Impaired glucose tolerance and hyperinsulinaemia are common features of obesity. Since oxytocin has been shown to influence glucose metabolism and insulin secretion, the objective of the present ...study was to investigate whether the plasma level of oxytocin is elevated in obese subjects and if so, whether it is affected by weight reduction following gastric banding. Repeated blood samples were collected in connection with ingestion of a liquid test meal from subjects weighing about 130 kg. Normal weight subjects were tested likewise. Further tests were performed on obese subjects 6 months after operation with gastric banding and a subsequent weight reduction of about 30 kg. Plasma levels of oxytocin were measured by radioimmunoassay. It was found that plasma levels of oxytocin were 4-fold higher in the obese subjects when compared to the control subjects. Analysis with high performance liquid chromatography demonstrated that the oxytocin-like material, as determined by radioimmunoassay, in extracted plasma from one obese subject coeluted with synthetic oxytocin standard. Ingestion of a test meal did not seem to influence oxytocin levels. The mean oxytocin level was equally elevated in male and female obese subjects. Following operation oxytocin levels decreased significantly, but were still significantly higher than in the control subjects. The mechanism behind the hyperoxytocinaemia and possible consequence of it remain obscure.
Antenatal corticosteroids (ACS) are widely prescribed to improve outcomes following preterm birth. Significant knowledge gaps surround their safety, long-term effects, optimal timing and dosage. ...Almost half of women given ACS give birth outside the "therapeutic window" and have not delivered over 7 days later. Overtreatment with ACS is a concern, as evidence accumulates of risks of unnecessary ACS exposure.
The Consortium for the Study of Pregnancy Treatments (Co-OPT) was established to address research questions surrounding safety of medications in pregnancy. We created an international birth cohort containing information on ACS exposure and pregnancy and neonatal outcomes by combining data from four national/provincial birth registers and one hospital database, and follow-up through linked population-level data from death registers and electronic health records.
The Co-OPT ACS cohort contains 2.28 million pregnancies and babies, born in Finland, Iceland, Israel, Canada and Scotland, between 1990 and 2019. Births from 22 to 45 weeks' gestation were included; 92.9% were at term (≥ 37 completed weeks). 3.6% of babies were exposed to ACS (67.0% and 77.9% of singleton and multiple births before 34 weeks, respectively). Rates of ACS exposure increased across the study period. Of all ACS-exposed babies, 26.8% were born at term. Longitudinal childhood data were available for 1.64 million live births. Follow-up includes diagnoses of a range of physical and mental disorders from the Finnish Hospital Register, diagnoses of mental, behavioural, and neurodevelopmental disorders from the Icelandic Patient Registers, and preschool reviews from the Scottish Child Health Surveillance Programme. The Co-OPT ACS cohort is the largest international birth cohort to date with data on ACS exposure and maternal, perinatal and childhood outcomes. Its large scale will enable assessment of important rare outcomes such as perinatal mortality, and comprehensive evaluation of the short- and long-term safety and efficacy of ACS.
Couples requesting PGT-M involving a de novo mutation pose a challenge when the PGT-M test used incorporates linkage analysis, as parental samples cannot be used to determine the mutant and normal ...allele haplotypes. In our experience, de novo mutations represent approximately 6-7% of clinical referrals, and thus it is important to have strategies in place to be able to offer PGT-M for these patients.
Historically, we have employed two main strategies for these couples. If the mutation in question was paternal, we would perform single sperm analysis to determine the mutant haplotype. When the mutation was maternal, we would perform single chromosome sorting to determine the mutant haplotype. We would then confirm the phase when we obtained samples from clinical embryos.
More recently, we began to question if determining phase prior to a PGT-M cycle was necessary, as we were confirming the phase as part of the cycle. We decided to evaluate if it was quicker and simpler to aim to determine phase directly from the embryos created as part of the clinical PGT-M.
Haplotype determination was performed for the cases, utilising biopsies from clinically usable embryos. In addition, in order to obtain enough sample numbers to determine phase, when there were less than 4-5 embryos biopsied, we also requested samples from embryos with poor morphological development. Karyomapping was the PGT-M test performed, in combination with a method to detect the mutation from MDA amplifications from the biopsied samples. A grandparental DNA reference was available in all cases to evaluate SNP coverage prior.
We obtained 3-7 samples from each of 14 cases to determine mutant and normal haplotypes. On 8/14 (57%) occasions, there were not enough samples from clinically usable embryos to provide us with the required sample numbers, so additional samples from embryos with poor morphological development were requested. Phase was established in all 14 cases. In all 12/14 (86%) cases the de novo mutation had a grandpaternal origin consistent with previous cases showing 89% of these de novo mutations have arisen in a sperm.
This strategy proved successful in all 14 cases, allowing PGT-M to proceed without any delay. Additional samples from morphologically poor embryos were required 57% of the time, in order to obtain the necessary sample numbers to determine the mutant haplotype. This strategy can be employed to facilitate fast access to Karyomapping based PGT-M for cases involving de novo mutations, with a back-up strategy of using the above mentioned other methods if sample numbers are lacking.
Calcific aortic stenosis is the third most common cardiovascular disease in the United States. We hypothesized that the mechanism for aortic valve calcification is similar to skeletal bone formation ...and that this process is mediated by an osteoblast-like phenotype.
To test this hypothesis, we examined calcified human aortic valves replaced at surgery (n=22) and normal human valves (n=20) removed at time of cardiac transplantation. Contact microradiography and micro-computerized tomography were used to assess the 2-dimensional and 3-dimensional extent of mineralization. Mineralization borders were identified with von Kossa and Goldner's stains. Electron microscopy and energy-dispersive spectroscopy were performed for identification of bone ultrastructure and CaPO4 composition. To analyze for the osteoblast and bone markers, reverse transcriptase-polymerase chain reaction was performed on calcified versus normal human valves for osteopontin, bone sialoprotein, osteocalcin, alkaline phosphatase, and the osteoblast-specific transcription factor Cbfa1. Microradiography and micro-computerized tomography confirmed the presence of calcification in the valve. Special stains for hydroxyapatite and CaPO4 were positive in calcification margins. Electron microscopy identified mineralization, whereas energy-dispersive spectroscopy confirmed the presence of elemental CaPO4. Reverse transcriptase-polymerase chain reaction revealed increased mRNA levels of osteopontin, bone sialoprotein, osteocalcin, and Cbfa1 in the calcified valves. There was no change in alkaline phosphatase mRNA level but an increase in the protein expression in the diseased valves.
These findings support the concept that aortic valve calcification is not a random degenerative process but an active regulated process associated with an osteoblast-like phenotype.
Evolution of resistance by pests can reduce the efficacy of transgenic crops that produce insecticidal toxins from the bacterium Bacillus thuringiensis Berliner (Bt). In conjunction with refuges of ...non-Bt host plants, fitness costs can delay the evolution of resistance. Furthermore, fitness costs often vary with ecological conditions, suggesting that agricultural landscapes can be manipulated to magnify fitness costs and thereby prolong the efficacy of Bt crops. In the current study, we tested the effects of four species of entomopathogenic nematodes (Steinernematidae and Heterorhabditidae) on the magnitude and dominance of fitness costs of resistance to Bt toxin CrylAc in pink bollworm, Pectinophora gossypiella (Saunders) (Lepidoptera: Gelechiidae). For more than a decade, field populations of pink bollworm in the United States have remained susceptible to Bt cotton Gossypium hirsutum L. producing CrylAc; however, we used laboratory strains that had a mixture of susceptible and resistant individuals. In laboratory experiments, dominant fitness costs were imposed by the nematode Steinernema riobrave Cabanillas, Poinar, and Raulston but no fitness costs were imposed by Steinernema carpocapsae Weiser, Steinernema sp. (ML18 strain), or Heterorhabditis sonorensis Stock, Rivera-Orduño, and Flores-Lara. In computer simulations, evolution of resistance to CrylAc by pink bollworm was substantially delayed by treating some non-Bt cotton refuge fields with nematodes that imposed a dominant fitness cost, similar to the cost observed in laboratory experiments with S. riobrave. Based on the results here and in related studies, we conclude that entomopathogenic nematodes could bolster insect resistance management, but the success of this approach will depend on selecting the appropriate species of nematode and environment, as fitness costs were magnified by only two of five species evaluated and also depended on environmental factors.
This study was performed in order to investigate whether activation of sensory fibres within the sciatic and vagal nerves might influence the release of oxytocin. In anaesthetized rats the sciatic ...and vagal nerves were stimulated electrically in an afferent direction with a variety of stimuli. Rats were also stroked on their backs or nociception was inflicted by pinching a foot. Plasma oxytocin levels were measured with a highly sensitive radioimmunoassay in samples drawn from the carotid artery. Afferent electrical stimulations of both sciatic and vagal nerves at 5 V, 0.2-2 ms and 3-10 Hz caused immediate significant elevations of oxytocin levels. Thus, basal levels increased by 30-184%. Furthermore, in response to touch and nociceptive stimuli, oxytocin levels rose by 181% and 206%, respectively. These data indicate that oxytocin can be released by stimulation of peripheral nerves originating in the skin and/or muscle and in the gastrointestinal tract and thus these organs may be involved in the control of oxytocin secretion.
Serum profiles of oxytocin were studied by means of a continuous blood sampling system in five young healthy women before and during treatment with a combined oral contraceptive. Oxytocin levels were ...determined by a specific radioimmunoassay in blood samples collected in 10-min fractions from 22.00 to 06.00. The values were further analyzed by the pulse detection program PULSAR. Great individual differences in oxytocin profiles were observed, and in some of the women these differences were also pronounced between the two sampling occasions. All 10 profiles demonstrated irregular peaks which occurred with varying frequency. Although the baseline level of oxytocin increased in all women and the average concentration increased in four of the women during treatment, there was no clear-cut effect on the peak frequency. Based on results from animal experiments, it is suggested that the increase in oxytocin levels may be related to an excitatory effect exerted by estrogen on oxytocin secreting neurons.
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