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Study question: Can morphokinetic analysis be used as a tool to predict the ploidy status of blastocysts? Summary answer: A blastocyst is more likely to be aneuploid when it divides slowly to two cells and eight cells but quickly to three cells. What is known already: Existing data suggests morphokinetic analysis and PGT-A both have advantages and limitations when used independently. However, the hope is that if strong associations can be found linking morpho kinetic qualities of embryos and their ploidy status, then this can be used as a predictive tool. Currently, morphokinetic analysis cannot be used as a predic tive tool for euploidy. However, there is some existing data that suggests that clinics can correlate morphokinetics and ploidy status using their in-house data. Study design, size, duration: The study was retrospective and involved the assessment of blastocysts that had undergone PGT-A with next genera tion sequencing (NGS) and had a confirmed outcome of aneuploid or euploid between January 2021 and June 2022. Only patients who obtained genetic results showing they had at least one aneuploid embryo and at least one eu ploid embryo were included to allow for a matched case-control study – this resulted in 89 aneuploid and 89 euploid embryos being analysed. Participants/materials, setting, methods: All embryos were cultured in the same conditions, including the same incubators, media (both from Vitrolife, SWE), and standard operating procedures. Morphokinetic data was exported and analysed from annotations made on the EmbryoScope annota tion software. Embryos that could not be fully annotated were excluded from analysis. A conditional logistic regression was performed in order to ascertain the effects of each morphokinetic parameter on the likelihood that the em bryo will be aneuploid or euploid. Main results and the role of chance: From 89 patients, 178 embryos were analysed, of which half were euploid and half were aneuploid. The mor phokinetic time poin

The scale of the SARS-CoV-2 pandemic has thrust a spotlight on the sex-based differences in response to viral diseases; morbidity and mortality are greater in men than women. We outline the mechanisms by which being female offers a degree of protection from COVID19, that persists even when confounders such as comorbidities are considered. The physiological and immunological mechanisms are fascinating and range from incomplete X chromosome inactivation of immune genes, a crucial role for angiotensin converting enzyme 2 (ACE2), and regulation of both immune activity and ACE2 by sex steroids. From this flows understanding of why lung and other organs are more susceptible to COVID19 damage in men, and how their distinct immunological landscapes need to be acknowledged to guide prognosis and treatment. Pregnancy, menopause, and hormone replacement therapy bring changed hormonal environments and the need for better stratification in COVID19 studies. We end by noting clinical trials based on increasing estrogens or progesterone or anti-testosterone drugs; excellent examples of translational physiology.

In smooth muscle tissues, calcium-activated chloride channels (CaCC) provide the major anionic channel. Opening of these channels leads to chloride efflux and depolarization of the myocyte membrane. In this way, activation of the channels by a rise of intracellular [Ca2+], from a variety of sources, produces increased excitability and can initiate action potentials and contraction or increased tone. We now have a good mechanistic understanding of how the channels are activated and regulated, due to identification of TMEM16A (ANO1) as the molecular entity of the channel, but key questions remain. In reviewing these channels and comparing two distinct smooth muscles, myometrial and vascular, we expose the differences that occur in their activation mechanisms, properties, and control. We find that the myometrium only expresses “classical,” Ca2+-activated, and voltage sensitive channels, whereas both tonic and phasic blood vessels express classical, and non-classical, cGMP-regulated CaCC, which are voltage insensitive. This translates to more complex activation and regulation in vascular smooth muscles, irrespective of whether they are tonic or phasic. We therefore tentatively conclude that although these channels are expressed and functionally important in all smooth muscles, they are probably not part of the mechanisms governing phasic activity. Recent knockdown studies have produced unexpected functional results, e.g. no effects on labour and delivery, and tone increasing in some but decreasing in other vascular beds, strongly suggesting that there is still much to be explored concerning CaCC in smooth muscle.