Factors affecting female sexual well-being: a 5-year follow-up of a randomised clinical trial on post-abortion contraception.

INTRODUCTION: Sexual well-being is associated with general well-being. Several factors, such as overweight, infertility, anxiety and sex hormones, also play a role, but the effects of hormonal contraception remain a point of debate. We characterised the factors associated with sexual well-being in fertile-aged women following induced abortion. METHODS: A 5-year follow-up of a nested, longitudinal, cohort study examining the effects of routine provision of intrauterine contraception as part of abortion care. Sexual well-being, anxiety and quality of life were assessed annually using validated questionnaires (McCoy Female Sexuality Questionnaire, State-Trait Anxiety Inventory and EuroQoL), along with data on general and reproductive health, and relationship status. Of the 742 women participating in the trial, 290 (39%) provided sufficient follow-up data and were included in this study. RESULTS: Based on trajectories of McCoy scores across the 5-year follow-up, two groups were identified: those with stable and higher (n=223, 76.9%) and those with declining sexual well-being (n=67, 23.1%). Women in the group of declining sexual well-being had significantly higher levels of anxiety and lower quality of life at all time points. They also had chronic diseases more often and were less happy in their relationships. No differences were found in method of contraception when classified as hormonal versus non-hormonal, or long-acting versus short-acting reversible contraception. CONCLUSIONS: Lower anxiety and higher quality of life are associated with stable and higher sexual well-being. Method of contraception or relationship status are not associated with sexual well-being during long-term follow-up in fertile-aged women.

Pregnancy outcomes following routine early provision of intrauterine device after first-trimester induced abortion-A secondary analysis of a randomized controlled trial with a 5-year follow up.

INTRODUCTION: Women undergoing an induced abortion are highly fertile and at risk of subsequent unplanned pregnancy. We recently completed a randomized clinical trial showing that routine provision of intrauterine device (IUD) at the time of abortion significantly reduced the risk of subsequent abortion during a 5-year follow up. As the use of highly effective contraception may affect all subsequent pregnancies, we analyzed the rate and distribution of all subsequent pregnancies (deliveries, miscarriages, and abortions), and the risk factors for these various pregnancy outcomes in the above-mentioned randomized clinical trial. MATERIAL AND METHODS: We enrolled adult women requesting first-trimester induced abortion and candidates for IUD for post-abortion contraception. Women (n = 751) were randomized to receive an IUD (either levonorgestrel-releasing IUD or copper IUD) by the clinic responsible for abortion care vs. routine care of IUD provision in primary health care with oral contraceptives for interval contraception. In the present secondary analysis, we identified all deliveries, miscarriages, and abortions in the intervention (n = 375) and control (n = 373) cohorts during the 5-year follow up using the Finnish national registries. The trial is registered at Clinical Trials (NTC01223521). RESULTS: The overall delivery, miscarriage, and abortion rates were 42.0, 12.0 and 32.1/1000 years of follow up (yFU). Any new pregnancy occurred in 98 women in the intervention and in 129 women in the control cohort (hazard ratio 0.73, 95% confidence interval 0.56-0.95, p = 0.023). The effect of routine IUD provision in reducing pregnancies was limited to the first 2 yFU. The number of subsequent induced abortions and of women undergoing it were significantly reduced, and time to abortion was prolonged by the intervention. However, the overall number, the number of women with subsequent delivery or miscarriage, and the times to these events were not significantly affected. History of previous pregnancy (delivery or abortion) and smoking were risk factors for subsequent induced abortion, but not for delivery or miscarriage. CONCLUSIONS: Routine provision of IUD as part of abortion care did not reduce the rates of delivery or miscarriage during the 5-year follow up. The rates of all pregnancies and the need of subsequent induced abortion were reduced by IUD provision during the first 2 yFU.

Impact of physico-chemical properties on the toxicological potential of reduced graphene oxide in human bronchial epithelial cells.

The increasing use of graphene-based materials (GBM) requires their safety evaluation, especially in occupational settings. The same physico-chemical (PC) properties that confer GBM extraordinary functionalities may affect the potential toxic response. Most toxicity assessments mainly focus on graphene oxide and rarely investigate GBMs varying only by one property. As a novelty, the present study assessed the in vitro cytotoxicity and genotoxicity of six reduced graphene oxides (rGOs) with different PC properties in the human bronchial epithelial 16HBE14o - cell line. Of the six materials, rGO1-rGO4 only differed in the carbon-to-oxygen (C/O) content, whereas rGO5 and rGO6 were characterized by different lateral size and number of layers, respectively, but similar C/O content compared with rGO1. The materials were characterized by transmission electron microscopy, X-ray photoelectron spectroscopy, laser diffraction and dynamic light scattering, and Brunauer-Emmett-Teller analysis. Cytotoxicity (Luminescent Cell Viability and WST-8 assays), the induction of reactive oxygen species (ROS; 2',7'-dichlorofluorescin diacetate-based assay), the production of cytokines (enzyme-linked immunosorbent assays) and genotoxicity (comet and micronucleus assays) were evaluated. Furthermore, the internalization of the materials in the cells was confirmed by laser confocal microscopy. No relationships were found between the C/O ratio or the lateral size and any of the rGO-induced biological effects. However, rGO of higher oxygen content showed higher cytotoxic and early ROS-inducing potential, whereas genotoxic effects were observed with the rGO of the lowest density of oxygen groups. On the other hand, a higher number of layers seems to be associated with a decreased potential for inducing cytotoxicity and ROS production.

Role of Chemical Reduction and Formulation of Graphene Oxide on Its Cytotoxicity towards Human Epithelial Bronchial Cells.

Graphene-based materials may pose a potential risk for human health due to occupational exposure, mainly by inhalation. This study was carried out on bronchial epithelial 16HBE14o- cells to evaluate the role of chemical reduction and formulation of graphene oxide (GO) on its cytotoxic potential. To this end, the effects of GO were compared to its chemically reduced form (rGO) and its stable water dispersion (wdGO), by means of cell viability reduction, reactive oxygen species (ROS) generation, pro-inflammatory mediators release and genotoxicity. These materials induced a concentration-dependent cell viability reduction with the following potency rank: rGO > GO >> wdGO. After 24 h exposure, rGO reduced cell viability with an EC50 of 4.8 µg/mL (eight-fold lower than that of GO) and was the most potent material in inducing ROS generation, in contrast to wdGO. Cytokines release and genotoxicity (DNA damage and micronucleus induction) appeared low for all the materials, with wdGO showing the lowest effect, especially for the former. These results suggest a key role for GO reduction in increasing GO cytotoxic potential, probably due to material structure alterations resulting from the reduction process. In contrast, GO formulated in a stable dispersion seems to be the lowest cytotoxic material, presumably due to its lower cellular internalization and damaging capacity.

Effect of Surface Modification on the Pulmonary and Systemic Toxicity of Cellulose Nanofibrils.

Cellulose nanofibrils (CNFs) have emerged as sustainable options for a wide range of applications. However, the high aspect ratio and biopersistence of CNFs raise concerns about potential health effects. Here, we evaluated the in vivo pulmonary and systemic toxicity of unmodified (U-CNF), carboxymethylated (C-CNF), and TEMPO (2,2,6,6-tetramethyl-piperidin-1-oxyl)-oxidized (T-CNF) CNFs, fibrillated in the same way and administered to mice by repeated (3×) pharyngeal aspiration (14, 28, and 56 µg/mouse/aspiration). Toxic effects were assessed up to 90 days after the last administration. Some mice were treated with T-CNF samples spiked with lipopolysaccharide (LPS; 0.02-50 ng/mouse/aspiration) to assess the role of endotoxin contamination. The CNFs induced an acute inflammatory reaction that subsided within 90 days, except for T-CNF. At 90 days post-administration, an increased DNA damage was observed in bronchoalveolar lavage and hepatic cells after exposure to T-CNF and C-CNF, respectively. Besides, LPS contamination dose-dependently increased the hepatic genotoxic effects of T-CNF.

Surface functionalization and size modulate the formation of reactive oxygen species and genotoxic effects of cellulose nanofibrils.

BACKGROUND: Cellulose nanofibrils (CNFs) have emerged as a sustainable and environmentally friendly option for a broad range of applications. The fibrous nature and high biopersistence of CNFs call for a thorough toxicity assessment, but it is presently unclear which physico-chemical properties could play a role in determining the potential toxic response to CNF. Here, we assessed whether surface composition and size could modulate the genotoxicity of CNFs in human bronchial epithelial BEAS-2B cells. We examined three size fractions (fine, medium and coarse) of four CNFs with different surface chemistry: unmodified (U-CNF) and functionalized with 2,2,6,6-tetramethyl-piperidin-1-oxyl (TEMPO) (T-CNF), carboxymethyl (C-CNF) and epoxypropyltrimethylammonium chloride (EPTMAC) (E-CNF). In addition, the source fibre was also evaluated as a non-nanosized material. RESULTS: The presence of the surface charged groups in the functionalized CNF samples resulted in higher amounts of individual nanofibrils and less aggregation compared with the U-CNF. T-CNF was the most homogenous, in agreement with its high surface group density. However, the colloidal stability of all the CNF samples dropped when dispersed in cell culture medium, especially in the case of T-CNF. CNF was internalized by a minority of BEAS-2B cells. No remarkable cytotoxic effects were induced by any of the cellulosic materials. All cellulosic materials, except the medium fraction of U-CNF, induced a dose-dependent intracellular formation of reactive oxygen species (ROS). The fine fraction of E-CNF, which induced DNA damage (measured by the comet assay) and chromosome damage (measured by the micronucleus assay), and the coarse fraction of C-CNF, which produced chromosome damage, also showed the most effective induction of ROS in their respective size fractions. CONCLUSIONS: Surface chemistry and size modulate the in vitro intracellular ROS formation and the induction of genotoxic effects by fibrillated celluloses. One cationic (fine E-CNF) and one anionic (coarse C-CNF) CNF showed primary genotoxic effects, possibly partly through ROS generation. However, the conclusions cannot be generalized to all types of CNFs, as the synthesis process and the dispersion method used for testing affect their physico-chemical properties and, hence, their toxic effects.

Role of Surface Chemistry in the In Vitro Lung Response to Nanofibrillated Cellulose.

Wood-derived nanofibrillated cellulose (NFC) has emerged as a sustainable material with a wide range of applications and increasing presence in the market. Surface charges are introduced during the preparation of NFC to facilitate the defibrillation process, which may also alter the toxicological properties of NFC. In the present study, we examined the in vitro toxicity of NFCs with five surface chemistries: nonfunctionalized, carboxymethylated, phosphorylated, sulfoethylated, and hydroxypropyltrimethylammonium-substituted. The NFC samples were characterized for surface functional group density, surface charge, and fiber morphology. Fibril aggregates predominated in the nonfunctionalized NFC, while individual nanofibrils were observed in the functionalized NFCs. Differences in surface group density among the functionalized NFCs were reflected in the fiber thickness of these samples. In human bronchial epithelial (BEAS-2B) cells, all NFCs showed low cytotoxicity (CellTiter-GloVR luminescent cell viability assay) which never exceeded 10% at any exposure time. None of the NFCs induced genotoxic effects, as evaluated by the alkaline comet assay and the cytokinesis-block micronucleus assay. The nonfunctionalized and carboxymethylated NFCs were able to increase intracellular reactive oxygen species (ROS) formation (chloromethyl derivative of 2',7'-dichlorodihydrofluorescein diacetate assay). However, ROS induction did not result in increased DNA or chromosome damage.

Genotoxicity and cellular uptake of nanosized and fine copper oxide particles in human bronchial epithelial cells in vitro.

We studied the genotoxicity and cellular uptake of nanosized (<50 nm) and fine (<10 µm) copper oxide (CuO) particles in vitro in human bronchial epithelial (BEAS-2B) cells. In addition, the effect of dispersing the particles using bovine serum albumin (BSA) on DNA damage induction was investigated. DNA damage was assessed by the alkaline comet (single cell gel electrophoresis) assay after 3-h, 6-h and 24-h exposures. The cytokinesis-block micronucleus assay was applied to study chromosome damage. Both fine- and nanosized CuO particles induced a dose-dependent increase in DNA damage at all timepoints tested. However, nanosized CuO damaged DNA at lower doses and higher levels compared with fine CuO. Dispersing the nanoparticles in the presence of BSA (0.6 mg/mL) resulted in a small and inconsistent decrease in DNA damage compared with dispersions in serum-free cell culture medium only. CuO nanoparticles induced a clear dose-dependent increase in micronucleated cells at doses that strongly increased cytostasis and were markedly cytotoxic at 24 and 48 h. Fine CuO showed a slight induction of micronuclei. Hyperspectral microscopy indicated a substantial cellular uptake of both types of particles after a 3-h exposure to a dose of 20 µg/cm2. The number of particles internalized by the cells was higher for nanosized than fine CuO, as quantified by the frequency of spectral matches in the total cell area and by the number of spectrally matched visible particles or agglomerates per cell. The particle uptake was limited by particle size. The stronger genotoxic activity of nanosized than fine CuO particles is likely to derive from the higher cellular uptake and more effective intracellular dissolution of nanoparticles.

Early provision of intrauterine contraception as part of abortion care-5-year results of a randomised controlled trial.

STUDY QUESTION: Can the incidence of subsequent termination of pregnancy (TOP) be reduced by providing intrauterine contraception as part of the abortion service? SUMMARY ANSWER: Provision of an intrauterine device (IUD) as part of TOP services reduced the need for subsequent TOP but the effect was limited to the first 3 years of the 5-year follow-up. WHAT IS KNOWN ALREADY: An IUD is highly effective in preventing subsequent TOP. Prompt initiation of IUD use leads to a higher usage rate during follow-up, as compliance with post-TOP IUD insertion visits is low. STUDY DESIGN, SIZE, DURATION: The objective of this randomised controlled trial was to assess the effect of early comprehensive provision of intrauterine contraception after TOP, with primary outcome being the incidence of subsequent TOP during the 5 years of follow-up after the index abortion. This study was conducted at a tertiary care centre between 18 October 2010 and 21 January 2013. Altogether, 748 women undergoing a first trimester TOP were recruited and randomised into two groups. The intervention group (n = 375) was provided with an IUD during surgical TOP or 1-4 weeks following medical TOP at the hospital providing the abortion care. Women in the control group (n = 373) were advised to contact primary health care for follow-up and IUD insertion. Subsequent TOPs during the 5-year follow-up were identified from the Finnish Register on induced abortions. PARTICIPANTS/MATERIALS, SETTING, METHODS: The inclusion criteria were age ≥18 years, duration of gestation ≤12 weeks, residence in Helsinki and accepting intrauterine contraception. Women with contraindications to IUD were excluded. MAIN RESULTS AND THE ROLE OF CHANCE: The overall numbers of subsequent TOPs were 50 in the intervention and 72 in the control group (26.7 versus 38.6/1000 years of follow-up, P = 0.027), and those of requested TOPs, including TOPs and early pregnancy failures, were 58 and 76, respectively (30.9 versus 40.8/1000, P = 0.080). Altogether 40 (10.7%) women in the intervention and 63 (16.9%) in the control group underwent one or several subsequent TOPs (hazard ratio 1.67 [95% CI 1.13 to 2.49], P = 0.011). The number of TOPs was reduced by the intervention during years 0-3 (22.2 versus 46.5/1000, P = 0.035), but not during years 4-5 (33.3 versus 26.8/1000, P = 0.631). LIMITATIONS, REASONS FOR CAUTION: Both medical and surgical TOP were used. This may be seen as a limitation, but it also reflects the contemporary practice of abortion care. The immediate post-TOP care was provided by two different organizations, allowing us to compare two different ways of contraceptive service provision following TOP. WIDER IMPLICATIONS OF THE FINDINGS: Providing TOP and IUD insertion comprehensively in the same heath care unit leads to significantly higher rates of attendance, IUD use and a significantly lower risk of subsequent TOP. STUDY FUNDING/COMPETING INTEREST(S): This study was supported by Helsinki University Central Hospital Research funds and by research grants provided by the Jenny and Antti Wihuri Foundation, the Yrjö Jahnsson Foundation and Finska Läkaresällskapet. E.P. has received a personal research grant from the Finnish Medical Society. The City of Helsinki supported the study by providing the IUDs. The funding organisations had no role in planning or execution of the study, or in analysing the study results. TRIAL REGISTRATION NUMBER: The trial was registered at clinicaltrials.gov (NCT01223521). TRIAL REGISTRATION DATE: 18 October 2010. DATE OF FIRST PATIENT'S ENROLMENT: 18 October 2010.

Size, Surface Functionalization, and Genotoxicity of Gold Nanoparticles In Vitro.

Several studies suggested that gold nanoparticles (NPs) could be genotoxic in vitro and in vivo. However, gold NPs currently produced present a wide range of sizes and functionalization, which could affect their interactions with the environment or with biological structures and, thus, modify their toxic effects. In this study, we investigated the role of surface charge in determining the genotoxic potential of gold NPs, as measured by the induction of DNA damage (comet assay) and chromosomal damage (micronucleus assay) in human bronchial epithelial BEAS-2B cells. The cellular uptake of gold NPs was assessed by hyperspectral imaging. Two core sizes (~5 nm and ~20 nm) and three functionalizations representing negative (carboxylate), positive (ammonium), and neutral (poly(ethylene glycol) (PEG)ylated) surface charges were examined. Cationic ammonium gold NPs were clearly more cytotoxic than their anionic and neutral counterparts, but genotoxicity was not simply dependent on functionalization or size, since DNA damage was induced by 20-nm ammonium and PEGylated gold NPs, while micronucleus induction was increased by 5-nm ammonium and 20-nm PEGylated gold NPs. The 5-nm carboxylated gold NPs were not genotoxic, and evidence on the genotoxicity of the 20-nm carboxylated gold NPs was restricted to a positive result at the lowest dose in the micronucleus assay. When interpreting the results, it has to be taken into account that cytotoxicity limited the doses available for the ammonium-functionalized gold NPs and that gold NPs were earlier described to interfere with the comet assay procedure, possibly resulting in a false positive result. In conclusion, our findings show that the cellular uptake and cytotoxicity of gold NPs are clearly enhanced by positive surface charge, but neither functionalization nor size can single-handedly account for the genotoxic effects of the gold NPs.

Predicting poor compliance with follow-up and intrauterine contraception services after medical termination of pregnancy.

BACKGROUND: Attendance at post-abortion follow-up visits is poor, but little is known about factors affecting it. OBJECTIVE: To assess the factors associated with non-compliance with post-abortion services and to evaluate differences in rates of attendance and intrauterine device (IUD) insertion according to the type of service provision. METHODS: 605 women undergoing a first trimester medical termination of pregnancy (MTOP) and planning to use intrauterine contraception were randomised into two groups. Women in the intervention group (n=306) were booked to have IUD insertion 1-4 weeks after the MTOP at the hospital providing the abortion, while women in the control group (n=299) were advised to contact their primary healthcare (PHC) centre for follow-up and IUD insertion. RESULTS: In the intervention group, 21 (6.9%) women failed to attend the follow-up visit, whereas in the control group 67 (22.4%) women did not contact the PHC to schedule a follow-up (p<0.001). In both groups, non-attendance was associated with history of previous pregnancy and abortion. Not having an IUD inserted within 3 months was significantly more common in the control group (73.6% (n=220)) than in the intervention group (9.2% (n=28), p<0.001). In the intervention group, predictive factors for not having an IUD inserted were anxiety, history of pregnancy and abortion. However, we identified no significant predictive factors in the control group. CONCLUSIONS: Factors predicting low compliance with post-MTOP follow-up are few. Comprehensive provision of abortion care and post-abortion services seems beneficial for minimising the loss to follow-up and delay in initiation of effective contraception. TRIAL REGISTRATION NUMBER: NCT01223521;Results.

Sexual well-being after first trimester termination of pregnancy: Secondary analysis of a randomized contraceptive trial.

INTRODUCTION: Although termination of pregnancy is one of the most common procedures conducted worldwide, little is known about sexual well-being after termination of pregnancy. The objective of this study was to assess sexual well-being after termination of pregnancy, and factors affecting it during a 1-year follow up. MATERIAL AND METHODS: In total, 748 women requesting first trimester termination of pregnancy and participating in a randomized controlled trial on early provision of intrauterine contraception were provided with questionnaires regarding their sexual life, anxiety, quality of life and contraceptive method used at the time of termination of pregnancy, 3 and 12 months after termination of pregnancy. Sexual well-being was measured by the 9-item McCoy Female Sexuality Questionnaire. Anxiety and quality of life were assessed by the State-Trait Anxiety Inventory (STAI) Scale and EuroQoL questionnaire (EQoL). RESULTS: The McCoy index remained unchanged during the follow up. At all three time-points measured, higher (ie, better) McCoy scores were associated with a lower STAI index (mean difference -2.26 [95% CI -3.23 to -1.29], P < 0.001; -3.76 [95% CI -4.79 to -2.74], P < 0.001; -4.50 [95% CI -5.88 to -3.12], P < 0.001) and being in a relationship (1.16 [95% CI 0.08-2.25], P = 0.023; 1.67 [95% CI 0.43-2.89], P < 0.001; 2.81 [95% CI 1.28-4.34], P < 0.001), and correlated positively with a higher EQoL index (r = 0.20, r = 0.20, r = .27, P < 0.001) and higher frequency of intercourse (r = 0.50, r = 0.46, r = 0.42, P < 0.001). Women using intrauterine contraception had higher McCoy index measurements at 3 months compared with others. There were no significant differences between users of hormonal vs non-hormonal contraceptive methods. CONCLUSIONS: Sexual well-being does not change significantly after termination of pregnancy. Instead, it is strongly and positively associated with quality of life, relationship status and frequency of intercourse. Anxiety is negatively associated with sexual well-being.

Intrauterine contraception after medical abortion: factors affecting success of early insertion.

OBJECTIVE: To assess the success and factors affecting early intrauterine device (IUD) provision after first trimester medical termination of pregnancy (MTOP). STUDY DESIGN: Subgroup analysis of a randomized contraceptive trial assessing the long-term effects of early provision of intrauterine contraception following abortion. Altogether, 606 women undergoing MTOP were included and followed for 3 months. The intervention group (n=307) was offered an IUD (either the levonorgestrel-releasing intrauterine system or copper-IUD) at a follow-up visit 1-4 weeks after MTOP. The control group (n=299) contacted primary health care for follow-up and contraceptive provision. Adverse events (infections, bleeding, residual tissue and incomplete abortion) were analyzed on intention-to-treat basis and IUD expulsions on per-protocol (PP) basis. RESULTS: In the intervention group, 234 women (76.2%) received the IUD as scheduled, 46 later (altogether 91.2%). In the control group, the corresponding figures were 8 (2.7%) and 64 [altogether 24.1%, Odds ratio (OR) (95% Confidence interval (CI))=32.7 (20.3-52.6)]. Eighty-five (27.7%) women in the intervention group and 38 (12.7%) in the control group received treatment (administration of antibiotics, misoprostol or surgical evacuation) because of presumed adverse event [2.63 (1.72-4.01)], mainly residual tissue. In the control group, 23 (60.5%) of these occurred during the first 2 weeks. IUD expulsion occurred in 12 (5.4%) of the 222 women in the intervention group (PP basis). CONCLUSIONS: When provided as part of abortion service, most early insertions following MTOP were performed as planned. The main reason for postponement was overdiagnosis of adverse events suspected at follow-up. The rate of IUD expulsion was similar to that reported previously. IMPLICATIONS: Early insertion following MTOP is safe, and the rate of IUD expulsion is low. Most adverse events possibly delaying IUD insertion occur early. Based on timing of adverse events in the control group, IUD insertion at approximately 2 weeks after completed MTOP seems optimal.

Genotoxic and inflammatory effects of nanofibrillated cellulose in murine lungs.

Nanofibrillated cellulose (NFC) is a sustainable and renewable nanomaterial, with diverse potential applications in the paper and medical industries. As NFC consists of long fibres of high aspect ratio, we examined here whether TEMPO-(2,2,6,6-tetramethyl-piperidin-1-oxyl) oxidised NFC (length 300-1000nm, thickness 10-25nm), administrated by a single pharyngeal aspiration, could be genotoxic to mice, locally in the lungs or systemically in the bone marrow. Female C57Bl/6 mice were treated with four different doses of NFC (10, 40, 80 and 200 µg/mouse), and samples were collected 24h later. DNA damage was assessed by the comet assay in bronchoalveolar lavage (BAL) and lung cells, and chromosome damage by the bone marrow erythrocyte micronucleus assay. Inflammation was evaluated by BAL cell counts and analysis of cytokines and histopathological alterations in the lungs. A significant induction of DNA damage was observed at the two lower doses of NFC in lung cells, whereas no increase was seen in BAL cells. No effect was detected in the bone marrow micronucleus assay, either. NFC increased the recruitment of inflammatory cells to the lungs, together with a dose-dependent increase in mRNA expression of tumour necrosis factor α, interleukins 1ß and 6, and chemokine (C-X-C motif) ligand 5, although there was no effect on the levels of the respective proteins. The histological analysis showed a dose-related accumulation of NFC in the bronchi, the alveoli and some in the cytoplasm of macrophages. In addition, neutrophilic accumulation in the alveolar lung space was observed with increasing dose. Our findings showed that NFC administered by pharyngeal aspiration caused an acute inflammatory response and DNA damage in the lungs, but no systemic genotoxic effect in the bone marrow. The present experimental design did not, however, allow us to determine whether the responses were transient or could persist for a longer time.

Anxiety and quality of life after first-trimester termination of pregnancy: a prospective study.

INTRODUCTION: Possible effects of termination of pregnancy (TOP) on mental health are a matter of debate. MATERIAL AND METHODS: We assessed anxiety and quality of life during a one-year follow up after first-trimester TOP using the State-Trait Anxiety Inventory (STAI) Scale and EuroQoL Quality of Life Questionnaire (EQ-5D, EQ-VAS) in 742 women participating in a randomized controlled trial on early provision of intrauterine contraception. The measurements were performed before TOP, at 3 months and 1 year after TOP. Inclusion criteria were age ≥18 years, residence in Helsinki, duration of gestation <12 weeks, non-medical indication for TOP, and approval of intrauterine contraception. The trial was registered with Clinical Trials [NCT01223521]. RESULTS: When compared with baseline, the overall anxiety level was significantly lower and quality of life higher at 3 months and at 1 year. Reduction of anxiety and improvement of quality of life was especially evident (p < 0.001) in the 58% of women reporting clinically relevant anxiety at baseline. High levels of anxiety at baseline, history of psychiatric morbidity and smoking predicted significantly greater risk of poorer quality of life and elevated level of anxiety during the follow up. CONCLUSIONS: TOP is associated with a significant overall reduction of anxiety and an improvement of quality of life among women undergoing it for non-medical indications. High baseline anxiety, history of psychiatric morbidity and smoking are risk factors of persistently high levels of anxiety and poor quality of life after an induced abortion. These data are important when designing and providing post-abortion care.

Effect of particle size and dispersion status on cytotoxicity and genotoxicity of zinc oxide in human bronchial epithelial cells.

Data available on the genotoxicity of zinc oxide (ZnO) nanoparticles (NPs) are controversial. Here, we examined the effects of particle size and dispersion status on the cytotoxicity and genotoxicity of nanosized and fine ZnO, in the presence and absence of bovine serum albumin (BSA; 0.06%) in human bronchial epithelial BEAS-2B cells. Dynamic light scattering analysis showed the most homogenous dispersions in water alone for nanosized ZnO and in water with BSA for fine ZnO. After a 48-h treatment, both types of ZnO were cytotoxic within a similar, narrow dose range (1.5-3.0µg/cm(2)) and induced micronuclei at a near toxic dose range (1.25-1.75µg/cm(2)), both with and without BSA. In the comet assay, nanosized ZnO (1.25-1.5µg/cm(2)), in the absence of BSA, caused a statistically significant increase in DNA damage after 3-h and 6-h treatments, while fine ZnO did not. Our findings may be explained by better uptake or faster intracellular dissolution of nanosized ZnO without BSA during short treatments (3-6h; the comet assay), with less differences between the two ZnO forms after longer treatments (>48h; the in vitro micronucleus test). As ZnO is genotoxic within a narrow dose range partly overlapping with cytotoxic doses, small experimental differences e.g. in the dispersion of ZnO particles may have a substantial effect on the genotoxicity of the nominal doses added to the cell culture.

In vitro and in vivo genotoxic effects of straight versus tangled multi-walled carbon nanotubes.

Some multi-walled carbon nanotubes (MWCNTs) induce mesothelioma in rodents, straight MWCNTs showing a more pronounced effect than tangled MWCNTs. As primary and secondary genotoxicity may play a role in MWCNT carcinogenesis, we used a battery of assays for DNA damage and micronuclei to compare the genotoxicity of straight (MWCNT-S) and tangled MWCNTs (MWCNT-T) in vitro (primary genotoxicity) and in vivo (primary or secondary genotoxicity). C57Bl/6 mice showed a dose-dependent increase in DNA strand breaks, as measured by the comet assay, in lung cells 24 h after a single pharyngeal aspiration of MWCNT-S (1-200 µg/mouse). An increase was also observed for DNA strand breaks in lung and bronchoalveolar lavage (BAL) cells and for micronucleated alveolar type II cells in mice exposed to aerosolized MWCNT-S (8.2-10.8 mg/m(3)) for 4 d, 4 h/d. No systemic genotoxic effects, assessed by the γ-H2AX assay in blood mononuclear leukocytes or by micronucleated polychromatic erythrocytes (MNPCEs) in bone marrow or blood, were observed for MWCNT-S by either exposure technique. MWCNT-T showed a dose-related decrease in DNA damage in BAL and lung cells of mice after a single pharyngeal aspiration (1-200 µg/mouse) and in MNPCEs after inhalation exposure (17.5 mg/m(3)). In vitro in human bronchial epithelial BEAS-2B cells, MWCNT-S induced DNA strand breaks at low doses (5 and 10 µg/cm(2)), while MWCNT-T increased strand breakage only at 200 µg/cm(2). Neither of the MWCNTs was able to induce micronuclei in vitro. Our findings suggest that both primary and secondary mechanisms may be involved in the genotoxicity of straight MWCNTs.