Outcomes of in-vitro fertilization after bariatric surgery: a national register-based case-control study.

STUDY QUESTION: Does previous bariatric surgery (BS) in women affect cumulative live birth rate in IVF? SUMMARY ANSWER: Women having had BS seem to have the same cumulative live birth rate as non-operated women of the same BMI at IVF treatment. WHAT IS KNOWN ALREADY: Because of the perinatal risks of obesity to mother and infant as well as impaired outcomes of IVF, obese women are advised to reduce their weight, but it is not clear whether previous BS could affect IVF results. STUDY DESIGN, SIZE, DURATION: This national register-based case-control study included all cases of BS (n = 30 436) undergoing IVF (n = 153) from 2007 until 2017. PARTICIPANTS/MATERIALS, SETTING, METHODS: Swedish women between 18 and 45 years operated with BS, with at least one first started cycle of IVF after surgery, were included. For each woman having IVF after BS (n = 153), up to five non-operated control women (n = 744) starting their first IVF cycle during the study period were matched for age, parity and BMI at treatment. The primary outcome in this study was the cumulative live birth rate (CLBR) after the first IVF cycle, defined as all live births after the first cycle including fresh and frozen embryo transfers. MAIN RESULTS AND THE ROLE OF CHANCE: There was no significant difference in CLBR between the BS group and the matched controls (29.4% compared to 33.1%), even though the number of retrieved oocytes (7.6 vs 8.9, P = 0.005) and frozen embryos (1.0 vs 1.5, P = 0.041) were significantly fewer in the BS group. There was no association between cumulative live birth and BS, adjusted odds ratio 1.04, 95% CI (0.73, 1.51). However, the birth weight was significantly lower in the children born to mothers with previous BS, mean (SD) 3190 (690) vs 3478 (729) g, P = 0.037. LIMITATIONS, REASONS FOR CAUTION: Confounders such as age, BMI and previous childbirth were accounted for by the matching design of the study, but there were no data on indication for IVF, anti-Müllerian hormone, smoking or previous comorbidities. The study was exploratory and did not reach sufficient power to detect potential smaller differences in live birth rates. WIDER IMPLICATIONS OF THE FINDINGS: The findings concur with those in previously published smaller studies and provide somewhat reassuring results considering IVF outcomes after BS with a CLBR comparable to that of controls, despite a lower mean birth weight. STUDY FUNDING/COMPETING INTEREST(S): This research was funded by grants from the Southern Health Care Region of Sweden. The authors have no competing interests to declare. TRIAL REGISTRATION NUMBER: N/A.

Nano-plastics in the aquatic environment.

The amount of plastics released to the environment in modern days has increased substantially since the development of modern plastics in the early 1900s. As a result, concerns have been raised by the public about the impact of plastics on nature and on, specifically, aquatic wildlife. Lately, much attention has been paid to macro- and micro-sized plastics and their impact on aquatic organisms. However, micro-sized plastics degrade subsequently into nano-sizes whereas nano-sized particles may be released directly into nature. Such particles have a different impact on aquatic organisms than larger pieces of plastic due to their small size, high surface curvature, and large surface area. This review describes the possible sources of nano-sized plastic, its distribution and behavior in nature, the impact of nano-sized plastic on the well-being of aquatic organisms, and the difference of impact between nano- and micro-sized particles. We also identify research areas which urgently need more attention and suggest experimental methods to obtain useful data.

The all-fiber cladding-pumped Yb-doped gain-switched laser.

Gain-switching is an alternative pulsing technique of fiber lasers, which is power scalable and has a low complexity. From a linear stability analysis of rate equations the relaxation oscillation period is derived and from it, the pulse duration is defined. Good agreement between the measured pulse duration and the theoretical prediction is found over a wide range of parameters. In particular we investigate the influence of an often present length of passive fiber in the cavity and show that it introduces a finite minimum in the achievable pulse duration. This minimum pulse duration is shown to occur at longer active fibers length with increased passive length of fiber in the cavity. The peak power is observed to depend linearly on the absorbed pump power and be independent of the passive fiber length. Given these conclusions, the pulse energy, duration, and peak power can be estimated with good precision.

Maternal smoking during pregnancy and daughters' risk of gestational diabetes and obesity.

AIMS/HYPOTHESIS: The primary aim of the study was to investigate the risk of developing gestational diabetes in women who were exposed to tobacco smoke in utero. Secondary aims were to assess the risk of obesity and non-gestational diabetes. METHODS: Data were retrieved from the Medical Birth Register of Sweden for women who were born in 1982 (when smoking data were first registered) or later and who had given birth to at least one child; 80,189 pregnancies were included. The associations between in utero smoking exposure (three categories: non-smokers, 1-9 cigarettes/day [moderately exposed] and >9 cigarettes/day [heavily exposed]) and subsequent gestational diabetes (n = 291), non-gestational diabetes (n = 280) and obesity (n = 7,300) were assessed. RESULTS: The adjusted ORs (aORs) of gestational diabetes were increased among women who were moderately (1.62, 95% CI 1.24, 2.13) and heavily (1.52, 95% CI 1.12, 2.06) exposed. The corresponding aORs of obesity were 1.36 (95% CI 1.28, 1.44) and 1.58 (95% CI 1.48, 1.68), respectively. A reduced OR for non-gestational diabetes was seen in the offspring of heavy smokers (aOR 0.66, 95% CI 0.45, 0.96). CONCLUSIONS/INTERPRETATION: Women exposed to smoking during fetal life were at higher risk of developing gestational diabetes and obesity.

Gain-switched CW fiber laser for improved supercontinuum generation in a PCF.

We demonstrate supercontinuum generation in a PCF pumped by a gain-switched high-power continuous wave (CW) fiber laser. The pulses generated by gain-switching have a peak power of more than 700 W, a duration around 200 ns, and a repetition rate of 200 kHz giving a high average power of almost 30 W. By coupling such a pulse train into a commercial nonlinear photonic crystal fiber, a supercontinuum is generated with a spectrum spanning from 500 to 2250 nm, a total output power of 12 W, and an infrared flatness of 6 dB over a bandwidth of more than 1000 nm with a power density above 5 dBm/nm (3 mW/nm). This is considerably broader than when operating the same system under CW conditions. The presented approach is attractive due to the high power, power scalability, and reduced system complexity compared to picosecond-pumped supercontinuum sources.

PRIMA-1(MET) induces nucleolar accumulation of mutant p53 and PML nuclear body-associated proteins.

We have previously identified PRIMA-1, a low molecular weight compound that restores the transcriptional transactivation function to mutant p53 and induction of apoptosis. To explore the molecular mechanism for PRIMA-1-induced mutant p53-dependent apoptosis, we examined the intracellular distribution of mutant p53 upon treatment with PRIMA-1(MET) by immunofluorescence staining. We found that PRIMA-1(MET) induced nucleolar translocation of mutant p53 and the promyelocytic leukemia (PML) nuclear body-associated proteins PML, CBP and Hsp70. Levels of Hsp70 were significantly enhanced by PRIMA-1(MET) treatment. PRIMA-Dead, a compound structurally related to PRIMA-1 but unable to induce mutant p53-dependent apoptosis, failed to induce nucleolar translocation of mutant p53. Our results suggest that redistribution of mutant p53 to nucleoli plays a role in PRIMA-1-induced apoptosis.

One-legged bicycling as an assessment tool for patients with stroke.

OBJECTIVE: To assess whether one-legged bicycling correlates with muscle strength and thereby could work as an outcome measure for persons with stroke. METHODS: The study comprised 29 men (age 35-65) with a first occurrence of stroke 6-35 months earlier. Each leg was evaluated separately. A ramp protocol was used (10 W/min), with continuous recording of the ventilatory uptake (Vo(2)) and heart rate. An isokinetic dynamometer was used to assess strength and endurance. Enzyme assays were performed on muscle biopsy samples. RESULTS: The peak isometric strength and isokinetic strength of the paretic leg correlated with the max. W on the bicycle. The oxidative enzyme citrate synthase correlated with the workload for both legs on the bicycle and lactate dehydrogenase correlated with peak isometric strength in both legs. CONCLUSIONS: The one-legged bicycle exercise test can be used to assess endurance in persons with a previous stroke as it correlates with dynamometer testing and muscle biopsies.

Elemental analyses of pine bark and wood in an environmental study.

Bark and wood samples were taken from the same individuals of Scots pine (Pinus sylvestris L.) from a polluted area close to a Cu-Ni smelter in Harjavalta and from some relatively unpolluted areas in western Finland. The samples were analysed by thick-target particle induced X-ray emission (PIXE) after preconcentration by dry ashing at 550 degrees C. The elemental contents of pine bark and wood were compared to study the impact of heavy metal pollution on pine trees. By comparison of the elemental contents in ashes of bark and wood, a normalisation was obtained. For the relatively clean areas, the ratios of the concentration in bark ash to the concentration in wood ash for different elements were close to 1. This means that the ashes of Scots Pine wood and bark have quite similar elemental composition. For the samples from the polluted area the mean concentration ratios for some heavy metals were elevated (13-28), reflecting the effect of direct atmospheric contamination. The metal contents in the ashes of pine bark and wood were also compared to recommendations for ashes to be recycled back to the forest environment. Bark from areas close to emission sources of heavy metal pollution should be considered with caution if aiming at recycling the ash. Burning of bark fuel of pine grown within 6 km of the Cu-Ni smelter is shown to generate ashes with high levels of Cu, Ni as well as Cd, As and Pb.

Hsp90 binds CpG oligonucleotides directly: implications for hsp90 as a missing link in CpG signaling and recognition.

CpG motifs originating from bacterial DNA (CpG DNA) can act as danger signals for the mammalian immune system. These CpG DNA motifs like many other pathogen-associated molecular patterns are believed to be recognized by a member of the toll-like receptor family, TLR-9. Here we show results suggesting that heat shock protein 90 (hsp90) is also implicated in the recognition of CpG DNA. Hsp90 was characterized as a binder to oligodeoxynucleotides (ODNs) containing CpG motifs (CpG ODNs) after several purification steps from crude protein extracts of peripheral blood mononuclear cells. This finding was further supported by direct binding of CpG ODNs to commercially available human hsp90. Additionally, immunohistochemistry studies showed redistribution of hsp90 upon CpG ODN uptake. Thus, we propose that hsp90 can act as a ligand transfer molecule and/or play a central role in the signaling cascade induced by CpG DNA.

Effects of wood-related sterols on the offspring of the viviparous blenny, Zoarces viviparus L.

The parent generation of the viviparous blenny, Zoarces viviparus L., were exposed to phytosterols (a) from oogenesis to parturition and (b) from breeding to parturition. The experiments were performed under laboratory conditions in a test unit supplied with continuous renewal of brackish water. After parturition the offspring were further reared either in clean or in phytosterol-contaminated brackish water. The objective was to study the significance of preexposure of the parent on the effects of phytosterols on the offspring in comparison with effects occurring directly on previously unexposed offspring. The phytosterol concentrations used were (a) 0, 10, 20, and 30 microg/L and (b) 0, 10, and 20 microg/L. Offspring exposed in (a) was further reared in clean water and in (b) offspring from parents exposed to 10 microg/L was either exposed further in the same concentration or left in clean water. Offspring from parents exposed to 20 microg/L was further exposed in the same concentration. Finally one group from unexposed parents was exposed to 10 microg/L after birth. The offspring was studied for 6 months after birth. The results showed that blenny offspring are affected by phytosterols at exposure through the parental generation. The results imply that phyto- sterols affect embryological development of the larvae before hatching as well as the levels of circulating hormones of the parent fish. The larvae contained higher levels of phytosterols as did controls and the bile of exposed female fish contained lower levels of phytosterols implying a link between the higher levels in larvae and lower excretion of the females. The growth of the larvae at 10 microg/L was stimulated regardless of whether the larvae were further exposed, indicating that newborn larvae carried within the female are sensitive to exposure to phytosterols.

Effects of pulp mill effluents and restricted diet on growth and physiology of rainbow trout (Oncorhynchus mykiss).

Juvenile female rainbow trout was exposed for 4.5 months (June to October) to two dilutions of untreated and activated sludge treated whole mill effluent from a pulp mill producing bleached ECF pulp. Two controls were used, on fed ad libitum and a second receiving 0.5% feed of the body weight. All effluent exposed groups were fed ad libitum. Mean weight of the fish was measured monthly. At the end of the experiment a number of physiological and biochemical parameters were analyzed in order to establish the physiological status of the exposed fish in comparison with unexposed fish that obtained ad libitum or restricted amount of feed. The fish exposed to treated effluent grew significantly more than ad libitum control fish until August, whereupon growth retarded in fish exposed to the lower effluent dilution (400 v/v). The growth of fish exposed to untreated effluent did not deviate significantly from the control fed ad libitum. The results from the hematological analysis clearly showed that fish fed restricted amount of feed deviated significantly in most parameters compared with the control fed ad libitum. Fish exposed to treated effluent showed a response pattern similar to that of the control fed restricted amount of feed, whereas the fish exposed to untreated effluent showed a response pattern that did not deviate from that of the ad libitum control. The metabolic parameters suggested that fish exposed to treated effluent had a higher metabolic demand than ad libitum control and that the energy allocation at the end of the experiment was directed to processes other than growth. The responses on hematology were mainly a consequence of the increased energy demand and were not primary effects. The implications of using feed related parameters at field studies are discussed.

Proteins associated with the promyelocytic leukemia gene product (PML)-containing nuclear body move to the nucleolus upon inhibition of proteasome-dependent protein degradation.

Several recent findings have indicated that the promyelocytic leukemia gene product (PML) oncogenic domains (PODs) are involved in proteasome-mediated degradation of ubiquitinated proteins. We wanted to examine the intracellular distribution of PML protein in the presence of a proteasome inhibitor. We used high-resolution microscopy to study the distribution of PML protein and other POD-associated proteins along with the proteasomes themselves under normal conditions and in cells treated with the proteasome inhibitor, MG132. Inhibition of the proteasomes in MCF-7, HeLa, and IB-4 cell lines resulted in a radical redistribution of the POD-associated proteins PML, Sp100, and SUMO-1. After 6-10 h of MG132 treatment, PML, Sp100, and SUMO-1 were no longer detectable in the PODs and accumulated mainly in the nucleolus. Moreover, MG132 treatment changed the cellular distribution of the proteasomes. Interestingly, this included the accumulation in euchromatin areas of the nucleus and within the nucleoli. Several non-POD-associated proteins did not change their cellular distribution under the same conditions. The accumulation of POD-associated proteins and proteasomes in the nucleoli of MG132-treated cells indicates that these proteins may target the nucleoli under normal conditions and that the nucleolus may have a function in the regulation of proteasomal protein degradation.

SH2D1A and SLAM protein expression in human lymphocytes and derived cell lines.

The gene defect responsible for the X-linked lymphoproliferative disease (XLP) is associated with an impaired control of Epstein-Barr virus (EBV) infection. The gene has been recently identified and the encoded protein (designated SH2D1A, DSHP or SAP) was characterized. It is a 128 amino acid (aa) protein, containing a single Src homology 2 (SH2) domain. It interacts with signaling lymphocytic activation molecule (SLAM) expressed on the surface of activated T and B cells. We show that activated T, but not activated B, cells express the SH2D1A protein. NK cells express the protein as well. Tumor lines originating from B, T or NK cells exhibited similar SH2D1A protein expression as the corresponding normal cells, with some notable exceptions. EBV-carrying, tumor phenotype representative (type I), but not EBV-carrying lymphoblastoid cell line (LCL)-like (type III) or EBV-negative Burkitt lymphoma (BL) lines expressed SH2D1A. The phenotypic switch from type I to type III in the EBV-carrying BL line Mutu was associated with a down-regulation of SH2D1A and up-regulation of SLAM. In contrast to normal ex vivo and long-term activated NK cells, 2 of 3 NK leukemia lines expressed SLAM. All 3 lines expressed SH2D1A, like their normal counterparts.

Modulation of A-type potassium channels by a family of calcium sensors.

In the brain and heart, rapidly inactivating (A-type) voltage-gated potassium (Kv) currents operate at subthreshold membrane potentials to control the excitability of neurons and cardiac myocytes. Although pore-forming alpha-subunits of the Kv4, or Shal-related, channel family form A-type currents in heterologous cells, these differ significantly from native A-type currents. Here we describe three Kv channel-interacting proteins (KChIPs) that bind to the cytoplasmic amino termini of Kv4 alpha-subunits. We find that expression of KChIP and Kv4 together reconstitutes several features of native A-type currents by modulating the density, inactivation kinetics and rate of recovery from inactivation of Kv4 channels in heterologous cells. All three KChIPs co-localize and co-immunoprecipitate with brain Kv4 alpha-subunits, and are thus integral components of native Kv4 channel complexes. The KChIPs have four EF-hand-like domains and bind calcium ions. As the activity and density of neuronal A-type currents tightly control responses to excitatory synaptic inputs, these KChIPs may regulate A-type currents, and hence neuronal excitability, in response to changes in intracellular calcium.

Effects of wood-related sterols on the reproduction, egg survival, and offspring of brown trout (Salmo trutta lacustris L.).

Maturing lake trout (Salmo trutta lacustris) of both sexes were exposed to 10 and 20 microg/liter phytosterols, mainly ss-sitosterol, for 4.5 months prior to spawning. Eggs from preexposed females were artificially fertilized with milt from preexposed males in clean water, whereupon the eggs were incubated in clean water until hatching. Yolk sac fry were followed until swim-up, and mortality as well as deformities was recorded. The physiological status of the parent fish was documented, as was the occurrence of phytosterols in bile liquid and gonads. In addition, eggs from preexposed females were fertilized with milt from unexposed males to evaluate the existence of possible sex-linked differences. The results indicate a markedly increased dose-dependent egg mortality, smaller egg size, and lower mean weight of the the yolk sac stage larvae. There was a higher prevalence of deformed or otherwise diseased larvae, especially at the higher dose, but also in the groups where unexposed males were used for fertilization, indicating a female-linked effect mechanism. A causal link between effects on eggs and brood was obtained through a dose-dependent increase in phytosterols in the roe. Several physiological parameters (higher plasma estradiol, higher 7-ethoxyresorufin O-deethylase activity) implied slower maturation of the exposed female fish, whereas indications of accelerated maturation were obtained for the male fish from the same groups. The results indicate that naturally occurring wood-derived compounds in pulp mill effluents may be responsible for reproductive impacts previously observed in fish both in the laboratory and in the receiving waters of pulp mill effluents. The results also suggest that more attention should be paid to process streams emanating from the unbleached part of the mill.

Experimental field exposure of brown trout to river water receiving effluent from an integrated newsprint mill.

Effects of effluents from mechanical pulp production on brown trout were studied for 8 weeks at environmentally relevant concentrations. The exposure took place in laboratory-based pools upstream and downstream of the effluent discharge point of an integrated newsprint mill using ground wood/thermomechanical pulp. The mill had no secondary treatment of the wastewater. The pools were supplied with water pumped directly from the river. To determine the relevance of this approach, wild fish were also caught at the respective sites upstream and downstream from the mill. Sublethal effects were assessed using physiological and biochemical parameters including liver histology, hematology, serum biochemistry, and hepatic enzyme assays. Exposure was verified by analyzing water samples, fish bile, and tissues for resin acid concentrations. The downstream experimental fish and captured feral fish displayed responses and changes in physiological parameters similar to those previously observed in laboratory experiments with untreated effluents. The most obvious effects were liver damage and growth inhibition.

Agrin acts via a MuSK receptor complex.

Formation of th neuromuscular junction depends upon reciprocal inductive interactions between the developing nerve and muscle, resulting in the precise juxtaposition of a differentiated nerve terminal with a highly specialized patch on the muscle membrane, termed the motor endplate. Agrin is a nerve-derived factor that can induced molecular reorganizations at the motor endplate, but the mechanism of action of agrin remains poorly understood. MuSK is a receptor tyrosine kinase localized to the motor endplate, seemingly well positioned to receive a key nerve-derived signal. Mice lacking either agrin or MuSK have recently been generated and exhibit similarly profound defects in their neuromuscular junctions. Here we demonstrate that agrin acts via a receptor complex that includes MuSK as well as a myotube-specific accessory component.

Receptor tyrosine kinase specific for the skeletal muscle lineage: expression in embryonic muscle, at the neuromuscular junction, and after injury.

While a number of growth factors have been described that are highly specific for particular cell lineages, neither a factor nor a receptor uniquely specific to the skeletal muscle lineage has previously been described. Here we identify a receptor tyrosine kinase (RTK) specific to skeletal muscle, which we term "MuSK" for muscle-specific kinase. MuSK is expressed at low levels in proliferating myoblasts and is induced upon differentiation and fusion. In the embryo, it is specifically expressed in early myotomes and developing muscle. MuSK is then dramatically down-regulated in mature muscle, where it remains prominent only at the neuromuscular junction; MuSK is thus the only known RTK that localizes to the neuromuscular junction. Strikingly, MuSK expression is dramatically induced throughout the adult myofiber after denervation, block of electrical activity, or physical immobilization. In humans, MuSK maps to chromosome 9q31.3-32, which overlaps with the region reported to contain the Fukuyama muscular dystrophy mutation. Identification of MuSK introduces a novel receptor-factor system that seems sure to play an important and selective role in many aspects of skeletal muscle development and function.

The anticoagulation factor protein S and its relative, Gas6, are ligands for the Tyro 3/Axl family of receptor tyrosine kinases.

We report the identification of ligands for Tyro 3 (alternatively called Sky, rse, brt, or tif) and Axl (alternatively, Ark or UFO), members of a previously orphan family of receptor-like tyrosine kinases. These ligands correspond to protein S, a protease regulator that is a potent anticoagulant, and Gas6, a protein related to protein S but lacking any known function. Our results are reminiscent of recent findings that the procoagulant thrombin, a protease that drives clot formation by cleaving fibrinogen to form fibrin, also binds and activates intracellular signaling via a G protein-coupled cell surface receptor. Proteases and protease regulators that also activate specific cell surface receptors may serve to integrate coagulation with associated cellular responses required for tissue repair and growth, as well as to coordinate protease cascades and associated cellular responses in other systems, such as those involved in growth and remodeling of the nervous system.

Neurotrophic factor receptors and their signal transduction capabilities in rat astrocytes.

Until recently, astrocytes were not considered as sites for neurotrophic factor action. We show here that, both in vivo and in vitro, astrocytes express receptors for two separate families of neurotrophic factors. In the intact adult rat CNS, astrocytes express the extracellular domain of the neurotrophin receptor TrkB and, in a more restricted population, the low-affinity nerve growth factor receptor p75LNGFR. In the lesioned CNS, expression of the alpha component of the receptor for ciliary neurotrophic factor (CNTFR alpha) switches from a purely neuronal localization to cells in the glial scar at the edge of the wound. Using cultured hippocampal astrocytes as a model to address the functional status of these receptors, we have found only the truncated forms of TrkB and TrkC, which are incapable of signal transduction as measured by protein tyrosine phosphorylation or immediate early gene induction. In contrast, a fully functional CNTF receptor complex capable of signal transduction is present on cultured astrocytes. Thus, the neurotrophin receptors may act primarily to sequester or present the neurotrophins, whereas in the case of CNTF a functional response can be initiated within the astrocyte.