Maternal cardiovascular disease after twin pregnancies complicated by hypertensive disorders of pregnancy: a population-based cohort study

Background:People whose singleton pregnancy is affected by hypertensive disorders of pregnancy (HDP) are at risk of future cardiovascular disease. It is unclear, however, whether this association can be extrapolated to twin pregnancies. We aimed to compare the association between HDP and future cardiovascular disease after twin and singleton pregnancies.Methods:We conducted a population-based retrospective cohort study that included nulliparous people in Ontario, Canada, 1992–2017. We compared the future risk of cardiovascular disease among pregnant people from the following 4 groups: those who delivered a singleton without HDP (referent) and with HDP, and those who delivered twins either with or without HDP.Results:The populations of the 4 groups were as follows: 1 431 651 pregnant people in the singleton birth without HDP group; 98 631 singleton birth with HDP; 21 046 twin birth without HDP; and 4283 twin birth with HDP. The median duration of follow-up was 13 (interquartile range 7–20) years. The incidence rate of cardiovascular disease was lowest among those with a singleton or twin birth without HDP (0.72 and 0.74 per 1000 person-years, respectively). Compared with people with a singleton birth without HDP, the risk of cardiovascular disease was highest among those with a singleton birth and HDP (1.47 per 1000 person-years; adjusted hazard ratio [HR] 1.81 [95% confidence interval (CI) 1.72–1.90]), followed by people with a twin pregnancy and HDP (1.07 per 1000 person-years; adjusted HR 1.36 [95% CI 1.04–1.77]). The risk of the primary outcome after a twin pregnancy with HDP was lower than that after a singleton pregnancy with HDP (adjusted HR 0.74 [95% CI 0.57–0.97]), when compared directly.Interpretation:In a twin pregnancy, HDP are weaker risk factors for postpartum cardiovascular disease than in a singleton pregnancy.

Cardiovascular disease has been shown to be the leading cause of death among women.^1–3 Classic risk factors for cardiovascular disease include obesity, diabetes mellitus, hypertension and family history of cardiovascular disease. ³ More recently, an association has been established between a history of hypertensive disorders of pregnancy (HDP) — gestational hypertension and pre-eclampsia — and future risk of cardiovascular disease.^1,4–11 Consequently, some recommend using a history of HDP for cardiovascular disease risk stratification in women.^3,12The leading hypothesis for the pathogenesis of HDP is that it results from abnormal placentation due to impaired trophoblast invasion,^13–16 resulting in reduced placental perfusion.^17–19 This, in turn, leads to abnormal secretion of the angiogenic factors soluble FMS-like tyrosine kinase 1 (sFlt1) and soluble endoglin (sEng),²⁰ which induce endothelial dysfunction and the clinical manifestations of HDP.^19,21–24 The mechanisms underlying the association between HDP and future cardiovascular disease are under debate.²⁵ One hypothesis is that HDP are merely a marker of underlying subclinical or clinical vascular risk factors that predispose a person to both HDP and future cardiovascular disease.A person who is pregnant with twins is at about 3–4 times higher risk of HDP than a person with a singleton pregnancy,^26–33 with rates of 14% and 5%, respectively.³⁴ The higher risk of HDP in twin pregnancies may be due to higher circulating sFlt1 and sEng owing to greater placental mass in twin pregnancies, ^35–37 and less related to the classic vascular risk factors for HDP in a singleton pregnancy. Therefore, a logical question is whether the established higher risk of future cardiovascular disease after singleton pregnancies with HDP also occurs in twin pregnancies with HDP. Limited data are available to answer this question.³⁸ In the current study, we aimed to test the hypothesis that the association between HDP and future cardiovascular disease is less pronounced in twin versus singleton pregnancies.     

Self-organised criticality in a genetic model of species-species interaction

Summary Genetics incorporated into a two trophic level species-species interaction model allows the populations of species to evolve. The system enters a regime where the extinction of species follows an erratic pattern in time and appears chaotic to the eye. Quantitative measurements suggest that the dynamics of the model exhibits self organised criticality. Fourier Transform analysis of the time series and autocorrelation function for the population data, as well as the distribution of lineage sizes and longevity of lineages, all show power law behavior. The lineages are the analogue of avalanches in other models of self organised criticality     

Gamma oscillations in primate primary visual cortex are severely attenuated by small stimulus discontinuities

Gamma oscillations (30 to 80 Hz) have been hypothesized to play an important role in feature binding, based on the observation that continuous long bars induce stronger gamma in the visual cortex than bars with a small gap. Recently, many studies have shown that natural images, which have discontinuities in several low-level features, do not induce strong gamma oscillations, questioning their role in feature binding. However, the effect of different discontinuities on gamma has not been well studied. To address this, we recorded spikes and local field potential from 2 monkeys while they were shown gratings with discontinuities in 4 attributes: space, orientation, phase, or contrast. We found that while these discontinuities only had a modest effect on spiking activity, gamma power drastically reduced in all cases, suggesting that gamma could be a resonant phenomenon. An excitatory–inhibitory population model with stimulus-tuned recurrent inputs showed such resonant properties. Therefore, gamma could be a signature of excitation–inhibition balance, which gets disrupted due to discontinuities.

Gamma oscillations (30-80 Hz) in visual cortex have been hypothesized to play an important role in feature binding, but this role has recently been questioned. This study shows that visual stimulus-induced gamma oscillations are highly attenuated with even small discontinuities in the stimulus. This "resonant" behaviour can be explained by a simple excitatory-inhibitory model in which discontinuities lead to a small reduction in lateral inputs.     

Engineering defensin α‐helix to produce high‐affinity SARS‐CoV‐2 spike protein binding ligands

The binding of severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) spike protein to the angiotensin‐converting enzyme 2 (ACE2) receptor expressed on the host cells is a critical initial step for viral infection. This interaction is blocked through competitive inhibition by soluble ACE2 protein. Therefore, developing high‐affinity and cost‐effective ACE2 mimetic ligands that disrupt this protein–protein interaction is a promising strategy for viral diagnostics and therapy. We employed human and plant defensins, a class of small (2–5 kDa) and highly stable proteins containing solvent‐exposed alpha‐helix, conformationally constrained by two disulfide bonds. Therefore, we engineered the amino acid residues on the constrained alpha‐helix of defensins to mimic the critical residues on the ACE2 helix 1 that interact with the SARS‐CoV‐2 spike protein. The engineered proteins (h‐deface2, p‐deface2, and p‐deface2‐MUT) were soluble and purified to homogeneity with a high yield from a bacterial expression system. The proteins demonstrated exceptional thermostability (Tm 70.7°C), high‐affinity binding to the spike protein with apparent K _d values of 54.4 ± 11.3, 33.5 ± 8.2, and 14.4 ± 3.5 nM for h‐deface2, p‐deface2, and p‐deface2‐MUT, respectively, and were used in a diagnostic assay that detected SARS‐CoV‐2 neutralizing antibodies. This work addresses the challenge of developing helical ACE2 mimetics by demonstrating that defensins provide promising scaffolds to engineer alpha‐helices in a constrained form for designing of high‐affinity ligands.     

Adrenocortical involvement during diverse stress in soft-shelled turtle Lissemys p. punctata Bonnoterre

Adrenocortical responses to diverse stressful situations (dehydration, formaldehyde treatment and salt loading) were studied in the adult female soft-shelled turtle, Lissenmys p. punctata. Dehydration, formaldehyde treatment (formalin, 1%: 0.1 ml/100 g body weight daily) or salt loading (NaCl, 1%: 0.1 ml/100 g body weight daily) treatments consecutively for 7 days caused hypertrophy of the adrenocortical cells with their nuclear diameter increased, and depletions of adrenal cholesterol and ascorbic acid concentrations followed by decreased acid phosphatase and alkaline phosphatase activities in turtles. Corticosterone levels were elevated in both the adrenal gland and serum of turtles after dehydration and formalin stress, but the hormone level remained unaltered after salt loading in turtles. The results suggest active involvement of adrenal cortex in stress for homeostasis in Lissemys turtles.     

Purification, characterization and antimicrobial spectrum of a bacteriocin produced by Pediococcus acidilactici

An antimicrobial peptide designated pediocin AcH was isolated from Pediococcus acidilactici strain H. The pediocin AcH was purified by ion exchange chromatography. The molecular weight of pediocin AcH was determined by SDS-PAGE to be about 2700 daltons. Pediocin AcH was sensitive to proteolytic enzymes, resistant to heat and organic solvents, and active over a wide range of pH. Pediocin AcH exhibited inhibition against several food spoilage bacteria and foodborne pathogens including Staphylococcus aureus, Clostridium perfringens and Listeria monocytogenes. It was bactericidal to sensitive cells and acted very rapidly. The bactericidal effect was not produced by either cell lysis or apparent loss of membrane permeability.     

Interaction of pressure, time and temperature of pressurization on viability loss of Listeria innocua

In this study, the combined effectiveness of pressures of 137.9–344.7MPa, temperatures of 25–50°C and exposure times of 5–15min on Listeria innocua viability in peptone solution is examined. The results showed that under the study conditions only the combination of 344.7MPa, 50°C and 9.1min can reduce the viability of this species by 7 logs, with a z value of 173.1MPa.