistant lines. We found 17 candidate pyrimidine transporter genes encoding for at least 3-TM domains that were down-regulated in both 5-fluorouracil-resistant lines. We overexpressed the most promising candidate genes in Tbb-5FURes and Lmex-5FURes cell lines, aiming to determine their contribution to the 5-FU uptake and resistance. Moreover, RNAi library screening for T. brucei for 5-FU and 6-AU resistance, with and without prior disruption of pyrimidine biosynthesis, was performed. Data generated by RIT-seq was compared to the RNA-seq results. Several candidate pyrimidine transporter genes were highlighted by the returned data. In conclusion, our results make several noteworthy contributions toward the eventual identification of the pyrimidine transporter gene and, by increasing our understanding of 5-FU toxicity in kinetoplastids, we gain insight into the complexities of pyrimidine metabolism in these parasites

Topics in the grammar of Zahrani spoken Arabic

Research Doctorate - Doctor of Philosophy (PhD)Saudi dialects such as Hijazi Arabic (henceforth HA) and Najdi Arabic (henceforth NA) have been studied for centuries. However, other lesser-known Saudi dialects have not been studied yet. Zahrani Spoken Arabic (henceforth ZSA) is a dialect from the southern region of Saudi Arabia, with around 35,000 speakers, which has not been described or analyzed. Due to migration and the loss of speakers across generations, it is now an endangered language. This thesis presents an analysis of the ZSA dialect, including a brief description of its history, speakers, and location. It is organized into eight chapters focusing on three main areas: phonology, morphology, and syntax. The phonological description provides information on consonants and vowels, syllable structure, word stress, and the main phonological processes in ZSA. As discussed in Chapter Three, verbs in ZSA are formed from two main types of root—triliteral and quadriliteral. Within these groups, there are six different classes of triliteral root: sound roots, double roots, hamzated (glottalized) roots, assimilated roots, hollow roots, and defective roots; and another three distinct classes are formed from the quadriliteral roots: sound roots, weak roots, and reduplicated roots. These different classes can be seen to form up to ten derivational forms. This chapter also deals with the inflectional forms of verbs, including subject-verb agreement, tense, aspect, mood, and voice. The discussion of nominal morphology covers both derivational and inflectional processes. It shows that ZSA has two main types of noun: these are derived nouns, which include verbal nouns and verbal derivatives, and non-derived nouns, which include proper nouns and borrowed nouns. Additionally, there are certain types of derived nouns that are named according to their meanings after the derivational processes have taken place. These are: unit nouns, instant nouns, nouns of place, occupational nouns, instrumental nouns, diminutive nouns, and common nouns. Adjectives in ZSA vary according to the derivational processes involved. They are derived from lexical roots or other parts of speech such as verbs. Some adjectives are derived from nouns by attaching nisbah suffixes. This thesis also provides a basic description of phrase structure in ZSA, including noun phrases, adjective phrases, prepositional phrases, and verb phrases. Following on from this discussion, other related issues such as word order and agreement are dealt with. Lastly, it provides a basic description of verbal and equational clauses in ZSA, including word order and agreement. A brief description of negation in both verbal and equational clauses is given, and the structure of interrogatives is also discussed

Effect of Different Cleaning Methods on Shear Bond Strength of Resin Cement to Contaminated Zirconia

The aim of this study was to evaluate the effect of different cleaning methods on the shear bond strength (SBS) of resin cement to contaminated zirconia specimens. Eighty rectangular-shaped specimens (2 × 5 × 10 mm) were fabricated from Zirconia blocks (IPS e.max ZirCAD) and randomly divided into 8 groups (n = 10). Group A (control) was not exposed to contaminants. The following tests specimens were contaminated with saliva and silicone indicating paste. Group B was coated with ceramic primer, then subjected to contamination. Groups C, D, E, F, G, and H were contaminated; cleaned with water rinse, Ivoclean, air particle abrasion, hydrofluoric acid, KATANATM Cleaner and ZirCleanTM, respectively, and then coated with ceramic primer and bonded to dual cure resin cement cylinders. All the specimens were subjected to artificial aging and surviving specimens were subjected to the SBS test. For statistical analysis, ANOVA and multiple comparison methods at the 0.05 significance level were used. There was no statistically significant difference among Ivoclean (21.48 ± 2.90 MPa), air particle abrasion (21.92 ± 2.85 MPa), and the control group (24.68 ± 5.46). The application of ceramic primer before contamination did not preserve the SBS of resin cement to zirconia. Cleaning the contaminated zirconia surface with hydrofluoric acid (15.03 ± 3.63) or KATANATM Cleaner (17.27 ± 7.63) did not restore SBS to the uncontaminated state, but it was significantly higher than simply rinsing with water (12.46 ± 5.17) or the use of ZirCleanTM (11.59 ± 5.53). The bond strength of resin cement to zirconia was influenced by cleaning methods

Epidemiology, Risk Factors for Gastric Cancer and Surveillance of Premalignant Gastric Lesions: A Prospective Cohort Study of Central Saudi Arabia

(1) Background: Saudi Arabia (SA) is a country with a low incidence of gastric cancer (GC). In this study, we sought to assess the epidemiology of GC, its clinicopathological profiles, and its association with risk factors as well as to identify premalignant gastric lesions (PGL) and examine neoplastic progression. (2) Methods: This five-year prospective study screened for GC and PGL in asymptomatic Saudi patients, aged 45–75 years (n = 35,640) and living in Al Kharj, Riyadh province in central SA. Those who were positive in a high-sensitivity guaiac fecal occult blood test (HSgFOBT+) and had negative results in colonoscopy offered to undergo upper GI endoscopy (n = 1242). Factors associated with GC were examined. (3) Results: The five-year participation rate was 87% (1080/1242). The incidence rate of GC was 26.9 new cases per 100,000 population per year (9.6 new cases per year/total population at risk—35,640), and it was 8.9 cases per 1000 persons per year among the 1080 subjects with HSgFOBT+ and negative colonoscopy results. The five-year mortality rate was 67% among patients with GC (n = 48), 3.0% among participants in the gastric screening program (n = 1080) and 0.09% among the original population participating in the colorectal screening program (n = 35,640). Intestinal-type adenocarcinoma was the most frequent type (77%), with the tumor most commonly located in the antrum (41%). Overall, 334 participants had PGL, and seven of them (2.1%) showed neoplastic progression to GC during the follow-up. Factors associated with GC were age, Helicobacter pylori (HP) infection, obesity (body mass index BMI > 30), smoking, a diet of salty preserved foods, low income and a family history of GC. (4) Conclusions: The incidence of GC is low in central SA, but screening for PGL and GC among patients with HSgFOBT+ and negative colonoscopy may prevent or result in the early treatment of GC. HP eradication, normal body weight, not smoking and adhering to a healthy diet can reduce the risk of GC. The resulting data provide important input for the improvement of national guidelines

Postpartum Depression Prevalence and Associated Factors: An Observational Study in Saudi Arabia

Background and Objectives: Postpartum depression (PPD) is a psychological disorder in women who recently gave birth. It can present as mild to severe depression. Multiple studies across the globe have used the Edinburgh Postnatal Depression Scale to reveal the factors that affect the prevalence of PPD. Results from various published studies showed a high prevalence of PPD in Saudi Arabia. The objective of this study is to investigate the major factors that increase PPD and other associated factors. Materials and Methods: An observational cross-sectional study was carried out at primary healthcare centres and military hospitals in Al Kharj. The study measured the rate of PPD among Saudi women during the postpartum period. We studied 279 women aged 19–45 (mean age 31.91, SD ± 6.45) in their postpartum period and followed up to 2 months after delivery. Results: The prevalence of PPD in our cohort was 32.8%. Multivariate logistic regression analysis showed that previous depression diagnosis (p = 0.001), lower education status (p = 0.029), unemployment (p = 0.014), and delivery disposition of C-section (p = 0.002) remained associated with an increased risk of developing PPD. Conclusions: The increasing number of Saudi women with PPD demonstrates that it is a highly prevalent condition. PPD affects not only the health of the mother but also that of her baby and other family members. Our results showed that the history of diagnosed depression, lower education status, unemployment, and delivery disposition of C-sections were independent predictors of PPD development. Raising awareness and controlling the vulnerable factors could decrease the high risk of its effects

Initial viral cycle threshold values in patients with COVID-19 and their clinical significance

Background: The connection between initial viral cycle threshold (Ct) values of the SARS-CoV-2 with symptoms and hospital course is not clearly studied. Methods: This is a retrospective study of hospitalized COVID-19 patients from Jun 1st 2020 to March 30th, 2021 examining the relationship between initial viral cycle threshold (Ct) values of SARS-CoV-2 as obtained from nasopharyngeal samples. The clinical presentations and outcomes were analyzed in relation to the initial Ct values. Results: The study included 202 hospitalized COVID-19 patients with a mean age (± SD) of 54.75 (± 15.93) and 123 (60.9%) males and 79 (39.1%) females. Of all the patients, the most frequent comorbidity was diabetes mellitus (95; 47%) and the most frequent symptoms were fever (148; 73.3%) and cough (141; 69.8%). There was no significant difference in relation to underlying conditions, clinical presentation, radiographic and laboratory data among those with low, medium and high Ct values. The mean Ct values showed no statistical change over the 10-month study period. Conclusions: Initial SARS-CoV-2 Ct values did not show any association with clinical symptoms and did not predict the need for mechanical intubation or death

Exploration of Succinimide Derivative as a Multi-Target, Anti-Diabetic Agent: In Vitro and In Vivo Approaches

Diabetes mellitus (DM) is counted among one of the leading challenges in the recent era, and it is a life-threatening disorder. Compound 4-hydroxy 3-methoxy phenylacetone (compound 1) was previously isolated from Polygonum aviculare. This compound was reacted with N-benzylmaleimide to synthesize the targeted compound 3. The purpose of this research is to exhibit our developed compound 3’s ability to concurrently inhibit many targets that are responsible for hyperglycemia. Compound 3 was capable of inhibiting α-amylase, α-glucosidase, and protein tyrosine phosphatase 1 B. Even so, outstanding in vitro inhibition was shown by the compound against dipeptidyl peptidase-4 (DPP-4) with an IC50 value of 0.07 µM. Additionally, by using DPPH in the antioxidant activity, it exhibited good antioxidant potential. Similarly, in the in vivo activity, the experimental mice proved to be safe by treatment with compound 3. After 21 days of examination, the compound 3 activity pattern was found to be effective in experimental mice. Compound 3 decreased the excess peak of total triglycerides, total cholesterol, AST, ALT, ALP, LDL, BUN, and creatinine in the STZ-induced diabetic mice. Likewise, the histopathology of the kidneys, liver, and pancreas of the treated animals was also evaluated. Overall, the succinimde moiety, such as compound 3, can affect several targets simultaneously, and, finally, we were successful in synthesizing a multi-targeted preclinical therapy

Exploration of Succinimide Derivative as a Multi-Target, Anti-Diabetic Agent: In Vitro and In Vivo Approaches

Diabetes mellitus (DM) is counted among one of the leading challenges in the recent era, and it is a life-threatening disorder. Compound 4-hydroxy 3-methoxy phenylacetone (compound 1) was previously isolated from Polygonum aviculare. This compound was reacted with N-benzylmaleimide to synthesize the targeted compound 3. The purpose of this research is to exhibit our developed compound 3’s ability to concurrently inhibit many targets that are responsible for hyperglycemia. Compound 3 was capable of inhibiting α-amylase, α-glucosidase, and protein tyrosine phosphatase 1 B. Even so, outstanding in vitro inhibition was shown by the compound against dipeptidyl peptidase-4 (DPP-4) with an IC50 value of 0.07 µM. Additionally, by using DPPH in the antioxidant activity, it exhibited good antioxidant potential. Similarly, in the in vivo activity, the experimental mice proved to be safe by treatment with compound 3. After 21 days of examination, the compound 3 activity pattern was found to be effective in experimental mice. Compound 3 decreased the excess peak of total triglycerides, total cholesterol, AST, ALT, ALP, LDL, BUN, and creatinine in the STZ-induced diabetic mice. Likewise, the histopathology of the kidneys, liver, and pancreas of the treated animals was also evaluated. Overall, the succinimde moiety, such as compound 3, can affect several targets simultaneously, and, finally, we were successful in synthesizing a multi-targeted preclinical therapy

New Succinimide–Thiazolidinedione Hybrids as Multitarget Antidiabetic Agents: Design, Synthesis, Bioevaluation, and Molecular Modelling Studies

Diabetes mellitus (DM) is a metabolic disorder majorly arising from the pathophysiology of the pancreas manifested as a decline in the insulin production or the tissue’s resistance to the insulin. In this research, we have rationally designed and synthesized new succinimide–thiazolidinedione hybrids for the management of DM. In a multistep reaction, we were able to synthesize five new derivatives (10a–e). All the compounds were new containing a different substitution pattern on the N-atom of the succinimide ring. Initially, all the compounds were tested against the in vitro α-glucosidase, α-amylase, PTP1B, and DPP4 targets. In all of these targets, the compound 10d was observed to be the most potential antidiabetic agent. Based on this, the antidiabetic activity of the compound 10d was further investigated in experimental animals, which overall gave us encouraging results. The molecular docking studies of the compound 10d was also performed against the target enzymes α-glucosidase, α-amylase, PTP1B, and DPP4 using MOE. Overall, we observed that we have explored a new class of compounds as potential antidiabetic agents