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OBJECTIVES To evaluate whether ultrasound can differentiate between cellulitis and angioedema from insect bites in pediatric patients. METHODS A prospective, pre-post study in an urban pediatric emergency department of patients younger than 21 years with soft tissue swelling from insect bites without abscesses were enrolled. Treating physician's pretest opinions regarding the diagnosis and need for antibiotics were determined. Ultrasound of the affected areas was performed, and effects on management were recorded. Further imaging, medications, and disposition were at the discretion of the enrolling physician. Phone call follow-ups were made within a week of presentation. RESULTS Among 103 patients enrolled with soft tissue swelling secondary to insect bites, ultrasound changed the management in 27 (26%) patients (95% confidence interval [CI], 18-35%). Of the patients who were indeterminate or believed to require antibiotics, ultrasound changed management in 6 (23%) of 26 patients (95% CI, 6%-40%). In those patients who were believed not to require antibiotics, ultrasound changed management in 12 (16%) 77 patients (95% CI, 7%-24%). Patients with diagnosis of local angioedema achieved symptom resolution 1.4 days sooner than patients diagnosed with cellulitis (mean, -1.389; 95% CI, -2.087 to -0.690; P < 0.001). No patient who was initially diagnosed as local angioedema received antibiotics upon patient follow-up. CONCLUSIONS Point-of-care ultrasound changed physician management in 1 of 4 patients in the pediatric emergency department with soft tissue swelling secondary to insect bites. Ultrasound may guide the management in these patients and lead to improved antibiotic stewardship in conjunction with history and physical examination.

Background In addition to their well characterized role in cellular energy production, new evidence has revealed the involvement of mitochondria in diverse signaling pathways that regulate a broad array of cellular functions. The mitochondrial genome (mtDNA) encodes essential components of the oxidative phosphorylation (OXPHOS) pathway whose expression must be coordinated with the components transcribed from the nuclear genome. Mitochondrial dysfunction is associated with disorders including cancer and neurodegenerative diseases, yet the role of the complex interactions between the mitochondrial and nuclear genomes are poorly understood. Results Using a Drosophila model in which alternative mtDNAs are present on a common nuclear background, we studied the effects of this altered mitonuclear communication on the transcriptomic response to altered nutrient status. Adult flies with the ‘native’ and ‘disrupted’ genotypes were re-fed following brief starvation, with or without exposure to rapamycin, the cognate inhibitor of the nutrient-sensing target of rapamycin (TOR). RNAseq showed that alternative mtDNA genotypes affect the temporal transcriptional response to nutrients in a rapamycin-dependent manner. Pathways most greatly affected were OXPHOS, protein metabolism and fatty acid metabolism. A distinct set of testis-specific genes was also differentially regulated in the experiment. Conclusions Many of the differentially expressed genes between alternative mitonuclear genotypes have no direct interaction with mtDNA gene products, suggesting that the mtDNA genotype contributes to retrograde signaling from mitochondria to the nucleus. The interaction of mitochondrial genotype (mtDNA) with rapamycin treatment identifies new links between mitochondria and the nutrient-sensing mTORC1 (mechanistic target of rapamycin complex 1) signaling pathway.

Recent scholarship uses the metaphor of language to articulate why, even with good intentions, we Christians can hand on meanings and values at odds with the Christian message. Our “native” languages foreground our worlds, readily conforming our minds to the very realm we are called to transform (Rom 12:2). Related to the problem of “languages” is the brokenness of our conversations, themselves. Conversation can become a tool of destruction rather than a means of transformation. We Christians need a “new foundational language” in which to communicate the kerygma. This language is capable not only of communicating meanings and values that are faithful to the Christian message, but it is also capable of healing the very conversations we have by healing “the conversation that we are.” This article suggests how we Christians can learn a new foundational language by unfolding the radical consequences of our Trinitarian belief.

Background. Healthcare simulations are used at most academic facilities to improve knowledge and performance on critical and key concepts and can also be used to enhance competency and teamwork. Group simulation scenarios often have individual team leaders, but these scenarios require a team to work together to efficiently care for the patient. Escape rooms can be utilized in healthcare as a fun educational activity to encourage teams to work together and think creatively to solve puzzles and challenges. One advantage of this type of activity in a healthcare setting is to dissolve any hierarchy amongst the team and build the confidence of novice or more passive participants. Escape rooms in a healthcare setting do not have to be medically themed to be effective, and rooms can be set up with minimal equipment. Aim. This article addresses the detailed steps required to set up a healthcare themed escape room that has been shown to work well. It is applicable to healthcare professionals and can be adapted for non-healthcare workers. Method. Based on the Escape Room video games and social activity phenomenon, teams compete to solve content-specific challenges to attain pieces of the final puzzle set forth by the instructors. Traditional quiz-type exercises, pictograms, and procedural based activities comprise the puzzles of the game. The first team to obtain all pieces of the final clue and put them together in the correct order in the shortest amount of time is deemed the winner. Gameplay is designed to conclude in approximately 20 minutes. Results and Conclusion. This game mimics interdisciplinary teamwork environments. Participating in interactive collaborative learning environments enhances the overall learning experience, allowing learners to apply knowledge.

The water-quality effects of low-density rural land-use activities are understudied but important because of large rural land coverage. We review and synthesize spatially extensive studies of oligotrophic mountain streams in the rural Southern Appalachian Mountains, concluding that rural land-use activities significantly degrade water quality through altered and mostly enhanced landscape-stream connections, despite high forest retention. Some connections (insolation, organic inputs, root-channel interactions, stream-field connectivity, individual landowner discharges) are controlled by near-stream land-use activities, whereas others (reduced nitrogen uptake and cycling, enhanced biological nitrogen fixation, nutrient subsidy, runoff from compacted soils, road runoff delivery) are controlled by basin-wide land use. These connections merge to alter basal resources and shift fish, salamander, and invertebrate assemblages toward species tolerant of higher turbidity and summer temperatures and those more competitive in mesotrophic systems. Rural water quality problems could be mitigated substantially with well-known best management practices, raising socioecological governance questions about best management practice adoption. National Science Foundation through the LTER program [DEB-1637522] Published version Thomas Prebyl created the land cover map. The Coweeta LTER and Coweeta Hydrologic Laboratory technicians, students, and investigators who worked on the synthesized projects are too numerous to name, but we thank all of them for their help. Jason Meador and Kelder Monar from Mainspring Conservation Trust provided input about their conservation programs, such as Shade Your Stream. Fred Benfield, John Maerz, Cathy Pringle, and Paul Bolstad helped conceptualize and frame this synthesis. This work was supported by multiple grants from the National Science Foundation through the LTER program, the last of which was grant no. DEB-1637522. Public domain – authored by a U.S. government employee

Liver transplantation is hampered by a severe shortage of donor organs. Normothermic machine perfusion (NMP) of donor livers allows dynamic preservation in addition to viability assessment before transplantation. Little is known about the injury and repair mechanisms induced during NMP. To investigate these mechanisms, we examined gene and protein expression changes in a cohort of discarded human livers, stratified by hepatocellular function, during NMP. Six human livers acquired through donation after circulatory death (DCD) underwent 12 h of NMP. Of the six livers, three met predefined criteria for adequate hepatocellular function. We applied transcriptomic profiling and protein analysis to evaluate temporal changes in gene expression during NMP between functional and nonfunctional livers. Principal component analysis segregated the two groups and distinguished the various perfusion time points. Transcriptomic analysis of biopsies from functional livers indicated robust activation of innate immunity after 3 h of NMP followed by enrichment of prorepair and prosurvival mechanisms. Nonfunctional livers demonstrated delayed and persistent enrichment of markers of innate immunity. Functional livers demonstrated effective induction of autophagy, a cellular repair and homeostasis pathway, in contrast to nonfunctional livers. In conclusion, NMP of discarded DCD human livers results in innate immune-mediated injury, while also activating autophagy, a presumed mechanism for support of cellular repair. More pronounced activation of autophagy was seen in livers that demonstrated adequate hepatocellular function. NEW & NOTEWORTHY We demonstrate that ischemia-reperfusion injury occurs in all livers during NMP, though there are notable differences in gene expression between functional and nonfunctional livers. We further demonstrate that activation of the liver’s repair and homeostasis mechanisms through autophagy plays a vital role in the graft’s response to injury and may impact liver function. These findings indicate that liver autophagy might be a key therapeutic target for rehabilitating the function of severely injured or untransplantable livers.

During the immediate postnatal (PN) period, the liver, with its role in energy metabolism and macromolecule synthesis, plays a central role in the perinatal transition. Using RNA microarrays and several complementary computational analyses, we characterized changes in hepatic gene expression in the rat across a developmental period starting with the late gestation fetus (embryonic day 21), and including 30 min PN, 4 h PN, 12 h PN, 1 day PN, and 1 week after birth. Following subtle changes in gene expression at the earliest PN time point, there were marked changes that occurred between 4 and 12 h after birth. These reflected changes in multiple metabolic pathways, with expression of enzymes involved in glycolysis and cholesterol synthesis showing the greatest change. Over 50% of nuclear-encoded mitochondrial genes changed in the first 7 days of PN life, with 25% changing within the first 24 h. We also observed changes coinciding with a transient period of synchronous hepatocyte proliferation that we had observed previously, which occurs during the first PN week. Analysis for upstream regulators of gene expression indicated multiple initiating factors, including cell stress, hormones, and cytokines. Also implicated were multiple canonical transcription factor networks. We conclude that changes in gene expression during the early phases of the perinatal transition involve a complex, choreographed network of signaling pathways that respond to a variety of environmental stimuli. This transcriptomic response during the immediate PN period reflects a complex metabolic adaptive response that incorporates a panoply of signaling pathways and transcriptional regulators.

Mutations in TP53 occur commonly in the majority of human tumors and confer aggressive tumor phenotypes, including metastasis and therapy resistance. CB002 and structural-analogs restore p53 signaling in tumors with mutant-p53 but we find that unlike other xanthines such as caffeine, pentoxifylline, and theophylline, they do not deregulate the G2 checkpoint. Novel CB002-analogs induce pro-apoptotic Noxa protein in an ATF3/4-dependent manner, whereas caffeine, pentoxifylline, and theophylline do not. By contrast to caffeine, CB002-analogs target an S-phase checkpoint associated with increased p-RPA/RPA2, p-ATR, decreased Cyclin A, p-histone H3 expression, and downregulation of essential proteins in DNA-synthesis and DNA-repair. CB002-analog #4 enhances cell death, and decreases Ki-67 in patient-derived tumor-organoids without toxicity to normal human cells. Preliminary in vivo studies demonstrate anti-tumor efficacy in mice. Thus, a novel class of anti-cancer drugs shows the activation of p53 pathway signaling in tumors with mutated p53, and targets an S-phase checkpoint.

Endotracheal intubation can be difficult in the emergent situation, and it is important to have an appropriate backup strategy. Supraglottic airway devices have provided an alternative method for pediatric airway management that is relatively easy to learn, with a high success rate. This issue reviews the use of supraglottic airway devices in pediatric patients including common devices, indications and techniques for placement, and complications associated with their use. The use of supraglottic airway devices in the patient with a difficult airway is also discussed.

Adventitious root (AR) formation is critically important in vegetative propagation through cuttings in some plants, especially woody species. However, the underlying molecular mechanisms remain elusive. Here, we report the identification of a poplar homeobox gene, PuHox52, which was induced rapidly (within 15 min) at the basal ends of stems upon cutting and played a key regulatory role in adventitious rooting. We demonstrated that overexpression of PuHox52 significantly increased the number of ARs while suppression of PuHox52 had the opposite effect. A multilayered hierarchical gene regulatory network (ML-hGRN) mediated by PuHox52 was reverse-engineered and demonstrated to govern AR formation. PuHox52 regulated AR formation through upregulation of nine hub regulators, including a jasmonate signaling pathway gene, PuMYC2, and an auxin signaling pathway gene, PuAGL12. We also identified coherent type 4 feed-forward loops within this ML-hGRN; PuHox52 repressed PuHDA9, which encodes a histone deacetylase, and led to an increase in acetylation and presumably expression of three hub regulators, PuWRKY51, PuLBD21 and PuIAA7. Our results indicate that the ML-hGRN mediated by PuHox52 governs AR formation at the basal ends of stem cuttings from poplar trees.

// Adeola O. Adebayo Michael 1, 7, * , Nagib Ahsan 2, 3, * , Valerie Zabala 1 , Heather Francois-Vaughan 1 , Stephanie Post 4 , Kate E. Brilliant 3 , Arthur R. Salomon 3, 5 , Jennifer A. Sanders 1, 6 , Philip A. Gruppuso 1, 5 1 Department of Pediatrics, Rhode Island Hospital and Brown University, Providence, RI, USA 2 Division of Biology and Medicine, Brown University, Providence, RI, USA 3 Center for Cancer Research Development, Proteomics Core Facility, Rhode Island Hospital, Providence, RI, USA 4 Department of Environmental and Evolutionary Biology, Brown University, Providence, RI, USA 5 Department of Molecular Biology, Cell Biology and Biochemistry, Brown University, Providence, RI, USA 6 Department of Pathology and Laboratory Medicine, Brown University, Providence, RI, USA 7 Current address: Department of Pathology, University of Pittsburgh, Pittsburgh, PA, USA * These authors contributed equally to this work Correspondence to: Philip A. Gruppuso, email: Philip_Gruppuso@brown.edu Keywords: hepatocellular carcinoma, liver, microdissection, proteomics, pre-neoplasia Received: December 22, 2016 Accepted: January 27, 2017 Published: February 09, 2017 ABSTRACT We have shown previously that rapamycin, the canonical inhibitor of the mechanistic target of rapamycin (mTOR) complex 1, markedly inhibits the growth of focal lesions in the resistant hepatocyte (Solt-Farber) model of hepatocellular carcinoma (HCC) in the rat. In the present study, we characterized the proteome of persistent, pre-neoplastic focal lesions in this model. One group was administered rapamycin by subcutaneous pellet for 3 weeks following partial hepatectomy and euthanized 4 weeks after the cessation of rapamycin. A second group received placebo pellets. Results were compared to unmanipulated control animals and to animals that underwent an incomplete Solt-Farber protocol to activate hepatic progenitor cells. Regions of formalin-fixed, paraffin-embedded tissue were obtained by laser capture microdissection (LCM). Proteomic analysis yielded 11,070 unique peptides representing 2,227 proteins. Quantitation of the peptides showed increased abundance of known HCC markers (e.g., glutathione S-transferase-P, epoxide hydrolase, 6 others) and potential markers (e.g., aflatoxin aldehyde reductase, glucose 6-phosphate dehydrogenase, 10 others) in foci from placebo-treated and rapamycin-treated rats. Peptides derived from cytochrome P450 enzymes were generally reduced. Comparisons of the rapamycin samples to normal liver and to the progenitor cell model indicated that rapamycin attenuated a loss of differentiation relative to placebo. We conclude that early administration of rapamycin in the Solt-Farber model not only inhibits the growth of pre-neoplastic foci but also attenuates the loss of differentiated function. In addition, we have demonstrated that the combination of LCM and mass spectrometry-based proteomics is an effective approach to characterize focal liver lesions.

This chapter explores mathematics education for students with mathematical difficulties (MD) and disabilities. Academic achievement measures have remained stagnant for this student population over the past 20 years (NAEP, 2013). The authors highlight Multi-Tiered System of Support and evidence-based strategies as a means to address the unique needs of students with disabilities within inclusion and general education contexts. Common characteristics of students with MD are challenges with working memory, number sense, symbols, basic fact computational fluency, word problem solving, and self-regulation. Educators can apply these specific recommendations to enhance mathematics instruction to address the critical factors for academic success for all students, but specifically students in special education or with MD. In order to implement these evidence-based strategies and ensure specially designed instruction is being provided, co-teaching models are reviewed as one way to provide instructional support in an inclusive setting.

Septic arthritis and osteomyelitis in pediatric patients represent true emergencies, and can quickly threaten life and limb. A high index of suspicion should be maintained, as these conditions often present with a subacute course of illness and vague signs and symptoms. Septic arthritis and osteomyelitis can occur concurrently, so suspicion for one should also prompt investigation for the other. The diagnostic evaluation should include blood work as well as samples from the infected joint or bone for culture. Management with antibiotics is a standard approach, but the duration of antibiotic therapy is controversial. This issue reviews the current literature and provides an evidence-based approach for the evaluation and management of pediatric patients with septic arthritis and osteomyelitis.

Limited nutrient availability is a cause of intrauterine growth restriction (IUGR), a condition that has important implications for the well being of the offspring. Using the established IUGR model of maternal fasting in the rat, we investigated mechanisms that control gene expression and mRNA translation in late-gestation fetal liver. Maternal fasting for 48 h during the last one-third of gestation was associated with a 10–15% reduction in fetal body weight and a disproportionate one-third reduction in total fetal liver protein. The fetal liver transcriptome showed only subtle changes consistent with reduced cell proliferation and enhanced differentiation in IUGR. Effects on the transcriptome could not be attributed to specific transcription factors. We purified translating polysomes to profile the population of mRNAs undergoing active translation. Microarray analysis of the fetal liver translatome indicated a global reduction of translation. The only targeted effect was enhanced translation of mitochondrial ribosomal proteins in IUGR, consistent with enhanced mitochondrial biogenesis. There was no evidence for attenuated signaling through the mammalian target of rapamycin (mTOR). Western blot analysis showed no changes in fetal liver mTOR signaling. However, eukaryotic initiation factor 2α (eIF2α) phosphorylation was increased in livers from IUGR fetuses, consistent with a role in global translation control. Our data indicate that IUGR-associated changes in hepatic gene expression and mRNA translation likely involve a network of complex regulatory mechanisms, some of which are novel and distinct from those that mediate the response of the liver to nutrient restriction in the adult rat.

Background Chest radiography (CXR) is the test of choice for diagnosing pneumonia. Lung ultrasonography (LUS) has been shown to be accurate for diagnosing pneumonia in children and may be an alternative to CXR. Our objective was to determine the feasibility and safety of substituting LUS for CXR when evaluating children suspected of having pneumonia. Methods We conducted a randomized control trial comparing LUS with CXR in 191 children from birth to 21 years of age suspected of having pneumonia in an ED. Patients in the investigational arm underwent LUS. If there was clinical uncertainty after ultrasonography, physicians had the option to perform CXR. Patients in the control arm underwent sequential imaging with CXR followed by LUS. The primary outcome was the rate of CXR reduction; secondary outcomes were missed pneumonia, subsequent unscheduled health-care visits, and adverse events between the investigational and control arms. Results There was a 38.8% reduction (95% CI, 30.0%-48.9%) in CXR among investigational subjects compared with no reduction (95% CI, 0.0%-3.6%) in the control group. Novice and experienced physician-sonologists achieved 30.0% and 60.6% reduction in CXR use, respectively. There were no cases of missed pneumonia among all study participants (investigational arm, 0.0%: 95% CI, 0.0%-2.9%; control arm, 0.0%: 95% CI, 0.0%-3.0%), or differences in adverse events, or subsequent unscheduled health-care visits between arms. Conclusions It may be feasible and safe to substitute LUS for CXR when evaluating children suspected of having pneumonia with no missed cases of pneumonia or increase in rates of adverse events. Trial Registry ClinicalTrials.gov; No.: NCT01654887; URL: www.clinicaltrials.gov

The liver serves a spectrum of essential metabolic and synthetic functions that are required for the transition from fetal to postnatal life. Processes essential to the attainment of adequate liver mass and function during fetal life include cell lineage specification early in development, enzymic and other functional modes of differentiation throughout gestation, and ongoing cell proliferation to achieve adequate liver mass. Available data in laboratory rodents indicate that the signaling networks governing these processes in the fetus differ from those that can sustain liver function and mass in the adult. More specifically, fetal hepatocytes may develop independent of key mitogenic signaling pathways, including those involving the Erk mitogen-activated protein kinases MAPK1/3 and the mechanistic target of rapamycin (mTOR). In addition, the fetal liver is subject to environmental influences that, through epigenetic mechanisms, can have sustained effects on function and, by extension, contribute to the developmental origin of adult metabolic disease. Finally, the mitogen-independent phenotype of rat fetal hepatocytes in late gestation makes these cells suitable for cell-based therapy of liver injury. In the aggregate, studies on the mechanisms governing fetal liver development have implications not only for the perinatal metabolic transition but also for the prevention and treatment of liver disorders throughout the lifespan.

The 2019 coronavirus disease (COVID-19) has not appeared to affect children as severely as adults. However, approximately 1 month after the COVID-19 peak in New York City in April 2020, cases of children with prolonged fevers abruptly developing inflammatory shock-like states have been reported in Western Europe and the United States. This case series describes four previously healthy children with COVID-19 infection confirmed by serologic antibody testing, but negative by nasopharyngeal RT-PCR swab, presenting to the Pediatric Emergency Department (PED) with prolonged fever (5 or more days) and abrupt onset of hemodynamic instability with elevated serologic inflammatory markers and cytokine levels (IL-6, IL-8 and TNF-α). Emergency physicians must maintain a high clinical suspicion for this COVID-19 associated post-infectious cytokine release syndrome, with features that overlap with Kawasaki Disease (KD) and Toxic Shock Syndrome (TSS) in children with recent or current COVID-19 infection, as patients can decompensate quickly., Highlights • COVID-19 post-infectious cytokine release syndrome is a novel disease in children. • This syndrome has similar features as Kawasaki Disease and Toxic Shock Syndrome. • Features include prolonged fever, gastrointestinal symptoms with or without rash.. • These patients decompensate quickly and require admission to monitor for stability

The study investigated dental hygienists’ scope of services and level of satisfaction as well as their awareness and support to the existing and proposed oral health workforce models: expanded function dental auxiliary (EFDA), dental therapist (DT), and advanced dental hygiene practitioner (ADHP). The study sample consisted of all 676 dental hygienists from Cuyahoga County, Ohio. Data were collected by a self-administered mail questionnaire that assessed hygienists’ scope of services, levels of satisfaction with the services, and their awareness as well as support for workforce models; the last two were assessed on a scale of 1–10. The effective response rate to the survey was 26 %. Respondents’ average ratings for the knowledge levels for DT, ADHP, and EFDA were as follows: 2.8 ± 2.6, 4.0 ± 3.4, and 8.1 ± 2.6. Hygienists were most supportive of the EFDAs (7.7 ± 2.9), followed by ADHP (7.0 ± 3.4), and DT (4.0 ± 3.4). Findings indicate a need to improve respondents’ awareness of the dental therapist position.

Pediatric skin conditions are variable and can be confusing for practitioners. This chapter covers various topics including tickborne rashes, erysipelas, impetigo, tinea infections, urticaria, burns, abscesses, herpetic infections, scabies, and pityriasis rosea.

Although group A Streptococcus (GAS) pharyngitis is the most common cause of bacterial pharyngitis in children and adolescents, many viral and bacterial infections mimic the symptoms of GAS pharyngitis. Emergency clinicians must recognize the symptomatology of GAS pharyngitis and use appropriate means of diagnosis and treatment to promote good antibiotic stewardship. This issue reviews the signs and symptoms of GAS pharyngitis, as well as associated complications, and provides recommendations for appropriate treatment that focuses on reducing the severity and duration of symptoms, reducing the incidence of nonsuppurative complications, and reducing transmission.

Background The limited availability of donor organs has led to a search for alternatives to liver transplantation to restore liver function and bridge patients to transplantation. We have shown that the proliferation of late gestation (embryonic day 19) fetal rat hepatocytes is mitogen-independent and that mechanisms regulating mRNA translation, cell cycle progression, and gene expression differ from those of adult rat hepatocytes. In the present study, we investigated whether E19 fetal hepatocytes can engraft and repopulate an injured adult liver. Methods Fetal hepatocytes were isolated using a monoclonal antibody against a hepatic surface protein, leucine amino peptidase (LAP). LAP+ and LAP- fractions were analyzed by immunofluorescence and microarray. Immunopurified E19 liver cells from DPPIV+ rats were transplanted via splenic injection into partial hepatectomized DPPIV- rats that had been pretreated with mitomycin C. Results More than a third of LAP+ fetal hepatocytes expressed ductal markers. Transcriptomic analysis revealed that these dual-expressing cells represent a population of less well-differentiated hepatocytes. Upon transplantation, LAP+ late gestation fetal hepatocytes formed hepatic, endothelial, and ductal colonies within 1 month. By 10 months, colonies derived from LAP+ cells increased so that up to 35% of the liver was repopulated by donor-derived cells. Conclusions Late gestation fetal hepatocytes, despite being far along in the differentiation process, possess the capacity for extensive liver repopulation. This is likely related to the unexpected presence of a significant proportion of hepatocyte marker-positive cells maintaining a less well-differentiated phenotype.

Traumatic wounds and lacerations are common pediatric presenting complaints to emergency departments. Although there is a large body of literature on wound care, many emergency clinicians base management of wounds on theories and techniques that have been passed down, so controversial, conflicting, and unfounded recommendations are prevalent. This issue reviews evidence-based recommendations for wound care and management, including wound cleansing and irrigation, anxiolysis/sedation techniques, closure methods, and post-repair wound care.

Obesity during childhood and beyond may have its origins during fetal or early postnatal life. At present, there are no suitable in vivo experimental models to study factors that modulate or perturb human fetal white adipose tissue (WAT) expansion, remodeling, development, adipogenesis, angiogenesis, or epigenetics. We have developed such a model. It involves the xenotransplantation of midgestation human WAT into the renal subcapsular space of immunocompromised SCID-beige mice. After an initial latency period of approximately 2 weeks, the tissue begins expanding. The xenografts are healthy and show robust expansion and angiogenesis for at least 2 months following transplantation. Data and cell size and gene expression are consistent with active angiogenesis. The xenografts maintain the expression of genes associated with differentiated adipocyte function. In contrast to the fetal tissue, adult human WAT does not engraft. The long-term viability and phenotypic maintenance of fetal adipose tissue following xenotransplantation may be a function of its autonomous high rates of adipogenesis and angiogenesis. Through the manipulation of the host mice, this model system offers the opportunity to study the mechanisms by which nutrients and other environmental factors affect human adipose tissue development and biology.

Many diseases that manifest throughout the lifetime are influenced by factors affecting fetal development. Fetal exposure to xenobiotics, in particular, may influence the development of adult diseases. Established animal models provide systems for characterizing both developmental biology and developmental toxicology. However, animal model systems do not allow researchers to assess the mechanistic effects of toxicants on developing human tissue. Human fetal tissue xenotransplantation models have recently been implemented to provide human-relevant mechanistic data on the many tissue-level functions that may be affected by fetal exposure to toxicants. This review describes the development of human fetal tissue xenotransplant models for testis, prostate, lung, liver, and adipose tissue, aimed at studying the effects of xenobiotics on tissue development, including implications for testicular dysgenesis, prostate disease, lung disease, and metabolic syndrome. The mechanistic data obtained from these models can complement data from epidemiology, traditional animal models, and in vitro studies to quantify the risks of toxicant exposures during human development.