Assessment of Helicobacter pylori cytotoxin-associated Gene A (Cag A) protein and its association with ferritin and vitamin B12 deficiencies among adult healthy asymptomatic residents in Sharjah, United Arab Emirates.

The United Arab Emirates (UAE) serves as an effective epidemiological site for assessing Helicobacter pylori (H. pylori) infection due to its diverse population. However, comprehensive studies on the prevalence of H. pylori in the UAE are notably scarce. In depth prevalence studies are needed as a preventive measure against gastric cancer and other emerging extra gastric diseases associated with H. pylori infection. Aim: This study aimed to assess H. pylori infection and its virulent oncoprotein, the Cytotoxin-Associated Gene (Cag A) and its association with ferritin and vitamin B12 deficiencies. Methods: The study was conducted on 1094 healthy asymptomatic volunteers residents in the Sharjah Emirate, UAE. Enzyme-linked immunosorbent assay (ELISA) was performed to assess H. pylori infection using H. pylori antibodies (IgG), and detection of CagA protein using Cag A antibody (IgG) in the human serum. Ferritin and vitamin B12 serum levels were assessed and correlated to H. pylori infection. Results: This study focuses mainly on the assessment of H. pylori and its virulent factor CagA, in relation to vitamin B12 and ferritin deficiencies. Remarkably, 49.6 % of the participants were detected positive for H. pylori, with over half of these cases involving CagA positive strains. Notably, among Emirati participants, 76.11 % of those with H. pylori infection were CagA positive. Statistical analysis revealed a significant correlation between H. pylori, CagA level, and ferritin/vitamin B12 deficiencies. Conclusion: These findings emphasize the importance of timely detection and eradication of H. pylori not only as a preventive strategy against gastric cancer but also as an effective strategy to rescue the adverse effects from ferritin and vitamin B12 deficiencies, thereby improving the overall health outcomes of individuals affected by H. pylori infection.

Gold Nanoparticle-Mediated Gene Therapy.

Gold nanoparticles (AuNPs) have gained increasing attention as novel drug-delivery nanostructures for the treatment of cancers, infections, inflammations, and other diseases and disorders. They are versatile in design, synthesis, modification, and functionalization. This has many advantages in terms of gene editing and gene silencing, and their application in genetic illnesses. The development of several techniques such as CRISPR/Cas9, TALEN, and ZFNs has raised hopes for the treatment of genetic abnormalities, although more focused experimentation is still needed. AuNPs, however, have been much more effective in trending research on this subject. In this review, we highlight recently well-developed advancements that are relevant to cutting-edge gene therapies, namely gene editing and gene silencing in diseases caused by a single gene in humans by taking an edge of the unique properties of the AuNPs, which will be an important outlook for future research.

Predictors of Coronary Artery Disease Progression among High-risk Patients with Recurrent Symptoms.

BACKGROUND: Despite the availability of new potent medical therapies, the rate of progression of angiographic coronary artery disease (CAD) is not well described. The aim of this analysis is to describe the rate and predictors of progression of CAD among patients with recurrent symptoms. MATERIALS AND METHODS: We reviewed 259 patients (mean age 61 ± 11 years, 70% males) who underwent two coronary angiograms between 2008 and 2013. Progressive CAD was defined as obstructive CAD in a previously disease-free segment or new obstruction in a previously nonobstructive segment. Patients who had coronary artery bypass surgery between these two angiograms were excluded from the analysis. Multivariate logistic regression was used to determine the independent predictors of progression of CAD. RESULTS: The included cohort had a high prevalence of coronary risk factors; hypertension (71%), diabetes (69%), and dyslipidemia (75%). Despite adequate medical therapy, more than half of the patients (61%) had CAD progression. Using multivariate logistic regression, a drop in the left ventricular ejection fraction (LVEF) by more than 5% was the predictor of CAD progression (adjusted odds ratio 5.8, P = 0.042, 95% confidence interval 1.1-31.2). CONCLUSION: Among high-risk patients with recurrent symptoms, the short-term rate of progression of CAD is high. A drop in LVEF >5% is a predictor of CAD progression. Further studies are needed to determine the prognostic value of CAD progression in the era of potent medical therapy.

The impact of digoxin on mortality in patients with chronic systolic heart failure: A propensity-matched cohort study.

BACKGROUND: Prior Studies showed mixed results in association of digoxin use with all-cause mortality (ACM). The aim of this analysis is to identify the impact of digoxin use on ACM in a contemporary heart failure (HF) cohort treated with guideline based therapy. METHODS: We included 2298 consecutive patients seen in an HF clinic between 2000 and 2015. Patients were considered to be a digoxin user if he/she received digoxin at any point during the enrollment period in the HF clinic. Patients were matched based on digoxin utility using propensity matching in 2-3:1 fashion. The primary outcome was ACM. RESULT: Of 2298 patients, 325 digoxin users were matched with 750 non-digoxin users. The Matched cohort did not have differences among demographics and clinical variables except for worse HF symptomatology and increased prevalence of atrial fibrillation. Overall, the prevalence of the use of guideline suggested therapies was 96%. After a median follow-up duration of 4years (IQR 2-6years), digoxin use was associated with increased ACM (21.8% versus 12.9%, unadjusted HR=1.81; 95% CI=1.33 to 2.45; p=0.001). This association remained significant after adjusting for the propensity score, atrial fibrillation, ejection fraction, and New York HF Class (HR=1.74; 95% CI=1.20 to 2.38; p<0.0001). CONCLUSION: In this analysis of well-treated HF patients, digoxin was associated with increased ACM. Further randomized controlled trials are needed to determine whether digoxin therapy should be used in well-treated HF patients. Until then, routine use of digoxin in clinical practice should be discouraged.

Design, synthesis and SAR analysis of potent BACE1 inhibitors: Possible lead drug candidates for Alzheimer's disease.

We have identified potent isophthalic acid derivatives armed with imidazol and indolyl groups as potent ß-secretase inhibitors. The most effective analogs demonstrated low nano-molar potency for the BACE1 (ß-secretase cleaving enzyme) as measured by FRET (Fluorescence Resonance Energy Transfer) and cell-based (ELISA) assays. Our design strategy followed a traditional SAR approach and was supported by molecular modeling studies based on previously reported hydroxyethylene transition state inhibitor derived from isophthalic acid I. In the FRET assay, the most potent compound, 10a, displayed an IC50 value for BACE1 of 75 nM, and exhibited cellular activity with an EC50 value of 0.81 µM. On the other hand, compound 11b was found to be the most potent compound in the cell-based assay with an EC50 value of 0.29 µM.

Design, Synthesis and Qualitative Structure Activity Relationship Evaluations of Quinoline-Based Bisarylimidazoles as Antibacterial Motifs.

BACKGROUND: The emergence of drug-resistant bacteria in clinical practice has propelled a concerted effort to find new classes of antibiotics that will circumvent current modes of resistance. We previously described a set of imidazopyridine antibacterial leads that contain a core composed of benzimidazole and a central phthalic acid linker. These compounds showed potent antibacterial properties against a wide range of Gram-positive and Gram-negative bacteria. In this respect, we conducted a systematic exploration of new disubstituted imidazole functionalities on quinoline 4-position as the central linker, to determine the factors that direct the potent antibacterial activity. We found that some of the newly synthesized compounds possessed more potent activity compared to currently available medications. The newly synthesized compounds were screened against several clinical isolates and Staphylococcus aureus, including the methicillinresistant (MRSA) and the methicillin-sensitive (MSAA). METHODS: The goal of this work is to undertake rigorous testing of new hybrid scaffolds of quinoline flanked by diaryl imidazoles and their structure-activity against a range of bacterial strains. Described herein is the account of the modification of the central linker region, the imidazole functionality, and substituents at the 4-position of the quinoline, and their effect on the antibacterial potency of the resulting derivatives. Our efforts here have been driven by previous reports on the applications of Pfitzinger cyclization protocol. This complexity-generating reaction transforms a relatively simple substrate, into a more complex products with the potential for diversification via functionalization of the resultant acid. RESULTS: We identified compounds that possess potent and broad-spectrum antibacterial activities against clinical isolates and drug resistant strains. Structure-Activity relationships of these compounds were further explored to determine the crucial structural features needed to enhance their antibacterial activity. In this respect, it was found that, hydrophobic and electron-withdrawing moieties, such as halogens, were required on each end of the isoquinoline-based bisaryl imidazole hybrid motifs to produce broad-spectrum activity against the tested strains. Thus, molecules containing halophenyl or pyridyl arms were found more potent than molecules containing thiophene and/or electron-releasing groups on the phenyl arms, which showed much less antibacterial activity against the tested strains. CONCLUSION: In summary, 4-(4,5-diphenyl-1H-imidazol-2-yl)-2-phenylquinoline systems can be assembled efficiently through the Pfitzinger ring expansion- condensation strategy. This approach appears to hold considerable synthetic utility. The particular value of such a synthetic route resides on the conciseness and efficiency through which imidazo-quinoline construction can be synthesized from structurally simple and accessible acetophenone precursors.

Impact of a nurse-led heart failure program on all-cause mortality.

BACKGROUND: Nurse-led heart failure programs (HFPs) have been shown to reduce readmissions and improve medication adherence rates. However, their impact on survival is not well demonstrated. OBJECTIVE: The purpose of this study was to evaluate the impact of a nurse-led HFP on all-cause mortality. METHODS: This retrospective review included 413 consecutive patients who were admitted with heart failure exacerbations in 2008 and 2009. All patients were invited to attend a nurse-led HFP; 199 (48%) patients agreed and were compared with the 214 (52%) who chose usual care. Patients were followed for all-cause mortality, which was confirmed by the national death index. Independent predictors of outcomes were identified using multivariable Cox regression. RESULTS: Patients followed in the HFP were younger, more often men with lower ejection fraction, blood urea nitrogen, and systolic blood pressure. After a median follow-up of 15 months (range, 6-30 months), a total of 55 patients died: 14 in the HFP group (7%) compared with 41 patients (19%) in the usual care group. Participation in the HFP was independently associated with reduction in all-cause mortality (hazard ratio, 0.4; 95% confidence interval, 0.2-0.8; P = .008). CONCLUSIONS: Our nurse-led HFP was independently associated with improved survival among patients with decompensated heart failure. Further research is required to confirm this finding.

Genetic variability of the serine-rich Entamoeba histolytica protein gene in clinical isolates from the United Arab Emirates.

The genetic diversity of 20 Entamoeba histolytica isolates from asymptomatic individuals from the UAE was investigated by analyzing polymorphism in the serine-rich E. histolytica gene (SREHP) by nested polymerase chain reaction (PCR) amplification followed by restriction fragment length polymorphism (RFLP) on DNA extracted directly from stool samples. The SREHP gene was successfully amplified in 15 out of 20 E. histolytica-positive samples. Four out of the remaining five isolates did not amplify for the SREHP gene. Despite successful amplification of the SREHP gene in the fifth isolate, AluI digestion of the amplified PCR product revealed no bands. As a result, all five samples were excluded from the study. Twelve different profiles were obtained from the 15 successfully amplified isolates. Thus, demonstrating extensive genetic variability and reinforcing the argument that E. histolytica has an extremely polymorphic genetic structure. Despite the sample size limitation, a finding in the study was the occurrence of one profile common to one Indian isolate while another profile common to one Pakistani isolate; indicating the possibility of clonal infection. Furthermore, we found one isolate from a Bangladeshi expatriate identical to 2 asymptomatic Bangladeshi isolates reported in an earlier study. No clear association between the different genotypes and the study population demographics was noted. The results also indicated the possibility of strains clustering by region.

Detection and molecular characterisation of Giardia lamblia genotypes in Sharjah, United Arab Emirates.

BACKGROUND: No data are available on Giardia lamblia genotypes in the United Arab Emirates (UAE). This study aimed to identify G. lamblia from DNA extracted from human stool samples to gain information on its prevalence and to perform molecular analysis on isolates collected from expatriates from different localities residing in Sharjah, UAE. METHODS: In total, 111 healthy expatriates residing in Sharjah were screened for G. lamblia using nested PCR amplification of the small subunit ribosomal RNA (ssu-rRNA) gene. Positive samples were genotyped using a nested PCR amplifying the triosephosphate isomerase (tpi) gene to differentiate between the two human assemblages (A and B). A subset of the PCR products (n=23) were sequenced and their phylogenetic relationships were determined. RESULTS: Of the 111 participants, 67 (60.4%) were identified as positive for the ssu-rRNA gene. When genotyped for the tpi gene, 18.9% (21/111) were of assemblage A, 17.1% (19/111) belonged to assemblage B and 5.4% (6/111) showed patterns compatible with mixed infections. A strong correlation between the presence of diarrhoea and assemblage B was observed (χ(2)=10.553; p=0.001). Moreover, an association was also observed between mixed infections (A+B) and diarrhoea (χ(2)=8.899; p=0.003). No correlation between age, gender and geographic origin of the infected individual was noted. Phylogenetic analysis showed three clusters for the tpi gene. No relationship between the clusters and the origin of samples was noted. CONCLUSION: This study is the first to determine the infection rate and genotypic composition of Giardia in Sharjah, UAE.

Differential detection of Entamoeba histolytica, Entamoeba dispar and Entamoeba moshkovskii in fecal samples by nested PCR in the United Arab Emirates (UAE).

Amoebiasis is one of the most important infectious diseases afflicting mainly tropical and subtropical countries. This study was carried out in the Sharjah Emirate, UAE in order to accurately detect and differentiate Entamoeba histolytica, Entamoeba dispar and E. moshkovskii in fecal samples collected from the Sharjah municipality public health clinic by ELISA and nested polymerase chain reaction (PCR). One hundred and twenty specimens were examined and the PCR was positive for E. histolytica, E. dispar and E. moshkovskii (collectively referred to as Entamoeba complex) in 19.2% (23 out of 120). Of those, 10% (12/120) were mono - infection with E. histolytica; 2.5% (3/120) with E. dispar; and 2.5% (3/120) E. moshkovskii. The nested PCR also detected mixed infections by both E. histolytica and E. dispar in 3.3% (4/120) and E. dispar and E. moshkovskii in 0.8% (1/120). The TechLab ELISA kit failed to detect E. histolytica in any of the E. histolytica PCR positive samples. Overall, the percentage of E. histolytica including those found in mixed infections was 13.3% (16/120). Compared to nested PCR, microscopy was found to have an overall sensitivity of 52.2% and a specificity of 75.2% for detection of Entamoeba complex. The present study indicates that E. histolytica is present in the UAE with an average incidence rate of 13.3%. However, larger studies need to be conducted in order to confirm these findings. We propose the use of PCR in both the routine diagnosis of amoebiasis and epidemiological survey in the UAE.

Tandem multicomponent reactions toward the design and synthesis of novel antibacterial and cytotoxic motifs.

The synthesis of polysubstituted imidazopyridines and imidazopyrazines through the orthogonal union of Groebke-Blackburn and Ugi reactions is described. These motifs were produced efficiently in a tandem operation without intermediate isolation. The synthesized scaffolds were biologically evaluated and found to possess potent anticancer and anti bacterial activities. Importantly, some of these motifs (e.g. compound 5) were found to possess specific anti-breast cancer activity against MCF7 cell line and others (e.g. compound 15) possess specific effects against melanoma cancer cell line (M8). Interestingly, the introduction of imidazobenzothiazole framework produced compounds with potent anti cancer activities (e.g. compounds 29 and 33) in vitro. Interestingly, many of synthesized compounds displayed potent and broad spectrum antibacterial activity against hospital-resistant clinical isolates namely, Escherichia coli, Klebsiellapneuomoniae, Staph. epidermidis, Ps. aeruginosa and Proteus vulgaris. Furthermore, many of the synthesized motifs were found to effective against Gram positive methicillin-sensitive Staphylococcus aureus (MMSA; ATCC 25923), andmethicillin-resistant Staphylococcus aureus (MRSA; ATCC 35591). These findings, however, form the foundation for further investigation in our continuing efforts to develop selective anticancer and antibacterial agents.

The state of antibody therapy.

Therapeutic antibodies are widely used in the treatment of various diseases and disease conditions, including cardiovascular diseases, autoimmune disorders, malignancies, and infections. With at least 23 therapeutic agents currently in clinical use and a successful business generating large revenues, major technological advances are now in place to improve the specificity and efficacy of those antibodies already in the market and also generate new, safe and effective macromolecules for the treatment of other ailments. This review provides a summary of the current state of antibody therapy, highlights and discusses recent developments in the field of antibody-based therapeutics production, combination therapy and shows the status of some of the agents that are in clinical trial.

Rates of infection and phylogenetic analysis of GB virus-C among Kuwaiti and Jordanian blood donors.

OBJECTIVES: GB virus-C/hepatitis G virus (GBV-C/HGV), collectively known as GBV-C, has been reported to be associated with non-A-E hepatitis. The aim of this study was to determine the rate of infection and genotypic characteristics of GBV-C among Kuwaiti and Jordanian blood donors. METHODS: A total of 334 plasma/serum samples from healthy blood donors in Kuwait (n = 130) and Jordan (n = 204) were screened using RT-PCR/nested PCR of the 5'-untranslated region (5'-UTR). Phylogenetic analysis was conducted by sequencing the 5'-UTR region of the randomly picked clones representative of the two populations. RESULTS: The results obtained showed that the rate of GBV-C infection in healthy Kuwaiti and Jordanian blood donors was 24.6 and 9.8%, respectively. Sequence analysis of the 5'-UTR using 4 and 6 clones from healthy Kuwaiti and Jordanian blood donors, respectively, revealed the prevalence of the European/North American genotype 2 when compared to the 6 reference genotypes in GenBank. CONCLUSION: GBV-C/HGV was detectable at rates relatively comparable with other regions in the world in Kuwaiti and Jordanian blood donors, although the significance of which remains controversial. More interesting is the dominance of GBV-C genotype 2 among the two populations, which remains to be explained.

Detection and genotyping of GBV-C virus in the United Arab Emirates.

GB virus-C/Hepatitis G virus (GBV-C/HGV), collectively known as GBV-C, is spread widely and has been reported to be associated with non A-E hepatitis. The aim of the current project was to determine the rate of infection and genotypic characteristics of GBV-C in the United Arab Emirates (UAE). A total of 379 plasma/serum samples representing different populations in the UAE and comprising healthy as well as patients positive for HBV and HCV were screened using RT-PCR/nested PCR of the 5'-untranslated region (UTR). National subjects (n=168) and non-nationals residing in the UAE (n=211) were tested. The results obtained showed that the rate of GBV-C infection in healthy nationals, and those positive for HCV or HBV were 11.1%, 14.3%, and 5.7%, respectively, compared to 8.3%, 33.3%, and 8.6%, respectively, in non-nationals. No statistically significant correlation between infection with GBV-C and HCV or HBV (P>0.05) was found. Sequence analysis of the 5'-UTR using 37 and 46 clones from 8 and 6 healthy nationals and non-nationals, respectively, revealed the prevalence of the European/North American genotype 2 when compared to the five reference genotypes in GenBank.