Persistent reversed end diastolic flow in the fetal middle cerebral artery: an ominous finding

Fetal persistent middle cerebral artery reversed end diastolic flow is a rare and ominous finding. Previous cases have been associated with intracranial hemorrhage, growth restriction, anaemia, and hepatic anomaly. Intrauterine demise or early neonatal death is a common outcome. We report the case of persistent middle cerebral artery reversed end diastolic flow in a well-grown fetus at 32 weeks’ gestation resulting from acute, severe anaemia due to a large feto-maternal hemorrhage. An emergency cesarean section was performed and the neonate required advanced resuscitation and immediate blood transfusion. Postnatal magnetic resonance imaging confirmed a hemorrhagic parietal infarct and bilateral ischaemic changes in the basal ganglia. This provides further evidence that persistent middle cerebral artery reversed end diastolic flow in any fetus is an ominous finding warranting urgent diagnostic evaluation and/or delivery.     

Rules of formation of H–C–N–O compounds at high pressure and the fates of planetary ices

The solar system’s outer planets, and many of their moons, are dominated by matter from the H–C–N–O chemical space, based on solar system abundances of hydrogen and the planetary ices H2O, CH4, and NH3. In the planetary interiors, these ices will experience extreme pressure conditions, around 5 Mbar at the Neptune mantle–core boundary, and it is expected that they undergo phase transitions, decompose, and form entirely new compounds. While temperature will dictate the formation of compounds, ground-state density functional theory allows us to probe the chemical effects resulting from pressure alone. These structural developments in turn determine the planets’ interior structures, thermal evolution, and magnetic field generation, among others. Despite its importance, the H–C–N–O system has not been surveyed systematically to explore which compounds emerge at high-pressure conditions, and what governs their stability. Here, we report on and analyze an unbiased crystal structure search among H–C–N–O compounds between 1 and 5 Mbar. We demonstrate that simple chemical rules drive stability in this composition space, which explains why the simplest possible quaternary mixture HCNO—isoelectronic to diamond—emerges as a stable compound and discuss dominant decomposition products of planetary ice mixtures.

Crystal structure prediction coupled to electronic structure calculations has emerged as a powerful tool in computational materials science, in particular in the area of high-pressure science, where it can overcome the chemical imagination attuned to ambient conditions: The predictions—and subsequent experimental confirmations—of unusual compounds such as Na2He, H3S, or LaH10 attest to the predictive power of these approaches (1–6). The planetary ices H2O, CH4, and NH3 may dominate the interiors of icy planets, but under extreme conditions (7–10). High-pressure phases of these ices have been explored computationally, and some predictions of exotic phases of individual ices have also been confirmed by experiments (11–15). Arguably, computational predictions in this field are of crucial importance because of the challenges for laboratory experiments and the indirect nature of astronomical observations. However, with increasing number of constituents the structure searches become computationally much more demanding. Hence, while structure predictions for elemental and binary systems are routine there are far fewer extensive searches of ternary systems, and none for quaternary systems.The situation in the H–C–N–O quaternary system reflects this. A vast number of publications exist on the high-pressure evolution of the individual constituents H, C, N, and O (16–19). Binary systems have also been looked at in great detail (20–24). The ternary systems are much less investigated: While H–C–O, H–N–O, and C–N–O phase diagrams have been reported (25–27), the H–C–N ternary has not, for example. The PubChem database (28) lists just under 4.8 million molecular H–C–N compounds. Overall, it contains 44.6 million H–C–N–O compounds at ambient pressure, 78% of which are of true quaternary composition—this highlights both the complexity and the relevance of this quaternary system for organic chemistry. Back in the high-pressure area, some binary mixtures of planetary ices, for instance H2O–NH3 or N2–CH4 mixtures, which form a subset of the H–N–O and H–C–N ternaries, have been studied in simulations into the megabar pressure range (29–32). However, despite the overall importance of H–C–N–O both to planetary science and Earth-bound chemical and life sciences, to our knowledge there are no computational high-pressure studies of this system, or even subsets that include all four elements, for example binary or ternary molecular mixtures such as CO2–NH3 or NH3–H2O–CH4. Here, we explore the full H–C–N–O chemical space via crystal structure searches performed at 500 GPa. This resembles the pressure—if not the temperature—at Neptune’s core–mantle boundary and therefore helps illuminate potential pressure-induced chemical reactions in the deep interiors of the outer planets and giant icy exoplanets. It also helps us understand more generally what rules govern a familiar composition space at highly unfamiliar external conditions.     

Contraceptive efficacy of a depot progestin and androgen combination in men

WHO studies provided proof of concept for hormonal male contraception using a prototype androgen-alone regimen. Combined testosterone plus progestin regimens offer more practical promise, but no contraceptive efficacy studies have been completed. The objective of this study was to establish the proof of principle for depot hormonal androgen/progestin combination as a male contraceptive. We performed a contraceptive efficacy study of 55 healthy men in stable fertile relationships seeking a change in contraceptive method. Testosterone (four 200-mg implants, every 4 or 6 months) and 300 mg depot medroxyprogesterone acetate, im, every 3 months were administered. Once sperm output was suppressed (<1 million/ml for 2 consecutive months), men entered a 12-month contraceptive efficacy period, ceasing other contraception. The main outcome measure was contraceptive failure (pregnancy) rate. No pregnancies occurred in 426 person-months (35.5 person-years; 95% confidence limits for contraceptive failure rate, 0-8%/annum), superior to the first year failure rate of condoms, the only reversible male method. Sperm density fell rapidly, so 94% of men entered the efficacy phase by 3 months, with only 2 of 55 (3.6%) men not sufficiently suppressed to enter efficacy. A few men treated with testosterone implants at 6-month intervals demonstrated androgen deficiency symptoms and/or escape of gonadotropin and spermatogenic suppression between months 5 and 6; after a protocol amendment, all men receiving testosterone implants at 4-month intervals avoided androgen deficiency or loss of gonadotropin and sperm output suppression. Recovery was complete (median, 3.6 months to sperm reappearance and 5.0 months to 20 million sperm/ml) in all but one man with an incidental testicular disorder. Discontinuations were for protocol-related reasons (n = 15) or altered personal circumstances (n = 12), but there were no serious adverse effects related to drug exposure. The first male contraceptive efficacy study using a prototype depot androgen/progestin combination demonstrates high contraceptive efficacy with satisfactory short-term safety and recovery of spermatogenesis. Further studies of purpose-developed products are required to extend the overall safety and efficacy experience with depot androgen/progestin combinations, the most promising approach to hormonal male contraception.     

What Online Communities Can Tell Us About Electronic Cigarettes and Hookah Use: A Study Using Text Mining and Visualization Techniques

Background

The rise in popularity of electronic cigarettes (e-cigarettes) and hookah over recent years has been accompanied by some confusion and uncertainty regarding the development of an appropriate regulatory response towards these emerging products. Mining online discussion content can lead to insights into people’s experiences, which can in turn further our knowledge of how to address potential health implications. In this work, we take a novel approach to understanding the use and appeal of these emerging products by applying text mining techniques to compare consumer experiences across discussion forums.

Objective

This study examined content from the websites Vapor Talk, Hookah Forum, and Reddit to understand people’s experiences with different tobacco products. Our investigation involves three parts. First, we identified contextual factors that inform our understanding of tobacco use behaviors, such as setting, time, social relationships, and sensory experience, and compared the forums to identify the ones where content on these factors is most common. Second, we compared how the tobacco use experience differs with combustible cigarettes and e-cigarettes. Third, we investigated differences between e-cigarette and hookah use.

Methods

In the first part of our study, we employed a lexicon-based extraction approach to estimate prevalence of contextual factors, and then we generated a heat map based on these estimates to compare the forums. In the second and third parts of the study, we employed a text mining technique called topic modeling to identify important topics and then developed a visualization, Topic Bars, to compare topic coverage across forums.

Results

In the first part of the study, we identified two forums, Vapor Talk Health & Safety and the Stopsmoking subreddit, where discussion concerning contextual factors was particularly common. The second part showed that the discussion in Vapor Talk Health & Safety focused on symptoms and comparisons of combustible cigarettes and e-cigarettes, and the Stopsmoking subreddit focused on psychological aspects of quitting. Last, we examined the discussion content on Vapor Talk and Hookah Forum. Prominent topics included equipment, technique, experiential elements of use, and the buying and selling of equipment.

Conclusions

This study has three main contributions. Discussion forums differ in the extent to which their content may help us understand behaviors with potential health implications. Identifying dimensions of interest and using a heat map visualization to compare across forums can be helpful for identifying forums with the greatest density of health information. Additionally, our work has shown that the quitting experience can potentially be very different depending on whether or not e-cigarettes are used. Finally, e-cigarette and hookah forums are similar in that members represent a “hobbyist culture” that actively engages in information exchange. These differences have important implications for both tobacco regulation and smoking cessation intervention design.     

Epigenetic dysregulation of virulence gene expression in severe Plasmodium falciparum malaria

Chronic infections with the human malaria parasite Plasmodium falciparum depend on antigenic variation. P. falciparum erythrocyte membrane protein 1 (PfEMP1), the major erythrocyte surface antigen mediating parasite sequestration in the microvasculature, is encoded in parasites by a highly diverse family of var genes. Antigenic switching is mediated by clonal variation in var expression, and recent in vitro studies have demonstrated a role for epigenetic processes in var regulation. Expression of particular PfEMP1 variants may result in parasite enrichment in different tissues, a factor in the development of severe disease. Here, we study in vivo human infections and provide evidence that infection-induced stress responses in the host can modify PfEMP1 expression via the perturbation of epigenetic mechanisms. Our work suggests that severe disease may not be the direct result of an adaptive virulence strategy to maximize parasite survival but that it may indicate a loss of control of the carefully regulated process of antigenic switching that maintains chronic infections.     

Pulmonary and systemic effects of mononuclear leukapheresis

Background and Objectives There is increasing evidence that monocytes play a key role in the pathogenesis of acute lung inflammation. Mononuclear cell (MNC) leukapheresis can be used to remove large numbers of monocytes from circulating blood; however, the detailed characteristics of monocyte subpopulations removed by MNC leukapheresis, and the biological effects on the lung, remain incompletely defined. Material and Methods Six healthy male volunteers underwent MNC leukapheresis of four total blood volumes. Blood was collected at 0, 2, 4, 6, 8 and 24 h; bronchoscopy with bronchoalveolar lavage (BAL) was performed at 8–9 h. Multiparameter flow cytometry was used to identify subpopulations of monocytes in blood and monocyte‐like cells in BAL fluid. Results A median of 5·57 × 10⁹ monocytes were retrieved. Blood monocyte counts indicated that the circulating blood monocyte pool was actively replenished during leukapheresis and subsequently contained a greater proportion of classical (CD14⁺⁺ CD16^?) monocytes. A particular subpopulation of monocyte‐like cells, reminiscent of classical monocytes, was also prominent in BAL fluid after leukapheresis. Conclusion Mononuclear cell leukapheresis was safe. The greater proportion of classical monocytes present in blood after MNC leukapheresis may be clinically significant. MNC leukapheresis also appears to affect the proportion of monocyte‐like cells in the lung; however, we found no evidence that leukapheresis has a clinically important pro‐inflammatory effect in the human lung.