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Abstract Background The outcome of endodontic treatment is generally assessed using a range of patient and clinician-centred, non-standardised clinical and radiographic outcome measures. This makes it difficult to synthesise evidence for systematic analysis of the literature and the development of clinical guidelines. Core outcome sets (COS) represent a standardised list of outcomes that should be measured and reported in all clinical studies in a particular field. Recently, clinical researchers and guideline developers have focussed on the need for the integration of a patient-reported COS with clinician-centred measures. This study aims to develop a COS that includes both patient-reported outcomes and clinician-centred measures for various endodontic treatment modalities to be used in clinical research and practice. Methods To identify reported outcomes (including when and how they are measured), systematic reviews and their included clinical studies, which focus on the outcome of endodontic treatment and were published between 1990 and 2020 will be screened. The COSs will be defined by a consensus process involving key stakeholders using semi-structured interviews and an online Delphi methodology followed by an interactive virtual consensus meeting. A heterogeneous group of key ‘stakeholders’ including patients, general dental practitioners, endodontists, endodontic teachers, clinical researchers, students and policy-makers will be invited to participate. Patients will establish, via interactive interviews, which outcomes they value and feel should be included in a COS. In the Delphi process, other stakeholders will be asked to prioritise outcomes identified from the literature and patient interviews and will have the opportunity at the end of the first round to add outcomes that are not included, but which they consider relevant. Feedback will be provided in the second round, when participants will be asked to prioritise the list again. If consensus is reached, the remaining outcomes will be discussed at an online meeting and agreement established via defined consensus rules of outcome inclusion. If consensus is not reached after the second round, a third round will be conducted with feedback, followed by the online meeting. Following the identification of a COS, we will proceed to identify how and when these outcomes are measured. Discussion Using a rigorous methodology, the proposed consensus process aims to develop a COS for endodontic treatment that will be relevant to stakeholders. The results of the study will be shared with participants and COS users. To increase COS uptake, it will also be actively shared with clinical guideline developers, research funders and the editors of general dental and endodontology journals. Trial registration COMET 1879. 21 May 2021.

Particulate matter of vehicle exhaust is known to contain carcinogenic compounds such as polycyclic aromatic hydrocarbons (PAH) and is suggested to increase lung cancer risk in humans. This study examines the differences in diesel and gasoline-derived PAH binding to DNA in a human bronchial epithelial cell line (BEAS-2B). Particulate matter (PM) of gasoline exhaust was collected from passenger cars on filters and semi-volatile compounds on polyurethane foam (PUF). The soluble organic fraction (SOF) extracted from the particles was used to expose the cells and to perform PAH analysis. Gasoline extracts, benzo[a]pyrene (B[a]P) and reference materials (SRM 1650 and 1587) were used to study dose-dependent adduct formation in BEAS-2B cells. The levels of DNA adducts were in good accord with the 10 DNA adduct-forming PAH concentrations analyzed in the extracts. Gasoline extracts, SRM 1650, SRM 1587 and B[a]P formed DNA adducts dose-dependently in BEAS-2B cells. The time-dependent DNA adduct formation of 5.0 µM B[a]P was lower than that of 2.5 µM B[a]P. The results of this study indicate that reformulated and standard diesel fuels formed about 11- and 31-fold more adducts than gasoline, respectively, when PAH-DNA adduct levels were calculated on an emission basis (adducts/mg PM/km), whereas on a particulate basis (adducts/mg PM) no difference between the diesel and gasoline extracts was observed. We conclude that the genotoxicity of diesel fuel is based on higher particulate emission rates compared to gasoline emission and although the concentration of PAH compounds was higher in diesel particulate extracts, DNA binding by the gasoline particulate-bound PAH compounds was more pronounced than that by the diesel particulate-bound PAH compounds. [ABSTRACT FROM AUTHOR]

Advanced maternal age is the obvious indication to PGD for aneuploidy. It is very well know indeed how chromosomal abnormalities originating from meiotic errors are the main cause for reduced oocyte quality. More and more data are contributing to an understanding of the reasons for this condition, including the possibility of an age-related diminished energy supply that might affect spindle formation with a consequent increase in meiotic errors. Non-disjunction and random segregation of homologues as well as precocious separation of sister chromatids result in aneuploidy in a way that is strictly dependent on several factors, such as timed loss of chromatid cohesion, cell-cycle control, and granulosa cell functioning. It is not surprising that many years ago, outstanding experts in reproductive biology came to the conclusion that aneuploidy testing on preimplantation embryos could alleviate the age effects by removing from transfer those embryos having an abnormal chromosomal complement. The expectation was to obtain in older patients the same reproductive performance as in younger women. Several studies have supported this hypothesis reporting higher implantation rates concomitantly with lower incidence of spontaneous abortions and trisomic conceptions following embryo selection by FISH analysis. Unfortunately, none of these studies met the proper criteria of a RCT (randomized controlled trial) and their results must be interpreted with caution. Nevertheless, one point is clear, and relates to the need for highly skilled operators and professional training to perform a technique that is very specialized in all its steps. There is no doubt the 'well' biopsied embryos are undisturbed in their implantation potential and this statement represents the starting point for any study aimed at dealing with the clinical application of embryos undergoing PGD. Current knowledge of the meiotic process at oogenesis and the data from clinical pregnancies after PGD for aneuploidy either on embryos or on polar bodies represent the rationale supporting the application of this technique. If the rationale is correct, then there must be a clinical advantage. On the contrary, if no clinical advantage is demonstrated or, even worse, if there is a clinical disadvantage, then we have the duty to understand why and to identify the reasons for this inconsistency and the weak points in our current train of thought. [ABSTRACT FROM AUTHOR]

Background: Constantly increasing health care costs have led countries and health care providers to the point where health care systems must be reinvented. Consequently, electronic health (eHealth) has recently received a great deal of attention in social sciences in the domain of Internet studies. However, only a fraction of these studies focuses on the acceptability of eHealth, making consumers' subjective evaluation an understudied field. This study will address this gap by focusing on the acceptance of MyData-based preventive eHealth services from the consumer point of view. We are adopting the term "MyData", which according to a White Paper of the Finnish Ministry of Transport and Communication refers to "1) a new approach, a paradigm shift in personal data management and processing that seeks to transform the current organization centric system to a human centric system, 2) to personal data as a resource that the individual can access and control.", Objective: The aim of this study was to investigate what factors influence consumers' intentions to use a MyData-based preventive eHealth service before use., Methods: We applied a new adoption model combining Venkatesh's unified theory of acceptance and use of technology 2 (UTAUT2) in a consumer context and three constructs from health behavior theories, namely threat appraisals, self-efficacy, and perceived barriers. To test the research model, we applied structural equation modeling (SEM) with Mplus software, version 7.4. A Web-based survey was administered. We collected 855 responses., Results: We first applied traditional SEM for the research model, which was not statistically significant. We then tested for possible heterogeneity in the data by running a mixture analysis. We found that heterogeneity was not the cause for the poor performance of the research model. Thus, we moved on to model-generating SEM and ended up with a statistically significant empirical model (root mean square error of approximation [RMSEA] 0.051, Tucker-Lewis index [TLI] 0.906, comparative fit index [CFI] 0.915, and standardized root mean square residual 0.062). According to our empirical model, the statistically significant drivers for behavioral intention were effort expectancy (beta=.191, P<.001), self-efficacy (beta=.449, P<.001), threat appraisals (beta=.416, P<.001), and perceived barriers (beta=-.212, P=.009)., Conclusions: Our research highlighted the importance of health-related factors when it comes to eHealth technology adoption in the consumer context. Emphasis should especially be placed on efforts to increase consumers' self-efficacy in eHealth technology use and in supporting healthy behavior., (©Timo Koivumäki, Saara Pekkarinen, Minna Lappi, Jere Väisänen, Jouni Juntunen, Minna Pikkarainen. Originally published in the Journal of Medical Internet Research (http://www.jmir.org), 22.12.2017.)

Background: As a result of digitalization, data is available about almost every aspect of our lives. Personal data collected by individuals themselves or stored by organizations interacting with people is known as a digital footprint. The purpose of this study was to identify prerequisites for collecting and using digital data that could be valuable for health data analytics and new health services., Methods: Researchers and their contacts involved in a nationwide research project focusing on digital health in Finland were asked to participate in a pilot study on collecting their own personal data from various organizations of their own choice, such as retail chains, banks, insurance companies, and healthcare providers. After the pilot, a qualitative inquiry was adopted to collect semi-structured interview data from twelve active participants in the pilot. Interviews comprised themes such as the experiences of collecting personal data, as well as the usefulness of the data in general and for the participants themselves. Interview data was then analyzed thematically., Results: Even if the participants had an academic background and were highly motivated to collect and use their data, they faced many challenges, such as quite long delays in the provision of the data, and the unresponsiveness of some organizations. Regarding the usefulness of the acquired personal data, our results show that participants had high expectations, but they were disappointed with the small amount of data and its irrelevant content. For the most part, the data was not in a format that would be useful for health data analytics and new health services. Participants also found that there were actual mistakes in their health data reports., Conclusions: The study revealed that collecting and using digital footprint data, even by knowledgeable individuals, is not an easy task. As the usefulness of the acquired personal health data mainly depended on its form and usability for services or solutions relevant to an individual, rather than on the data being valuable as such, more emphasis should be placed on providing the data in a reusable form.

Background: Human mature oocytes are very susceptible to cryodamage. Several reports demonstrated that vitrification might preserve oocyte better than slow freezing. However, this is still controversial. Thus, larger clinical, biological and experimental trials to confirm this concept are necessary. The aim of the study was to evaluate and compare fine morphological features in human mature oocytes cryopreserved with either slow freezing or vitrification., Methods: We used 47 supernumerary human mature (metaphase II) oocytes donated by consenting patients, aged 27-32 years, enrolled in an IVF program. Thirtyfive oocytes were cryopreserved using slow freezing with 1.5 M propanediol +0.2 M sucrose concentration (20 oocytes) or a closed vitrification system (CryoTip Irvine Scientific CA) (15 oocytes). Twelve fresh oocytes were used as controls. All samples were prepared for light and transmission electron microscopy evaluation., Results: Control, slow frozen/thawed and vitrified/warmed oocytes (CO, SFO and VO, respectively) were rounded, 90-100 μm in diameter, with normal ooplasm showing uniform distribution of organelles. Mitochondria-smooth endoplasmic reticulum (M-SER) aggregates and small mitochondria-vesicle (MV) complexes were the most numerous structures found in all CO, SFO and VO cultured for 3-4 hours. M-SER aggregates decreased, and large MV complexes increased in those SFO and VO maintained in culture for a prolonged period of time (8-9 hours). A slight to moderate vacuolization was present in the cytoplasm of SFO. Only a slight vacuolization was present in VO, whereas vacuoles were almost completely absent in CO. Amount and density of cortical granules (CG) appeared abnormally reduced in SFO and VO, irrespective of the protocol applied., Conclusions: Even though, both slow freezing and vitrification ensured a good overall preservation of the oocyte, we found that: 1) prolonged culture activates an intracellular membrane "recycling" that causes the abnormal transformation of the membranes of the small MV complexes and of SER into larger rounded vesicles; 2) vacuolization appears as a recurrent form of cell damage during slow freezing and, at a lesser extent, during vitrification using a closed device; 3) premature CG exocytosis was present in both SFO and VO and may cause zona pellucida hardening.

Objective: To update results on outcomes with frozen/thawed oocytes using a differential sucrose concentration during dehydration (0.2 M) and rehydration (0.3 M), combined with a one-step propanediol exposure., Design: Retrospective cohort study., Setting: Private IVF centers., Patient(s): Infertile couples undergoing IVF treatment., Intervention(s): Oocyte thawing cycles between May 2004 and December 2010., Main Outcome Measure(s): Survival, fertilization, and cleavage rates were reported to evaluate biological outcomes. Clinical pregnancy and implantation rates were analyzed as markers of efficiency., Result(s): Three hundred forty-two patients and 443 cycles were monitored; the survival was 71.8%, fertilization 77.9%, and of the embryos obtained 83.8% were classified as grade 1 and 2. Three hundred ninety-four transfers were performed, resulting in 90 pregnancies. The pregnancy rate per transfer was 22.8% and per patient was 26.3%, with 122 gestational sacs. The implantation rate per embryo was 13.5%. Patients were divided into three groups according to their age: ≤ 34 years (group A), 35-38 years (group B), and ≥ 39 years (group C). Biological outcomes were comparable in all three groups, whereas the pregnancy rate per transfer was higher in the first group (27.7% vs. 21.4% and 17.6%). The implantation rates per injected egg were 11.8%, 8.0%, and 7.5% for the three groups, respectively., Conclusion(s): The biological and clinical data obtained on 443 cycles are consistent with our previous results showing that slow freezing of oocytes can be a valid tool in IVF practice when performed with a suitable protocol., (Copyright © 2012 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.)

Thanks to the recent advances in cancer care, more and more young women can survive but suffer from infertility as a result of cancer treatment that had to be submitted. There are a variety of methods to preserve fertility, as chemoprotection, ovariopexy, and some assisted reproductive technologies, although some of these are promising but still highly experimental techniques. Cryopreservation of embryos for example is already established, while the oocyte banking is still considered an experimental practice. Many experiments have been conducted around the world on the cryopreservation of ovarian tissue and maturation of ovarian follicles, in an attempt to demonstrate its potential use in fertility preservation. Although in recent years there has been major improvements in the preservation of ovarian tissue, there are still many unresolved technical issues related to these procedures. In this chapter we examine the recent evidence of the pathophysiology of chemotherapy / radiotherapy-induced gonadal toxicity, and recent data regarding the indications and results of the techniques used to preserve fertility in women with cancer.

Objective: To identify factors that might affect the clinical outcome of oocyte slow freezing., Design: Retrospective study., Setting: Reproductive Medicine Unit, Italian Society for the Study of Reproductive Medicine, Bologna, Italy., Patient(s): Patients with spare metaphase II cryopreserved oocytes performing 371 thawing cycles., Intervention(s): Oocytes were cryopreserved by slow freezing<40 hours after hCG administration (group A) and >or=40 hours after hCG administration (group B). Thawed oocytes were inseminated by intracytoplasmic sperm injection., Main Outcome Measure(s): Clinical pregnancy, implantation, abortion, and delivery rates., Result(s): Clinical pregnancy rate per thawed cycle (PR) and implantation rate (IR) were significantly higher in group A compared with group B both in young (PR: 25% vs. 9.6%; IR: 18.9% vs. 8.8%) and in older patients (PR: 25% vs. 10.1%; IR: 17.5% vs. 6.7%). In the young patient subgroup, clinical pregnancy and implantation rates with three transferred embryos were higher in group A vs. group B (PR: 72.7% vs. 25%, and IR: 36.4% vs. 12.5%, respectively). This difference was not found in the subgroup of older patients., Conclusion(s): The timing at which oocyte cryopreservation is performed and the number of transferred embryos play a key role in the clinical outcome. The suggested cut-off time for cryopreservation is between 39 and 40 hours after hCG administration., (Copyright (c) 2010 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.)

Objective: To verify whether the morphologic evaluation of zygotes and embryos derived from thawed oocytes could provide some relevant information regarding their developmental performance., Design: Fertilization, zygote, and embryo morphology from sibling fresh and frozen oocytes was compared., Setting: Reproductive Medicine Unit, Società Italiana Studi Medicina della Riproduzione, Bologna, Italy., Patient(s): Two hundred thirty-four patients underwent intracytoplasmic sperm injection cycles from which 1,101 spare metaphase II oocytes were cryopreserved. Subsequently, 256 thawing cycles were performed, and 997 oocytes were thawed., Intervention(s): Intracytoplasmic sperm injection was performed on both fresh and frozen oocytes., Main Outcome Measure(s): Fertilization rates, pronuclear zygote morphology, and embryo cleavage rates., Result(s): Thawed oocytes had lower chances of being fertilized and developing into top-quality zygotes and regularly cleaving embryos when compared with sibling fresh oocytes irrespective of female age. As a result, the percentage of transferred cycles was significantly lower in frozen cycles compared with fresh cycles (79% and 93%, respectively); the proportion of transferred top-quality embryos followed the same trend., Conclusion(s): Reduced fertilization and cleavage rates in frozen cycles when compared with sibling fresh oocytes suggest that, even if surviving thawing, the process of slow freezing has a negative impact on the potential of further growth that is evident as early as the first cleavage divisions., (Copyright 2010. Published by Elsevier Inc.)

Objective: To verify clinical outcome after injection of spermatozoa that have undergone the acrosome reaction (reacted spermatozoa) vs. those still having an intact acrosome (nonreacted spermatozoa)., Design: Prospective, randomized study., Setting: Reproductive Medicine Unit, Italian Society for the Study of Reproductive Medicine, Bologna, Italy., Patient(s): According to a prospective randomization including 71 couples with severe male factor infertility, intracytoplasmic sperm injection (ICSI) was performed under polarized light that permitted analysis of the pattern of birefringence in the sperm head. Twenty-three patients had their oocytes injected with reacted spermatozoa, 26 patient's oocytes were injected with nonreacted spermatozoa, and in 22 patients both reacted and nonreacted spermatozoa were injected., Intervention(s): Intracytoplasmic sperm injection was performed under polarized light to selectively inject acrosome-reacted and acrosome-nonreacted spermatozoa., Main Outcome Measure(s): Rates of fertilization, cleavage, pregnancy, implantation, and ongoing implantation., Result(s): There was no effect on the fertilizing capacity and embryo development of either type of sperm, whereas the implantation rate was higher in oocytes injected with reacted spermatozoa (39.0%) vs. those injected with nonreacted spermatozoa (8.6%). The implantation rate was 24.4% in the group injected with both reacted and nonreacted spermatozoa. The delivery rate per cycle followed the same trend., Conclusion(s): Spermatozoa that have undergone the acrosome reaction seem to be more prone to supporting the development of viable ICSI embryos., (Copyright 2010 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.)

Purpose: The use of vigabatrin (VGB) as an antiepileptic drug (AED) has been limited by evidence showing that it causes vigabatrin-attributed visual field loss (VAVFL) in at least 20-40% of patients exposed at school age or later. VGB is an effective drug for infantile spasms, but there are no reports on later visual field testing after such treatment. Our aim was to investigate the risk of VAVFL in school-age children who had received VGB in infancy., Methods: Visual fields of 16 children treated with VGB for infantile spasms were examined by Goldmann kinetic perimetry at age 6-12 years. Normal fields were defined as the temporal meridian extending to more than 70 degrees , and mild VAVFL between 50 and 70 degrees . Abnormal findings were always confirmed by repeating the test. Exposure data were collected from hospital charts., Results: Vigabatrin was started at a mean age of 7.6 (range, 3.2-20.3) months. The mean duration of therapy was 21.0 (9.3-29.8) months and cumulative dose 655 g (209-1,109 g). Eight children were never treated with other AEDs, five received only adrenocorticotropic hormone (ACTH) in addition to VGB, and three children had been treated with other AEDs. Fifteen children had normal visual fields. Mild VAVFL was observed in one child (6%) who had been treated with VGB for 19 months and who received a cumulative dose of 572 g., Conclusions: The risk of VAVFL may be lower in children who are treated with VGB in infancy compared to patients who receive VGB at a later age.

The characteristics of the nucleation mode particles of a Euro IV heavy-duty diesel vehicle exhaust were studied. The NOx and PM emissions of the vehicle were controlled through the use of cooled EGR and high-pressure fuel injection techniques; no exhaust gas after-treatment was used. Particle measurements were performed in vehicle laboratory and on road. Nucleation mode dominated the particle number size distribution in all the tested driving conditions. According to the on-road measurements, the nucleation mode was already formed after 0.7 s residence time in the atmosphere and no significant changes were observed for longer residence times. The nucleation mode was insensitive to the fuel sulfur content, dilution air temperature, and relative humidity. An increase in the dilution ratio decreased the size of the nucleation mode particles. This behavior was observed to be linked to the total hydrocarbon concentration in the diluted sample. In volatility measurements, the nucleation mode particles were observed to have a nonvolatile core with volatile species condensed on it. The results indicate that the nucleation mode particles have a nonvolatile core formed before the dilution process. The core particles have grown because of the condensation of semivolatile material, mainly hydrocarbons, during the dilution.

The semivolatile mass fraction of diesel exhaust particles was studied using size-resolved on-line techniques (DMA-ELPI; TDMA-ELPI). The average density of the semivolatile liquid on the particles was measured to be approximately 0.8 g/cm3. The measured size resolved values of mass transfer imply that condensation, or diffusion-limited mass transfer, plays a major role in driving the volatile matter to the diesel exhaust particles. The measured mass change values correspond to highly size dependent mass fractions for the semivolatile component, ranging from approximately 20-80%. Integrated over particle size distribution, the volatile mass fractions were 25 and 45% for the two load points studied. Calculation, based on the measured particle properties, indicates that only 10% volatile mass fraction could be explained by monolayer adsorption. The size resolved changes in particle effective density, fractal dimension, volatile mass fractions and mass are all in agreement with theoretical considerations of condensation.

Objective: To analyze embryo morphology in relation to the corresponding chromosomal status, in order to evaluate the effects of aneuploidy over fragmentation, delayed cleavage, and arrested cleavage., Design: Retrospective study., Setting: Reproductive Medicine Unit, Società Italiana di Studi di Medicina della Riproduzione, Bologna, Italy., Patient(s): A total of 662 patients with a poor prognosis for pregnancy underwent 916 cycles of preimplantation genetic diagnosis for aneuploidy., Intervention(s): The chromosomes XY, 13, 15, 16, 18, 21, and 22 were analyzed in blastomeres biopsied from day 3 embryos., Main Outcome Measure(s): Embryo morphology, chromosomal status of the analyzed blastomeres, and spreading and reanalysis of nontransferred embryos., Result(s): The incidence of chromosomal abnormalities was significantly higher in arrested or slow-cleaving embryos, and in embryos cleaving too fast, compared to embryos with eight cells at 62 hours after insemination. The presence of an uneven number of blastomeres or fragments scattered in the perivitelline space was associated with an increased incidence of chromosomal abnormalities., Conclusion(s): A correlation between embryo development and chromosomal complement makes the incidence of chromosomal abnormalities significantly higher in embryos dividing according to a time frame and a symmetry plan which are different from what are expected. The type of fragmentation is also related to chromosomal status, which explains why the extrusion of fragments might severely affect embryo viability.

Background: Pronuclear morphology has been proposed as an indicator of embryo development and chromosomal complement. In this study, the morphology of pronuclear zygotes generated from euploid oocytes [diagnosed by first polar body (PB1) analysis] was evaluated and compared with the configurations observed in chromosomally normal embryos (diagnosed by blastomere analysis)., Materials and Methods: Group 1--238 patients underwent 273 assisted conception cycles in combination with the screening of aneuploidy on PB1 for the chromosomes 13, 15, 16, 18, 21 and 22. Only normal oocytes were inseminated. Group 2--218 patients underwent 318 assisted conception cycles with aneuploidy screening on day 3 embryos. In both groups, oocytes were checked for fertilization and pronuclear morphology at 16 h after insemination., Results: Seventy-three percent of zygotes from Group 1 had the configurations with centralized and juxtaposed pronuclei, large-size aligned or scattered nucleoli and PB located in the longitudinal or perpendicular axis of pronuclei. In Group 2, these configurations corresponded to those with the highest proportion of chromosomally normal embryos. Accordingly, in both groups, these configurations had a higher implantation rate than all the others., Conclusions: These observations confirm that some patterns of pronuclear morphology are associated with a higher proportion of euploidy and implantation reaffirming the relevance of this scoring system for the prediction of zygote viability.

Objective: To investigate chromosomal errors detected by first polar body (PB) biopsy in relation to the nuclear maturity of the oocytes., Design: Retrospective study., Setting: Reproductive medicine unit., Patient(s): Eighty-seven cycles were examined by PB biopsy for aneuploidy. Indications were maternal age >or=38 years (49 cycles), repeated IVF failures (22 cycles), and others (16 cycles)., Intervention(s): First polar bodies were analyzed for the chromosomes 13, 16, 18, 21, and 22 in both in vivo and in vitro matured oocytes. Euploid oocytes were inseminated by intracytoplasmic sperm injection., Main Outcome Measure(s): Chromosomal status of the analyzed oocytes, development after intracytoplasmic sperm injection, pregnancy, and implantation rates., Result(s): In in vitro matured oocytes, the proportion of chromosomal abnormalities was higher than in in vivo matured oocytes (70% vs. 54%, P<.005), with complex abnormalities being the prevailing defect (62% vs. 40%, P<.001). Conversely, the presence of an extra chromatid or the lack of a chromatid was more frequent in in vivo than in in vitro matured oocytes (55% vs. 34%, P<.001)., Conclusion(s): The low viability of in vitro matured oocytes from stimulated cycles could be related to a significantly higher proportion of chromosomal abnormalities compared with in vivo matured oocytes. Complex abnormalities, involving two or more chromosomes, gave the strongest contribution to the detected increase.

Heterozygous familial hypercholesterolemia (HeFH) is associated with elevated cholesterol levels and early-onset atherosclerosis. We assessed the efficacy and safety for up to 2 yr of pravastatin treatment in 19 girls and 11 boys (age range, 4.1-18.5 yr) with HeFH. Pravastatin was started at 10 mg/d, with a forced titration by 10 mg at 2, 4, 6, and 12 months until the target cholesterol level [< or =194 mg/dl (< or =5 mmol/liter)] was reached. By 2, 4, 6, 12, and 24 months of treatment, the total cholesterol levels had, respectively, decreased by 19, 20, 23, 27, and 26%, and the low-density lipoprotein cholesterol levels had decreased by 25, 27, 29, 33, and 32% compared with the dietary baseline values. Seventeen percent of patients had lipid deposits (carotid plaque, xanthomas, or corneal arcus) at baseline, and 27% had deposits at 1 yr. The side effects were mild, and no clinically significant elevations in alanine aminotransferase, creatine kinase, or creatinine were seen. Growth and pubertal maturation remained normal in all subjects. In conclusion, pravastatin treatment was safe and well tolerated. The efficacy in children with slight or moderate hypercholesterolemia was satisfactory, but in children with severe hypercholesterolemia, it was insufficient.

Particulate matter of vehicle exhaust is known to contain carcinogenic compounds such as polycyclic aromatic hydrocarbons (PAH) and is suggested to increase lung cancer risk in humans. This study examines the differences in diesel and gasoline-derived PAH binding to DNA in a human bronchial epithelial cell line (BEAS-2B). Particulate matter (PM) of gasoline exhaust was collected from passenger cars on filters and semi-volatile compounds on polyurethane foam (PUF). The soluble organic fraction (SOF) extracted from the particles was used to expose the cells and to perform PAH analysis. Gasoline extracts, benzo[a]pyrene (B[a]P) and reference materials (SRM 1650 and 1587) were used to study dose-dependent adduct formation in BEAS-2B cells. The levels of DNA adducts were in good accord with the 10 DNA adduct-forming PAH concentrations analyzed in the extracts. Gasoline extracts, SRM 1650, SRM 1587 and B[a]P formed DNA adducts dose-dependently in BEAS-2B cells. The time-dependent DNA adduct formation of 5.0 micro M B[a]P was lower than that of 2.5 micro M B[a]P. The results of this study indicate that reformulated and standard diesel fuels formed about 11- and 31-fold more adducts than gasoline, respectively, when PAH-DNA adduct levels were calculated on an emission basis (adducts/mg PM/km), whereas on a particulate basis (adducts/mg PM) no difference between the diesel and gasoline extracts was observed. We conclude that the genotoxicity of diesel fuel is based on higher particulate emission rates compared to gasoline emission and although the concentration of PAH compounds was higher in diesel particulate extracts, DNA binding by the gasoline particulate-bound PAH compounds was more pronounced than that by the diesel particulate-bound PAH compounds.

In this study we compared the ability of extractable organic material from particulate and semivolatile fractions of gasoline emission to induce mutations in bacteria and form adducts with calf thymus (CT) DNA with corresponding data obtained from diesel exhaust. Exhaust particles from gasoline-powered passenger cars were collected on filters and semivolatile compounds were collected on polyurethane foam (PUF). The mutagenicity of the soluble organic fraction (SOF) was determined in Salmonella typhimurium strain TA98 and the DNA binding of aromatic compounds in the extracts was assessed by in vitro incubations with CT DNA and rat liver S9 (oxidative activation) or xanthine oxidase (reductive activation) followed by butanol-enhanced (32)P-postlabeling analysis. Semivolatile fractions of gasoline emission collected on PUF formed more CT DNA adducts than filter extracts under all reaction conditions, but showed a lower mutagenic potential than the corresponding particulate samples. This suggests that the capacity of PUF to collect exhaust particle-derived compounds and/or the efficiency of xanthine oxidase and enzymes in the rat liver S9 to activate these compounds to DNA binding metabolites was higher than expected. Gasoline extracts, benzo[a]pyrene and diesel particulate matter (SRM 1650) formed more S9-mediated DNA adducts as their dose increased, although a linear dose-response was not observed for the gasoline exhausts. Lower concentrations of gasoline and diesel extracts bound to DNA with greater efficiency than did 8-fold higher doses, suggesting complex interactions and/or an inhibition of S9 enzyme activities by the high doses. Diesel extracts formed higher levels of adducts than gasoline extracts, especially with the reductive activation system, suggesting that diesel extracts contain high levels of nitro-polycyclic aromatic hydrocarbons (nitro-PAHs). The higher direct-acting Salmonella mutagenicity in diesel extracts in comparison with gasoline extracts is consistent with diesel extracts containing higher concentrations of nitro-PAHs. The results of this study indicate that diesel extracts are more mutagenic and form more DNA adducts than gasoline extracts and that the effects of extract dose on DNA adduct formation are complex., (Copyright 2003 Wiley-Liss, Inc.)

Background: Comparative postoperative non-steroidal anti-inflammatory drug (NSAID) studies in orthopedic patients have usually been restricted in time to the first postoperative day. The opioid-sparing effect of NSAIDs may be beneficial postoperatively as long as pain otherwise restricts ambulation and rehabilitation. We therefore compared the analgesic efficacy of the maximum recommended doses of diclofenac and ketoprofen for 3 days after knee arthroplasty., Methods: We studied 64 knee arthroplasty patients, operated on under spinal anesthesia. In a randomized, double-blind and placebo-controlled fashion, the patients received either i.v. diclofenac 75 mg (n = 24), ketoprofen 100 mg (n = 24) or saline (n = 16) in the recovery room, followed by oral diclofenac 150 mg/day, ketoprofen 300 mg/day or placebo, respectively, for 3 days, supplemented by patient-controlled analgesia (PCA) with i.v. oxycodone., Results: The mean consumption of oxycodone during the first, second and third study days was 45.3, 22.3 and 15.2 mg in the diclofenac group, 43.5, 37.5 and 21.8 mg in the ketoprofen group, and 61.2, 45.9 and 36.1 mg, respectively, in the placebo group. Oxycodone consumption was significantly lower (P < 0.05) in the ketoprofen group than in the placebo group in the postoperative period 13-24 h and 61-72 h. Diclofenac was superior to placebo in the postoperative period 25-48 h (P < 0.01), 49-60 h (P < 0.05) and to ketoprofen at 49-60 h (P < 0.05). During administration of diclofenac on days 1-3 and ketoprofen on day 2, the mean pain scores (VAS) were lower than in the placebo group (P < 0.05). Six patients had difficulties in operating the PCA device. There were no differences in blood loss., Conclusion: We conclude that in the first day after knee arthroplasty (13-24 h), ketoprofen exerted an opioid-sparing effect. After day 1 (25-60 h), with the doses used, diclofenac proved to be better than placebo, whereas ketoprofen was not.

Objective: The purpose of the study was to determine the nature and course of ophthalmic abnormalities in long-chain 3-hydroxyacyl-CoA dehydrogenase (LCHAD) deficiency, a recently discovered disorder of mitochondrial fatty acid beta-oxidation., Study Design: The study design was a cohort (case series)., Participants: A retrospective review of the records of 15 children who had died during their first 2 years was performed. Also performed were a longitudinal reanalysis and cross-sectional clinical examination of four long-term survivors aged 5 to 31 years., Main Outcome Measures: Visual acuity, refraction, visual fields, ophthalmoscopy, fluorescein angiography, biometry, corneal topography, electroretinography (ERG), visual-evoked potentials (VEPs), color vision, and dark adaptation were measured., Results: In seven children, ophthalmoscopic findings were within normal limits at 3 days to 13 months of age (median, 4.8 months). In 11 children, a granular retinal pigment epithelium (RPE), with or without pigment clumping in the macula, was seen at 4 months to 5 years of age (median, 9 months). Two long-term survivors, 16 and 31 years of age, eventually had circumscribed atrophy of the choroid, RPE, and retina, which coincided with a posterior staphyloma type 1. They had progressive axial myopia starting at 6 and 12 years of age and later paracentral scotomas leading to poor central vision. They suffered from early difficulty with mesopic vision, glare, and a severe generalized color vision deficiency that started as a tritanomaly. A third survivor was mildly myopic at 5 years of age. All four surviving patients had visually insignificant, flake-like supranuclear opacities in the lens. The ERG initially was normal but deteriorated during the first decade and later was unrecordable. The VEP responses remained fairly normal. Initially, angiography showed no blockade of the choroidal fluorescence because of the thin RPE. Filling of choroidal vessels was delayed, and the choriocapillaris and, later, larger choroidal vessels in the posterior pole became nonperfused., Conclusions: In LCHAD deficiency, the fundus is normal at birth (stage 1). Soon, however, pigment dispersion occurs in the RPE (stage 2), followed by circumscribed chorioretinal atrophy, occlusion of choroidal vessels, and deterioration of central vision, often with relative sparing of the peripheral fundus (stage 3). Finally, posterior staphylomas and central scotomas may develop (stage 4). Developmental cataract, progressive myopia, and deterioration of visual fields and color vision are new findings in LCHAD deficiency. The chorioretinopathy and abnormal ERG precede the development of myopia and posterior staphyloma, which, in turn, coincide with the loss of macular vision. The authors postulate that the RPE or choriocapillaris is primarily affected. Awareness of the characteristic ocular features is important because of an opportunity for dietary treatment, genetic counseling, and prenatal diagnosis.

In this 8-year-old boy, who had been exposed to alcohol and oxazepam during pregnancy, visual failure was the first symptom of a neuronal ceroid lipofuscinosis (NCL) disorder, noticed at the age of 5 years. Ophthalmological examinations revealed a cystic type of macular degeneration, which would be more likely to be found in variant late infantile NCL. However, vacuolated lymphocytes were found in peripheral blood films and a diagnosis of the juvenile form of NCL (JNCL) was made. Molecular genetic studies showed the patient to be homozygous for the major mutation of JNCL, a 1.02-kb deletion. In whole-night polysomnography, there was significantly more epileptiform activity than in other JNCL patients under 10 years of age. Using magnetic resonance imaging, the signal intensity of the white matter was increased, especially in the periventricular area. In addition, there were enlarged perivascular spaces in the watershead areas. The corpus callosum was thin. Finally, in the autonomic ganglion cells of the submucosal nerve plexus there were membrane-enclosed homogeneous and granular cytosomes resembling the granular osmiophilic deposits of infantile NCL. However, extraneural cells, including blood capillaries and smooth muscle, showed inclusions with fingerprint and curvilinear profiles. The features of the present case indicated a phenotypic variant of JNCL.