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Background: Inflammation is a sequela of cardiovascular critical illness and a risk factor for mortality. Objectives: This study aimed to evaluate the association between white blood cell count (WBC) and mortality in a broad population of patients admitted to the cardiac intensive care unit (CICU). Methods: This retrospective cohort study included patients admitted to the Mayo Clinic CICU between 2007 and 2018. We analyzed WBC as a continuous variable and then categorized WBC as low (<4.0 × 103/mL), normal (≥4.0 to <11.0 × 103/mL), high (≥11.0 to <22.0 × 103/mL), or very high (≥22.0 × 103/mL). The association between WBC and in-hospital mortality was evaluated using multivariable logistic regression and random forest models. Results: We included 11,699 patients with a median age of 69.3 years (37.6% females). Median WBC was 9.6 (IQR: 7.4-12.7). Mortality was higher in the low (10.5%), high (12.0%), and very high (33.3%) WBC groups relative to the normal WBC group (5.3%). A rising WBC was incrementally associated with higher in-hospital mortality after adjustment (AICc adjusted OR: 1.03 [95% CI: 1.02-1.04] per 1 × 103 increase in WBC). After adjustment, only the high (AICc adjusted OR: 1.37 [95% CI: 1.15-1.64]) and very high (AICc adjusted OR: 1.99 [1.47-2.71]) WBC groups remained associated with increased risk of in-hospital mortality. Conclusions: Leukocytosis is associated with an increased mortality risk in a diverse cohort of CICU patients. This readily available marker of systemic inflammation may be useful for risk stratification within the increasingly complex CICU patient population.
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The connections between the five facets of mindfulness, well-being, and mental health across the lifespan have traditionally been investigated using variable-centered approaches. Less research has investigated these relationships from a person-centered, profile-based approach. In this work, we aimed to identify the profiles of mindfulness in a Canadian lifespan sample (14 to 90 years of age) and investigate how these profiles compared on age, well-being, and mental health. An age- and gender-balanced sample of 1,600 participants completed a questionnaire that measured the five facets of mindfulness; life satisfaction; existential well-being; and anxiety, depression, and stress symptoms. A latent profile analysis was conducted. Five profiles based on the five-facet model of mindfulness were identified: high mindfulness, moderate mindfulness, low mindfulness, nonjudgmentally aware, and judgmentally observing. The 3-step approach to profile comparisons was used to assess age, mental health, and well-being differences across the profiles. Those in the high mindfulness and nonjudgmentally aware profiles were generally older, while the judgmentally observing profile contained younger individuals. Those in the high mindfulness and nonjudgmentally aware profiles reported the greatest mental health and well-being. Conversely, those in the low mindfulness and judgmentally observing profiles had worse mental health than the other profiles. The moderate mindfulness profile was situated between these profile groups on age, mental health, and well-being outcomes. This pattern of results has implications for mindfulness-based intervention research and practice to better account for heterogeneity in mindfulness and better support well-being across the lifespan.
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Many plant species, particularly legumes, protect themselves with saponins. Previously, a correlation was observed between levels of oleanolic acid-derived saponins, such as hederagenin-derived compounds, in the legume Medicago truncatula and caterpillar deterrence. Using concentrations that reflect the foliar levels of hederagenin-type saponins, the sapogenin hederagenin was not toxic to 4th instar caterpillars of the cabbage looper Trichoplusia ni nor did it act as a feeding deterrent. Female caterpillars consumed more diet than males, presumably to obtain the additional nutrients required for oogenesis, and are, thus, exposed to higher hederagenin levels. When fed the hederagenin diet, male caterpillars expressed genes encoding trypsin-like proteins (LOC113500509, LOC113501951, LOC113501953, LOC113501966, LOC113501965, LOC113499659, LOC113501950, LOC113501948, LOC113501957, LOC113501962, LOC113497819, LOC113501946, LOC113503910) as well as stress-responsive (LOC113503484, LOC113505107) proteins and cytochrome P450 6B2-like (LOC113493761) at higher levels than females. In comparison, female caterpillars expressed higher levels of cytochrome P450 6B7-like (LOC113492289). Bioinformatic tools predict that cytochrome P450s could catalyze the oxygenation of hederagenin which would increase the hydrophilicity of the compound. Expression of a Major Facilitator Subfamily (MFS) transporter (LOC113492899) showed a hederagenin dose-dependent increase in gene expression suggesting that this transporter may be involved in sapogenin efflux. These sex-related differences in feeding and detoxification should be taken into consideration in insecticide evaluations to minimize pesticide resistance.
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Moths , Oleanolic Acid , Oleanolic Acid/analogs & derivatives , Saponins , Transcriptome , Animals , Female , Male , Saponins/metabolism , Saponins/chemistry , Oleanolic Acid/metabolism , Oleanolic Acid/pharmacology , Oleanolic Acid/chemistry , Moths/drug effects , Moths/physiology , Moths/genetics , Transcriptome/drug effects , Larva/drug effects , Larva/genetics , Sex CharacteristicsABSTRACT
BACKGROUND: Integrated Pest Management (IPM) seeks to combine multiple management strategies for optimal pest control. One method that is successfully employed in IPM is the use of beneficial organisms. However, in severe circumstances when pest insects exceed threshold limits, insecticides may still need to be implemented. Thus, understanding the effects of insecticides on biocontrol agents, such as parasitoid wasps, is paramount to ensure sustainable agroecosystems. Sublethal effects of the bioinsecticide spinosyn, a mixture of the bacterial Saccharopolyspora spinosa (Mertz and Yao) fermentation products spinosyn A and D, on eggs of Trichoplusia ni (Hübner), a cruciferous crop pest, and its egg parasitoid Trichogramma brassicae (Bezdenko) was investigated. RESULTS: The LC50 for spinosyn A and D (dissolved in ethanol) on T. ni eggs is 54 ng mL-1. Transcriptomics on caterpillars (1st and 3rd instars) that hatched from eggs treated with sublethal concentrations of spinosyn identified the upregulation of several genes encoding proteins that may be involved in insecticide resistance including detoxification enzymes, such as cytochrome P450s, glutathione S-transferases and esterases. Sublethal T. ni egg treatments did not affect parasitoid emergence, however, there was a marked increase in the size of T. brassicae hind tibia and wings that emerged from spinosyn-treated eggs. CONCLUSIONS: For the caterpillar, treatment of eggs with sublethal concentrations of spinosyn may induce insecticide resistance mechanisms. For the parasitoids, their increased size when reared in spinosyn-treated eggs suggests that the emerged wasps may have higher performance. © 2024 The Authors. Pest Management Science published by John Wiley & Sons Ltd on behalf of Society of Chemical Industry.
Subject(s)
Insecticides , Larva , Macrolides , Moths , Ovum , Wasps , Animals , Moths/parasitology , Moths/drug effects , Wasps/drug effects , Wasps/physiology , Ovum/drug effects , Ovum/parasitology , Insecticides/pharmacology , Macrolides/pharmacology , Larva/growth & development , Larva/drug effects , Pest Control, BiologicalABSTRACT
This study investigated how youth attachment anxiety and avoidance are associated with informant discrepancies of intrafamilial aggression within families where youth have clinically significant mental health challenges (N = 510 youth-parent dyads). Using polynomial regressions, we tested whether youth attachment avoidance and anxiety moderated the absolute magnitude of the association between youth- and parent-reports of aggression toward each other. Furthermore, difference scores were computed to test whether youth attachment was associated with the direction of youths' reports of the frequency of aggression relative to parents (i.e., did youth under- or over-report). Dyads' reports of youth-to-parent aggression were more strongly related at high than low levels of attachment anxiety. Results also revealed that youth attachment anxiety was associated with youth over-reporting of youth-to-parent and parent-to-youth aggression (relative to parents), whereas attachment avoidance was associated with youth over-reporting parent-to-youth aggression (relative to parents). These findings highlight the importance of understanding the source of informant discrepancies in social-emotional development and family functioning.
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ABSTRACT: Objective: To identify and describe characteristics of patients with sepsis who could be treated with minimally invasive sepsis (MIS) approach without intensive care unit (ICU) admission and to develop a prediction model to select candidates for MIS approach. Methods: A secondary analysis of the electronic database of patients with sepsis at Mayo Clinic, Rochester, MN. Candidates for the MIS approach were adults with septic shock and less than 48 hours of ICU stay, who did not require advanced respiratory support and were alive at hospital discharge. Comparison group consisted of septic shock patients with an ICU stay of more than 48 hours without advanced respiratory support at the time of ICU admission. Results: Of 1795 medical ICU admissions, 106 patients (6%) met MIS approach criteria. Predictive variables (age >65 years, oxygen flow >4 L/min, temperature <37°C, creatinine >1.6 mg/dL, lactate >3 mmol/L, white blood cells >15 × 10 9 /L, heart rate >100 beats/min, and respiration rate >25 breaths/min) selected through logistic regression were translated into an 8-point score. Model discrimination yielded the area under the receiver operating characteristic curve of 79% and was well fitted (Hosmer-Lemeshow P = 0.94) and calibrated. The MIS score cutoff of 3 resulted in a model odds ratio of 0.15 (95% confidence interval, 0.08-0.28) and a negative predictive value of 91% (95% confidence interval, 88.69-92.92). Conclusions: This study identifies a subset of low-risk septic shock patients who can potentially be managed outside the ICU. Once validated in an independent, prospective sample our prediction model can be used to identify candidates for MIS approach.
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Sepsis , Shock, Septic , Adult , Humans , Aged , Prospective Studies , Retrospective Studies , Intensive Care Units , World Health Organization , Prognosis , ROC CurveABSTRACT
Epithelial-mesenchymal signaling in the gastrointestinal system is vital in establishing regional identity during organogenesis and maintaining adult stem cell homeostasis. Although recent work has demonstrated that Wnt ligands expressed by mesenchymal cells are required during gastrointestinal development and stem cell homeostasis, epigenetic mechanisms driving spatiotemporal control of crosstalk remain unknown. Here, we demonstrate that gastrointestinal mesenchymal cells control epithelial fate and function through Polycomb Repressive Complex 2-mediated chromatin bivalency. We find that while key lineage-determining genes possess tissue-specific chromatin accessibility, Polycomb Repressive Complex 2 controls Wnt expression in mesenchymal cells without altering accessibility. We show that reduction of mesenchymal Wnt secretion rescues gastrointestinal fate and proliferation defects caused by Polycomb Repressive Complex 2 loss. We demonstrate that mesenchymal Polycomb Repressive Complex 2 also regulates niche signals to maintain stem cell function in the adult intestine. Our results highlight a broadly permissive chromatin architecture underlying regionalization in mesenchymal cells, then demonstrate further how chromatin architecture in niches can influence the fate and function of neighboring cells.
Subject(s)
Gastrointestinal Tract , Intestines , Gastrointestinal Tract/metabolism , Polycomb Repressive Complex 2/metabolism , Chromatin/genetics , Epigenesis, Genetic , Cell Differentiation/geneticsABSTRACT
Background: Delirium is common in patients with severe coronavirus disease-19 (COVID-19). The purpose of our study was to determine whether severe COVID-19 is an independent risk factor for the development of delirium in patients treated in the intensive care unit (ICU). Methods: This prospective observational cohort study involved 162 critically ill patients admitted to a multidisciplinary ICU during 2019 and 2020. A validated screening tool was used to diagnose delirium. Multiple delirium risk factors were collected daily including clinical characteristics, hospital course, lab values, vital signs, surgical exposure, drug exposure, and COVID-19 characteristics. After univariate analysis, a multivariate logistic regression analysis was performed to determine independent risk factors associated with the development of delirium. Results: In our study population, 50 (31%) patients developed delirium. A total of 39 (24.1%) tested positive for COVID-19. Initial analysis showed COVID-19 to be more prevalent in those patients that developed delirium (40% vs. 17%; P = 0.003). Multivariate analysis showed opioid use (odds ratio [OR]: 24 [95% confidence intervals (CI): 16-27]; P ≤ 0.001), benzodiazepine use (OR: 23 [95% CI: 16-63] P = 0.001), and estimated mortality based on acute physiology and chronic health evaluation IV score (OR: 1.04 [95% CI: 1.01-1.07] P = 0.002) to be independently associated with delirium development. COVID-19 (OR: 1.44 [95% CI: 0.13-10.6]; P = 0.7) was not found to be associated with delirium. Conclusion: Delirium is prevalent in critically ill patients admitted to the ICU, including those with COVID-19. However, after adjustment for important covariates, we found in this cohort that COVID-19 was not an independent risk factor for delirium.
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BACKGROUND: Neuroinflammation causing disruption of the blood-brain barrier and immune cell extravasation into the brain parenchyma may cause delirium; however, knowledge of the exact pathophysiologic mechanism remains incomplete. The purpose of our study was to determine whether cytokine profiles differ depending on whether delirium occurs in the setting of sepsis, coronavirus disease 2019 (COVID-19), or recent surgery. METHODS: This prospective observational cohort study involved 119 critically ill patients admitted to a multidisciplinary intensive care unit (ICU) during 2019 and 2020. Delirium was identified using the validated confusion assessment method for the ICU. Multiple delirium risk factors were collected daily including clinical characteristics, hospital course, lab values, vital signs, surgical exposure, drug exposure, and COVID-19 characteristics. Serums samples were collected within 12 hours of ICU admission and cytokine levels were measured. RESULTS: The following proinflammatory cytokines were elevated in our delirium population: tumor necrosis factor (TNF)-α, interleukin (IL)-6, IL-18, C-C motif ligand (CCL) 2, CCL3, C-X-C motif chemokine ligand (CXCL)1, CXCL10, IL-8, IL-1 receptor antagonist, and IL-10. Analysis of relative cytokine levels in those patients that developed delirium in the setting of sepsis, COVID-19, and recent surgery showed elevations of CCL2, CXCL10, and TNF-α in both the sepsis and COVID-19 group in comparison to the postsurgical population. In the postsurgical group, granulocyte colony-stimulating factor was elevated and CXCL10 was decreased relative to the opposing groups. CONCLUSIONS: We identify several cytokines and precipitating factors known to be associated with delirium. However, our study suggests that the cytokine profile associated with delirium is variable and contingent upon delirium precipitating factors.
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OBJECTIVES: The pathophysiology of delirium is complex and incompletely understood. Inflammation is hypothesized to be integral to its development due to effects on blood brain barrier integrity, facilitation of leukocyte extravasation into brain parenchyma, and propagation of neuroinflammation. Septic shock is the prototypical condition associated with ICU delirium; however, the relative contribution of resultant hypotension and systemic inflammation to the development of delirium is unknown. DESIGN: This was a prospective exploratory study. SETTING: A multidisciplinary ICU at an academic medical center in Phoenix, AZ. PATIENTS: Critically ill patients older than or equal to 18 years old admitted to the ICU. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Screening for delirium was performed using the Confusion Assessment Method for the ICU tool. The levels of C-C motif ligand 2 (CCL2), C-C motif ligand 3, C-X-C motif chemokine ligand 1, C-X-C motif chemokine ligand 10, and interleukin-8 were measured in serum samples obtained within 12 hours of ICU admission. Univariate and multivariate analyses were performed to assess the association of delirium with patient data pertaining to hospital course, laboratory values, vital signs, medication administration, and levels of the aforementioned chemokines. Forty-one of 119 patients (34.5%) in the study cohort developed ICU delirium. Each chemokine studied was associated with delirium on univariate analyses; however, CCL2 was the only chemokine found to be independently associated with the development of delirium on multivariable analysis. The association of increased CCL2 levels with delirium remained robust in various models controlling for age, presence of shock, Sequential Organ Failure Assessment score, Acute Physiology and Chronic Health Evaluation IV score, mean arterial pressure at presentation, lowest mean arterial pressure, and total opioid, midazolam, propofol, and dexmedetomidine exposure. CONCLUSIONS: The demonstrated relationship between CCL2 and delirium suggests this chemokine may play a role in the development of delirium and warrants further investigation.
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Development of the gastrointestinal system occurs after gut tube closure, guided by spatial and temporal control of gene expression. However, it remains unclear what forces regulate these spatiotemporal gene expression patterns. Here we perform single-cell chromatin profiling of the primitive gut tube to reveal organ-specific chromatin patterns that reflect the anatomical patterns of distinct organs. We generate a comprehensive map of epigenomic changes throughout gut development, demonstrating that dynamic chromatin accessibility patterns associate with lineage-specific transcription factor binding events to regulate organ-specific gene expression. Additionally, we show that loss of Sox2 and Cdx2, foregut and hindgut lineage-specific transcription factors, respectively, leads to fate shifts in epigenomic patterns, linking transcription factor binding, chromatin accessibility, and lineage fate decisions in gut development. Notably, abnormal expression of Sox2 in the pancreas and intestine impairs lineage fate decisions in both development and adult homeostasis. Together, our findings define the chromatin and transcriptional mechanisms of organ identity and lineage plasticity in development and adult homeostasis.
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Chromatin , Gastrula , Adult , Chromatin/genetics , Endoderm , Epigenomics , Humans , Transcription FactorsABSTRACT
The incidence of cervical cancer has decreased in recent years due to widespread vaccination and routine screenings. It can be treated successfully, and the prognosis is also excellent if detected early. However, the 5-year survival rate for patients with stage IV cervical cancer is only 17% even with aggressive systemic chemotherapy. With the Food and Drug Administration (FDA)'s approval of immunotherapy, the prognosis has improved. We present a patient with stage IV cervical cancer who could not tolerate platinum-based chemotherapy and bevacizumab, so she was started on an immune checkpoint inhibitor, as her tumor was 100% programmed cell death ligand-1 (PD-L1) positive. She survived more than 2 years since the diagnosis of stage IV cervical cancer without any significant side effects. Based on our patient's response, the use of immune checkpoint inhibitors as a single agent needs further research and probably can be considered in patients with stage 4 cervical cancer who cannot tolerate standard chemotherapy.
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PURPOSE: To report outcomes of glaucoma drainage device (GDD) surgery based on primary or secondary glaucoma diagnosis and lens status. DESIGN: Single-center, retrospective, consecutive cohort study. METHODS: University of Florida patients aged 18 to 93 years who underwent nonvalved GDD surgery between 1996 and 2015 with a minimum of 1-year follow-up were examined. Of the 186 eyes of 186 patients enrolled, 108 had a primary glaucoma and 78 a secondary glaucoma diagnosis. Excluding 13 aphakic patients, 57 eyes were phakic and 116 pseudophakic. Mean intraocular pressure (IOP), mean number of medications, visual acuity (VA), surgical complications, and failure (IOP ≥18âmm Hg, IOP <6âmm Hg, reoperation for glaucoma, or loss of light perception) were the main outcome measures. RESULTS: No significant difference was noted in mean IOP and mean medication use (12.8â±â4.5 and 13.0â±â6.6 mm Hg on 2.0â±â1.2 and 1.5â±â1.1 medication classes, respectively), mean VA (1.08â±â0.98 and 0.94â±â0.89, respectively), failure, or numbers of complications and reoperations (Pâ>â0.05) between eyes with primary and secondary glaucomas at up to 5âyears postoperatively. Comparison of phakic and pseudophakic eyes showed a statistically significant higher success rate for the pseudophakic patient group at the ≥18âmm Hg upper limit and <6 mm Hg lower limit (Pâ=â0.01), and significantly fewer eyes required reoperation to lower IOP (6.9% vs 23%). CONCLUSIONS: GDD surgery appears equally effective for secondary glaucomas as for primary glaucomas, and has a better outcome for pseudophakic eyes than phakic eyes.
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Glaucoma Drainage Implants , Glaucoma , Cohort Studies , Follow-Up Studies , Glaucoma/surgery , Humans , Intraocular Pressure , Retrospective Studies , Treatment OutcomeABSTRACT
Radionuclide therapies have shown to be an effective treatment for certain types of cancer and other disorders. When determining the appropriate course of treatment, various factors are considered. This article discusses indications and procedures for certain radionuclide therapies including radioiodine for thyroid disorders, radioimmunotherapy, theranostics, and radioembolization for hepatocellular carcinoma.
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Radioimmunotherapy , Radioisotopes/therapeutic use , Carcinoma, Hepatocellular/diagnostic imaging , Carcinoma, Hepatocellular/radiotherapy , Humans , Iodine Radioisotopes/therapeutic use , Liver Neoplasms/diagnostic imaging , Liver Neoplasms/radiotherapy , Precision MedicineABSTRACT
PRECIS: A comparison of 186 glaucoma patients with mixed diagnoses who underwent nonvalved glaucoma drainage device (GDD) implant surgery showed similar long-term intraocular pressure (IOP), medication, and visual acuity (VA) outcomes between those with prior failed trabeculectomy surgery versus those without. PURPOSE: The purpose of this study was to evaluate whether prior failed trabeculectomy adversely affects the outcome of glaucoma tube surgery. PATIENTS AND METHODS: A total of 186 eyes of 186 patients who underwent a nonvalved GDD implant surgery by a single surgeon between 1996 and 2015 at a University practice were included. Patients were of mixed diagnoses and over 18 years old. Before the GDD surgery, 65 had a previous failed glaucoma filtering surgery and 121 had no prior glaucoma surgery. Demographic information, preoperative and postoperative IOP, medication, VA, and complications were collected from chart review. RESULTS: No significant difference was noted in mean IOP and mean medication use (13.0 and 12.6 mm Hg on 2.0 and 1.7 medication classes at 5 y postoperatively, respectively), mean VA and change in VA from baseline, or numbers of complications (P>0.05), between eyes that had a prior failed filtration surgery and those that had not. Kaplan-Meier plots for failure over 5 years using a lower limit of <5 mm Hg and an upper limit of ≥18, ≥15, or ≥12 mm Hg did not show a significant difference between groups. Subanalyses were performed to examine only primary glaucoma eyes and results were similar. Further group subanalyses comparing those with baseline IOP ≥25 or <25 mm Hg, age 65 and above or below 65 years and those specifically with Baerveldt 350 mm2 implants also did not show significant differences. CONCLUSION: Prior failed filtration surgery does not appear to affect the outcome of future GDD surgery.
Subject(s)
Glaucoma Drainage Implants , Glaucoma , Trabeculectomy , Adolescent , Aged , Follow-Up Studies , Glaucoma/surgery , Humans , Intraocular Pressure , Prosthesis Implantation , Retrospective Studies , Treatment OutcomeABSTRACT
OBJECTIVE: Peripherally inserted central catheters are a popular means of obtaining central venous access in critically ill patients. However, there is limited data regarding the rapidity of the peripherally inserted central catheter procedure in the presence of acute illness or obesity, both of which may impede central venous catheter placement. We aimed to determine the feasibility, safety, and duration of peripherally inserted central catheter placement in critically ill patients, including obese patients and patients in shock. METHODS: This retrospective cohort study was performed using data on 55 peripherally inserted central catheters placed in a 30-bed multidisciplinary intensive care unit in Mayo Clinic Hospital, Phoenix, Arizona. Information on the time required to complete each step of the peripherally inserted central catheter procedure, associated complications, and patient characteristics was obtained from a prospectively assembled internal quality assurance database created through random convenience sampling. RESULTS: The Median Procedure Time, beginning with the first needle puncture and ending when the procedure is complete, was 14 (interquartile range: 9-20) min. Neither critical illness nor obesity resulted in a statistically significant increase in the time required to complete the peripherally inserted central catheter procedure. Three (5.5%) minor complications were observed. CONCLUSION: Critical illness and obesity do not delay the acquisition of vascular access when placing a peripherally inserted central catheter. Concerns of delayed vascular access in critically ill patients should not deter a physician from selecting a peripherally inserted central catheter to provide vascular access when it would otherwise be appropriate.
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Catheterization, Central Venous , Catheterization, Peripheral , Intensive Care Units , Shock/therapy , Aged , Catheterization, Central Venous/adverse effects , Catheterization, Peripheral/adverse effects , Critical Illness , Databases, Factual , Feasibility Studies , Female , Humans , Male , Middle Aged , Obesity/complications , Retrospective Studies , Risk Assessment , Risk Factors , Shock/complications , Shock/diagnosis , Time FactorsABSTRACT
The gastrointestinal (GI) tract consists of a remarkable series of organs that spatially and temporally coordinate the vital process of digestion to extract key nutrients required to sustain our day-to-day functions. During development, it undergoes complex and highly specialized morphogenetic events to form functionally distinct organs. Its failure to develop properly leads to serious congenital diseases, which if left untreated are particularly devastating and often result in premature death. These GI diseases have been estimated to impact approximately 8-16 of every 10,000 newborns [1, 2]. Importantly, the clinical manifestations of these diseases are severe, with untreated cases having high mortality rates. While some disorders, such as Hirschsprung's disease, can be treated effectively with surgery, the efficacy of this management strategy is far lower for other diseases, such as necrotizing enterocolitis. Moreover, children often face complications from these surgical procedures, leading to secondary ailments. Consequently, a better understanding of gastrointestinal development is fundamental to the treatment and prevention of congenital GI maladies. This chapter will explore some of the most prevalent and biologically complex congenital diseases of the GI system, with emphasis on animal models that both elucidate their underlying causes and lay the essential groundwork for the advancement of translational medicine.
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Disease Models, Animal , Gastrointestinal Diseases/congenital , Animals , Enterocolitis, Necrotizing/congenital , Hirschsprung Disease , HumansABSTRACT
In this work, the first synthesis of poly(amidoamine) (PAMAM) dendrimers whose branches are hybridized with peptide segments (DendriPeps) is reported. The intercalation of amino acids within the branches of PAMAMs provides supplementary internal functionalities to the coronal groups. Four DendriPep prototypes are synthesized with lysine or glutamic acid as "guest" amino acids, displaying, respectively, a primary amine or a carboxyl group, on generation (G)2 and G3 PAMAMs as host scaffolds. The precise control over the number, type, and topological placement of functional groups expands the functional behavior of DendriPeps beyond current PAMAM dendrimers toward new frontiers or colloids, drug delivery vectors, and catalysis.