Effects Of Long Exposure Research Articles

P-160 Repeated treatment with the same sperm donor during the second cycle does not improve pregnancy rate, live birth rate nor risk of miscarriage

Abstract Study question Can repeated treatment with the same sperm donor in intrauterine insemination (IUI) and IVF/ICSI in the second cycle improve the outcome? Summary answer Pregnancy rate, live birth and miscarriage were not affected by repeated treatment with the same sperm donor in the second cycle with IUI or IVF/ICSI. What is known already Women with a longer exposure to paternal antigens have a higher chance of successful placentation and the use of donated gametes increases the risk for disorders related to placental insufficiency. Local exposure to seminal fluid has been shown to improve pregnancy rate. However, it is unknown how repeated exposure to the same donor, as opposed to changing donor, affects the outcome and currently there is no evidence suggesting that one method is superior to the other. Study design, size, duration This is a retrospective cohort study from three IVF clinics in Sweden including 868 women who have undergone reproductive treatments with donated sperms between 2014 and 2022. The outcomes pregnancy rate, live birth rate and risk of miscarriage were compared between women who had used the same donor in the second treatment cycle with women who were treated with a new donor. Participants/materials, setting, methods 631 nulliparous women undergoing IUI or IVF/ICSI with donated sperm using the same donor during two consecutive treatment cycles were compared to 237 nulliparous women who had changed donor between the treatments. All medical indications for treatment were included in the study. Oocyte donation cycles and frozen embryo transfer cycles were excluded. Statistical analyses were performed using logistic regression, adjusting for year of treatment, maternal age, treatment method and clinic. Main results and the role of chance No differences in pregnancy rate nor live birth rate were found when comparing repeated treatments with the same donor with change of donor in IUI or IVF/ICSI (odds ratio (OR); 0.95, 95% CI 0.67-1.34, p = 0.77; OR 1.30, 95% CI 0.86-1.95, p = 0.21 respectively). A significant difference was found in miscarriage (OR 0.38, 95% CI 0.18-0.79, p = 0.01). However, after adjusting for year of treatment, maternal age, treatment method and clinic, no significant differences were found in any of the outcomes: pregnancy rate (adjusted OR (aOR) 0.94, 95% CI 0.65-1.38, p = 0.77), live birth rate (aOR 1.21, 95% CI 0.78-1.88, p = 0.40) nor miscarriage (aOR 0.44, 95% CI 0.19-1.03, p = 0.06). Limitations, reasons for caution In addition to the retrospective study design, the restricted number of patients is a limitation. The possibility of undocumented confounders that could impact the results is also a reason for caution. Furthermore, as only two subsequent treatments were studied, any effect of longer exposure could not be evaluated. Wider implications of the findings Our results could not show that using the same sperm donor repeatedly is superior to changing donor regarding pregnancy, live birth or miscarriage. Further research on additional exposure to the same donor as well as outcomes specific to placental insufficiency is needed to address the issue further. Trial registration number NA

The effect of long exposure to uvb rays on histological features of wistar rats (Rattus norvegicus) in photoaging model

Introduction: Indonesia is a tropical country with exposure to UV rays from the sun throughout the year, so the Indonesian population is very vulnerable to skin aging, especially extrinsic skin aging due to prolonged exposure to UV rays. This study aimed to determine the effect of long exposure to UVB rays on the thickness of the epidermis, the thickness of the dermis, and the number of blood vessels and sunburn cells in (Rattus norvegicus) Wistar strain. Methods: This research was a post-test-only control group design using 27 rats which were divided into 3 groups, namely: control group K was untreated rats, and treatment groups P1 and P2 were rats exposed to UVB radiation for 3 weeks and 6 respectively exposure weeks. Test the effect on the study using the One-Way ANOVA test and Tukey’s Post Hoc Test. Results: The results indicated an increase in epidermal thickness of groups P1 (44.87 μm) and P2 (56.90 μm) (significant p<0.05). A decrease in dermis thickness occurred in groups P1 (726.91 μm) and P2 (559.40 μm) (significant p<0.05). In the photoaging area, there was an increased amount of sunburn cells in group P1 (6.40) and P2 (11.40) (significant p<0.05). There was a difference in the number of blood vessels between groups K and P2 and groups P1 and P2 (p<0.05). Conclusion: There was an effect of long exposure to UVB rays on histology in rats (Rattus norvegicus) of the photoaging model including the thickness of the epidermis layer and dermis layer, the number of blood vessels, and sunburn cells.

Experimental evaluation of the impact of real sun patch on radiant floor heating in highly glazed spaces

When the floor heating system is integrated into highly glazed buildings, the uneven distribution of temperature and humidity caused by the long exposure to the direct solar radiation becomes more and more prominent, which affects the indoor thermal comfort. Given that this issue has already been studied by means of mainly numerical simulations in previous studies and that thermal comfort already needs to be considered by means of a questionnaire, leaving a large room for improvement in terms of experimental considerations. This study quantitatively and qualitatively analyses the evaluation of the impact of real moving sun patch on radiant floor heating for thermal comfort consideration. The effects of long exposure to sun patch on both thermal comfort and thermal sensation are objectively assessed by means of experimental measurements conducted on a thermal manikin placed in a controlled and monitored test cell exposed to non-controlled climatic conditions. The results show that the indoor air temperature exceeds 26 °C, even in winter season, when the sun patch appears and is exaggerated when its duration is extended. The decrease of floor surface temperature is positively correlated with the decrease of sun patch area. Extending the sun patch duration allows the heat absorbed by the floor increase the outlet water temperature and, thus, impact the thermal sensation and thermal comfort. Based on this, future contributions may be to eliminate overheating by combining ventilation systems, intelligent control systems, as well as to recover the radiant heat generated by the sun patch.

Karakteristik Uji Stabilitas Pigmen dan Antioksida Hasil Ekstraksi Pewarna Alami dari Kulit Buah Naga Merah

This article aims to determine the level of anthocyanins in natural colors derived from dragon fruit, especially on the skin. Completely Randomized Design (CRD) with SPSS was used as the research method for this article, as well as two treatments, namely variations in solvent volume A and immersion time (B). Each treatment consisted of three levels and three repetitions, namely the first factor of variation in solvent volume (A) consisted of (A1) 0.29%, (A2) 0.432%, (A3) 0.576%. The second factor is the immersion time (B1) 42 hours, (B2) 48 hours, (B3) 72 hours. Extraction of anthocyanin pigment from red dragon fruit skin was carried out using maceration extraction. The test parameters in this study were the color stability test, anthocyanin content test and the yield of dragon fruit peel extract. The pH value was measured using a pocket pH meter. In this study, a spectrophotometer was used to determine the brightness level of anthocyanins. Measurement of the weight % yield of anthocyanin pigment was carried out using the yield formula below. The research results show; (1) the best treatment resulted in extraction using citric acid solvent: water which produced an absorbance of 0.479 – 0.439 at λmax 517 nm; (2) radar antioxidant activity in anthocyanins from dragon fruit peels of 76.71%; (3) the stability of anthocyanin dyes is stable at acidic pH from pH 2 – pH 5, at a temperature of 80˚C and the effect of long exposure to the lamp makes the anthocyanin dyes unstable; and (4) dragon fruit syrup was stable at almost the same pH of dragon fruit syrup without coloring and added dragon fruit syrup, namely 3.42 and 3.89.

Assessment of the Effect of Blue Light on Visual Acuity among College Students

Visual acuity is the acuteness or clarity of vision which is dependent on the shortness of the retinal focus within the eye, and the sensitivity of the interpretative faculty of the brain. It is expressed as a fraction, such as 20/20 or 6/6 which is the normal visual acuity. Poor or impaired visual acuity is expressed as 20/40 and below or 6/9 and below. Blue light, which is one of the visible rays from the sun and also an artificial constituent of many modern devices, is a source of illumination which among other factors strongly affects our visual acuity. The present rapid, steady advancement in technology has led to a great increase in our usage and exposure to blue light. It is not uncommon nowadays to easily find someone who spends his entire day on digital screen, and many times even a great deal of the nighttime is also spent on blue-light-emitting technologies. The aim of this study is to assess and determine how this blue light affects college students and perhaps their productivity. A descriptive cross-sectional study was conducted using the focus group discussion (FGD) technique amongst 100 college students across five departments in College of Health Sciences, Nnamdi Azikiwe University, Nnewi Campus. The mean age of the respondents was 22.06 years. More of the respondents were females (66%) while 34% were males. The prevalence of visual acuity impairment after a considerably long usage of blue light was 37%. The majority of the respondents (87%) use a light-emitting diode (LED) technology torch/lantern during their night studies. 82% also uses their mobile phones for their studies and other academic works in which they have to spend many hours at once on the screen. Many others are exposed to other sources of blue light, and more even combine usage of different sources of blue light at once. The prevalence of visual acuity status below 6/6 amongst the students was high, and this is worrisome with regards to its long term effects or cumulative effects on their vision. Adequate sensitization on the harmful effects of long exposure to blue lights, usage of blue light filters/glasses (photochromic lens, for instance), taking frequent breaks from digital screens, encouraging outdoor use of blue light screens, early and proper management of impaired vision and more intakes of foods that enhance eyesight are recommended.

EFFECT OF LENGTH EXPOSURE AND TYPES OF VOICE ON CORN SEEDS (Zea Mays) VIABILITY AND EARLY GROWTH

Seed quality includes three aspects, namely genetic quality, physical quality and physiological quality. Physiological quality is an aspect of seed quality as indicated by seed viability and vigor. This study aims to analyze the effect of different types of sound exposure on viability and early growth of corn seeds, and to analyze the effect of long exposure to sound on viability and early growth of maize seeds. The research was carried out in the laboratory of the Faculty of Agriculture, Teuku Umar University. on September 20 - October 19, 2019. This study used a Split Plot with the main plot type of sound exposure consisting of four levels, and the main sub-plot, namely the length of sound exposure consisting of three levels. Observed parameters; germination rate, growth speed, synchronous growth (KST), stomata openings. Based on the research results, the best germination rate, growth rate, growth impregnability, leaf width, and stomatal openings were found in the Murrotal Al-Quran exposure. In the long exposure to sound treatment, it showed that the length of exposure to sound had no significant effect on germination, growth speed, growth impregnability, leaf width of maize plants, and stomata opening of maize plants.

PEMERIKSAAN KADAR ALANIN AMINOTRANSFERASE (ALT) TERHADAP LAMA PAPARAN KARBON MONOKSIDA PADA PEKERJA BENGKEL DI JEMUR WONOSARI SURABAYA

Carbon monoxide is one of the most important pollutants and has toxic properties if the gas is inhaled by humans. Levels of alanine aminotransferase (ALT) and ALT enzymes become one of the biomarkers that affect liver damage. The ALT enzyme is a transferase enzyme that is released when the liver is damaged. The purpose of this study was to determine the effect of long exposure to carbon monoxide (CO) on workshop workers on the examination of ALT levels. The research method used is an experimental method with a one-shot case study design on 27 respondents of workshop workers in the Jemur Wonosari area of ​​Surabaya. ALT levels were measured using a photometer and analysis of ALT levels was carried out using the One-way ANOVA statistical test using SPSS. The results showed the average ALT levels in group X1 (long working 1-5 years) of 38.26 u/l while the average result in group X2 (long working 6-10 years) was 40.38 u/l and average results in group X3 (long working 11-15 years old) is 41.11 u/l. One way ANOVA statistical test obtained a significance value of 0.484> 0.05. So the conclusion obtained in this study is that there is no effect of long exposure to carbon monoxide on the examination of ALT levels in the blood of workshop workers in Jemur Wonosari Surabaya.

THE EFFECT OF LONG EXPOSURE OF UV RADIATION ON ERYTHEMA AND MELANIN INDEX

UV radiation are divided into 3, namely UV A (400 – 315 nm), UV B (315-280 nm), UV C (280 – 100 nm). UV C radiation have the greatest effect on skin damage compared to UV A and UV B. UV radiation can reach the earth's surface, that can cause burning of the skin with signs such as redness of the skin (erythema), pain, blistering and peeling of the skin. Until now there has been no research on the effect of long exposure of UV C radiation on the erythema and melanin index, so aim this research is know about the effect of long exposure of UV C radiation on the erythema and melanine index. This research was conducted by giving exposure to rat that had been shaved with variations in exposure time, namely 5 minutes, 10 minutes, 15 minutes and 20 minutes. The skin that has been exposed with UV radiation will be photographed for color analysis using a chromometer. The results showed that exposure of UV radiation for 10 minutes caused the greatest increase in the melanin and erythema index

Effect of Long Exposure Against Quantity and Quality of DNA in Toothpick Samples as an Alternative for Individual Identification

Effect of Long Exposure Against Quantity and Quality of DNA in Toothpick Samples as an Alternative for Individual Identification

Cadmium effects on plant reproductive organs: Physiological, productive, evolutionary and ecological aspects

AbstractStudies involving the effects of long‐term exposure of plants to cadmium (Cd) are not usual, hence, data about Cd‐induced impacts on plant reproductive organs are scarce. The lack of robust information about this matter is surprising and also worrying because it is not yet clear whether (and how strong) Cd influences yield, and quality of fruits and seeds. Such information is necessary to guide strategies to manage crops and to avoid negative impacts on the environment and human health. This review gathers information about the effects of long exposure of flowers, fruits and seeds to Cd. A critical analysis of the data related to this matter, which have been published in the last 30 years, was performed. Ecological and evolutionary aspects were also discussed, and new insights were provided. The information about Cd‐induced effects on fruit and seed quality is relevant to support not only further scientific studies, but also environmental, economic and health policies in times of increasing heavy metal pollution in agricultural areas.

Effects of Long Exposures of Peppermint Aroma on Awareness in Simulated Driving

Effects of Long Exposures of Peppermint Aroma on Awareness in Simulated Driving

EFFECT OF ROOM TEMPERATURE ON THE QUALITY OF DNA FROM EARPHONE SWAB BY OBSERVING MITOCHONDRIAL DNA [mtDNA] D-LOOP REGION OF 126 bp (HVS II, nt 34-159) AND 143 bp (HVS I, nt 16268-16410)

The objects contained in crime scene and its surroundings have significance in the examination of forensic identification. The most commonly used specimens in the examination for identification are blood/blood spots, semen patches, vaginal swabs, buccal swabs and bones, including items often used by the perpetrator/victim the last time. For example, a mobile phone hearing aid (headset/earphone). In the use of earphones attached to the outer ear skin so it is suspected there is a serumen attached to the tool. One factor that can affect the quality of DNA is the prolonged exposure. Until now in Indonesia the effect of long exposure to room temperature on the quality of DNA on the DNA material of earphone swabs through DNA analysis has not been widely known. The type of study was laboratory experimental. Used earphones are exposed at room temperature within 1, 7, 14 and 20 days. The results of this study indicate that the environmental effect, ie the duration of exposure, affects the decrease in DNA content significantly from day 1 to 20. Detection of PCR mtDNA D-Loop HVS I visualization results 143 bp nt: 16268 16410 shows positive detection results (+) Only at day 1 exposure to room temperature [4 sample/66,67%] and day 7 [3 sample/50%]. Visualization of PCR results mtDNA D-Loop HVS II 126bp nt: 34 -159 was performed on day 1 day room exposure [2 sample/33,37%] and day 7 [6 sample/100%]. Conclusion, the duration of exposure to room temperature affect the quality of DNA from earpiece swab material. Decreased levels of earphones DNA swabs showed a significance value (p <0.005) against the effect of long time exposure to room temperature.

Effects of long exposure to spent potliner on seeds, root tips, and meristematic cells of Allium cepa L.

Spent potliner (SPL) is a solid waste generated in the aluminum mining and processing industry. It is sometimes dumped into the environment and leach in contact with water, thereupon affecting living beings, which are likely to be exposed to the waste for long periods. Considering this, we aimed to evaluate the effects of extended exposure to SPL through bioassays using Allium cepa as plant model system. Seeds of A. cepa were either directly exposed to SPL (continuous exposure) or first germinated in water and then exposed to SPL (discontinuous exposure). The germination rate was determined from 24 to 192h of exposure. The maximum effects of SPL on germination were observed after 96h in both exposure approaches. For the parameter root elongation, the discontinuous treatment was more efficient in demonstrating differences among the applied SPL concentrations (60% of reduction). Microscopic analysis was carried out in root tip cells discontinuously exposed to SPL for 96h. A mitodepressive effect was observed (above 50%), as well as increased rate of chromosome abnormalities (up to 100-fold) and induction of cell death. The consequences of exposure to SPL for longer periods are discussed.

Role of oxygen-containing functional surface groups of activated carbons on the elimination of 2-hydroxybenzothiazole from waters in A hybrid heterogeneous ozonation system

AbstractThe influence of the variation of chemical surface properties of activated carbons on the sorption capacity of activated carbons used in hybrid heterogeneous ozonation systems is still under discussion. In this study, the effect of long exposure of activated carbon to ozone and its implication on the removal of emerging organic pollutants from waters is evaluated. A commercial activated carbon (Filtrasorb-400) is used here as a raw material. It is chemically modified by continuous ozone exposure. 2-hydroxybenzothiazole (OHBT) is chosen as a target organic contaminant, representative of emerging micro-pollutants. Results obtained here reveal that extensive exposition of activated carbon surface to ozone weakens adsorbate–adsorbent interactions. Highly exposed activated carbon to ozone increases the concentration of oxygen-containing acidic functional groups, leading to a higher concentration of surface electron-withdrawing groups such as carboxylic acid anhydrides and carboxylic acids and reducing the sorption capacity toward OHBT in the hybrid heterogeneous ozonation system. At pH conditions around the point of zero charge (pH

Separate and combined effects of a 10-d exposure to hypoxia and inactivity on oxidative function in vivo and mitochondrial respiration ex vivo in humans.

An integrative evaluation of oxidative metabolism was carried out in 9 healthy young men (age, 24.1 ± 1.7 yr mean ± SD) before (CTRL) and after a 10-day horizontal bed rest carried out in normoxia (N-BR) or hypoxia (H-BR, FiO2 = 0.147). H-BR was designed to simulate planetary habitats. Pulmonary O2 uptake (V̇o2) and vastus lateralis fractional O2 extraction (changes in deoxygenated hemoglobin+myoglobin concentration, Δ[deoxy(Hb+Mb)] evaluated using near-infrared spectroscopy) were evaluated in normoxia and during an incremental cycle ergometer (CE) and one-leg knee extension (KE) exercise (aimed at reducing cardiovascular constraints to oxidative function). Mitochondrial respiration was evaluated ex vivo by high-resolution respirometry in permeabilized vastus lateralis fibers. During CE V̇o2peak and Δ[deoxy(Hb+Mb)]peak were lower (P < 0.05) after both N-BR and H-BR than during CTRL; during KE the variables were lower after N-BR but not after H-BR. During CE the overshoot of Δ[deoxy(Hb+Mb)] during constant work rate exercise was greater in N-BR and H-BR than CTRL, whereas during KE a significant difference vs. CTRL was observed only after N-BR. Maximal mitochondrial respiration determined ex vivo was not affected by either intervention. In N-BR, a significant impairment of oxidative metabolism occurred downstream of central cardiovascular O2 delivery and upstream of mitochondrial function, possibly at the level of the intramuscular matching between O2 supply and utilization and peripheral O2 diffusion. Superposition of hypoxia on bed rest did not aggravate, and partially reversed, the impairment of muscle oxidative function in vivo induced by bed rest. The effects of longer exposures will have to be determined.

Safe and prolonged survival with long-term exposure to pomalidomide in relapsed/refractory myeloma

The IFM2009-02 trial studied pomalidomide (4 mg daily, 21/28 versus 28/28) and dexamethasone in very advanced relapsed or refractory multiple myeloma (RRMM). We observed that 40% of patients had a prolonged progression-free survival (PFS) and subsequently overall survival (OS). We sought to analyze the characteristics of these patients and study the effect of long exposure to pomalidomide. We separated the studied population into two groups: 3 months to 1 year (<1 year) and more than 1 year (≥1 year) of treatment with pomalidomide and dexamethasone based on clinical judgment and historical control studies. We then analyzed the characteristics of patients according to duration of treatment. The overall response rate (ORR) for the <1-year group was 43%, the median PFS 4.6 months [95% confidence interval (95% CI) 3.8-6.4] with only 6% at 12 months, and the median OS was 15 months (11.7-20.3) and 40% at 18 months. For the ≥1-year group, the response rate and survival were strikingly different, ORR at 83%, median PFS 20.7 months (14.7-35.4), median OS not reached, and 91% at 18 months. Pomalidomide and dexamethasone favored prolonged and safe exposure to treatment in 40% of heavily treated and end-stage RRMM, a paradigm shift in the natural history of RRMM characterized with a succession of shorter disease-free intervals and ultimately shorter survival. Although an optimization of pomalidomide-dexamethasone regimen is warranted in advanced RRMM, we claim that pomalidomide has proven once more to change the natural history of myeloma in this series, which should be confirmed in a larger study.

Daily exposure to summer temperatures affects the motile subpopulation structure of epididymal sperm cells but not male fertility in an in vivo rabbit model

High temperatures have negative effects on sperm quality leading to temporary or permanent sterility. The aim of the study was to assess the effect of long exposure to summer circadian heat stress cycles on sperm parameters and the motile subpopulation structure of epididymal sperm cells from rabbit bucks. Twelve White New Zealand rabbit bucks were exposed to a daily constant temperature of the thermoneutral zone (from 18 °C to 22 °C; control group) or exposed to a summer circadian heat stress cycles (30 °C, 3 h/day; heat stress group). Spermatozoa were flushed from the epididymis and assessed for sperm quality parameters at recovery. Sperm total motility and progressivity were negatively affected by high temperatures (P < 0.05), as were also specific motility parameters (curvilinear velocity, linear velocity, mean velocity, straightness coefficient, linearity coefficient, wobble coefficient, and frequency of head displacement; P < 0.05, but not the mean amplitude of lateral head displacement). Heat stress significantly increased the percentage of less-motile sperm subpopulations, although the percentage of the high-motile subpopulation was maintained, which is consistent with the fact that no effect was detected on fertility rates. However, prolificacy was reduced in females submitted to heat stress when inseminated by control bucks. In conclusion, our results suggest that environmental high temperatures are linked to changes in the proportion of motile sperm subpopulations of the epididymis, although fertility is still preserved despite the detrimental effects of heat stress. On the other hand, prolificacy seems to be affected by the negative effects of high temperatures, especially by altering female reproduction.

Long-Term Exposure to Pomalidomide-Dexamethasone in Pts with Refractory Myeloma

Background. The IFM2009-02 study was launched in 2009, and randomized 84 patients (pts) with pomalidomide (oral 4 mg daily) and dexamethasone (oral 40 mg weekly) given either 21 days out of 28 or continuous. Whilst the overall median PFS was 4.6 months - this end stage very advanced RRMM population, we observed that 40% of the patients had a prolonged PFS and subsequently OS in the trial.We sought to analyze the characteristics of 58 pts that had more than 3 months of pomalidomide to study the effect of long exposure to Pomalidomide.Method. IFM 2009-02 was a multicentre phase 2 study of pts with RRMM who had at best a stable disease with the last course of bortezomib and of lenalidomide, or who were refractory to bortezomib and lenalidomide (IMWG). This analysis was performed on the ITT population combining data from the 2 study arms. We have analyzed the characteristics of pts according to duration of treatment with pomalidomide and dexamethasone 3 months to one year (<1 year) or more than one year (≥1 year).Results. 60% and 40% of pts were exposed to pomalidomide for <1 year and ≥1 year, respectively. The ORR for the <1 year group was 43%, the median PFS 4.6 months (CI95% 4;6) with only 6% at 12 months, and the median OS 15 months (4;6) and 65% at 12 months, 40% at 18 months. For the ≥1 year group, the response rate and survival were strikingly different, ORR at 83%, PFS 20.7 months, OS not reached (CI95% 40;-) and 100% at 12 months, 91% at 18 months. Of the pts in the <1 year, 87% have died versus 35% in the ≥1 year group. Of note, death of most pts occurred during the follow up period post pomalidomide therapy , however in a far greater extent for the <1 year group, 96% versus 67%, that could suggest it was more difficult to salvage these pts post pomalidomide.We next sought to identify the characteristics of the 2 groups. Interestingly, the median number of prior lines was similar across groups, 5 (range 1-10), with 89% and 79% of the pts exposed to more than 3 lines and 17% and 22% exposed to more than 6 lines, for the <1 year and ≥1 year groups, respectively. 40% and 48% of pts had Bortezomib as last line, 29% and 43% Lenalidomide, 43% and 26% and alkylating agent. Similarly, 80% and 74% of pts were refractory to Bortezomib, 89% versus 87% to Lenalidomide, 65% versus 75% to alkylating agents, 74% and 87% to the last line of therapy, respectively. 74% and 70% were double refractory (Bortezomib and Lenalidomide) and 60% and 70% were triple refractory (double +last line), respectively. The time from diagnosis to IFM 2009-02 study entry was also similar between cohorts, 5.8 and 6.5 years for <1 year and ≥1 year groups; however with 6% versus 26% of pts, entering the study in less than 3 years since diagnosis. There was no difference in terms of patients characteristics between groups, either patients-based such as gender, age, weight, or myeloma-based characteristics.However, serum beta 2m level was higher at diagnosis in the <1 year compared to the ≥1 year, 54% versus 35%, with a slightly more adverse cytogenetic profile 35% versus 12%, with the limitation that this was not available for all the patients. Presence of plasmacytoma/EMD was also greater in the former group, 20% versus 4%, respectively. It seems that the <1 year had more intrinsic adverse features of the tumor cells compared to the ≥1 year group.There was no clear difference in terms of safety management of pomalidomide and/or dexamethasone, with respect to the daily dose intensity of Pomalidomide (median, 3.0 and 2.9 mg/day), and the relative dose intensity of pomalidomide that was 89% and 84%, respectively; similar to the rate of dose reduction and dose interruption.Conclusion. Pomalidomide and dexamethasone is effective and well tolerated in these heavily pre-treated MM pts refractory to Bortezomib and Lenalidomide, with approximately 40% of the patients having a prolonged exposure to treatment, which translated into a significantly prolonged OS. Our study suggests that patients with more intrinsic adverse features of Myeloma tumor cells could not have prolonged exposure to pomalidomide as they progressed within a year from start of pomalidomide. Future studies should examine optimizing pomalidomide therapy in those patients, such as using multidrug pomalidomide-based combined regimens to prolong exposure to pomalidomide and improve the survival of these patients. DisclosuresKarlin:Janssen: Honoraria; celgene: Consultancy, Honoraria; Sandoz: Consultancy. Stoppa:Celgene Jansen: Honoraria.

Saturation diving; physiology and pathophysiology.

In saturation diving, divers stay under pressure until most of their tissues are saturated with breathing gas. Divers spend a long time in isolation exposed to increased partial pressure of oxygen, potentially toxic gases, bacteria, and bubble formation during decompression combined with shift work and long periods of relative inactivity. Hyperoxia may lead to the production of reactive oxygen species (ROS) that interact with cell structures, causing damage to proteins, lipids, and nucleic acid. Vascular gas-bubble formation and hyperoxia may lead to dysfunction of the endothelium. The antioxidant status of the diver is an important mechanism in the protection against injury and is influenced both by diet and genetic factors. The factors mentioned above may lead to production of heat shock proteins (HSP) that also may have a negative effect on endothelial function. On the other hand, there is a great deal of evidence that HSPs may also have a "conditioning" effect, thus protecting against injury. As people age, their ability to produce antioxidants decreases. We do not currently know the capacity for antioxidant defense, but it is reasonable to assume that it has a limit. Many studies have linked ROS to disease states such as cancer, insulin resistance, diabetes mellitus, cardiovascular diseases, and atherosclerosis as well as to old age. However, ROS are also involved in a number of protective mechanisms, for instance immune defense, antibacterial action, vascular tone, and signal transduction. Low-grade oxidative stress can increase antioxidant production. While under pressure, divers change depth frequently. After such changes and at the end of the dive, divers must follow procedures to decompress safely. Decompression sickness (DCS) used to be one of the major causes of injury in saturation diving. Improved decompression procedures have significantly reduced the number of reported incidents; however, data indicate considerable underreporting of injuries. Furthermore, divers who are required to return to the surface quickly are under higher risk of serious injury as no adequate decompression procedures for such situations are available. Decompression also leads to the production of endothelial microparticles that may reduce endothelial function. As good endothelial function is a documented indicator of health that can be influenced by regular exercise, regular physical exercise is recommended for saturation divers. Nowadays, saturation diving is a reasonably safe and well controlled method for working under water. Until now, no long-term impact on health due to diving has been documented. However, we still have limited knowledge about the pathophysiologic mechanisms involved. In particular we know little about the effect of long exposure to hyperoxia and microparticles on the endothelium.

Akt Kinase Mediates the Prosurvival Effect of Smoking Compounds in Pancreatic Ductal Cells

Cigarette smoking is a major risk factor for pancreatic cancer (PaCa). However, the mechanisms of smoking-induced PaCa remain unknown. Here we investigated the effect of smoking compounds on cell death pathways in pancreatic ductal cells, precursors of PaCa. Human pancreatic ductal cells (HPDE6-c7) were cultured with cigarette smoke extract (CSE) or smoking compound 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK). Apoptosis and autophagy were assessed by DNA fragmentation and immunofluorescence, respectively. Exposure to CSE or NNK decreased DNA fragmentation and up-regulated BclXL. Akt kinase was activated by smoking compounds through reactive oxygen species-dependent mechanism. Specifically, Akt activation was prevented by inhibition of nicotinamide adenine dinucleotide oxidase. Molecular or pharmacologic inhibitions of Akt prevented the antiapoptotic effect of smoking compounds. Smoking compounds stimulated rapid (1 hour) and transient activation of 5'-adenosine monophosphate-activated protein kinase and formation of autophagic vacuoles, indicating stimulation of autophagy. Repeated exposure to CSE/NNK (48 hours or longer) abolished the early activation of autophagic markers. Inhibition of Akt prevented the antiautophagic effect of long exposure to smoking compounds, indicating that smoking-induced late activation of Akt prevents autophagy. Long exposure of pancreatic ductal cells to smoking compounds inhibited apoptosis and autophagy. The results revealed a central role for Akt kinase in mediating key procarcinogenic effects of smoking compounds.