Clinical, molecular, and drug resistance epidemiology of HIV in Jordan, 2019-2021: A national study.

BACKGROUND: Limited epidemiologic studies have been conducted in Jordan describing the HIV epidemic. This study aimed to address this gap to inform HIV prevention and control. METHODS: A nationally-representative cross-sectional study was conducted among adults living with HIV in Jordan. Laboratory testing included HIV viral load and next-generation-sequencing-based clinical genotype. Log-binomial regression estimated risk ratios (RRs) and 95% confidence intervals (CIs). RESULTS: Among 231 (70%) participants, most were male (184/80%), and from Jordan (217/94%). Among 188 treatment-experienced-participants (>6 months), 165 (88%) were virally suppressed. High-level resistance was most frequent against nucleoside reverse transcriptase inhibitor (13/81%), and integrase-strand transfer inhibitor (INSTI) (10/62%) drugs among viremic (≥1000 HIV copies/mL) treatment-experienced participants with drug-resistant mutations (DRMs, n = 16). Common HIV subtypes (n = 43) were B (6/14%), A1 (5/12%), and CRF01_AE (5/12%); additionally, novel recombinant forms were detected. In multivariate analysis, independently higher risk for late diagnosis (n = 49) was observed with diagnosis through blood donation (vs check-up: RR 2.20, 95%CI 1.16-4.17) and earlier time-period of diagnosis (1986-2014 vs 2015-2021: RR 2.87, 95%CI 1.46-5.62). CONCLUSIONS: Late diagnosis and INSTI resistance endanger national HIV prevention and treatment in Jordan-high-level resistance to INSTI suggests therapeutic drug monitoring is needed for treatment efficacy and conservation of treatment options.

Early Remodeling of the Left Atrium Following Catheter Ablation of Atrial Fibrillation: Insights From DECAAFII.

BACKGROUND: Left atrial (LA) enlargement is prevalent among atrial fibrillation (AF) patients and constitutes an important marker of atrial myopathy. Several studies have described reduction in LA volume post-catheter ablation (CA) of AF, however, none have investigated differences related to additional ablation outside the pulmonary veins (PVs). OBJECTIVES: The authors sought to study early LA remodeling following CA of persistent AF and the impact of additional, fibrosis-guided extra-PV ablation. METHODS: In this DECAAF II (Effect of MRI-Guided Fibrosis Ablation vs Conventional Catheter Ablation on Atrial Arrhythmia Recurrence in Patients With Persistent Atrial Fibrillation) trial subanalysis, patients with persistent AF were randomized to receive pulmonary vein isolation (PVI) only or PVI + fibrosis-guided ablation. Late gadolinium enhancement magnetic resonance imaging (LGE-MRI) was performed before and 3 months after CA. Patients were followed up with single-lead electrocardiogram devices for 12 to18 months. AF burden was calculated as days with AF divided by days monitored. RESULTS: This analysis included 733 patients. The mean LA volume index (LAVI) before ablation was 62.0 mm3/m2 and after ablation was 51.3 mm3/m2, with a mean reduction of 10.7 mm3/m2 (P < 0.001). Patients in the fibrosis-guided ablation arm had more volume reduction than did those in the PVI-only group (12.1 mm3/m2 vs 9.3 mm3/m2; P = 0.02). LAVI reduction was greater in patients with heart failure (15.7 vs 8.9; P = 0.001) and was associated with improved left ventricular ejection fraction (LVEF) (r = 0.23; P < 0.001), reduced AF burden (r = -0.173; P < 0.001), improved LVEF, and improved quality of life (r = 0.146; P < 0.001). CONCLUSIONS: We confirmed the presence of LA remodeling within 3 months after ablation for persistent AF. Importantly, we saw more LA volume reductions in patients in the PVI + fibrosis-guided ablation arm in comparison with PVI only, and in patients with LV dysfunction. LA volume reduction in response to CA is associated with decreased arrhythmia recurrence, reduced AF burden, and improved LVEF and quality of life.

Antopol Goldman lesion: A case report.

Antopol Goldman lesion is a renal pelvis subepithelial hematoma or hemorrhage, a sporadic disease. Although the causes are not well established yet, multiple factors were linked. Radiology is the cornerstone for the diagnosis. However, it may be mistaken for renal tumors. Herein we present a case of a 17-year-old male who presented with recurrent flank pain and gross hematuria and was diagnosed with an Antopol Goldman lesion.

COVID-19 Vaccine Acceptance among Vulnerable Groups: Syrian Refugees in Jordan.

Despite the wide distribution of COVID-19 vaccines, refugees remain last in line for the intake of vaccines. Syrian refugees in Jordan reach up to 700,000 registered and almost up to 700,000 unregistered refugees. This study aims to assess the willingness of Syrian refugees in Jordan to take the COVID-19 vaccine. Participants in the Zaatari refugee camp in Jordan were invited through social media to complete the survey between January and March 2022. A total of 230 refugees participated in our study, with almost half the participants of male gender. The majority of the participants had secondary school as their highest education level and were unemployed, being below the social poverty line. Interestingly, Syrian refugees showed a high vaccine acceptance rate, as 89.6% were willing to take the vaccine. Moreover, they showed high knowledge regarding the vaccine, the disease, and the virus. Our findings highlight the importance of knowledge and awareness of the COVID-19 vaccine to increase the acceptance rate. This is very important as refugees represent a vulnerable group to infection and complications and require close attention, especially with their significant numbers in Jordon and challenges of providing adequate vaccine supplies at their camps. We hope that, with proper dissemination of knowledge and awareness and with easy accessibility to the vaccines, it will ensure high immunization to reach herd immunity in Jordan.

The effect of stone and patient characteristics in predicting extra-corporal shock wave lithotripsy success rate: A cross sectional study.

INTRODUCTION: We determine the effect of patient characteristics (age, sex, and body mass index BMI) and stone characteristics (density, location, and size) by non-contrast computed tomography of the kidneys, ureters, and bladder (CT-KUB) in predicting the success of extracorporeal shock wave lithotripsy (ESWL) in the treatment of kidney and ureteric stones. We present this study to further enrich the knowledge of physicians towards the effect of different patient characteristics upon predicting extra-corporal shock wave lithotripsy success rates. METHODS: We evaluated 155 patients who received ESWL for renal and ureteric stone measuring 3-20 mm (mm), over a 3-month period. The stone size in millimeters, density in Hounsfield units (HU) and its location was determined on pre-treatment CT-KUB. ESWL was successful if post-treatment residual renal stone fragments were ≤3 mm and for ureteric stones should be totally cleared. RESULTS: The overall success of ESWL treatment was observed in 65.8% of the 155 patients. There was no significant difference seen when the effect of patients age, sex and BMI were studied with ESWL outcome with P values were 0.155, 0.101 and 0.415 respectively. Also, stone location either in the kidney or ureter has no statistically significant effect on ESWL response rate. while stone density and size determined on CT KUB have statistically significant effect on the success rate of ESWL with a P-value of 0.002 and 0.000 respectively. CONCLUSIONS: This study shows that determination of stone density and stone size on CT KUB pre ESWL can help to predict the outcome of ESWL. We propose that stone density <500 HU and stone size < 5 mm are highly likely to result in successful ESWL.

The impact of pharmaceutical care on the efficacy and safety of transdermal glucosamine sulfate and capsaicin for joint pain.

Background Arthritis is a common chronic joint disease. It progressively causes joint pain, stiffness, and disability. Glucosamine sulfate has been shown to be an effective symptom-relieving biological agent. Pharmaceutical care, including patient counseling, is very important to overcome inconsistencies in compliance and adherence. Objective The aim of this study is to evaluate the impact of pharmaceutical care on the efficacy and safety of transdermal glucosamine sulfate and capsaicin (TGC-Plus cream) in the management of chronic joint pain. Settings A rheumatology outpatient clinic, Jordan University Hospital, Amman, Jordan. Methods A cross sectional study with a single treatment group was conducted. One hundred (100) patients diagnosed with either osteoarthritis, rheumatoid arthritis or chronic joint pains were recruited. Patients started on TGC-Plus cream applied twice daily for duration of 12 weeks. Patients received pharmaceutical care services during the study duration. Main outcome measure Efficacy and safety of TGC-Plus cream in pain relief and joint function improvement (alleviating joint stiffness) the need of alternative analgesics and number of doctor's visits. Results There was a significant reduction of numerical pain score (7 ± 1.40 vs. 3.53 ± 2.13, p < 0.05), with significant reduction in the limitation of joint movement (6.18 ± 2.14 vs. 3.47 ± 2.23, p < 0.05) after 12 weeks. In addition, the need for analgesics and the number of doctor's visits were significantly reduced (1.99 ± 2.77 vs. 0.71 ± 1.90, p < 0.05), (1.11 ± 1.28 vs. 0.06 ± 0.293, p < 0.05) respectively. Conclusion Pharmacist supervised treatment with the TGC-Plus cream significantly reduces pain and enhances locomotor function in patients with chronic pain who failed to achieve adequate prior pain relief.

IL10 Promoter Polymorphisms are Associated with Rheumatic Heart Disease in Saudi Arabian Patients.

Rheumatic heart disease (RHD) is an inflammatory disease that develops following streptococcal infections. IL10 helps to balance immune responses to pathogens. IL10 polymorphisms have been associated with RHD, although results remain inconclusive. Our aim was to investigate the association between IL10 polymorphisms and RHD in Saudi Arabian patients. IL10 promoter polymorphisms (-1082A/G, -829C/T, and -592C/A) were genotyped in 118 RHD patients and 200 matched controls using the TaqMan allelic discrimination assay. There was a significant difference in IL10-1082 genotype frequency between patients and controls (p = 0.01). -1082G allele carriage (GG+GA vs AA) and the (-1082, -819, -592) GCC haplotype carriage were associated with an increased risk of RHD (p = 0.004, OR 2.1, 95% CIs 1.7-3.4 and p = 0.004, OR 2, 95% CIs 1.3-3.4, respectively). The ACC haplotype was associated with a decrease in RHD risk (p = 0.015, OR 0.6, 95% CIs 0.4-0.9). IL10 promoter polymorphisms may play an important role in the development of RHD and provide an opportunity for therapeutic stratification.

Xanthine oxidase inhibitory activity of the methanolic extracts of selected Jordanian medicinal plants.

BACKGROUND: The search for novel xanthine oxidase (XO) inhibitors with a higher therapeutic activity and fewer side effects are desired not only to treat gout but also to combat various other diseases associated with the XO activity. At present, the potential of developing successful natural products for the management of XO-related diseases is still largely unexplored. In the present study, we have screened the methanolic extracts of various Jordanian medicinal plants for their XO inhibitory activities using an optimized protocol. MATERIALS AND METHODS: The methanolic extracts of 23 medicinal plants, belonging to 12 families, were tested in vitro, at 200 µg/ml concentrations, for their XO inhibitory potential. The dose-dependent inhibition profiles of the most active plants were further evaluated by estimating the IC(50) values of their corresponding extracts. RESULTS: Six plants were found most active (% inhibition more than 39%). These plants are Salvia spinosa L. (IC(50) = 53.7 µg/ml), Anthemis palestina Boiss. (168.0 µg/ml), Chrysanthemum coronarium L. (199.5 µg/ml), Achillea biebersteinii Afansiev (360.0 µg/ml), Rosmarinus officinalis L. (650.0 µg/ml), and Ginkgo biloba L. (595.8 µg/ml). Moreover, four more plants, namely Lavandula angustifolia Mill. (28.7% inhibition), Helianthemum ledifolium (L.) Mill. (28.4%), Majorana syriaca (L.) Kostel. (25.1%), and Mentha spicata L. (22.5%) showed a XO inhibitory activity in the range of 22-30%. CONCLUSION: The study showed that many of the tested plant species are potential sources of natural XO inhibitors that can be developed, upon further investigation, into successful herbal drugs for treatment of gout and other XO-related disorders.

Epigenetic modulation of the retinoid X receptor alpha by green tea in the azoxymethane-Apc Min/+ mouse model of intestinal cancer.

We investigated the possible mechanisms of inhibition of colorectal carcinogenesis by green tea (GT) in azoxymethane-treated (AOM) Apc(Min/+) mice. Mice received water or a 0.6% (w/v) solution of GT as the only source of beverage. GT treatment commenced at the 8th week of age and lasted for 8 wk. The treatment caused a statistically significant reduction in the number of newly formed tumors (28%, P < 0.05). Immunohistochemical analysis showed that GT decreased the levels of beta-catenin and its downstream target cyclin D1. To probe a mechanism, we further investigated the expression of retinoic X receptor alpha (RXR alpha) in AOM/Apc(Min/+) tumors. Our results show that RXR alpha is selectively downregulated in AOM/Apc(Min/+) mouse intestinal tumors. In contrast, other retinoic receptors including retinoic acid receptor alpha (RAR alpha), RAR beta, RXR beta, and RXR gamma were all expressed in Apc(Min/+) adenomas. Furthermore, our results show that RXR alpha downregulation is an early event in colorectal carcinogenesis and is independent of beta-catenin expression. GT significantly increased the protein levels of RXR alpha. In addition, RT-PCR analysis showed that GT induced a similar increase in the levels of RXR alpha mRNA. Genomic bisulfite treatment of colonic DNA followed by pyrosequencing of 24 CpG sites in the promoter region of RXR alpha gene showed a significant decrease in CpG methylation with GT treatment. The results suggest that a low concentration of GT is sufficient to desilence RXR alpha and inhibit intestinal tumorigenesis in the Apc(Min/+) mouse.

Green tea selectively targets initial stages of intestinal carcinogenesis in the AOM-ApcMin mouse model.

One of the liabilities of the Apc(Min) mouse as a model for colon cancer is its lack of a robust tumor response in the large bowel. In our protocol, we treated the Apc(Min) mouse with azoxymethane, a colon-selective carcinogen. This protocol induced a 4-fold increase in the number of colon tumors. We utilized this protocol to investigate the possible mechanisms of inhibition of colorectal carcinogenesis by green tea. Mice received water or a 0.6% (w/v) solution of green tea as the only source of beverage. Green tea treatment commenced at the eighth week of age and lasted for either 4 or 8 weeks. Green tea significantly inhibited the formation of new adenomas, but was ineffective against larger tumors. Mechanistically, we investigated the effects of green tea on the expression of biomarkers involved in colon carcinogenesis. Western blotting analysis showed that green tea decreased the total levels of the early carcinogenesis biomarker beta-catenin and its downstream target cyclin D1. In contrast, the expression of COX-2 was not altered. Immunohistochemical analysis showed that green tea inhibited the formation of adenomas overexpressing beta-catenin and cyclin D1, but did not reduce the number of COX-2-expressing adenomas. Our results suggest that green tea specifically targets initial stages of colon carcinogenesis; the time of administration of green tea is pivotal for effective chemoprevention. Beverage levels of green tea do not inhibit the progress of any large adenomas or adenocarcinomas existing prior to the tea administration.

Functional studies of twelve mutant V2 vasopressin receptors related to nephrogenic diabetes insipidus: molecular basis of a mild clinical phenotype.

X-linked nephrogenic diabetes insipidus (NDI) is a rare disease with defective renal and extrarenal arginine vasopressin V2 receptor responses due to mutations in the AVPR2 gene in Xq28. To study the cause of loss of function of mutant V2 receptors, we expressed 12 mutations (N55H, L59P, L83Q, V88M, 497CC-->GG, deltaR202, I209F, 700delC, 908insT, A294P, P322H, P322S) in COS-7 cells. Eleven of these, including P322H, were characterized by a complete loss of function, but the mutation P322S demonstrated a mild clinical and in vitro phenotype. This was characterized by a late diagnosis without any growth or developmental delay and a significant increase in urine osmolality after intravenous 1-deamino[D-Arg8]AVP administration. In vitro, the P322S mutant was able to partially activate the Gs/adenylyl cyclase system in contrast to the other V2R mutants including P322H, which were completely inactive in this regard. This showed not only that Pro 322 is important for proper V2R coupling, but also that the degree of impairment is strongly dependent on the identity of the substituting amino acid. Three-dimensional modeling of the P322H and P322S mutant receptors suggested that the complete loss of function of the P322H receptor could be due, in part, to hydrogen bond formation between the His 322 side chain and the carboxyl group of Asp 85, which does not occur in the P322S receptor.

Properties of a new radioiodinated antagonist for human vasopressin V2 and V1a receptors.

A vasopressin receptor antagonist, [1-(beta-mercapto-beta,beta-pentamethylenepropionic acid), 2-o-ethyl-D-tyrosine, 4-valine, 9-tyrosylamide] arginine vasopressin (d(CH2)5[o-ethyl-D-Tyr2,Val4,Tyr-NH9(2)]AVP), has been prepared. This antagonist is a potent antiantidiuretic, antivasopressor and antioxytocic peptide with pA2 values of 7.69-7.94 and affinities of 1.12-11.0 nM. When radioiodinated at the phenyl moiety of the tyrosylamide residue at position 9, this peptide was demonstrated to bind to vasopressin V2 and V1a receptors with a dissociation constant of 0.22-0.75 nM. This ligand is a good tool for further studies on human vasopressin V2 receptor localization and characterization, when used in combination with a selective vasopressin V1a ligand.

[Hereditary nephrogenic diabetes insipidus]. / Diabète insipide néphrogénique héréditaire.

Congenital nephrogenic diabetes insipidus (NDI) is a rare inherited disorder characterized by the inability of the kidney to concentrate urine in response to vasopressin (AVP). Following the recent characterization of the cDNA and genomics sequences encoding the human V2 receptor to AVP (AVPR2), X-linked NDI has been found to be due to mutations in the AVPR2 gene that maps to the chromosome Xq28 region. To date more than 30 mutations, insertions or deletions have been reported in independent families, without any significant differences in the phenotypic expression of the disease. The AVPR2 is a member of the superfamily of 7 transmembrane domain, G protein-coupled receptor, linked to cyclic AMP second messenger system. Other types of inheritance have been described in NDI, and recently, a mutation of the aquaporin-2 gene, encoding a water channel of the renal collecting duct, has been reported in an autosomal recessive form of NDI.

Tyr115 is the key residue for determining agonist selectivity in the V1a vasopressin receptor.

Using a three-dimensional model of G protein-coupled receptors (GPCR), we have previously succeeded in docking the neurohypophysial hormone arginine-vasopressin (AVP) into the V1a receptor. According to this model, the hormone is completely embedded in the transmembrane part of the receptor. Only the side chain of the Arg residue at position 8 projects outside the transmembrane core of the receptor and possibly interacts with a Tyr residue located in the first extracellular loop at position 115. Residue 8 varies in the two natural neurohypophysial hormones, AVP and oxytocin (OT); similarly, different residues are present at position 115 in the different members of the AVP/OT receptor family. Here we show that Arg8 is crucial for high affinity binding of AVP to the rat V1a receptor. Moreover, when Tyr115 is replaced by an Asp and a Phe, the amino acids naturally occurring in the V2 and in the OT receptor subtypes, the agonist selectivity of the V1a receptor switches accordingly. Our results indicate that the interaction between peptide residue 8 and the receptor residue at position 115 is not only crucial for agonist high affinity binding but also for receptor selectivity.

Molecular basis for agonist selectivity in the vasopressin/oxytocin receptor family.

Vasopressin (AVP) and oxytocin (OT) are two nonapeptides differing at position 3, in the cyclic part of the peptide, and at position 8, in the C-terminal tripeptide. In this study, we have evaluated the interactions between these two positions of the hormones and the oxytocin receptor (OTR), the V1a and the V2 vasopressin receptors. The contribution of these two positions to receptor selectivity was analyzed by using several peptide analogues bearing substitutions at either position 3 or 8. The putative interactions between receptor residues and hormone residues at position 3 and 8 were then deduced by using a three dimensional model of the neurohypophysial hormones docked into their respective receptors. On the basis of this model, we found that the lateral chain of residue 8 might interact with residues located in the first extracellular loop. By using site-directed mutagenesis on the cloned receptors, we identified a non-conserved residue in the first extracellular loop that interacts with the lateral chain of residue 8 in the hormone. We demonstrated that this interaction is crucial for receptor selectivity to the different agonists.

Hypoxia/reoxygenation stimulates endothelial cells to promote interleukin-1 and interleukin-6 production. Effects of free radical scavengers.

Vascular endothelium produces and/or interferes with various cytokines. Previous studies have demonstrated interactions of these inflammatory and immunological mediators with oxygen-derived free radicals. The present work examines the relationship between hypoxia/reoxygenation (H/R) and cytokine production by cultured endothelial cells. Human umbilical vein endothelial cell (HUVEC) monolayers were incubated for 24 h in normoxia or submitted to 5 h hypoxia/19 h reoxygenation. Then, interleukin-1 (IL-1) alpha and beta, and interleukin-6 (IL-6), were measured in culture supernatants by specific enzyme immunoassays and bioassays, respectively. Under these conditions, the spontaneous production of IL-1 and IL-6, detected in normoxic HUVEC, greatly increased after H/R treatment. The observed enhancement was cycloheximide-sensitive and, consequently, reflected a de novo protein synthesis. Superoxide dismutase and glutathione peroxidase prevented H/R-induced IL-1 and IL-6 increase. These results constitute the first demonstration that H/R stimulates HUVEC to promote IL-1 and IL-6 production and strongly suggest a role for oxygen-derived free radicals in the cytokine synthesis.