Headspace aroma and secondary metabolites profiling in 3 Pelargonium taxa using a multiplex approach of SPME-GC/MS and high resolution-UPLC/MS/MS coupled to chemometrics.

BACKGROUND: The present study focuses on the aroma and secondary metabolites profiling of three Pelargonium graveolens cultivars, baladi (GRB), sondos (GRS) and shish (GRSH), grown in Egypt. Utilizing a multiplex approach combining high resolution-ultraperformance liquid chromatography (HR-UPLC)/tandem mass spectrometry (MS/MS) and gas chromatography (GC)-MS coupled with chemometrics, the study aims to identify and profile various secondary metabolites and aroma compounds in these cultivars. RESULTS: HR-UPLC/MS/MS analysis led to the annotation of 111 secondary metabolites, including phenolics, flavonoids, terpenes and fatty acids, with several compounds being reported for the first time in geranium. Multivariate data analysis identified vinylanisole, dimethoxy-flavonol, and eicosadienoic acid as discriminatory metabolites among the cultivars, particularly distinguishing the GRS cultivar in its phenolics profile. In total, 34 aroma compounds were detected using headspace solid-phase microextraction coupled with GC-MS, including alcohols, esters, ketones, ethers and monoterpene hydrocarbons. The major metabolites contributing to aroma discrimination among the cultivars were ß-citronellol in GRB, α-farnesene in GRS and isomenthone in GRSH. CONCLUSION: The study provides a comprehensive profiling of the secondary metabolites and aroma compounds in the three Pelargonium graveolens cultivars. The GRS cultivar was identified as particularly distinct in both its phenolics and aroma profiles, suggesting its potential as a premium variety for cultivation and use. Future studies should focus on isolating and investigating the newly detected metabolites and exploring the biological effects of these compounds in food applications and other uses. © 2024 Society of Chemical Industry.

Nanoemulsions of Jasminum humile L. and Jasminum grandiflorum L. Essential Oils: An Approach to Enhance Their Cytotoxic and Antiviral Effects.

Unprecedented nanoemulsion formulations (NE) of Jasminum humile and Jasminum grandiflorum essential oils (EO) were prepared, and examined for their cytotoxic and antiviral activities. NE characterization and stability examination tests were performed to ensure formula stability. The antiviral activity was determined against hepatitis A (HAV) and herpes simplex type-1 (HSV-1) viruses using MTT assay, while the cytotoxic potential was determined against liver (HepG-2), breast (MCF-7), leukemia (THP-1) cancer cell lines and normal Vero cells. Statistical significance was determined in comparison with doxorubicin as cytotoxic and acyclovir as antiviral standard drugs. GC-MS analysis indicated twenty four compounds in the EO of J. humile and seventeen compounds in the EO of J. grandiflorum. Biological investigations of pure EOs revealed weak cytotoxic and antiviral effects. Nevertheless, their NE formulations exhibited high biological value as cytotoxic and antiviral agents. NE formulations also showed feasible selectivity index for the viral-infected and cancer cells (especially HepG-2) than normal Vero cells. Both nanoemulsions showed lower IC50 than standard doxorubicin against HepG-2 (26.65 and 22.58 vs. 33.96 µg/mL) and MCF-7 (36.09 and 36.19 vs. 52.73 µg/mL), respectively. The study results showed the dramatic effect of nanoemulsion preparation on the biological activity of EOs and other liposoluble phytopharmaceuticals.

Cytotoxic effects of extracts obtained from plants of the Oleaceae family: bio-guided isolation and molecular docking of new secoiridoids from Jasminum humile.

CONTEXT: Traditionally, Oleaceae plants are used to treat many diseases, such as rheumatism, hypercholesterolaemia, or ulcers. OBJECTIVES: To investigate the cytotoxic potential of Jasminum humile L., Jasminum grandiflorum L., and Olea europaea L. (Oleaceae) extracts against selected human cancer cells lines, followed by a phytochemical investigation of the most potent one. MATERIALS AND METHODS: The 95% ethanol extracts of aerial parts of three oleaceous plants were examined for their cytotoxicity against HepG-2, MCF-7, and THP-1 cell lines using MTT assay and doxorubicin (positive control). J. humile was bio-selected and submitted to bio-guided fractionation. Chromatographic workup of ethyl acetate and n-butanol fractions afforded two new compounds; 1-methoxyjasmigenin (1) and 1-methyl-9-aldojasmigenin (2), along with five known ones (3-7). Structures were unambiguously elucidated using 1D/2D NMR and ESI-HRMS. Isolated compounds were assessed for their anti-proliferative potential, and both selectivity index and statistical significance were determined. Molecular docking was conducted against the Mcl-1 receptor using (AZD5991) as a standard. RESULTS: Jasmoside (5) was the most potent anticancer compound showing IC50 values of 66.47, 41.32, and 27.59 µg/mL against HepG-2, MCF-7, and THP-1 cell lines, respectively. Moreover, isojasminin (4) exhibited IC50 values of 33.49, 43.12, and 51.07 µg/mL against the same cell lines, respectively. Interestingly, 5 exhibited the highest selectivity index towards MCF-7 and THP-1, even greater than doxorubicin. Molecular docking results were in full agreement with the MTT assay and the proposed SAR. CONCLUSION: In this study, two new compounds were purified. The biological activity highlighted jasmoside (5) as a lead anticancer drug for further future investigation.

Heavy metals concentration, and antioxidant activity of the essential oil of the wild mint (Mentha longifolia L.) in the Egyptian watercourses.

In the present study, we assessed seasonal variation in the accumulation potential of wild mint (Mentha longifolia) to heavy metals as well as the chemical composition and antioxidant activity of the essential oil of mint in polluted and unpolluted watercourses. The results indicated that the wild mint showed seasonal fluctuations in accumulation potential for heavy metals proved by bioaccumulation factor (BF) and translocation factor (TF). The all measured heavy metals, except Pb were retained in the underground parts. Summer plants accumulated the highest concentrations of Al, Cd, Cr and Fe in their root, while the lowest concentration of Ni in their shoot. The bioaccumulation factor for Cd, Cu, Mn, Ni, Zn and Co was greater than one, while the translocation factor of the investigated metals (except Pb) did not exceed one, indicating the potential of wild mint for phytostabilization of these metals in contaminated wetlands. The yield and composition of mint essential oil (MEO) were affected by harvesting season and heavy metals pollution. GC/MS showed that isomenthone, cis-piperitenone oxide, menthone and pulegone, were the main oil constituents. Mint essential oil show promising antioxidant activity by 2,2'-diphenyl-1-picrylhydrazyl (DPPH) radical scavenging assay under pollution stress. The maximum reducing power of MEO were obtained during autumn and summer seasons (polluted canals).In conclusion, summer is the ideal season for harvesting wild mint plants for the maximum plant biomass, oil yield, high radical scavenging activity of MEO and to monitor pollution in contaminated wetlands.

High-Resolution UPLC-MS Profiling of Anthocyanins and Flavonols of Red Cabbage (Brassica oleracea L. var. capitata f. rubra DC.) Cultivated in Egypt and Evaluation of Their Biological Activity.

In this paper, biological investigations and a high-resolution UPLC-PDA-ESI-qTOF-HRMS technique were employed for Brassica oleracea L. var. capitata f. rubra DC. (red cabbage) of the family Brassicaceae (Cruciferae), cultivated in Egypt, for the first time. The positive ionization mode is usually performed to identify anthocyanins. However, this technique cannot differentiate between anthocyanins and corresponding non-anthocyanin polyphenols. Thus, the negative ionization mode was also used, as it provided a series of characteristic ions for the MS analysis of anthocyanins. This helped in identifying five kaempferol derivatives for the first time in red cabbage, as well as nine-previously reported-anthocyanins. For the biological investigations, the acidified methanolic extract of fresh leaves and the methanolic extract of air-dried powdered leaves were examined for their antioxidant, antimicrobial, and anticancer activities. The freshly prepared phenolic extract was proven to be more biologically potent. Statistical significance was determined for its anticancer activity in comparison with standard doxorubicin.

Nasal gene expression differentiates COPD from controls and overlaps bronchial gene expression.

BACKGROUND: Nasal gene expression profiling is a promising method to characterize COPD non-invasively. We aimed to identify a nasal gene expression profile to distinguish COPD patients from healthy controls. We investigated whether this COPD-associated gene expression profile in nasal epithelium is comparable with the profile observed in bronchial epithelium. METHODS: Genome wide gene expression analysis was performed on nasal epithelial brushes of 31 severe COPD patients and 22 controls, all current smokers, using Affymetrix Human Gene 1.0 ST Arrays. We repeated the gene expression analysis on bronchial epithelial brushes in 2 independent cohorts of mild-to-moderate COPD patients and controls. RESULTS: In nasal epithelium, 135 genes were significantly differentially expressed between severe COPD patients and controls, 21 being up- and 114 downregulated in COPD (false discovery rate < 0.01). Gene Set Enrichment Analysis (GSEA) showed significant concordant enrichment of COPD-associated nasal and bronchial gene expression in both independent cohorts (FDRGSEA < 0.001). CONCLUSION: We identified a nasal gene expression profile that differentiates severe COPD patients from controls. Of interest, part of the nasal gene expression changes in COPD mimics differentially expressed genes in the bronchus. These findings indicate that nasal gene expression profiling is potentially useful as a non-invasive biomarker in COPD. TRIAL REGISTRATION: ClinicalTrials.gov registration number NCT01351792 (registration date May 10, 2011), ClinicalTrials.gov registration number NCT00848406 (registration date February 19, 2009), ClinicalTrials.gov registration number NCT00807469 (registration date December 11, 2008).

Diagnostic and prognostic significance of ischemic electrocardiographic changes with regadenoson-stress myocardial perfusion imaging.

BACKGROUND: The diagnostic and prognostic value of regadenoson-induced ST-segment depression (ST↓) is not defined. Due to the low incidence of ST↓ ≥1.0 mm with vasodilator stress, a lower threshold to define ischemic ECG response may provide improved clinical utility. METHODS: We conducted a retrospective cohort study of patients who underwent regadenoson-stress SPECT myocardial perfusion imaging (MPI) followed by coronary angiography within 6 months. Ischemic ST↓ was defined as ≥0.5 mm. The prevalence of angiographically severe coronary artery disease (CAD) and the rates of major adverse cardiac events (MACE) including cardiac death, myocardial infarction, and coronary revascularization were determined. RESULTS: In a diagnostic cohort of 629 subjects, 117 (18.6%) had ST↓ ≥0.5 mm. Severe CAD was more prevalent in the ST↓ ≥0.5 vs ST <0.5 group (13.7% vs 5.3%, P = .001). Among patients with normal MPI (n = 229), the prevalence of severe CAD was higher in the ST↓ ≥0.5 group (8.2% vs 2.2%, P = .04). Adjusting for clinical and imaging covariates, ST↓ ≥0.5 mm was independently predictive of severe CAD [odds ratio = 3.37, 95% confidence interval (CI) = 1.67-6.83, P = .001], and provided incremental diagnostic value (Chi square increment = 10.3, P = .001). In an outcome cohort of 748 subjects, after adjusting for clinical and imaging covariates, ST↓ ≥0.5 mm was associated with increased MACE rate in the entire cohort [hazard ratio = 1.41, CI 1.01-1.96, P = .04] and in the subgroup of patients with normal MPI [hazard ratio = 2.2, CI 1.11-4.39, P = .02], and provided incremental prognostic value (Chi square increment = 3.9, P = .049). A diagnostic ST↓ threshold of 0.5 mm provided greater discriminatory capacity than a 1.0 mm cutoff (P = .03). CONCLUSIONS: Among patients selected to undergo coronary angiography, regadenoson-induced ST↓ ≥0.5 mm was associated with higher rates of severe CAD and MACE, irrespective of MPI finding.

The impact of regimented aminophylline use on extracardiac radioisotope activity in patients undergoing regadenoson stress SPECT myocardial perfusion imaging: a substudy of the ASSUAGE trial.

BACKGROUND: In patients undergoing regadenoson stress SPECT myocardial perfusion imaging (MPI), the impact of the regimented administration of aminophylline on the cardiac-to-extracardiac photon activity ratio is unknown. METHODS: This is a substudy of the ASSUAGE trial (NCT01250496); a double-blinded, randomized, placebo-controlled clinical trial which investigated the attenuation of regadenoson-related adverse effects using 75 mg of intravenous aminophylline vs placebo, administered 90 seconds following (99m)Tc-tetrofosmin injection in patients undergoing regadenoson stress SPECT-MPI. In subjects with normal MPI enrolled in the trial, we sampled from the antero-posterior planar projection of the post-stress scintigraphic data the mean photon activity in the myocardium, liver, bowel, and lungs. The mean cardiac-to-extracardiac activity ratios were compared between patients randomized to aminophylline vs placebo. RESULTS: We studied 158 eligible subjects, randomized to receive aminophylline (n = 86) or placebo (n = 72). The means of photon activity ratios of the heart-to-liver, heart-to-bowel, heart-to-lungs, inferior wall of the heart-to-liver, and inferior wall of the heart-to-bowel were not statistically different between those who received aminophylline vs placebo (P values > .30). Only the time lapse between stress (99m)Tc-tetrofosmin injection and stress SPECT acquisition independently correlated with higher heart-to-liver and heart-to-bowel activity ratios (P values ≤ .01). Patients' body mass index independently correlated with lower heart-to-lung ratio (P = .009). CONCLUSION: The regimented intravenous aminophylline use following regadenoson stress does not significantly improve the cardiac-to-extracardiac photon activity ratio in patients undergoing regadenoson stress (99m)Tc-tetrofosmin SPECT-MPI.

Investigating the promising SARS-CoV-2 main protease inhibitory activity of secoiridoids isolated from Jasminum humile; in silico and in Vitro assessments with structure-activity relationship.

The proteolytic enzyme 3 C-like protease (3Clpro or Mpro) is considered the most important target for SARS-CoV-2 which could be attributed to its crucial role in viral maturation and/or replication. Besides, natural phytoconstituents from plant origin are always promising lead compounds in the drug discovery area. Herein, the previously isolated and identified seven compounds from Jasminum humile (J. humile) were examined in vitro and in silico against the SARS-CoV-2 Mpro. First, the Vero E6 cells were utilized to pursue the potential of the investigated compounds (both in fractions and individual isolates) using the MTT assay. The total extract (T1) displayed the most significant activity against SARS-CoV-2 with IC50 = 29.36 µg/mL. Besides, the fractions (Fr1 and Fr3) showed good activity against the SARS-CoV-2 with IC50 values of 70.42, and 73.09 µg/mL, respectively. Then, the SARS-CoV-2 Mpro inhibitory assay was utilized to emphasize the inhibitory potential of the investigated isolates. MJN, JMD, and IJM candidates displayed prominent Mpro inhibitory potentials with IC50 = 30.44, 30.24, and 56.25 µM, respectively. Moreover, molecular docking of the identified seven compounds against the Mpro of SARS-CoV-2 showed that the five secoiridoids achieved superior results. MJN, JSM, IJM, and JMD showed higher affinities towards the Mpro target compared to the co-crystallized antagonist. Furthermore, the most active complexes (MJN, JSM, IJM, and JMD-Mpro) were subjected to MD simulations run for 150 ns and MM-GBSA calculations, compared to the co-crystallized inhibitor (O6K-Mpro). Finally, the SAR study clarified that JMD achieved the best anti-SARS-CoV-2 Mpro activity followed by MJN.Communicated by Ramaswamy H. Sarma.

HIGHLIGHTSSeven isolates from J. humile, besides different extracts, were examined both in vitro and in silico.Anti-SARS-CoV-2 using the MTT assay and anti-SARS-CoV-2 Mpro inhibitory assay were performed.Compounds MJN, JMD, and IJM displayed prominent SARS-CoV-2 Mpro inhibition.Molecular docking, molecular dynamics simulations, and MM-GBSA calculations were carried out.SAR study was conducted on the isolated compounds.

Unusual presentation of maxillary plasma cell gingivitis mistakenly treated as aggressive periodontitis. (A case report).

INTRODUCTION: A rare benign inflammatory condition of gingiva of unknown etiology, characterized by diffuse and massive infiltration of plasma cells into the sub-epithelial gingival tissue. Plasma Cell Gingivitis (PCG) is characterized by macular lesions that are bright red, velvety, sharply circumscribed, and flat to slightly elevated. PRESENTATION OF CASE: Female patient 38 years old, complain of mobility of upper right 7 with dull pain and swelling related to it. She also mentioned that the upper wisdom molar at the same side was extracted a year before due to the same reason. Extraction of upper right 7 and excisional biopsy of surrounding soft tissue swelling and by laboratory investigation and analysis to the biopsy we found that the lesion is gingival plasmacytosis. Microscopic examination revealed marked squamous hyperplasia with focal ulceration and diffuse dense subepithelial plasmacytic infiltrate consistent with PCG. At higher magnification, plasma cells were seen without cellular atypia. The individual plasma cells had eccentric round nuclei with cartwheel chromatin patterns and abundant cytoplasm. DISCUSSION: In the current report, the surgical team performed complete scaling and root planning to remove the associated plaque to decrease any chance of recurrence or plaque induced exacerbation. The patient was instructed to change her habits to avoid the possibility of exacerbation by unknown allergen. The lesion was excised by enblock removal to decrease recurrence possibility. CONCLUSION: Plasma cell gingivitis needs radical management and a thorough diagnosis should be done to rule out and differentiate it from the malignant type of plasma cell tumors like multiple myeloma.

Role of Thymosin Beta 4 in the diagnosis of Nonalcoholic Fatty Liver and its relation to Metabolic Syndrome in Egyptian patients.

Nonalcoholic fatty liver disease (NAFLD) is a spectrum of hepatic diseases linked to metabolic and cardiovascular disorders that impair quality of life and increase morbidity and mortality. There has been significant interest in replacing conventional diagnostic tools such as liver biopsy with non-invasive biomarkers for the diagnosis of NAFLD. Thymosin Beta 4 (Tß4) is a G-actin sequestering peptide involved in many critical biological processes. This study aimed to evaluate the role of Tß4 in the diagnosis of NAFLD, and its relation to metabolic syndrome. Eighty patients were enrolled in this study, divided into two equal groups of NAFLD cases (n=40) and a control group (n=40). The two groups were subjected to history taking, physical examination, measurement of waist circumference and body mass index (BMI). Laboratory workup included serum Tß4, insulin resistance (HOMA-IR), fibrosis-4 score (FIB-4), fatty liver index (FLI) and NAFLD fibrosis score (NFL) were calculated for both groups. Serum Tß4 was significantly lower in NAFLD patients (P < 0.001) and there was a significant positive correlation between serum Tß4 and HDL (P = 0.034). On the other hand, there was a significant negative correlation between serum Tß4 and waist circumference (P < 0.001), total cholesterol level (P < 0.001), insulin level (P < 0.001), HOMA-IR (P < 0.001), serum triglycerides (P= 0.025) and FLI (P = 0.004). Serum Tß4 at a cut-off value of ≤900 ng/ml had 100 % sensitivity, 100 % specificity, 100% positive predictive value and 100% negative predictive value for the prediction of NAFLD. In conclusion, serum Tß4 could be used as a biomarker for the diagnosis of NAFLD.

Bevacizumab (Avastin) as an adjunct to vitrectomy in the management of severe proliferative diabetic retinopathy: a prospective case series.

PURPOSE: To evaluate the role of preoperative intravitreal bevacizumab as an adjunct to vitrectomy in diabetic eye disease. METHODS: Twenty eyes of 18 patients were recruited and underwent a single intravitreal injection of bevacizumab 1.25 mg 1 week prior to vitrectomy. Fundus fluorescein angiography (FFA) was done before and 1 week after injections. Best corrected visual acuity (BCVA) and ophthalmic evaluation were done before, 1 week after injections, 1 day, 1 week and monthly for 3 months after vitrectomy. RESULTS: The mean age was 47.7 ± 10.39 years. The male:female ratio was 2:3. Mean preinjection BCVA (logMAR) was 1.460 ± 0.439. FFA showed a dramatic reduction in dye leakage 1 week after injection. Intraoperative bleedings were minimal in most cases (85%, n = 17). Postoperatively, 16 patients had no bleeding (80%), 4 had minimal bleeding (20%), and 1 had recurrent fibrovascular proliferation (5%). The mean BCVA on day 1, week 1, months 2 and 3 after surgery were 1.645 ± 0.422, 1.300 ± 0.413, 1.065 ± 0.538 and 1.065 ± 0.538 logMAR, respectively (p = 0.078, 0.123, 0.002 and 0.002, respectively). CONCLUSION: Bevacizumab administered prior to vitrectomy was well tolerated and was particularly useful during surgery.

Multidisciplinary Management of Subclavian Artery Perforation and Complications.

The radial approach to cardiac catheterization and percutaneous coronary interventions has increased in popularity due to the favorable side effect profile relative to the femoral approach. Mediastinal hematoma after radial access cardiac catheterization has scarcely been reported in the literature and, if present, the exact location of the bleed was rarely identified. In this case presentation, we describe an elective transradial coronary angiography resulting in subclavian artery perforation in close proximity to the vertebral artery, with subsequent mediastinal and cervical hematoma formation. This scenario was managed by immediate imaging of the chest after sudden deterioration raised suspicion of an adverse event during wire navigation. Formation of a mediastinal hematoma is the equivalent of retroperitoneal bleed from the femoral approach and requires rapid recognition, interdisciplinary collaboration, and endovascular management.

Iatrogenic Arterial Perforation During Endovascular Interventions.

The use of minimally invasive endovascular procedures has increased, and as such, the frequency of associated vascular complications has also increased. Regardless of the access site location, rarely, arterial perforation can occur, which can be fatal if not properly managed. Interventionalists should be aware of the risk factors for perforation, commonly perforated vessels, and how different sites of perforation are diagnosed and managed. Rapid recognition and endovascular management reduce the need for open surgical repair, and thus reduce the morbidity and mortality of these complications. This review outlines the presentation, diagnosis, and management of iatrogenic perforations of the subclavian artery, thyrocervical trunk (TT), common carotid artery, superficial femoral artery (SFA), and external iliac artery.

The value of prednisolone acetate provocative test before intravitreal triamcinolone acetonide injections.

PURPOSE: The aim of this study was to investigate the diagnostic value of a topical prednisolone acetate 1% provocative test for steroid-induced ocular hypertension before intravitreal triamcinolone acetonide injection. METHODS: This is a prospective, single-center, randomized controlled study at Kasr El Aini Hospital, Cairo University. Patients scheduled for intravitreal triamcinolone acetonide were enrolled and randomly allocated in a ratio 2:1 to either Group A: received prednisolone acetate provocative test and those who did not develop SIOH proceeded with intravitreal triamcinolone acetonide or Group B: did not receive prednisolone acetate provocative test and proceeded directly to intravitreal triamcinolone acetonide. Intraocular pressures were measured weekly for 4 weeks following intravitreal triamcinolone acetonide. Steroid-induced ocular hypertension is defined as intraocular pressure increase of 5 mmHg or more from baseline after prednisolone acetate provocative test or intravitreal triamcinolone acetonide. RESULTS: A total of 66 eyes (66 patients) were included. Of which, 10 eyes (23.8%) showed prednisolone acetate provocative test steroid-induced ocular hypertension during the 4-week period. Intravitreal triamcinolone acetonide steroid-induced ocular hypertension was less likely to develop in Group A (prednisolone acetate provocative test non-steroid-induced ocular hypertension, n = 32, 31.25%) than in group B (n = 24, 54.2%) (p = 0.006, odds ratio: 0.178, 95% CI: 0.53-0.596). Our test achieved a negative predictive value of 68.75%. CONCLUSION: The topical prednisolone acetate provocative test may be a useful method to predict a steroid-induced ocular hypertension following intravitreal triamcinolone acetonide.

Identifying a nasal gene expression signature associated with hyperinflation and treatment response in severe COPD.

Hyperinflation contributes to dyspnea intensity in COPD. Little is known about the molecular mechanisms underlying hyperinflation and how inhaled corticosteroids (ICS) affect this important aspect of COPD pathophysiology. To investigate the effect of ICS/long-acting ß2-agonist (LABA) treatment on both lung function measures of hyperinflation, and the nasal epithelial gene-expression profile in severe COPD. 117 patients were screened and 60 COPD patients entered a 1-month run-in period on low-dose ICS/LABA budesonide/formoterol (BUD/F) 200/6 one inhalation b.i.d. Patients were then randomly assigned to 3-month treatment with either a high dose BDP/F 100/6 two inhalations b.i.d. (n = 31) or BUD/F 200/6 two inhalations b.i.d. (n = 29). Lung function measurements and nasal epithelial gene-expression were assessed before and after 3-month treatment and validated in independent datasets. After 3-month ICS/LABA treatment, residual volume (RV)/total lung capacity (TLC)% predicted was reduced compared to baseline (p < 0.05). We identified a nasal gene-expression signature at screening that associated with higher RV/TLC% predicted values. This signature, decreased by ICS/LABA treatment was enriched for genes associated with increased p53 mediated apoptosis was replicated in bronchial biopsies of COPD patients. Finally, this signature was increased in COPD patients compared to controls in nasal, bronchial and small airways brushings. Short-term ICS/LABA treatment improves RV/TLC% predicted in severe COPD. Furthermore, it decreases the expression of genes involved in the signal transduction by the p53 class mediator, which is a replicable COPD gene expression signature in the upper and lower airways.Trial registration: ClinicalTrials.gov registration number NCT01351792 (registration date May 11, 2011), ClinicalTrials.gov registration number NCT00848406 (registration date February 20, 2009), ClinicalTrials.gov registration number NCT00158847 (registration date September 12, 2005).

Ghrelin gene polymorphism as a genetic biomarker for prediction of therapy induced clearance in Egyptian chronic HCV patients.

Ghrelin (GHRL) has important implications for liver disease. It has anti-inflammatory effects, regulates cell proliferation, modulates the fibrogenic response and protects liver tissue. Genetic variations in the GHRL gene may play a crucial role in the development of chronic hepatitis (CH), liver cirrhosis (LC) and hepatocellular carcinoma (HCC). Therefore, we examined the association of GHRL gene polymorphisms (rs26312 and rs27647), and its serum level to virologic responses to combined sofosbuvir and Simeprevir therapy for a course of 12 successive weeks in Egyptian chronic hepatitis C (CHC) patients. METHODS: Human genomic and clinical data were collected from 100 Egyptian participants in this study, 90 HCV patients who received sofosbuvir and Simeprevir and 10 non-HCV healthy subjects. Genotyping of GHRL rs26312 and rs27647, were determined with the TaqMan qRT-PCR allele detection assay. The serum GHRL concentrations were determined using enzyme-linked immunosorbent assay (ELISA). RESULTS: GHRL polymorphisms (rs26312 and rs27647) genotype distributions and allele frequencies did not differ between HCV patients and normal healthy subjects or between patient groups when compared according to the therapeutic response. In addition, we found significant lower serum GHRL levels in CHC patients compared with the healthy controls. However, there was no significant association of the GHRL rs26312 and rs27647 polymorphisms with GHRL levels in CHC patients. We conclude that GHRL SNPs (rs26312 and rs27647) do not affect response to combined sofosbuvir and Simeprevir treatment in chronic Egyptian HCV patients.

Lacrimal punctum occlusion in the treatment of severe keratoconjunctivitis Sicca caused by Sjögren syndrome: a uniocular evaluation.

PURPOSE: A controlled uniocular study to evaluate the short-term efficacy of lacrimal punctum occlusion in the treatment of severe dry eye caused by Sjögren syndrome. METHODS: Uniocular punctum occlusion by punctum plug in the upper and lower puncta in 1 eye was performed in 20 patients with severe keratoconjunctivitis Sicca caused by Sjögren syndrome. To overcome possible interindividual variability between patients, the other eye, in the same patient, was not occluded and served as a control eye. The eye to be occluded was randomly selected. The patients were instructed to continue using their dry eye medications. Tear function tests (Schirmer test, rose Bengal test, and debris in de cul-de-sac) were performed in both eyes. Subjective complaints (discomfort) were registered for both eyes. All the above-mentioned data were collected before starting the treatment and at least 6 weeks later. The above-mentioned parameters were compared and statistically analyzed in both eyes. RESULTS: Of the 20 patients, 7 patients dropped out. The remaining 13 patients completed the final analysis. In the occluded eye, we found a significant improvement in both the subjective complaints and the rose Bengal score, but the Schirmer test and the tear mucus score did not change. CONCLUSION: Punctum occlusion therapy in a short-term study improved the rose Bengal score and discomfort score in our patients and thus may be helpful in the treatment of severe dry eye caused by Sjögren syndrome.

Measurement of pharyngeal cross-sectional area by finite element analysis.

A noninvasive measurement of pharyngeal cross-sectional area (CSA) during sleep would be advantageous for research studies. We hypothesized that CSA could be calculated from the measured pharyngeal pressure and flow by finite element analysis (FEA). The retropalatal airway was visualized by using a fiber-optic scope to obtain the measured CSA (mCSA). Flow was measured with a pneumotachometer, and pharyngeal pressure was measured with a pressure catheter at the palatal rim. FEA was performed as follows: by using a three-dimensional image of the upper airway, a mesh of finite elements was created. Specialized software was used to allow the simultaneous calculation of velocity and area for each element by using the measured pressure and flow. In the development phase, 677 simultaneous measurements of CSA, pressure, and flow from one subject during non-rapid eye movement (NREM) and rapid eye movement (REM) sleep were entered into the software to determine a series of equations, based on the continuity and momentum equations, that could calculate the CSA (cCSA). In the validation phase, the final equations were used to calculate the CSA from 1,767 simultaneous measurements of pressure and flow obtained during wakefulness, NREM, and REM sleep from 14 subjects. In both phases, mCSA and cCSA were compared by Bland-Altman analysis. For development breaths, the mean difference between mCSA and cCSA was 0.0 mm2 (95% CI, -0.1, 0.1 mm2). For NREM validation breaths, the mean difference between mCSA and cCSA was 1.1 mm2 (95% CI 1.3, 1.5 mm2). Pharyngeal CSA can be accurately calculated from measured pharyngeal pressure and flow by FEA.

Reversibility of minimal hepatic encephalopathy following liver transplantation in Egyptian cirrhotic patients.

AIM: To evaluate the reversibility of minimal hepatic encephalopathy (MHE) following liver transplantation (LT) in Egyptian cirrhotic patients. METHODS: This prospective study included twenty patients with biopsy-proven liver cirrhosis listed for LT and twenty age- and sex-matched healthy control subjects. All underwent neuro-psychiatric examination, laboratory investigations, radiological studies and psychometric tests including trail making test A (TMT A), TMT B, digit symbol test and serial dotting test. The psychometric hepatic encephalopathy score (PHES) was calculated for patients to diagnose MHE. Psychometric tests were repeated six months following LT in the cirrhotic patient group. RESULTS: Before LT, psychometric tests showed highly significant deficits in cirrhotic patients in comparison to controls (P < 0.001). There was a statistically significant improvement in test values in the patient group after LT; however, their values were still significantly worse than those of the controls (P < 0.001). The PHES detected MHE in 16 patients (80%) before LT with a median value of -7 ± 3.5. The median PHES value was significantly improved following LT, reaching -4.5 ± 5 (P < 0.001), and the number of patients with MHE decreased to 11 (55%). The pre-transplant model for end-stage liver disease (MELD) score ≥ 15 was significantly related to the presence of post-transplant MHE (P = 0.005). More patients in whom reversal of MHE was observed had a pre-transplant MELD score < 15. CONCLUSION: Reversal of MHE in cirrhotic patients could be achieved by LT, especially in those with a MELD score < 15.