A late-preterm infant with a prenatal diagnosis of non-immune hydrops was born with hypotonia, poor respiratory effort, chylothorax, encephalopathy, coagulopathy, progressive hepatic failure, and refractory pulmonary hypertension. Life support was withdrawn at 7 days of life due to multisystem organ failure. Rapid whole exome sequencing revealed novel compound heterozygous mutations in the gene encoding S-adenosylhomocysteine hydrolase (AHCY); each novel variant was carried by an asymptomatic parent. Reports of neonates with other AHCY mutations describe a pathology of varying severity. AHCY mutations should be considered when seeking an etiology for neonates with the combination of non-immune hydrops, hypotonia, encephalopathy, and liver failure.
The soil bacterium Myxococcus xanthus is a model organism with a set of diverse behaviors. These behaviors include the starvation-induced multicellular development program, in which cells move collectively to assemble multicellular aggregates. After initial aggregates have formed, some will disperse, with smaller aggregates having a higher chance of dispersal. Initial aggregation is driven by two changes in cell behavior: cells slow down inside of aggregates and bias their motion by reversing direction less frequently when moving towards aggregates. However, the cell behaviors that drive dispersal are unknown. Here we use fluorescent microscopy to quantify changes in cell behavior after initial aggregates have formed. We observe that after initial aggregate formation, cells adjust the bias in reversal timings by initiating reversals more rapidly when approaching unstable aggregates. Using agent-based modeling, we then show dispersal is predominantly generated by this change in bias, which is strong enough to overcome slowdown inside aggregates. Notably, the change in reversal bias is correlated with the nearest aggregate’s size, connecting cellular activity to previously observed correlations between aggregate size and fate. To determine if this connection is consistent across strains, we analyze a second M. xanthus strain with reduced levels of dispersal. We find that far fewer cells near smaller aggregates modified their bias. This implies that aggregate dispersal is under genetic control, providing a foundation for further investigations into the role it plays in the life cycle of M. xanthus.
Cryptophthalmos may be partial or complete, unilateral or bilateral, apparently nonsyndromal or syndromal. A recent study of 2 stillborn infants at the University of Utah prompted an analysis of the developmental aspects of the syndromal form (Fraser syndrome). We conclude that, per se, cryptophthalmos is a developmental field defect on the basis of heterogeneity (autosomal dominant and recessive forms) and phylogeneity (occurrence also in the pheasant, rabbit, pigeon, dog, and mouse). In humans this autosomal recessive disorder maps to 4q21, is homologous to the bleb (bl/bl) mouse, and is due to mutations in the FRAS1 gene that codes for a 4007 amino acid protein 85% identical to the Fras1 gene of the bleb mouse. Commonest anomalies in humans are cryptophthalmos, cutaneous syndactyly of digits, abnormal ears and genitalia, renal agenesis, and congenital heart defects. Almost half of affected infants are stillborn or die in infancy, and mental retardation is common. The pathogenesis evidently involves abnormal epithelial integrity during prenatal life. Older (mostly German) publications, some dating to the 19th century, provide a fascinating historical insight into the process of syndrome delineation.
The Accreditation Council for Graduate Medical Education (ACGME) has provided guidance for specialty and subspecialty fellowship training programs by defining 6 core competencies that must be met. Furthermore, the ACGME has defined several program requirements for pathology training, including those applicable to several pathology subspecialties. However, the requirements are broad and lack specific details, particularly as they pertain to the unique nature of pediatric pathology. The Fellowship Committee of the Society for Pediatric Pathology examined the ACGME requirements and interpreted the guidelines with respect to their application to training in pediatric pathology. The Committee worked within the ACGME guidelines to provide an expanded and more comprehensive set of guidelines for use by pediatric pathology fellowship directors and trainees. The resultant document lists the educational goals, core competencies, and program requirements with specific application to pediatric pathology. In addition, methods for assessing and documenting the progress of the individual trainees as they progress through each requirement are provided. It is to be emphasized that many of the guidelines set forthwith are flexible, and allowances should be made for individual differences of each training program.
The soil bacterium Myxococcus xanthus is a model organism with a set of diverse behaviors. These behaviors include the starvation-induced multicellular development program, in which cells move collectively to assemble multicellular aggregates. After initial aggregates have formed, some will disperse, with smaller aggregates having a higher chance of dispersal. Initial aggregation is driven by two changes in cell behavior: cells slow down inside of aggregates and bias their motion by reversing direction less frequently when moving towards aggregates. However, the cell behaviors that drive dispersal are unknown. Here we use fluorescent microscopy to quantify changes in cell behavior after initial aggregates have formed. We observe that after initial aggregate formation, cells adjust the bias in reversal timings by initiating reversals more rapidly when approaching unstable aggregates. Using agent-based modeling, we then show dispersal is predominantly generated by this change in bias, which is strong enough to overcome slowdown inside aggregates. Notably, the change in reversal bias is correlated with the nearest aggregate’s size, connecting cellular activity to previously observed correlations between aggregate size and fate. To determine if this connection is consistent across strains, we analyze a second M. xanthus strain with reduced levels of dispersal. We find that far fewer cells near smaller aggregates modified their bias. This implies that aggregate dispersal is under genetic control, providing a foundation for further investigations into the role it plays in the life cycle of M. xanthus.
Radiation safety is a broad term that refers to the activities and control measures that can be used to limit the amount of radiation exposure received by radiation workers, members of the general public, and patients undergoing radiologic procedures. The Nuclear Regulatory Commission (NRC) is a branch of the federal government that provides regulatory oversight for radiation safety issues that pertain to nuclear medicine and nuclear pharmacy practice. The key regulatory documents relating to NRC oversight of nuclear medicine/nuclear pharmacy can be found in the Code of Federal Regulations (CFR) under Title 10: Energy, Part 19: Notices, Instructions and Reports to Workers: Inspections and Investigations (10 CFR 19)1; Part 20: Standards for Protection Against Radiation (10 CFR 20)2; and Part 35: Medical Use of Byproduct Material (10 CFR 35).3
As perinatal pathologists, we acknowledge that some families would like to take their placenta home with them from the hospital for various sociocultural and/or religious beliefs and practices (eg, special burial, and, not uncommonly, consumption by encapsulation and/or other means of direct ingestion or placentophagy).1–5 Despite the increasing popularity of this practice, most states in the United States lack clear guidelines for release of the placenta from hospitals.1,3,5 We respect that the placenta is the property of the family, but feel it is important to offer our insights into the matter, based on our collective experiences and currently available literature.1–5 This is a proposed consensus guideline constructed by a panel of experts on placental pathology, which aims to (1) guide our colleagues who might be navigating through such requests for the first time and (2) educate on the potential health risks and hospital liabilities that the process may entail.The group's recommendations are as follows:Recommendation 1: An institution-tailored policy should, at the minimum, involve representatives from the obstetrics department, the pathology department, infection control, risk management, and the legal department.1 A suggested outline for forming this group is depicted in Figure 1.Recommendation 2: The obstetric provider should inform the patient and family that taking the placenta home will prevent gross and microscopic assessment of the placenta by the pathology department and thus the potential diagnosis of clinically significant diseases, including those contributing to recurrent adverse pregnancy outcomes.3Recommendation 3: Further, it is the obstetric provider's responsibility to determine if placental pathologic evaluation is indicated, and to assess the safety risks of releasing the placenta, based on the clinical history (eg, meconium-stained placentas, clinical chorioamnionitis, known maternal viral infections such as HIV and hepatitis B and C among others, and placentas of heavy smokers/substance abusers, which may be deemed unsafe for release)4; to discuss with the family the importance and potential value of placental pathologic examination; and, following this discussion, to come to a shared decision with the family as to the final placental disposition.Recommendation 4: Placentas requested for release must not be delivered to the pathology department but must be retained with the mother or in the labor and delivery ward pending discharge from the hospital. Moreover, placentas released to the family must be wrapped in sturdy leak-proof opaque containers, placed in biohazard bags, and kept refrigerated while awaiting transport.3Recommendation 5: A signed waiver of responsibility/specimen release form must be obtained from the family (preferably the mother), which informs the family of the potential biohazardous nature of the placenta and its care in transport and releases the hospital from liabilities that may occur if the placenta carries any infectious disease, which may induce cross-contamination, or if toxic substances cause illness to the recipient.1,3Recommendation 6: Placental consumption is strongly discouraged based on the lack of empirical data confirming benefits of such practice,1–5 as well as reports of adverse outcomes, including maternal-to-fetal transfer of infectious agents causing life-threatening neonatal sepsis2 and potential accumulation of toxic substances in the placenta.3Recommendation 7: Patient and family must be informed by the obstetric provider that examining the placenta in the pathology laboratory may result in the inability to release the placenta owing to potential contamination in the laboratory. In fact, many institutions do not permit the release of placenta following examination. However, there are institutions that have the capabilities to examine and sample placenta in a quasi-sterile/clean fashion that is subsequently deemed suitable for release post processing; availability of such services must be confirmed and arranged with the pathology department ahead of time. Nevertheless, in our collective opinion, it is safer not to release placentas following pathologic examination (whether in fresh or formalin-fixed state). In case the pathology department (or the hospital) would like to have the option to release the placenta post pathologic evaluation, the risks to the recipient must be outlined in the waiver. Additionally, certain hospital liabilities may arise from releasing placentas that are later found to carry infectious diseases by pathologic examination.An example of a placenta disposition flowchart (Figure 2) is provided as an overview, which may be used as a quick reference or may be modified depending on an individual institution's policy.While this matter is deeply personal, some aspects of it—particularly relating to placentophagy, which inevitably requires involvement of medical practitioners for hospital-based deliveries—invite potential risks and liabilities that must be taken into consideration by medical providers and administrators.This manuscript was also reviewed by the Star Legacy Foundation.
