Delivery of a baby with severe combined immunodeficiency at 31 weeks gestation following an extreme preterm prelabour spontaneous rupture of the membranes: a case report

<p>Abstract</p> <p>Introduction</p> <p>If left untreated, severe combined immunodeficiency can lead to an acute susceptibility to infection. The intrauterine environment is sterile until the amniotic membranes rupture. The vaginal flora then ascends into the genital tract, thus increasing the risk of chorioamnionitis. An extremely premature and prolonged membrane rupture is associated with a dismal prognosis for an immunocompetent preterm fetus. There are no case reports to date that detail the outcome of an immunocompromised preterm baby following prolonged rupture of membranes.</p> <p>Case presentation</p> <p>We present the case of a 32-year-old Indian woman who delivered a 31-week gestational baby who had a severe combined immunodeficiency following premature prelabour prolonged rupture of the membranes at the 14^thweek of gestation.</p> <p>Conclusion</p> <p>Extreme preterm prelabour spontaneous rupture of membranes in an underlying condition of severe combined immunodeficiency does not necessarily lead to an unfavourable outcome.</p

Prenatal dexamethasone ‘programmes’ hypotension, but stress-induced hypertension in adult offspring

Low birth weight in humans is predictive of hypertension in adult life. Although the mechanisms underlying this link remain unknown, fetal overexposure to glucocorticoids has been implicated. We previously showed that prenatal dexamethasone (DEX) exposure in the rat lowers birth weight and programmes adult hypertension. The current study aimed to further investigate the nature of this hypertension and to elucidate its origins. Unlike previous studies, we assessed offspring blood pressure (BP) with radiotelemetry, which is unaffected by stress artefacts of measurement. We show that prenatal DEX during the last week of pregnancy results in offspring of low birth weight (14% reduction) that have lower basal BP in adulthood (∼4–8 mmHg lower); with the commonly expected hypertensive phenotype only being noted when these offspring are subjected to even mild disturbance or a more severe stressor (up to 30 mmHg higher than controls). Moreover, DEX-treated offspring sustain their stress-induced hypertension for longer. Promotion of systemic catecholamine release (amphetamine) induced a significantly greater rise of BP in the DEX animals (77% increase) over that observed in the vehicle controls. Additionally, we demonstrate that the isolated mesenteric vasculature of DEX-treated offspring display greater sensitivity to noradrenaline and other vasoconstrictors. We therefore conclude that altered sympathetic responses mediate the stress-induced hypertension associated with prenatal DEX programming

Post-prandial changes in salivary glucocorticoids: Effects of dietary cholesterol and associations with bile acid excretion

Mechanisms to explain post-prandial increases in circulating glucocorticoids are not well understood and may involve increased adrenal secretion and/or altered steroid metabolism. We have compared salivary levels of cortisol and cortisone levels in healthy male and female volunteers fed either a low or cholesterol-rich midday meal. Urinary levels of steroids, bile acids and markers of lipid peroxidation were also measured. Males and females showed expected circadian changes in salivary steroids and postprandial peaks within 1h of feeding. After a high-cholesterol meal, postprandial cortisol increases were higher in males whereas post-prandial cortisone levels were higher in females. Urinary cortisol but not cortisone levels were higher on the day when males and females ate a high-cholesterol meal. Urinary bile acid excretion and anti-oxidant markers of lipid peroxidation, thiobarbituric acid reactive substances (TBARS), and total phenol content were not affected by dietary cholesterol but tended to be higher in males. Cross-tabulation of correlation coefficients indicated positive associations between urinary markers of peroxidation, bile acids, and cortisol:cortisone ratios. We conclude that dietary cholesterol (a substrate for steroidogenesis) does not have an acute effect on adrenal glucocorticoid synthesis and that gender but not a high-cholesterol meal may influence the interconversion of cortisol and cortisone. Longer term studies of the effects of dietary cholesterol are needed to analyze the associations between bile acids, steroid metabolism, and secretion and lipid peroxidation.11pubpub

An analysis of terrorist attack perpetrators in England and Wales: Comparing lone actors, lone dyads, and group actors

Three types of terrorist attackers, sentenced between 1983 and 2021, were compared using a sample of 143 individuals convicted of extremist offenses in England and Wales. Attackers were classified as either lone actors, lone dyads, or group actors, and these groups were compared in relation to sociodemographics, ideological affiliation, mental health status, online activities, plot characteristics, and assessments of risk. Data were obtained from coding the content of specialist risk assessment reports. Key findings include that lone actors and lone dyads were significantly more likely to present with mental health issues than group actors. Attackers affiliated with the extreme right wing were more likely to commit attacks alone or in pairs, in contrast to Islamist extremists who were more likely to attack as a group. In terms of trends over time, lone-actor attacks have become increasingly prominent, while the opposite is true for group attacks. The internet was also found to play an important role in radicalization pathways and attack preparation for lone actors and lone dyads, but a lesser role for group-based attackers. No differences were found between attacker groups in assessments of risk by professionals. Gaining an increased understanding of those assuming attacker roles can help guide counterterrorism approaches and future policy

Discovery of a Transiting Planet Near the Snow-Line

In most theories of planet formation, the snow-line represents a boundary between the emergence of the interior rocky planets and the exterior ice giants. The wide separation of the snow-line makes the discovery of transiting worlds challenging, yet transits would allow for detailed subsequent characterization. We present the discovery of Kepler-421b, a Uranus-sized exoplanet transiting a G9/K0 dwarf once every 704.2 days in a near-circular orbit. Using public Kepler photometry, we demonstrate that the two observed transits can be uniquely attributed to the 704.2 day period. Detailed light curve analysis with BLENDER validates the planetary nature of Kepler-421b to >4 sigmas confidence. Kepler-421b receives the same insolation as a body at ~2AU in the Solar System and for a Uranian albedo would have an effective temperature of ~180K. Using a time-dependent model for the protoplanetary disk, we estimate that Kepler-421b's present semi-major axis was beyond the snow-line after ~3Myr, indicating that Kepler-421b may have formed at its observed location.Comment: 14 pages, 10 figures, 3 tables. Accepted in Ap

Sensing and discrimination of explosives at variable concentration with a large-pore MOF as part of a luminescent array

Metal–organic frameworks (MOFs) have shown great promise for sensing of dangerous chemicals, including environmental toxins, nerve agents, and explosives. However, challenges remain, such as the sensing of larger analytes and the discrimination between similar analytes at different concentrations. Herein, we present the synthesis and development of a new, large-pore MOF for explosives sensing and demonstrate its excellent sensitivity against a range of relevant explosive compounds including trinitrotoluene and pentaerythritol tetranitrate. We have developed an improved, thorough methodology to eliminate common sources of error in our sensing protocol. We then combine this new MOF with two others as part of a three-MOF array for luminescent sensing and discrimination of five explosives. This sensor works at part-per-million concentrations and, importantly, can discriminate explosives with high accuracy without reference to their concentration

Mobilisation thresholds for coral rubble and consequences for windows of reef recovery

The proportional cover of rubble on reefs is predicted to increase as disturbances increase in intensity and frequency. Unstable rubble can kill coral recruits and impair binding processes that transform rubble into a stable substrate for coral recruitment. A clearer understanding of the mechanisms of inhibited coral recovery on rubble requires characterisation of the hydrodynamic conditions that trigger rubble mobilisation. Here, we investigated rubble mobilisation under regular wave conditions in a wave flume and irregular wave conditions in situ on a coral reef in the Maldives. We examined how changes in near-bed wave orbital velocity influenced the likelihood of rubble motion (e.g. rocking) and transport (by walking, sliding or flipping). Rubble mobilisation was considered as a function of rubble length, branchiness (branched vs. unbranched) and underlying substrate (rubble vs. sand). The effect of near-bed wave orbital velocity on rubble mobilisation was comparable between flume and reef observations. As near-bed wave orbital velocity increased, rubble was more likely to rock, be transported and travel greater distances. Averaged across length, branchiness and substrate, loose rubble had a 50 % chance of transport when near-bed wave orbital velocities reached 0.30 m s−1 in both the wave flume and on the reef. However, small and/or unbranched rubble pieces were generally mobilised more and at lower velocities than larger, branched rubble. Rubble also travelled further distances per day (∼2 cm) on substrates composed of sand than rubble. Importantly, if rubble was interlocked, it was very unlikely to move (&lt; 7 % chance) even at the highest velocity tested (0.4 m s−1). Furthermore, the probability of rubble transport declined over 3 d deployments in the field, suggesting rubble had snagged or settled into more hydrodynamically stable positions within the first days of deployment. We expect that snagged or settled rubble is transported more commonly in locations with higher-energy events and more variable wave environments. At our field site in the Maldives, we expect recovery windows for binding (when rubble is stable) to predominantly occur during the calmer north-eastern monsoon when wave energy impacting the atoll is less and wave heights are smaller. Our results show that rubble beds comprised of small rubble pieces and/or pieces with fewer branches are more likely to have shorter windows of recovery (stability) between mobilisation events, and thus be good candidates for rubble stabilisation interventions to enhance coral recruitment and binding.</p

Peripheral mechanisms contributing to the glucocorticoid hypersensitivity in proopiomelanocortin null mice treated with corticosterone.

Proopiomelanocortin (POMC) deficiency causes severe obesity through hyperphagia of hypothalamic origin. However, low glucocorticoid levels caused by adrenal insufficiency mitigate against insulin resistance, hyperphagia and fat accretion in Pomc-/- mice. Upon exogenous glucocorticoid replacement, corticosterone-supplemented (CORT) Pomc-/- mice show exaggerated responses, including excessive fat accumulation, hyperleptinaemia and insulin resistance. To investigate the peripheral mechanisms underlying this glucocorticoid hypersensitivity, we examined the expression levels of key determinants and targets of glucocorticoid action in adipose tissue and liver. Despite lower basal expression of 11beta-hydroxysteroid dehydrogenase type 1 (11beta-HSD1), which generates active glucocorticoids within cells, CORT-mediated induction of 11beta-HSD1 mRNA levels was more pronounced in adipose tissues of Pomc-/- mice. Similarly, CORT treatment increased lipoprotein lipase mRNA levels in all fat depots in Pomc-/- mice, consistent with exaggerated fat accumulation. Glucocorticoid receptor (GR) mRNA levels were selectively elevated in liver and retroperitoneal fat of Pomc-/- mice but were corrected by CORT in the latter depot. In liver, CORT increased phosphoenolpyruvate carboxykinase mRNA levels specifically in Pomc-/- mice, consistent with their insulin-resistant phenotype. Furthermore, CORT induced hypertension in Pomc-/- mice, independently of adipose or liver renin-angiotensin system activation. These data suggest that CORT-inducible 11beta-HSD1 expression in fat contributes to the adverse cardiometabolic effects of CORT in POMC deficiency, whereas higher GR levels may be more important in liver

Hypertension in mice lacking 11beta-hydroxysteroid dehydrogenase type 2

Deficiency of 11β-hydroxysteroid dehydrogenase type 2 (11β-HSD2) in humans leads to the syndrome of apparent mineralocorticoid excess (SAME), in which cortisol illicitly occupies mineralocorticoid receptors, causing sodium retention, hypokalemia, and hypertension. However, the disorder is usually incompletely corrected by suppression of cortisol, suggesting additional and irreversible changes, perhaps in the kidney. To examine this further, we produced mice with targeted disruption of the 11β-HSD2 gene. Homozygous mutant mice (11β-HSD2(–/–)) appear normal at birth, but ∼50% show motor weakness and die within 48 hours. Both male and female survivors are fertile but exhibit hypokalemia, hypotonic polyuria, and apparent mineralocorticoid activity of corticosterone. Young adult 11β-HSD2(–/–) mice are markedly hypertensive, with a mean arterial blood pressure of 146 ± 2 mmHg, compared with 121 ± 2 mmHg in wild-type controls and 114 ± 4 mmHg in heterozygotes. The epithelium of the distal tubule of the nephron shows striking hypertrophy and hyperplasia. These histological changes do not readily reverse with mineralocorticoid receptor antagonism in adulthood. Thus, 11β-HSD2(–/–) mice demonstrate the major features of SAME, providing a unique rodent model to study the molecular mechanisms of kidney resetting leading to hypertension. J. Clin. Invest. 103:683–689 (1999