Methylmalonic acidemia (MMA) in pregnancy: a case series and literature review

IntroductionWomen with inherited metabolic disorders, including those with previously life‐limiting conditions such as MMA, are reaching child‐bearing age more often due to advances in early diagnosis and improved pediatric care. Information surrounding maternal and fetal complications associated with the underlying disorders remains largely unexplored.MethodsPregnancies affected by maternal MMA were ascertained through study 04‐HG‐0127 “Clinical and Basic Investigations of Methylmalonic Acidemia and Related Disorders” (clinicaltrials.gov identifier: NCT00078078) and via literature review. Prenatal and delivery records in study participants were reviewed.ResultsSeventeen pregnancies were identified in women with isolated MMA, including three abortions, one termination, and 13 completed pregnancies [three cases with cblA (four pregnancies), four cases of mut‐ (one cobalamin responsive, three non‐responsive), five cases with unknown type of MMA]. Seventeen percent (3/17) of the pregnancies resulted in a first trimester abortion, while 38.5 % (5/13) of the completed pregnancies resulted in preterm deliveries. A cesarean delivery rate of 53.8 % (7/13) was noted among the cohort. Fetal distress or nonreassuring fetal status was the indication for 57 % (4/7) cesarean deliveries. One patient was reported to have metabolic crisis as well as episodes of mild hyperammonemia. Malformations or adverse outcomes in the progeny were not observed.ConclusionAlthough there have been a small number of pregnancies identified in women with MMA, the cumulative results suggest that the majority of pregnancies can be complicated by cesarean delivery and increased risk of prematurity. A pregnancy registry could clarify perinatal complications and define management approaches needed to ensure optimal maternal and fetal outcomes in this growing patient population.Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/147009/1/jimd0839.pd

Incidence of Postpartum Infection after Vaginal Delivery in Viet Nam

This study assessed the incidence of postpartum infection which is rarely clinically evaluated and is probably underestimated in developing countries. This prospective study identified infection after vaginal delivery by clinical and laboratory examinations prior to discharge from hospital and again at six weeks postpartum in Ho Chi Minh City, Viet Nam. Textbook definitions, physicians' diagnoses, symptomatic and verbal autopsy definitions were used for classifying infection. Logistic regression was used for determining associations of postpartum infection with socioeconomic and reproductive characteristics. In total, 978 consecutive, eligible consenting women were followed up at 42\ub17 (range 2-45) days postpartum (not associated with incidence). Ninety-eight percent took 'prophylactic' antibiotics. The most conservative estimate of the incidence of postpartum infection was 1.7%. The incidence of serious infection was 0.5%, but increased to 4.6% when verbal autopsy and symptomatic definitions were used. Postpartum infection, particularly serious infection, is greatly underestimated. Just preventing or treating infection could have a substantial impact on reducing maternal mortality in developing countries

Heterohexamers Formed by CcmK3 and CcmK4 Increase the Complexity of Beta Carboxysome Shells.

Bacterial microcompartments (BMCs) encapsulate enzymes within a selectively permeable, proteinaceous shell. Carboxysomes are BMCs containing ribulose-1,5-bisphosphate carboxylase oxygenase and carbonic anhydrase that enhance carbon dioxide fixation. The carboxysome shell consists of three structurally characterized protein types, each named after the oligomer they form: BMC-H (hexamer), BMC-P (pentamer), and BMC-T (trimer). These three protein types form cyclic homooligomers with pores at the center of symmetry that enable metabolite transport across the shell. Carboxysome shells contain multiple BMC-H paralogs, each with distinctly conserved residues surrounding the pore, which are assumed to be associated with specific metabolites. We studied the regulation of β-carboxysome shell composition by investigating the BMC-H genes ccmK3 and ccmK4 situated in a locus remote from other carboxysome genes. We made single and double deletion mutants of ccmK3 and ccmK4 in Synechococcus elongatus PCC7942 and show that, unlike CcmK3, CcmK4 is necessary for optimal growth. In contrast to other CcmK proteins, CcmK3 does not form homohexamers; instead CcmK3 forms heterohexamers with CcmK4 with a 1:2 stoichiometry. The CcmK3-CcmK4 heterohexamers form stacked dodecamers in a pH-dependent manner. Our results indicate that CcmK3-CcmK4 heterohexamers potentially expand the range of permeability properties of metabolite channels in carboxysome shells. Moreover, the observed facultative formation of dodecamers in solution suggests that carboxysome shell permeability may be dynamically attenuated by "capping" facet-embedded hexamers with a second hexamer. Because β-carboxysomes are obligately expressed, heterohexamer formation and capping could provide a rapid and reversible means to alter metabolite flux across the shell in response to environmental/growth conditions

The James Webb Space Telescope Mission

Twenty-six years ago a small committee report, building on earlier studies, expounded a compelling and poetic vision for the future of astronomy, calling for an infrared-optimized space telescope with an aperture of at least $4m$. With the support of their governments in the US, Europe, and Canada, 20,000 people realized that vision as the $6.5m$ James Webb Space Telescope. A generation of astronomers will celebrate their accomplishments for the life of the mission, potentially as long as 20 years, and beyond. This report and the scientific discoveries that follow are extended thank-you notes to the 20,000 team members. The telescope is working perfectly, with much better image quality than expected. In this and accompanying papers, we give a brief history, describe the observatory, outline its objectives and current observing program, and discuss the inventions and people who made it possible. We cite detailed reports on the design and the measured performance on orbit.Comment: Accepted by PASP for the special issue on The James Webb Space Telescope Overview, 29 pages, 4 figure

The Science Performance of JWST as Characterized in Commissioning

This paper characterizes the actual science performance of the James Webb Space Telescope (JWST), as determined from the six month commissioning period. We summarize the performance of the spacecraft, telescope, science instruments, and ground system, with an emphasis on differences from pre-launch expectations. Commissioning has made clear that JWST is fully capable of achieving the discoveries for which it was built. Moreover, almost across the board, the science performance of JWST is better than expected; in most cases, JWST will go deeper faster than expected. The telescope and instrument suite have demonstrated the sensitivity, stability, image quality, and spectral range that are necessary to transform our understanding of the cosmos through observations spanning from near-earth asteroids to the most distant galaxies.Comment: 5th version as accepted to PASP; 31 pages, 18 figures; https://iopscience.iop.org/article/10.1088/1538-3873/acb29

The Hologenome Concept: Helpful or Hollow?

With the increasing appreciation for the crucial roles that microbial symbionts play in the development and fitness of plant and animal hosts, there has been a recent push to interpret evolution through the lens of the "hologenome"--the collective genomic content of a host and its microbiome. But how symbionts evolve and, particularly, whether they undergo natural selection to benefit hosts are complex issues that are associated with several misconceptions about evolutionary processes in host-associated microbial communities. Microorganisms can have intimate, ancient, and/or mutualistic associations with hosts without having undergone natural selection to benefit hosts. Likewise, observing host-specific microbial community composition or greater community similarity among more closely related hosts does not imply that symbionts have coevolved with hosts, let alone that they have evolved for the benefit of the host. Although selection at the level of the symbiotic community, or hologenome, occurs in some cases, it should not be accepted as the null hypothesis for explaining features of host-symbiont associations

The etiology of maternal mortality in developing countries: what do verbal autopsies tell us?

OBJECTIVE: To reassess the practical value of verbal autopsy data, which, in the absence of more definitive information, have been used to describe the causes of maternal mortality and to identify priorities in programmes intended to save women's lives in developing countries. METHODS: We reanalysed verbal autopsy data from a study of 145 maternal deaths that occurred in Guerrero, Querétaro and San Luis Potosí, Mexico, in 1995, taking into account other causes of death and the WHO classification system. The results were also compared with information given on imperfect death certificates. FINDINGS: The reclassification showed wide variations in the attribution of maternal deaths to single specific medical causes. CONCLUSION: The verbal autopsy methodology has inherent limitations as a means of obtaining histories of medical events. At best it may reconfirm the knowledge that mortality among poor women with little access to medical care is higher than that among wealthier women who have better access to such care