Severe Food Protein-Induced Enterocolitis Syndrome After Hematopoietic Stem Cell Transplantation: Pediatric Case Report.

BACKGROUND: Food protein-induced enterocolitis syndrome (FPIES) is a non-IgE-mediated food allergy. In the last few years, after the publication of the consensus guidelines, with refined diagnostic criteria and improved awareness, FPIES is diagnosed with increased frequency. However, despite having a background of immune dysregulation, this complication has just been described once in the posttransplant setting, in an adult patient. To the best of our knowledge, there are no reports of pediatric patients developing FPIES after a hematopoietic stem cell transplant (HCT). METHODS: Retrospective review of a pediatric patient who developed severe FPIEs after a HCT. RESULTS: In this case report, the clinical presentation and diagnosis challenges of a pediatric patient who developed severe FPIES after HCT are described. The patient developed severe vomiting, diarrhea, lethargy, and shock and required admission to the pediatric intensive care unit in three occasions before the diagnosis was made. CONCLUSIONS: To the best of our knowledge, this is the first report of severe FPIES post-HCT in a pediatric patient. Physicians who are looking after pediatric patients in the post-HCT setting need to be aware of this possibility and include this entity in the differential diagnosis in order to reduce its associated morbidity.

A Request for Gender-Affirming Treatment in End-of-Life Care: A Case Study From an Inpatient VA Hospice Program.

Hospice care involves focusing on our patients' goals of care and good symptom management. This coincides with a focus on their comfort, dignity, and respect. Working with lesbian, gay, bisexual, transgender, queer and/or questioning (LGBTQ+) patients on a hospice service can be challenging for medical staff. Many of these potential challenges relate to lack of training of medical professionals. These patients often receive discriminatory care compared to those who do not identify as LGBTQ+. This case study describes an assigned-male-at-birth Veteran admitted to a Veterans Affairs Community Living Center (CLC) hospice service who, after admission, informed staff of the strong desire to go forward with gender reassignment. Despite a prognosis of 6 months, working with the Veteran to help achieve these goals, supporting the medical plans for providing gender-transition information, and focusing on addressing the Veteran with appropriate pronouns were critical to our medical team's support for our Veteran at this difficult time.

Pseudomonas aeruginosa and Bacillus cereus Isolated from Brazilian Cerrado Soil Act as Phosphate-Solubilizing Bacteria.

The phosphate-solubilizing microorganism is essential for soil quality and plant development and can serve as an alternative to reduce such Brazilian needs for importing phosphate overseas. Here, we isolated and selected bacteria from Brazilian Cerrado soils capable of solubilize phosphate. We obtained 53 bacteria isolates, of which 23 could solubilize phosphate at a pH of 7.0, 17 could solubilize phosphate at a pH of 6.0, and 8 could solubilize at a pH of 5.5. Using 16S rRNA gene sequences, we identified nine bacteria species clustered in four groups: Bacillus sp., Pseudomonas sp., Priestia sp., and Klebsiella sp. Our results revealed that the UFT01 (P. aeruginosa) and UFT42 (B. cereus) isolates exhibited the best phosphate solubilization performance at all tested pH values. We further recorded higher levels of solubilization and phosphate availability six days after the soil inoculation with P. aeruginosa, and enzymatic analysis of the soil samples revealed that the P. aeruginosa-inoculated samples resulted in four-fold higher enzymatic activities when compared to non-inoculated soils. The B. cereus soil inoculation increased ß-glucosidase activities and resulted in reduced the activities of arylsulfatase. Altogether, our findings demonstrated that P. aeruginosa and B. cereus isolated from Cerrado soils showed high phosphate solubilization potential.

Venous thromboembolism in pediatric patients with acute lymphoblastic leukemia under chemotherapy treatment. Risk factors and usefulness of thromboprophylaxis. Results of LAL-SEHOP-PETHEMA-2013.

INTRODUCTION: Symptomatic venous thromboembolism (VTE) is diagnosed in 3%-14% of patients during pediatric acute lymphoblastic leukemia (ALL) therapy. There are well-known risk factors, but the role of others as inherited thrombophilia is still controversial. Prophylaxis with low molecular weight heparin (LMWH) has been described, but its use is not globally accepted. METHODS: A retrospective multicentric study in ALL patients 1-18 years old following SEHOP-PETHEMA-2013 treatment guideline was performed to evaluate VTE rate, anticoagulant treatment, outcome, risk factors, and safety and usefulness of LMWH administration as primary thromboprophylaxis in children with inherited thrombophilia. RESULTS: A total of 652 patients were included in the study. VTE incidence was 8.7%. Most of the cases occurred during induction therapy associated with central venous catheter. Univariant analysis showed that family history of thrombosis, presence of mediastinal mass, high-risk treatment group, and inherited thrombophilia were statistically significant risk factors. LMWH administration seemed to decrease VTE rate in patients with inherited thrombophilia and those with T-cell ALL phenotype. CONCLUSION: Most of the VTE cases occurred in patients without inherited thrombophilia, but when it is present, the VTE risk is higher. LMWH administration was useful to decrease VTE in these patients.

Meaning Reconstruction in Bereaved Family Caregivers of Person's With Alzheimer's Disease: A Mixed-Methods Study.

The purpose of this descriptive study was to identify whether meaning reconstruction was associated with indicators of bereavement adaptation in 66 spouses and adult child caregivers of person's with Alzheimer's disease. A cross-sectional mixed-methods design was used. Hierarchical regression models were used to examine whether meaning making predicted grief, depression, and positive and states of mind in the sample. Qualitative interviews were conducted to gain further knowledge about ways in which Alzheimer's disease caregivers construct meaning during bereavement. The majority of participants reported experiencing positive aspects of meaning reconstruction. Benefit-finding and identity change contributed to reductions in grief, and benefit-finding contributed to positive states of mind. Being a spouse and female gender contributed to increased grief and depression. Bereaved caregivers who are at risk for high levels of grief should be targeted for grief therapy interventions that foster meaning making.

Nanoemulsion Formulations of Fungicide Tebuconazole for Agricultural Applications.

Tebuconazole (TBZ) nanoemulsions (NEs) were formulated using a low energy method. TBZ composition directly affected the drop size and surface tension of the NE. Water fraction and the organic-to-surfactant-ratio (RO/S) were evaluated in the range of 1-90 and 1-10 wt %, respectively. The study was carried out with an organic phase (OP) consisting of an acetone/glycerol mixture containing TBZ at a concentration of 5.4 wt % and Tween 80 (TW80) as a nonionic and Agnique BL1754 (AG54) as a mixture of nonionic and anionic surfactants. The process involved a large dilution of a bicontinuous microemulsion (ME) into an aqueous phase (AP). Pseudo-ternary phase diagrams of the OP//TW80//AP and OP//AG54//AP systems at T = 25 °C were determined to map ME regions; these were in the range of 0.49-0.90, 0.01-0.23, and 0.07-0.49 of OP, AP, and surfactant, respectively. Optical microscope images helped confirm ME formation and system viscosity was measured in the range of 25-147 cP. NEs with drop sizes about 9 nm and 250 nm were achieved with TW80 and AG54, respectively. An innovative low-energy method was used to develop nanopesticide TBZ formulations based on nanoemulsion (NE) technology. The surface tension of the studied systems can be lowered 50% more than that of pure water. This study's proposed low-energy NE formulations may prove useful in sustainable agriculture.

Validation of the National Institutes of Health Patient-Reported Outcomes Measurement Information System Survey as a Quality-of-Life Instrument for Patients with Malignant Brain Tumors and Their Caregivers.

At present there is a lack of well-validated surveys used to measure quality of life in patients with malignant brain tumors and their caregivers. The main objective of this pilot study was to validate the National Institutes of Health Patient-Reported Outcomes Measurement Information System (NIH PROMIS) survey for use as a quality-of-life measure in this population. This article presents the rationale for using the NIH PROMIS instrument as a quality-of-life measure for patients with malignant brain tumors and their caregivers.

Predictors of grief in bereaved family caregivers of person's with Alzheimer's disease: a prospective study.

The purpose of this prospective study was to identify factors in 66 spouses and adult child caregivers of person's with Alzheimer's disease prior to the death that predicted higher levels of grief in bereavement. A hierarchical regression model was tested. Predeath grief, dysfunctional coping, depression, social support, and decreased positive states of mind explained 54.7% of the variance in postdeath grief. Factors that contributed significantly to postdeath grief included predeath grief and depression. Results from this study indicate that risk factors for postdeath grief can be predicted prior to the death.

Expansion on stromal cells preserves the undifferentiated state of human hematopoietic stem cells despite compromised reconstitution ability.

Lack of HLA-matched hematopoietic stem cells (HSC) limits the number of patients with life-threatening blood disorders that can be treated by HSC transplantation. So far, insufficient understanding of the regulatory mechanisms governing human HSC has precluded the development of effective protocols for culturing HSC for therapeutic use and molecular studies. We defined a culture system using OP9M2 mesenchymal stem cell (MSC) stroma that protects human hematopoietic stem/progenitor cells (HSPC) from differentiation and apoptosis. In addition, it facilitates a dramatic expansion of multipotent progenitors that retain the immunophenotype (CD34+CD38-CD90+) characteristic of human HSPC and proliferative potential over several weeks in culture. In contrast, transplantable HSC could be maintained, but not significantly expanded, during 2-week culture. Temporal analysis of the transcriptome of the ex vivo expanded CD34+CD38-CD90+ cells documented remarkable stability of most transcriptional regulators known to govern the undifferentiated HSC state. Nevertheless, it revealed dynamic fluctuations in transcriptional programs that associate with HSC behavior and may compromise HSC function, such as dysregulation of PBX1 regulated genetic networks. This culture system serves now as a platform for modeling human multilineage hematopoietic stem/progenitor cell hierarchy and studying the complex regulation of HSC identity and function required for successful ex vivo expansion of transplantable HSC.

Nitric oxide signaling differentially affects habitat choice by two larval morphs of the sea slug Alderia willowi: mechanistic insight into evolutionary transitions in dispersal strategies.

In many marine animals, adult habitat is selected by lecithotrophic (non-feeding) larvae with a limited lifespan. In generalist species, larvae may increasingly accept sub-optimal habitat over time as energy stores are depleted ('desperate larva' hypothesis). If the fitness cost of suboptimal habitat is too high, larvae of specialists may prolong the searching phase until they encounter a high-quality patch or die ('death before dishonor' hypothesis). In generalists, starvation is hypothesized to lead to a decline in inhibitory nitric oxide (NO) signaling, thereby triggering metamorphosis. Here, we document alternative functions for identified signaling pathways in larvae having 'desperate' versus 'death before dishonor' strategies in lecithotrophic clutches of a habitat specialist, the sea slug Alderia willowi. In an unusual dimorphism, each clutch of A. willowi hatches both non-selective larvae that settle soon after hatching and siblings that delay settlement in the absence of cues from the alga Vaucheria, the sole adult food. Pharmacological manipulation of NO signaling induced metamorphosis in non-selective but not selective stages. However, decreased NO signaling in selective larvae lowered the threshold for response to habitat cues, mimicking the effect of declining energy levels. Manipulation of cGMP or dopamine production induced metamorphosis in selective and non-selective larvae alike, highlighting a distinct role for the NO pathway in the two larval morphs. We propose a model in which NO production (1) links nitrogen metabolism with sensory receptor signaling, and (2) shifts from a regulatory role in 'desperate larva' strategies to a modulatory role in 'death before dishonor' strategies. This study provides new mechanistic insight into how the function of conserved signaling pathways may change in response to selection on larval habitat choice behaviors.

Seasonal polyphenism in larval type: rearing environment influences the development mode expressed by adults in the sea slug Alderia willowi.

Dimorphisms occur when alternative developmental pathways produce discrete phenotypes within a species, and may promote evolutionary novelty in morphology, life history, and behavior. Among marine invertebrates, intra-specific dimorphism in larval type (poecilogony) is notably rare, but should provide insight into the selective forces acting on larval strategies. Most established cases of poecilogony appear to be allelic polymorphisms, with local expression regulated by population-genetic processes. Here, we present evidence that dimorphic larval development in the sea slug Alderia willowi is a seasonal polyphenism; the type of larvae produced by an adult slug depends on the rearing environment in which that slug matured. In field surveys of 1996-1999 and 2007-2009, the population in Mission Bay, San Diego (California, USA) produced only short-lived lecithotrophic larvae in summer and early fall, but a varying proportion of slugs expressed planktotrophy in winter and spring. In laboratory experiments, slugs reared under summer conditions (high temperature, high salinity) produced the highest proportion of lecithotrophic offspring, whereas winter conditions (low temperature, low salinity) induced the lowest proportion of lecithotrophy. The shift to a nondispersive morph under summer conditions may be an adaptive response to historical closure of coastal wetlands during the dry season in southern California, which would inhibit dispersal by larvae of back-bay taxa. In most animal polyphenisms, a single larval type is produced and the rearing environment determines which adult phenotype develops. In contrast, alternative larval morphs are produced by A. willowi in response to seasonal cues experienced by the adult stage, varying the phenotype and dispersal potential of offspring. As the only known case of polyphenism in mode of larval development, A. willowi should become a model organism for mechanistic studies of dimorphism and the evolution of alternative life histories.

Capture of particles by direct interception by cilia during feeding of a gastropod veliger.

Ciliary feeders vary in the arrangement of ciliary bands and mechanisms of capture of food. Some larvae use opposed parallel bands of preoral (prototroch) and postoral (metatroch) cilia. Hypotheses for the mechanism of particle capture include filtration by adhesion to a cilium that overtakes a particle (direct interception), but until now unequivocal evidence for this mechanism has been lacking. Here, high-speed video recordings of veliger larvae of the gastropod Lacuna vincta demonstrated direct interception of particles by prototrochal cilia. Adhesion between cilium and particle was seen when a prototrochal cilium tugged a diatom chain into the food groove while in contact with one part of the chain. In several recorded events, a prototochal cilium overtook a particle during its effective stroke and subsequently pulled the particle inward with its recovery stroke; thereupon, the particle was deposited onto the food groove and transported to the mouth. Captures varied, however. In some cases the particle was intercepted multiple times in one capture event; in others, several cilia passed a particle without interception. Particles occasionally remained in the area of recovery strokes, indicating retention without continuing adhesion to a cilium. In three events, a particle lost from prototrochal cilia was intercepted and moved into the food groove by metatrochal cilia. Particles as wide as or wider than the food groove were also captured and transported but were not ingested.

Evidence for costs of mating and self-fertilization in a simultaneous hermaphrodite with hypodermic insemination, the Opisthobranch Alderia willowi.

Simultaneous hermaphrodites offer the chance to study antagonistic coevolution between the sexes when individuals function in both roles. Traumatic mating by hypodermic insemination has repeatedly evolved in hermaphroditic taxa, but evidence for the fitness costs of such male-advantage traits is lacking. When reared in isolation, specimens of the sea slug Alderia willowi (Opisthobranchia: Sacoglossa) initially laid clutches of unfertilized eggs but 4 days later began self-fertilizing; this is only the third report of selfing in an opisthobranch. Hypodermic insemination may allow selfing in Alderia if penetration of the body wall bypasses internal mechanisms that promote outcrossing. Selfing specimens and slugs reared in pairs had reduced fecundity compared to isolated slugs laying unfertilized clutches, suggesting that hypodermic insemination imposes a cost of mating. Egg production increased for field-caught slugs separated after mating compared to slugs held in pairs, a further indication that accessibility to mates imposes a fitness cost to the female function. Such antagonism can confer a competitive advantage to slugs mating in the male role but diminish reproduction in the female role among hermaphrodites capable of long-term sperm storage. Alderia willowi is also a rare case of poecilogony, with adults producing either planktotrophic or lecithotrophic larvae. Our rearing studies revealed that most slugs switched between expressed development modes at some point; such reproductive flexibility within individuals is unprecedented, even among poecilogonous species.

Identification of novel murine parvovirus strains by epidemiological analysis of naturally infected mice.

Random-source DNA samples obtained from naturally infected laboratory mice (n=381) were evaluated by PCR and RFLP analysis to determine the prevalence of murine parvovirus strains circulating in contemporary laboratory mouse colonies. Mouse parvovirus (MPV) was detected in 77% of samples, Minute virus of mice (MVM) was detected in 16% of samples and both MVM and MPV were detected in 7% of samples. MVMm, a strain recently isolated from clinically ill NOD-mu chain knockout mice, was detected in 91% of MVM-positive samples, with the Cutter strain of MVM (MVMc) detected in the remaining samples. The prototypic and immunosuppressive strains of MVM were not detected in any of the samples. MPV-1 was detected in 78% of the MPV-positive samples and two newly identified murine parvoviruses, tentatively named MPV-2 and MPV-3, were detected in 21 and 1% of the samples, respectively. The DNA sequence encompassing coding regions of the viral genome and the predicted protein sequences for MVMm, MPV-2 and MPV-3 were determined and compared with those of other rodent parvovirus strains and LuIII parvovirus. The genomic organization for the newly identified viral strains was similar to that of other rodent parvoviruses, and nucleotide sequence identities indicated that MVMm was most similar to MVMc (96.1%), MPV-3 was most similar to hamster parvovirus (HaPV) (98.1%) and MPV-2 was most similar to MPV-1 (95.3%). The genetic similarity of MPV-3 and HaPV suggests that HaPV epizootics in hamsters may result from cross-species transmission, with mice as the natural rodent host for this virus.