Corneal biomechanical changes and intraocular pressure in patients with thyroid orbitopathy

AIM: To determine the relevance of the objective parameters addressing the altered biomechanical properties of cornea for glaucoma monitoring in patients with mild or moderate thyroid associated orbitopathy (TAO), and in healthy individuals. METHODS: Twenty-five patients with TAO (group 1) and 25 healthy adults (group 2) were included to the study. Both groups were of a similar age and the ratio women:man. For each patient, the following parameters of both eyes were measured with ocular response analyzer (ORA): corneal hysteresis (CH), corneal resistance factor (CRF), Goldmann correlated intraocular pressure (IOPg) and corneal compensated intraocular pressure (IOPcc). In both groups participating in our study, all measurements were performed within minutes to reduce the diurnal effects. RESULTS: The mean age in group 1 was 56±11y and 76% were women, 24% were men. The mean age in group 2 was 64±11y and 68% were women, 32% were men. CH correlated negatively with IOPg in group 1 (r2=0.10, P<0.05). IOPg strongly correlated with IOPcc in both groups (group 1: r2=0.79, P<0.0001; group 2: r2=0.85, P<0.0001). There was positive correlation between CRF and IOPg in group 1 (r2=0.12, P<0.05) and in group 2 (r2=0.31, P<0.0001). Statistical analysis revealed no significant correlation between CRF and IOPcc in group 1 (r2=0.009, P>0.05) and also no significant correlation in group 2 (r2=0.04, P>0.05). CRF mean value in group 2 (11.51±1.72 mm Hg) was higher than in group 1 (10.85±1.45 mm Hg) (P<0.05). IOPg strongly correlated with IOPcc in both groups (group 1: r2=0.79, P<0.0001; group 2: r2=0.85, P<0.0001). There was also strong correlation between CRF and CH in both populations: group 1: (r2=0.58, P<0.0001), group 2: (r2=0.41, P<0.0001). CONCLUSION: Biomechanical parameters of cornea, as quantified by CH and CRF, and measured together with IOPcc, precisely reveal glaucoma staging in TAO and thus are reliable for diagnosing and follow-up in clinical practice.     

Effect of the Partial Replacement of Cement with Waste Granite Powder on the Properties of Fresh and Hardened Mortars for Masonry Applications

Granite is a well-known building and decorative material, and, therefore, the amount of produced waste in the form of granite powder is a problem. Granite powder affects the health of people living near landfills. Dust particles floating in the air, which are blown by gusts of wind, can lead to lung silicosis and eye infections, and can also affect the immune system. To find an application for this kind of waste material, it was decided to study the effect of partially replacing cement with waste granite powder on the properties of fresh and hardened mortars intended for masonry applications. The authors planned to replace 5%, 10%, and 15% of cement with waste material. Series of mortar with the addition of granite powder achieved 50% to 70% of the compressive strength of the reference series, and 60% to 76% of the bending strength of the reference series. The partial replacement of cement with the granite powder significantly increased the water sorption coefficient. The consistency of the fresh mortar, and its density and water absorption also increased when compared to the reference series. Therefore, Granite powder can be used as a partial replacement of cement in masonry mortars.     

Health literacy and public health: A systematic review and integration of definitions and models

Background  

Health literacy concerns the knowledge and competences of persons to meet the complex demands of health in modern society. Although its importance is increasingly recognised, there is no consensus about the definition of health literacy or about its conceptual dimensions, which limits the possibilities for measurement and comparison. The aim of the study is to review definitions and models on health literacy to develop an integrated definition and conceptual model capturing the most comprehensive evidence-based dimensions of health literacy.     

Recurrent monocular exudative retinal detachment as the first manifestation of squamous cell lung cancer: A case report

Rationale:In this report, we present an extremely rare case of recurrent monocular exudative retinal detachment without concomitant ocular metastases. This turned out to be the first symptom of squamous cell lung cancer.Patient concerns:A 63-year-old woman was referred to our ophthalmology clinic by her primary care physician with a complaint of deteriorating vision in her right eye that had started four months prior, without concomitant pain.Diagnoses:We observed a detachment in the lower part of the retina during her ophthalmoscopy. We did not find any tears, holes, or degenerative changes in the periphery of the retina of the right eye during the surgery. In addition, plaques, tumor masses, and metastases were absent. Therefore, we diagnosed her with unilateral paraneoplastic exudative retinal detachment. Imaging tests performed before surgery revealed perihilar density with a visible air bronchogram in the middle field of the left lung. This turned out to be squamous cell carcinoma.Interventions:Patient underwent pars plana vitrectomy and routine laboratory and imaging tests before the procedure that utilized 20-gauge instrumentation. The subretinal fluid and was drained and a tamponade using Densiron (Fluoron Co, Neu-Ulm, Germany) was applied. After ophthalmic treatment, patient underwent complex oncological treatment based on chemotherapy and radiotherapy.Outcomes:Despite the application of heavy silicone oil (Densiron) into the vitreous chamber, we observed a recurrence of retinal detachment in the right eye during the follow-up visit, 13 months after the first ophthalmic surgery. Following subsequent pars plana vitrectomy, the Densiron and subretinal membranes were removed. Despite oncological treatment, the patient died, twenty months after the appearance of the first ocular symptoms.Lessons:Exudative retinal detachment without tumor metastasis to the eyeball can be one of the first signs of lung cancer in rare cases. Multidisciplinary care and imaging methods with greater accuracy will provide comprehensive care to the patients. It will not only facilitate timely detection and treatment of lung tumors but also for a plethora of oncological diseases.     

A truncating PET100 variant causing fatal infantile lactic acidosis and isolated cytochrome c oxidase deficiency

Isolated mitochondrial complex IV (cytochrome c oxidase) deficiency is an important cause of mitochondrial disease in children and adults. It is genetically heterogeneous, given that both mtDNA-encoded and nuclear-encoded gene products contribute to structural components and assembly factors. Pathogenic variants within these proteins are associated with clinical variability ranging from isolated organ involvement to multisystem disease presentations. Defects in more than 10 complex IV assembly factors have been described including a recent Lebanese founder mutation in PET100 in patients presenting with Leigh syndrome. We report the clinical and molecular investigation of a patient with a fatal, neonatal-onset isolated complex IV deficiency associated with multiorgan involvement born to consanguineous, first-cousin British Asian parents. Exome sequencing revealed a homozygous truncating variant (c.142C>T, p.(Gln48*)) in the PET100 gene that results in a complete loss of enzyme activity and assembly of the holocomplex. Our report confirms PET100 mutation as an important cause of isolated complex IV deficiency outside of the Lebanese population, extending the phenotypic spectrum associated with abnormalities within this gene.     

Human chronic lymphocytic leukemia B cells can escape DNA damage-induced apoptosis through the nonhomologous end-joining DNA repair pathway

Nonhomologous end-joining (NHEJ) DNA factors maintain genomic stability through their DNA double-strand break (DSB) repair and telomere-associated activities. Unrepaired or misrepaired DSBs can lead to apoptotic death or chromosomal damage. The B cells of some B-chronic lymphocytic leukemia (B-CLL) patients are resistant to radiation-induced apoptosis in vitro. We show here that the novel DNA-dependent protein kinase (DNA-PK) inhibitor, NU7026 (2-(morpholin-4-yl)-benzo[h]chomen-4-one), and the phosphatidylinositol 3 (PI-3) kinase inhibitor, wortmannin, restored sensitivity to DNA damage-induced apoptosis of otherwise resistant cells. These resistant malignant B cells also escaped DSB-induced apoptosis following exposure to etoposide or neocarzinostatin. We found that at 15 minutes after irradiation, the levels of NHEJ (as measured by an in vitro DSB end-ligation assay) and DNA-PK catalytic subunit (DNA-PKcs) activity were, respectively, 2-fold and 4-fold higher in radio-resistant than in radio-sensitive B-CLL cells or Epstein-Barr virus (EBV)-transformed B cells. Ku70/Ku80 heterodimer DNA end-binding activity was also 2- to 3-fold higher in the resistant B-CLL cell subset compared with the sensitive B-CLL cell subset. Our results provide the first evidence that overactivating the NHEJ DNA repair pathway impairs DNA damage-induced apoptosis in malignant B cells and that this may contribute to their resistance to current chemotherapy.     

Plasma vs heart tissue concentration in humans – literature data analysis of drugs distribution

Little is known about the uptake of drugs into the human heart, although it is of great importance nowadays, when science desires to predict tissue level behavior rather than to measure it. Although the drug concentration in cardiac tissue seems a better predictor for physiological and electrophysiological changes than its level in plasma, knowledge of this value is very limited. Tissue to plasma partition coefficients (Kp) come to rescue since they characterize the distribution of a drug among tissues as being one of the input parameters in physiologically based pharmacokinetic (PBPK) models. The article reviews cardiac surgery and forensic medical studies to provide a reference for drug concentrations in human cardiac tissue. Firstly, the focus is on whether a drug penetrates into heart tissue at a therapeutic level; the provided values refer to antibiotics, antifungals and anticancer drugs. Drugs that directly affect cardiomyocyte electrophysiology are another group of interest. Measured levels of amiodarone, digoxin, perhexiline and verapamil in different sites in human cardiac tissue where the compounds might meet ion channels, gives an insight into how these more lipophilic drugs penetrate the heart. Much data are derived from postmortem studies and they provide insight to the cardiac distribution of more than 200 drugs. The analysis depicts potential problems in defining the active concentration location, what may indirectly suggest multiple mechanisms involved in the drug distribution within the heart. Copyright © 2015 John Wiley & Sons, Ltd.     

CD38 gene polymorphisms and genetic predisposition to multiple myeloma

Single nucleotide polymorphisms (SNPs) of adhesion and signaling genes may influence the etiopathogenesis of multiple myeloma (MM). CD38 molecule and its ligand CD31 are expressed and interact in malignant plasma cells and MM microenvironment. In this study we evaluated allele frequencies and distribution of two potentially functional CD38 SNPs, intronic rs6449182 (184C>G) and missense rs1800561 (418C>T, Arg¹⁴⁰Trp) in 175 Caucasian patients with MM and 207 healthy blood donors. The carriers of variant G allele of the rs6449182 SNPs were found to have significantly elevated risk of MM as compared to non-carriers; odds ratio = 5.69 (95% confidence interval = 3.7–8.7), p < 0.0001. In contrast, rs1800561 SNP minor T allele was detected at very low and comparable frequencies in patients and controls groups. In conclusion, our data suggest that inherited genetic variation in CD38 gene may impact on the risk of MM development.