Understanding the Retention of Vaping Additives in the Lungs: Model Lung Surfactant Membrane Perturbation by Vitamin E and Vitamin E Acetate.

Deviations from the normal physicochemical and functional properties of pulmonary surfactants are associated with the incidence of lung injury and other respiratory disorders. This study aims to evaluate the alteration of the 2D molecular organization and morphology of pulmonary surfactant model membranes by the electronic cigarette additives α-tocopherol (vitamin E) and α-tocopherol acetate (vitamin E acetate), which have been associated with lung injury, termed e-cigarette or vaping-use-associated lung injury (EVALI). The model membranes used contained a 7:3 molar ratio of DPPC (1,2-dipalmitoyl-sn-glycero-3-phosphocholine) and POPG (1-palmitoyl-2-oleoyl-sn-glycero-3-phosphoglycerol) to which α-tocopherol and α-tocopherol acetate were added to form mixtures of up to 20 mol % additive. The properties of the neat tocopherol additives and DPPC/POPG (7:3) mixtures with increasing molar proportions of additive were evaluated by surface pressure-area isotherms, excess area calculations, Brewster angle microscopy, grazing incidence X-ray diffraction, X-ray reflectivity, and atomic force microscopy. The addition of either additive alters the essential phase balance of the model pulmonary surfactant membrane by generating a greater proportion of the fluid phase. Despite this net fluidization, both tocopherol additives have space-filling effects on the liquid-expanded and condensed phases, yielding negative excess areas in the liquid-expanded phase and reduced tilt angles in the condensed phase. Both tocopherol additives alter the stability of the fluid phase, pushing the eventual collapse of this phase to higher surface pressures than the model membrane in the absence of an additive.

Interactions between the Cell Membrane Repair Protein S100A10 and Phospholipid Monolayers and Bilayers.

Protein S100A10 participates in different cellular mechanisms and has different functions, especially at the membrane. Among those, it forms a ternary complex with annexin A2 and the C-terminal of AHNAK and then joins the dysferlin membrane repair complex. Together, they act as a platform enabling membrane repair. Both AHNAK and annexin A2 have been shown to have membrane binding properties. However, the membrane binding abilities of S100A10 are not clear. In this paper, we aimed to study the membrane binding of S100A10 in order to better understand its role in the cell membrane repair process. S100A10 was overexpressed by E. coli and purified by affinity chromatography. Using a Langmuir monolayer as a model membrane, the binding parameters and ellipsometric angles of the purified S100A10 were measured using surface tensiometry and ellipsometry, respectively. Phosphorus-31 solid-state nuclear magnetic resonance spectroscopy was also used to study the interaction of S100A10 with lipid bilayers. In the presence of a lipid monolayer, S100A10 preferentially interacts with unsaturated phospholipids. In addition, its behavior in the presence of a bilayer model suggests that S100A10 interacts more with the negatively charged polar head groups than the zwitterionic ones. This work offers new insights on the binding of S100A10 to different phospholipids and advances our understanding of the parameters influencing its membrane behavior.

Factor VIII inhibitor development in Egyptian hemophilia patients: does intron 22 inversion mutation play a role?

BACKGROUND: Hemophilia A (HA) is an X-linked recessive bleeding disorder characterized by qualitative and quantitative deficiency of factor VIII (FVIII). The development of inhibitor antibodies against FVIII is the most challenging complication of treatment. Mutations in the FVIII gene is one of the genetic factors that leads to development of FVIII inhibitors especially intron 22 inversion (Inv22). OBJECTIVES: This study was carried out to assess the frequency of Inv22 of FVIII gene in Egyptian patients with hemophilia A and its role as a risk factor for developing inhibitors. PATIENTS AND METHODS: Seventy-two patients with severe HA and 48 patients with moderate HA were enrolled in the current study. All patients were treated on demand with either plasma-derived factor VIII or recombinant factor VIII concentrates. Genotyping of FVIII Inv22 was performed by LD-PCR while the presence and magnitude of inhibitor activity in blood was determined by the Bethesda assay. RESULTS: Around 23% of all hemophilia cases had positive Inv22. Intron 22 inversion mutation was detected in 6 and 33% of patients with moderate and severe HA respectively. Twenty-one cases (18%) of all hemophilic patients developed inhibitors. Thirty-7% of patients with Inv22 had inhibitor in their blood, almost all, but one, had severe HA. The risk of an inhibitor development during replacement therapy was four folds higher among Inv22 positive cases as compared with mutation negative peers (OR 4.3, 95% CI 1.6-11.9, P = 0.003). CONCLUSIONS: The prevalence of Inv22 of F VIII in Egyptian hemophiliacs is nearly like that of other population. This mutation was more frequently detected among severe hemophilic patients as compared with moderately affected peers. The presence of Inv22 mutation significantly predispose to FVIII inhibitor development.

Phase Diagram for a Lysyl-Phosphatidylglycerol Analogue in Biomimetic Mixed Monolayers with Phosphatidylglycerol: Insights into the Tunable Properties of Bacterial Membranes.

Ion pairing between the major phospholipids of the Staphylococcus aureus plasma membrane (phosphatidylglycerol - PG and lysyl-phosphatidylglycerol - LPG) confers resistance to antimicrobial peptides and other antibiotics. We developed 3adLPG, a stable synthetic analogue which can substitute for the highy-labile native LPG, in biophysical experiments examining the membrane-protecting role of lipid ion pairing, in S. aureus and other important bacteria. Here we examine the surface charge and lipid packing characteristics of synthetic biomimetic mixtures of DPPG and DP3adLPG in Langmuir monolayers, using a combination of complementary surface-probing techniques such as infrared reflection-absorption spectroscopy and grazing-incidence x-ray diffraction. The resultant phase diagram for the ion paired lipids sheds light on the mixing behavior of lipids in monolayer models of resistant phenotype bacterial membranes, and provides a platform for future biophysical studies.

Interfacial Self-Assembly of Antimicrobial Peptide GL13K into Non-Fibril Crystalline ß-Sheets.

The need for new and potent antibiotics in an era of increasing multidrug resistance in bacteria has driven the search for new antimicrobial agents, including the design of synthetic antimicrobial peptides (AMPs). While a number of ß-sheet forming AMPs have been proposed, their similarity to ß-amyloids raises a number of concerns associated with neurodegenerative states. GL13K is an effective, synthetic AMP that selectively folds into ß-sheets at anionic interfaces. Moreover, it is one of relatively few AMPs that preferentially fold into ß-sheets without bridging disulfides. The interfacial activity of GL13K and its propensity to form amyloid fibrils have not been investigated. Using structural studies at the air/water interface and in the absence of anionic lipids, we demonstrate that while GL13K does form crystalline ß-sheets, it does not self-assemble into fibrils. This work emphasizes the requirement for a single charged amino acid in the hydrophobic face to prevent fibril formation in synthetic peptides.

Effect of packed red blood cell transfusion on IL-8 and sICAM-1 in premature neonates at different postnatal ages.

BACKGROUND: Transfusion-related immunomodulation (TRIM) has been described in adults; however, its existence in neonates is not confirmed. The generation of TRIM is attributed to increased concentrations of IL-8, sICAM-1 and other pro-inflammatory cytokines. This study aimed to monitor changes in IL-8, sICAM-1 as markers for TRIM in premature infants at different postnatal ages. METHODS: Preterm infants with a gestational age between 28 and 32 weeks who were receiving PRBC transfusion during the first 28 days of life were included in the study. Infants were stratified into two groups according to their postnatal age: Group 1 with postnatal ages of (0-14) days and Group 2 of (15-28) days. The concentrations of IL-8 and sICAM-1 were measured by enzyme-linked immunosorbent assay (ELISA) before transfusion, 6 h after the end of transfusion and in the donor's PRBCs bag immediately before infusion into the baby. RESULTS: IL-8 concentration in the PRBCs bags correlated with post-transfusion level in Group 2 (r = 0.59, p = 0.002) but not in Group 1 (r = 0.39, p = 0.06). sICAM-1 concentration in the bag correlated with infants'concentrations in neither group. In Group 1, pre-transfusion concentrations of both cytokines (IL-8 and sICAM-1) did not correlate whereas post-transfusion concentrations did correlate (r = -0.09, p = 0.68 and r = 0.4, p = 0.05 respectively). In Group 2, the concentrations of both cytokines did not correlate with each other during pre-transfusion (r = 0.11, p = 0.58) as well as post-transfusion (r = 0.12, p = 0.56). There was no significant increase in either cytokines after transfusion in each group. CONCLUSION: This study showed positive correlation between IL-8 concentration in the transfusion bag and post transfusion in Group 2 infants which could be attributed to passive transmission from the bags. This study does not support an immune modulatory effect for packed RBC in preterm infants.

The Effectiveness of Intraocular Methotrexate in the Treatment of Posterior Uveitis in Behçet's Disease Patients Compared to Retrobulbar Steroids Injection.

Aim of Work. To evaluate the efficacy of intravitreal methotrexate (MTX) compared to retrobulbar triamcinolone acetonide (TAA), in controlling posterior segment involvement and inducing remissions among Behçet's disease (BD) patients. Study Design. This is a cross-sectional nonrandomized comparative study. Patients and Methods. 31 adult BD male patients with a mean disease duration of 5.45 years who presented with bilateral posterior segment involvement were included. Each patient received intravitreal injection of 400 µg/0.1 mL (MTX) for the right eye (Group A) and 1 mL of retrobulbar 40 mg/mL TAA for the left eye (Group B). Results. 90% of eyes showed complete improvement of anterior chamber reaction, whereas an improvement in vitreous activity in 77% with no significant differences between both groups (p ≤ 0.1). BCVA improved in 77.4% eyes (Group A) compared to 87.1% (Group B) (p ≤ 0.4). Relapses were noted in 11 eyes (35.5%), in group A, with the mean duration of remission being 19.1 weeks ± 2.13 compared to 7.35 ± 2.8 in 20 eyes (64.5%) in group B (p ≤ 0.1). Conclusion. No statistical differences were found between both treatment modalities; however, based on clinical observations, intravitreal MTX may ensure better control of inflammatory reaction and may encourage longer remission as compared to retrobulbar TAA in BD patients.

Aerobic training suppresses exercise-induced lipid peroxidation and inflammation in overweight/obese adolescent girls.

This study aimed to determine whether aerobic training could reduce lipid peroxidation and inflammation at rest and after maximal exhaustive exercise in overweight/obese adolescent girls. Thirty-nine adolescent girls (14-19 years old) were classified as nonobese or overweight/obese and then randomly assigned to either the nontrained or trained group (12-week multivariate aerobic training program). Measurements at the beginning of the experiment and at 3 months consisted of body composition, aerobic fitness (VO2peak) and the following blood assays: pre- and postexercise lipid peroxidation (15F2a-isoprostanes [F2-Isop], lipid hydroperoxide [ROOH], oxidized LDL [ox-LDL]) and inflammation (myeloperoxidase [MPO]) markers. In the overweight/ obese group, the training program significantly increased their fat-free mass (FFM) and decreased their percentage of fat mass (%FM) and hip circumference but did not modify their VO2peak. Conversely, in the nontrained overweight/obese group, weight and %FM increased, and VO2peak decreased, during the same period. Training also prevented exercise-induced lipid peroxidation and/or inflammation in overweight/obese girls (F2-Isop, ROOH, ox-LDL, MPO). In addition, in the trained overweight/obese group, exercise-induced changes in ROOH, ox-LDL and F2-Isop were correlated with improvements in anthropometric parameters (waist-to-hip ratio, %FM and FFM). In conclusion aerobic training increased tolerance to exercise-induced oxidative stress in overweight/obese adolescent girls partly as a result of improved body composition.

Polycythemia in neonatal intensive care unit, risk factors, symptoms, pattern, and management controversy.

BACKGROUND: Polycythemia (PC) is defined as venous hematocrit (hct) ≥65%.( ) Its incidence is high among certain risk factors (RFs). Its management is controversy. AIMS: TO DETERMINE: (1) The incidence of PC in our neonatal intensive care unit (NICU). (2) Most common RF, symptoms, and laboratory abnormalities (LA) associated with PC and their effect on the length of hospital stay (LOS). (3) Whether noninvasive interventions are effective in reducing hct. (4) Hct pattern of PC neonates. DESIGN: Retrospective cohort study. SETTING: NICU at a maternity and children hospital. MATERIALS AND METHODS: Records review of all neonates from March 2011 to August 2013. Inclusions criteria were: (1) Venous hct ≥65%. (2) Neonates born in our institution. (3) Early umbilical cord clamping. (4) Gestational age ≥34 weeks. STATISTICAL ANALYSIS: Chi-square and multiple regression analysis. RESULTS: One hundred and one PC neonates were eligible. Incidence of PC in our NICU is 14.5%. The most common RF, symptoms, and LA were: Small for gestational age, jaundice and hypoglycemia respectively. Tachypnea (  P - 0.04) and oliguria (P - 0.03) significantly prolonged LOS. Noninvasive interventions or observation could not reduce the hct significantly (P - 0.24). The hcts mean peaked maximally at a mean of 2.8 h of age. CONCLUSION: PC incidence in our NICU is higher than the reported incidence in healthy newborns. Most of the PC neonates were either symptomatic or having LA. Noninvasive interventions or observation were not effective in reducing hct in polycythemic neonates. Hct in both healthy and PC neonates peaked at the same pattern.

Activity, inactivity and quality of life among Lebanese adolescents.

BACKGROUND: The aim of the present study was to investigate recent overweight and obesity prevalence rates for Lebanese adolescents, and to examine differences in physical activity, screen time (sum of time spent in front of TV, computer, and videogames), and health-related quality of life (HRQOL) for the first time among normal, overweight, and obese adolescents. METHODS: One thousand Lebanese adolescents (14-18 years old) from nine schools participated in the study. Height, weight, physical activity, screen time, and HRQOL variables were assessed using validated self-report questionnaires. RESULTS: A total of 7.8% of boys and 1.75% of girls were obese, and 22.5% of boys and 12.47% of girls were overweight. Normal-weight boys reported higher physical activity scores at health clubs than obese boys. Normal-weight girls reported higher leisure time and total physical activity scores than obese girls. In the normal-weight group, boys reported higher total screen time than girls. Normal-weight boys reported higher physical functioning scores than their obese peers. Normal-weight girls reported higher physical functioning and average HRQOL scores than obese girls. Normal-weight and overweight boys reported higher average HRQOL scores than girls. CONCLUSION: The present study is the first to provide data on physical activity, screen time, and HRQOL among Lebanese adolescents. Despite the need for further research, all those concerned with the pediatric population are urged to develop and implement effective strategies to increase physical activity and improve HRQOL among adolescents based on the present findings.

[Leptin, insulin, IGF-1 and bone mass in a group of sedentary adolescent girls]. / Leptine, insuline, IGF-1 et masse osseuse chez des adolescentes sédentaires.

AIM OF THE STUDY: To investigate the relationships between serum leptin, IGF-1, insulin and bone mineral content and density in a group of Lebanese sedentary adolescent girls. METHODS AND RESULTS: Twenty Lebanese sedentary adolescent girls participated in our study. Total body bone mineral content and density were measured by dual-energy X-ray absorptiometry (DEXA). In parallel, fasting leptin, IGF-1 and insulin concentrations were also measured. Serum leptin, IGF-1 and insulin concentrations were not associated with total body bone mineral content (BMC), total body bone mineral density (BMD) or pelvis BMD. CONCLUSION: Serum leptin, IGF-1 and insulin concentrations are not positive predictors of total body bone mineral content or density in this study group.

Exercise training and cardiovascular risk factors in type 1 diabetic adolescent girls.

Sixteen postmenarcheal Type 1 diabetic adolescent girls were randomized into training (involving aerobic and strength exercises) and nontraining groups. Body composition (skinfold thickness), aerobic fitness (PWC170), plasma lipids, serum apolipoproteins, lipoprotein(a), leptin, and adiponectin were assessed before and after the 6-month period. After the 6-month period, fat mass and leptin increased significantly in the nontraining group but not in the training group. Conversely, in the latter group, fat-free mass increased (P < .01). Moreover, PWC170 improved and apolipoproteinB:apolipoproteinA-1 ratio decreased with physical training (P < .05). Thus, physical training reduces cardiovascular risks and the increase of insulin resistance risk factors in diabetic adolescent girls.

Nutritional and plasmatic antioxidant vitamins status of ultra endurance athletes.

OBJECTIVE: The "Marathon des Sables" (MDS) is a competition known to induce oxidative stress. Antioxidant vitamins prevent exercise-induced oxidative damages. The purpose of this study was to evaluate daily intake and plasma level of the main antioxidant vitamins (alpha-tocopherol, vitamin C, beta-carotene and retinol) in 19 male athletes who participated in this competition. METHODS: Data collected before the beginning of the competition included daily dietary intake using a 7-day food record and plasma biochemical measurements (alpha-tocopherol, vitamin C, beta-carotene and retinol). RESULTS: First, total energy intake was obviously lower than the energetic intake usually observed in well-trained endurance athletes. Second, antioxidant vitamins intake was also insufficient. Indeed, the intake was lower than the French Dietary Reference Intakes (DRI) for this population in 18 subjects for vitamin E and 6 subjects for vitamin C, beta-carotene and Retinol Equivalent. As a significant relationship was found between total energy intake and the intake of vitamin E (r = 0.73; p < 0.001) and vitamin C (r = 0.78; p < 0.001), the low total energy intake contributed partially to the insufficient antioxidant vitamins intake. The dietary questionnaire analysis also revealed a low intake of vegetable oils, fruits and vegetables. However, plasma concentrations of these antioxidant vitamins were similar to the literature data observed in athletes. CONCLUSION: This study evidenced obvious insufficient energy intake in ultra endurance athletes associated with a low antioxidant vitamin intake.