Successful induction of ovulation and completed pregnancy using recombinant human luteinizing hormone and follicle stimulating hormone in a woman with Kallmann's syndrome

The induction of ovulation in women with hypogonado-trophic hypogonadism requires follicle stimulating hormone (FSH) for follicular growth and both FSH and luteinizing hormone (LH) to induce optimal follicular steroidogenesis. The development of human recombinant FSH and LH means that individually tailored doses of both hormones can be used with the aim of inducing unifollicular ovulation. This report describes the use of recombinant human FSH and LH for the induction of ovulation and conception in the second cycle of treatment, and subsequently a successfully completed pregnancy in a woman with Kallmann's syndrom

Aryl hydrocarbon receptor-mediated activity of gas-phase ambient air derived from passive sampling and an \u3cem\u3ein vitro\u3c/em\u3e bioassay

The gaseous fraction of hydrophobic organic contaminants (HOCs) in ambient air appears to be responsible for a significant portion of aryl hydrocarbon receptor (AhR)‐mediated activity, but the majority of compounds contributing to this activity remain unidentified. This study investigated the use of polyethylene passive samplers (PEs) to isolate gaseous HOCs from ambient air for use in in vitro bioassays and to improve our understanding of the toxicological relevance of the gaseous fraction of ambient air in urban and residential environments. Concentrations of polycyclic aromatic hydrocarbons (PAHs) and organic flame retardants (OFRs) were measured in PE extracts. Extracts were also analyzed using an in vitro bioassay to measure AhR‐mediated activity. Bioassay‐derived benzo[a]pyrene (BaP) equivalents (BaP‐Eqbio), a measure of potency of HOC mixtures, were greatest in the downtown Cleveland area and lowest at rural/residential sites further from the city center. BaP‐Eqbio was weakly correlated with concentrations of 2‐ring alkyl/substituted PAHs and one organophosphate flame retardant, ethylhexyl diphenyl phosphate (EHDPP). Potency predicted based on literature‐derived induction equivalency factors (IEFs) explained only 2‐23% of the AhR‐mediated potency observed in bioassay experiments. This study suggests that health risks of gaseous ambient air pollution predicted using data from targeted chemical analysis may underestimate risks of exposure, most likely due to augmentation of potency by unmonitored chemicals in the mixture, and the lack of relevant IEFs for many targeted analytes

A social mechanism facilitates ant colony emigrations overdifferent distances

Behavioural responses enable animals to react rapidly to fluctuating environments. In eusocial organisms, such changes are often enacted at the group level, but may be organised in a decentralised fashion by the actions of individuals. However, the contributions of different group members are rarely homogeneous, and there is evidence to suggest that certain ‘keystone’ individuals are important in shaping collective responses. Accordingly, investigations of the dynamics and structuring of behavioural changes at both the group and individual level are crucial for evaluating the relative influence of different individuals. Here, we examined the composition of tandem running behaviour during colony emigrations in the ant species Temnothorax albipennis. Tandem running is modulated in response to emigration distance, with more runs being conducted when a more distant nest site must be reached. We show that certain individuals are highly active in the tandem running process, attempting significantly more work in thetask. Contrary to expectations, however, such individuals are in fact no more successful at conducting tandem runs than their less active nest mates. Instead, it seems that when more tandem runs are required, colonies rely on greater recruitment of workers into the process. The implications of our study are that in some cases, even when apparently ‘key’ individuals exist within a group, their relative contribution to task performance may be far from decisive

Molecular modeling of a tandem two pore domain potassium channel reveals a putative binding Site for general anesthetics

[Image: see text] Anesthetics are thought to mediate a portion of their activity via binding to and modulation of potassium channels. In particular, tandem pore potassium channels (K2P) are transmembrane ion channels whose current is modulated by the presence of general anesthetics and whose genetic absence has been shown to confer a level of anesthetic resistance. While the exact molecular structure of all K2P forms remains unknown, significant progress has been made toward understanding their structure and interactions with anesthetics via the methods of molecular modeling, coupled with the recently released higher resolution structures of homologous potassium channels to act as templates. Such models reveal the convergence of amino acid regions that are known to modulate anesthetic activity onto a common three- dimensional cavity that forms a putative anesthetic binding site. The model successfully predicts additional important residues that are also involved in the putative binding site as validated by the results of suggested experimental mutations. Such a model can now be used to further predict other amino acid residues that may be intimately involved in the target-based structure–activity relationships that are necessary for anesthetic binding

Moderate hypothermia within 6 h of birth plus inhaled xenon versus moderate hypothermia alone after birth asphyxia (TOBY-Xe): a proof-of-concept, open-label, randomised controlled trial

Background Moderate cooling after birth asphyxia is associated with substantial reductions in death and disability, but additional therapies might provide further benefit. We assessed whether the addition of xenon gas, a promising novel therapy, after the initiation of hypothermia for birth asphyxia would result in further improvement. Methods Total Body hypothermia plus Xenon (TOBY-Xe) was a proof-of-concept, randomised, open-label, parallel-group trial done at four intensive-care neonatal units in the UK. Eligible infants were 36–43 weeks of gestational age, had signs of moderate to severe encephalopathy and moderately or severely abnormal background activity for at least 30 min or seizures as shown by amplitude-integrated EEG (aEEG), and had one of the following: Apgar score of 5 or less 10 min after birth, continued need for resuscitation 10 min after birth, or acidosis within 1 h of birth. Participants were allocated in a 1:1 ratio by use of a secure web-based computer-generated randomisation sequence within 12 h of birth to cooling to a rectal temperature of 33·5°C for 72 h (standard treatment) or to cooling in combination with 30% inhaled xenon for 24 h started immediately after randomisation. The primary outcomes were reduction in lactate to N-acetyl aspartate ratio in the thalamus and in preserved fractional anisotropy in the posterior limb of the internal capsule, measured with magnetic resonance spectroscopy and MRI, respectively, within 15 days of birth. The investigator assessing these outcomes was masked to allocation. Analysis was by intention to treat. This trial is registered with ClinicalTrials.gov, number NCT00934700, and with ISRCTN, as ISRCTN08886155. Findings The study was done from Jan 31, 2012, to Sept 30, 2014. We enrolled 92 infants, 46 of whom were randomly assigned to cooling only and 46 to xenon plus cooling. 37 infants in the cooling only group and 41 in the cooling plus xenon group underwent magnetic resonance assessments and were included in the analysis of the primary outcomes. We noted no significant differences in lactate to N-acetyl aspartate ratio in the thalamus (geometric mean ratio 1·09, 95% CI 0·90 to 1·32) or fractional anisotropy (mean difference −0·01, 95% CI −0·03 to 0·02) in the posterior limb of the internal capsule between the two groups. Nine infants died in the cooling group and 11 in the xenon group. Two adverse events were reported in the xenon group: subcutaneous fat necrosis and transient desaturation during the MRI. No serious adverse events were recorded. Interpretation Administration of xenon within the delayed timeframe used in this trial is feasible and apparently safe, but is unlikely to enhance the neuroprotective effect of cooling after birth asphyxia

Multiphase modelling of tumour growth and extracellular matrix interaction: mathematical tools and applications

Resorting to a multiphase modelling framework, tumours are described here as a mixture of tumour and host cells within a porous structure constituted by a remodelling extracellular matrix (ECM), which is wet by a physiological extracellular fluid. The model presented in this article focuses mainly on the description of mechanical interactions of the growing tumour with the host tissue, their influence on tumour growth, and the attachment/detachment mechanisms between cells and ECM. Starting from some recent experimental evidences, we propose to describe the interaction forces involving the extracellular matrix via some concepts coming from viscoplasticity. We then apply the model to the description of the growth of tumour cords and the formation of fibrosis

Histories of hating

This roundtable discussion presents a dialogue between digital culture scholars on the seemingly increased presence of hating and hate speech online. Revolving primarily around the recent #GamerGate campaign of intensely misogynistic discourse aimed at women in video games, the discussion suggests that the current moment for hate online needs to be situated historically. From the perspective of intersecting cultural histories of hate speech, discrimination, and networked communication, we interrogate the ontological specificity of online hating before going on to explore potential responses to the harmful consequences of hateful speech. Finally, a research agenda for furthering the historical understandings of contemporary online hating is suggested in order to address the urgent need for scholarly interventions into the exclusionary cultures of networked media

Correction to: Microbial communities associated with distance- and density-dependent seedling mortality in a tropical rainforest (Plant Ecology, (2020), 221, 1, (41-54), 10.1007/s11258-019-00989-y)

© 2020, Springer Nature B.V. The article entitled “Microbial communities associated with distance- and density-dependent seedling mortality in a tropical rainforest”, which is part of the special issue on “Applying microbial communities to improve restoration and conservation outcomes” was published prematurely in Volume 221, Issue 1, January 2020