The protective effect of breastfeeding on febrile seizures: a systematic review with meta-analysis.

Several potential risk factors have been identified in the etiopathogenesis of febrile seizures (FS), including the type and extent of breastfeeding (BF). Given the lack of conclusive data, this study aims to systematically evaluate the evidence on the association between BF and FS. We conducted a systematic review and meta-analysis according to PRISMA guidelines. The search was conducted using descriptors for FS, BF, and formula feeding in MEDLINE, Embase, and Web of Science databases. We included observational studies that compared the incidence of FS between those who had ever breastfed and those who were formula fed. The study protocol was registered on the PROSPERO platform under the number CRD42023474906. A total of 1,893,079 participants from 8 datasets were included. Our main analysis showed no significant association of any type of BF on the incidence of FS compared with formula-fed children (OR: 0.84; CI: 0.67-1.04; I2 = 78%; Cochran's Q = 0.0001), although meta-regression showed that BF was associated with a lower incidence of FS in preterm infants. Our secondary outcome showed a significantly reduced incidence of FS in children who received BF exclusively (OR: 0.80; CI: 0.65-0.99; I2 = 70%; Cochran's Q = 0.02).    Conclusion: There was no significant reduction in the incidence of FS in those who were breastfed compared to formula feeding. However, our meta-regression analysis indicated an association between BF and a lower incidence of FS in preterm infants. Additionally, children who exclusively received BF had a significantly reduced incidence of FS. These findings should be further investigated in prospective cohorts. What is Known: • Breastfeeding can modify risk factors for febrile seizures, such as susceptibility to viral and bacterial infections, micronutrient deficiencies, and low birth weight. • However, studies have shown conflicting results regarding the impact of breastfeeding on febrile seizures. What is New: • When comparing any breastfeeding pattern with no breastfeeding, there is no significant difference in the incidence of febrile seizures. • When comparing exclusive breastfeeding with no breastfeeding, there may be a decrease in the occurrence of febrile seizures.

Allergy, asthma, and proteomics: opportunities with immediate impact.

Allergy is widely discussed by researchers due to its complex mechanism that leads to disorders and injuries, but the reason behind the allergic status remains unclear. Current treatments are insufficient to improve the patient's quality of life significantly. New technologies in scientific and technological development are emerging. For instance, the union between allergy and peptidomics and bioinformatics tools may help fill the gaps in this field, diagnosis, and treatment. In this review, we look at peptidomics and address some findings, such as target proteins or biomarkers that help better understand mechanisms that lead to inflammation, organ damage, and, consequently, poor quality of life or even death.

Photobiomodulation Reduces the Cytokine Storm Syndrome Associated with COVID-19 in the Zebrafish Model.

Although the exact mechanism of the pathogenesis of coronavirus SARS-CoV-2 (COVID-19) is not fully understood, oxidative stress and the release of pro-inflammatory cytokines have been highlighted as playing a vital role in the pathogenesis of the disease. In this sense, alternative treatments are needed to reduce the level of inflammation caused by COVID-19. Therefore, this study aimed to investigate the potential effect of red photobiomodulation (PBM) as an attractive therapy to downregulate the cytokine storm caused by COVID-19 in a zebrafish model. RT-qPCR analyses and protein-protein interaction prediction among SARS-CoV-2 and Danio rerio proteins showed that recombinant Spike protein (rSpike) was responsible for generating systemic inflammatory processes with significantly increased levels of pro-inflammatory (il1b, il6, tnfa, and nfkbiab), oxidative stress (romo1) and energy metabolism (slc2a1a and coa1) mRNA markers, with a pattern similar to those observed in COVID-19 cases in humans. On the other hand, PBM treatment was able to decrease the mRNA levels of these pro-inflammatory and oxidative stress markers compared with rSpike in various tissues, promoting an anti-inflammatory response. Conversely, PBM promotes cellular and tissue repair of injured tissues and significantly increases the survival rate of rSpike-inoculated individuals. Additionally, metabolomics analysis showed that the most-impacted metabolic pathways between PBM and the rSpike treated groups were related to steroid metabolism, immune system, and lipid metabolism. Together, our findings suggest that the inflammatory process is an incisive feature of COVID-19 and red PBM can be used as a novel therapeutic agent for COVID-19 by regulating the inflammatory response. Nevertheless, the need for more clinical trials remains, and there is a significant gap to overcome before clinical trials can commence.

Marine-Derived Penicillium purpurogenum Reduces Tumor Size and Ameliorates Inflammation in an Erlich Mice Model.

BACKGROUND: This study addresses the antitumoral properties of Penicillium purpurogenum isolated from a polluted lagoon in Northeastern Brazil. METHODS: Ethyl Acetate Extracellular Extract (EAE) was used. The metabolites were studied using direct infusion mass spectrometry. The solid Ehrlich tumor model was used for antitumor activity. Female Swiss mice were divided into groups (n = 10/group) as follows: The negative control (CTL-), treated with a phosphate buffered solution; the positive control (CTL+), treated with cyclophosphamide (25 mg/kg); extract treatments at doses of 4, 20, and 100 mg/kg; animals without tumors or treatments (Sham); and animals without tumors treated with an intermediate dose (EAE20). All treatments were performed intraperitoneally, daily, for 15 days. Subsequently, the animals were euthanized, and the tumor, lymphoid organs, and serum were used for immunological, histological, and biochemical parameter evaluations. RESULTS: The extract was rich in meroterpenoids. All doses significantly reduced tumor size, and the 20 and 100 mg/kg doses reduced tumor-associated inflammation and tumor necrosis. The extract also reduced the cellular infiltration of lymphoid organs and circulating TNF-α levels. The extract did not induce weight loss or renal and hepatic toxic changes. CONCLUSIONS: These results indicate that P. purpurogenum exhibits immunomodulatory and antitumor properties in vivo. Thus, fungal fermentation is a valid biotechnological approach to the production of antitumor agents.

Proteomics in Veterinary Medicine and Animal Science: Neglected Scientific Opportunities with Immediate Impact.

Animal/veterinary proteomics is an evolving field which holds a great promise not only for fundamental and applied discoveries regarding biology and pathology of domestic species, but can also be implemented in comparative applications of human diseases research. Experimental proteomics in domestic animals have advantages over use of rodents, such as multiple sampling in time series and availability of biological samples in sufficient volume for multiple analyses, such that both experimental and natural disease processes can be investigated. While there are certain technical limitations in the expansion of the field, they can currently be circumvented and in the future mastered with a greater participation of proteomic experts, which will in turn drive the accessibility of species-specific reagents, data volume expansion in bioinformatic databases, and increased funding. This Viewpoint highlights some comparative proteomics studies addressing important issues and encourages readers to expand their horizons of domestic animal proteomics research. It will hopefully inspire new fruitful collaborations between veterinary and animal scientists and proteomic specialists for research in these areas that can have immediate and direct impact on health, society, and the economy.

Protein Content of Cervicovaginal Fluid Is Altered During Bacterial Vaginosis.

OBJECTIVES: The aim of the study was to compare, using a proteomic approach, cervicovaginal fluid (CVF) proteins of women with bacterial vaginosis (BV) with those presenting normal microbiota. MATERIALS AND METHODS: A total of 309 reproductive-aged women were cross-sectionally enrolled. Participants were tested for vaginal candidosis, Trichomonas vaginalis, Chlamydia trachomatis, and Neisseria gonorrhoeae and excluded if positive. Vaginal microbiota was classified microscopically according to Nugent criteria in normal, intermediate, and BV. Randomly selected CVF samples of 29 women with BV and an equal number with normal microbiota were subjected to proteomic analysis. Thus, a total of 58 CVF samples were evaluated using shotgun liquid chromatography-tandem mass spectrometry in a Q-Tof PREMIER API mass spectrometer (MicroMass/Waters) for peptide detection and relative quantification. RESULTS: Of the 309 women enrolled, 63 (20.4%) were excluded after testing positive for at least one of the tested co-infections or because of low-quality samples. Microscopic classification of vaginal microbiota on the remaining 246 samples revealed that 132 women (53.6%) had normal microbiota, 33 (13.4%) had intermediate microbiota, and 81 (33.0%) had BV. Proteomic analysis of CVF of 58 randomly selected women with normal microbiota (n = 29) or BV (n = 29) successfully identified 74 proteins. In addition, the comparison of abundance of those proteins between the groups showed that the following five (6.7%) were enriched in BV: neutrophil elastase, kaliocin-1, neutrophil defensin-1, Ig lambda-2 chain C regions, and protein S100-A7. All of which have a recognized role in host's immunity. CONCLUSIONS: Exclusive finding of BV affects immunity-related CVF components of reproductive-aged women.

Evaluation of software technical quality for collecting data from patients under palliative care.

OBJECTIVES: to evaluate software technical quality for collecting data from patients under palliative care. METHODS: this is methodological technology evaluation research, according to the technical standard International Organization for Standardization/International Electrotechnical Commission 25040-2011, developed from August 2021 to August 2023. Eight nurses and eight information technology professionals participated as judges, who evaluated six quality characteristics and 23 subcharacteristics. Items that reached a percentage of agreement greater than 70% were considered suitable. RESULTS: the characteristics evaluated by nurses/information technology professionals received the following percentages of agreement, respectively: functional suitability (94%-84%); reliability (100-70%); usability (89.9-66.8%); performance efficiency (95.8%-86.1%); compatibility (95.8-79.6%); and safety (96%-83.4%). CONCLUSIONS: the software was considered suitable in quality evaluation to offer support to nurses in collecting patient data under palliative care, with the potential to operationalize the first Nursing Process stage.

Algorithms for predicting COVID outcome using ready-to-use laboratorial and clinical data.

The pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is an emerging crisis affecting the public health system. The clinical features of COVID-19 can range from an asymptomatic state to acute respiratory syndrome and multiple organ dysfunction. Although some hematological and biochemical parameters are altered during moderate and severe COVID-19, there is still a lack of tools to combine these parameters to predict the clinical outcome of a patient with COVID-19. Thus, this study aimed at employing hematological and biochemical parameters of patients diagnosed with COVID-19 in order to build machine learning algorithms for predicting COVID mortality or survival. Patients included in the study had a diagnosis of SARS-CoV-2 infection confirmed by RT-PCR and biochemical and hematological measurements were performed in three different time points upon hospital admission. Among the parameters evaluated, the ones that stand out the most are the important features of the T1 time point (urea, lymphocytes, glucose, basophils and age), which could be possible biomarkers for the severity of COVID-19 patients. This study shows that urea is the parameter that best classifies patient severity and rises over time, making it a crucial analyte to be used in machine learning algorithms to predict patient outcome. In this study optimal and medically interpretable machine learning algorithms for outcome prediction are presented for each time point. It was found that urea is the most paramount variable for outcome prediction over all three time points. However, the order of importance of other variables changes for each time point, demonstrating the importance of a dynamic approach for an effective patient's outcome prediction. All in all, the use of machine learning algorithms can be a defining tool for laboratory monitoring and clinical outcome prediction, which may bring benefits to public health in future pandemics with newly emerging and reemerging SARS-CoV-2 variants of concern.

Digital technology for the prevention of healthcare-related infections in critical care.

OBJECTIVE: To develop digital technology for patient and family integration into the Intensive Care Unit care team, aiming to subsidize decision-making for the prevention of infections related to healthcare. METHOD: Methodological research of technological production in three phases: pre-production, production, and post-production in a teaching hospital in southern Brazil. Sixteen intensive care unit nurses participated. RESULTS: The research produced six videos: general guidelines on the Intensive Care Unit, Preventing infections: hand hygiene; Pneumonia associated with mechanical ventilation; Catheter-associated primary bloodstream infection; Catheter-related urinary tract infection. FINAL CONSIDERATIONS: The proposed technology was developed and aims to assist nurses in bringing patients and families closer to the routines of the intensive care environment to provide safety in the contact of the patient of intensive care units with family members and in the active participation for the prevention of infections related to healthcare.

Implementation of modified Seldinger technology for percutaneous catheterization in critically ill newborns.

OBJECTIVE: To describe the implementation of Modified Seldinger Technology for percutaneous catheterization in critically ill newborns. METHOD: A quasi-experimental before- and-after study, carried out with neonatologist nurses in a Neonatal Intensive Care Unit. RESULTS: Seven nurses participated in the research. Catheter pre-insertion, insertion and maintenance were assessed using the conventional and modified Seldinger technique. Reliability was satisfactory in pre-test, 5.40 (Md = 6.00), and post-test, 5.94 (Md = 7.00), and perfect in the items about device insertion and maintenance. There was low assertiveness in the items on indication, microintroduction procedure via ultrasound, limb repositioning and disinfection of connections/connectors. CONCLUSION: Despite the Modified Seldinger Technique expanding some stages of execution over the traditional method of percutaneous catheterization, nurses were more assertive after theoretical-practical training. The technology was implemented and is in the process of being implemented in the health service.

Fugulin scale for classifying pediatric patients in a respiratory inpatient unit: experience report.

OBJECTIVE: To describe the use of the Fugulin scale to classify pediatric patients hospitalized in a respiratory unit as a subsidy for the allocation of human resources given the increase in cases of Severe Acute Respiratory Syndrome. METHOD: Experience report conducted in a children's hospital in the Metropolitan Region of Curitiba with data collection from medical records and approved by the Institution and by the Research Ethics Committee. RESULTS: Between February and May 2022, the percentage of patients categorized in minimal and intermediate care decreased by 53 and 11.4%, respectively, while those in high dependency and semi-intensive care expanded by 31.2 and 84.2%. In addition, in just four months, there was a considerable increase in the positivity of virologies compared to the twelve months of 2021. The susceptibility of children to the development of severe respiratory infection was proven through the decrease in virologies with undetectable results. CONCLUSION: The results obtained allowed us to conclude there was a significant increase in the complexity of patients admitted to the respiratory unit, showing it is essential to provide a nursing team compatible with the care needs.

Single-Response Electronic Tongue and Machine Learning Enable the Multidetermination of Extracellular Vesicle Biomarkers for Cancer Diagnostics Without Recognition Elements.

Platforms based on impedimetric electronic tongue (nonselective sensor) and machine learning are promising to bring disease screening biosensors into mainstream use toward straightforward, fast, and accurate analyses at the point-of-care, thus contributing to rationalize and decentralize laboratory tests with social and economic impacts being achieved. By combining a low-cost and scalable electronic tongue with machine learning, in this chapter, we describe the simultaneous determination of two extracellular vesicle (EV) biomarkers, i.e., the concentrations of EV and carried proteins, in mice blood with Ehrlich tumor from a single impedance spectrum without using biorecognizing elements. This tumor shows primary features of mammary tumor cells. Pencil HB core electrodes are integrated into polydimethylsiloxane (PDMS) microfluidic chip. The platform shows the highest throughput in comparison with the methods addressed in the literature to determine EV biomarkers.

Taming the SARS-CoV-2-mediated proinflammatory response with BromAc®.

Introduction: In the present study, the impact of BromAc®, a specific combination of bromelain and acetylcysteine, on the SARS-CoV-2-specific inflammatory response was evaluated. Methods: An in vitro stimulation system was standardized using blood samples from 9 healthy donors, luminex assays and flow cytometry were performed. Results and discussion: BromAc® demonstrated robust anti-inflammatory activity in human peripheral blood cells upon SARS-CoV-2 viral stimuli, reducing the cytokine storm, composed of chemokines, growth factors, and proinflammatory and regulatory cytokines produced after short-term in vitro culture with the inactivated virus (iSARS-CoV-2). A combined reduction in vascular endothelial growth factor (VEGF) induced by SARS-CoV-2, in addition to steady-state levels of platelet recruitment-associated growth factor-PDGFbb, was observed, indicating that BromAc® may be important to reduce thromboembolism in COVID-19. The immunophenotypic analysis of the impact of BromAc® on leukocytes upon viral stimuli showed that BromAc® was able to downmodulate the populations of CD16+ neutrophils and CD14+ monocytes observed after stimulation with iSARS-CoV-2. Conversely, BromAc® treatment increased steady-state HLA-DR expression in CD14+ monocytes and preserved this activation marker in this subset upon iSARS-CoV-2 stimuli, indicating improved monocyte activation upon BromAc® treatment. Additionally, BromAc® downmodulated the iSARS-CoV-2-induced production of TNF-a by the CD19+ B-cells. System biology approaches, utilizing comprehensive correlation matrices and networks, showed distinct patterns of connectivity in groups treated with BromAc®, suggesting loss of connections promoted by the compound and by iSARS-CoV-2 stimuli. Negative correlations amongst proinflammatory axis and other soluble and cellular factors were observed in the iSARS-CoV-2 group treated with BromAc® as compared to the untreated group, demonstrating that BromAc® disengages proinflammatory responses and their interactions with other soluble factors and the axis orchestrated by SARS-CoV-2. Conclusion: These results give new insights into the mechanisms for the robust anti-inflammatory effect of BromAc® in the steady state and SARS-CoV-2-specific immune leukocyte responses, indicating its potential as a therapeutic strategy for COVID-19.

A novel insight on SARS-CoV-2 S-derived fragments in the control of the host immunity.

Despite all efforts to combat the pandemic of COVID-19, we are still living with high numbers of infected persons, an overburdened health care system, and the lack of an effective and definitive treatment. Understanding the pathophysiology of the disease is crucial for the development of new technologies and therapies for the best clinical management of patients. Since the manipulation of the whole virus requires a structure with an adequate level of biosafety, the development of alternative technologies, such as the synthesis of peptides from viral proteins, is a possible solution to circumvent this problem. In addition, the use and validation of animal models is of extreme importance to screen new drugs and to compress the organism's response to the disease. Peptides derived from recombinant S protein from SARS-CoV-2 were synthesized and validated by in silico, in vitro and in vivo methodologies. Macrophages and neutrophils were challenged with the peptides and the production of inflammatory mediators and activation profile were evaluated. These peptides were also inoculated into the swim bladder of transgenic zebrafish larvae at 6 days post fertilization (dpf) to mimic the inflammatory process triggered by the virus, which was evaluated by confocal microscopy. In addition, toxicity and oxidative stress assays were also developed. In silico and molecular dynamics assays revealed that the peptides bind to the ACE2 receptor stably and interact with receptors and adhesion molecules, such as MHC and TCR, from humans and zebrafish. Macrophages stimulated with one of the peptides showed increased production of NO, TNF-α and CXCL2. Inoculation of the peptides in zebrafish larvae triggered an inflammatory process marked by macrophage recruitment and increased mortality, as well as histopathological changes, similarly to what is observed in individuals with COVID-19. The use of peptides is a valuable alternative for the study of host immune response in the context of COVID-19. The use of zebrafish as an animal model also proved to be appropriate and effective in evaluating the inflammatory process, comparable to humans.

The Healthcare Failure Mode and Effect Analysis as a tool to evaluate care protocols.

OBJECTIVES: to identify, classify, and analyze modes of failure in the medication process. METHODS: evaluative research that used the Healthcare Failure Mode and Effect Analysis (HFMEA) in a service of bone marrow transplant from June to September 2018, with the participation of 35 health workers. RESULTS: 207 modes of failure were identified and classified as mistakes in verification (14%), scheduling (25.6%), administration (29%), dilution (16.4%), prescription (2.4%), and identification (12.6%). The analysis of risk showed a moderate (51.7%) and high (30.9%) need of intervention, leading to the creation of an internal quality assurance group and of continued education activities. CONCLUSIONS: the Healthcare Failure Mode and Effect Analysis showed itself to be a tool to actively identify, classify, and analyze failures in the process of medication, contributing for the proposal of actions aimed at patient safety.

Plasma proteome responses in zebrafish following λ-carrageenan-Induced inflammation are mediated by PMN leukocytes and correlate highly with their human counterparts.

Regulation of inflammation is a critical process for maintaining physiological homeostasis. The λ-carrageenan (λ-CGN) is a mucopolysaccharide extracted from the cell wall of red algae (Chondrus crispus) capable of inducing acute intestinal inflammation, which is translated into the production of acute phase reactants secreted into the blood circulation. However, the associated mechanisms in vertebrates are not well understood. Here, we investigated the crucial factors behind the inflammatory milieu of λ-CGN-mediated inflammation administered at 0, 1.75, and 3.5% (v/w) by i.p. injection into the peritoneal cavity of adult zebrafish (ZF) (Danio rerio). We found that polymorphonuclear leukocytes (neutrophils) and lymphocytes infiltrating the ZF peritoneal cavity had short-term persistence. Nevertheless, they generate a strong pattern of inflammation that affects systemically and is enough to produce edema in the cavity. Consistent with these findings, cell infiltration, which causes notable tissue changes, resulted in the overexpression of several acute inflammatory markers at the protein level. Using reversed-phase high-performance liquid chromatography followed by a hybrid linear ion-trap mass spectrometry shotgun proteomic approach, we identified 2938 plasma proteins among the animals injected with PBS and 3.5% λ-CGN. First, the bioinformatic analysis revealed the composition of the plasma proteome. Interestingly, 72 commonly expressed proteins were recorded among the treated and control groups, but, surprisingly, 2830 novel proteins were differentially expressed exclusively in the λ-CGN-induced group. Furthermore, from the commonly expressed proteins, compared to the control group 62 proteins got a significant (p < 0.05) upregulation in the λ-CGN-treated group, while the remaining ten proteins were downregulated. Next, we obtained the major protein-protein interaction networks between hub protein clusters in the blood plasma of the λ-CGN induced group. Moreover, to understand the molecular underpinnings of these effects based on the unveiled protein sets, we performed a bioinformatic structural similarity analysis and generated overlapping 3D reconstructions between ZF and humans during acute inflammation. Biological pathway analysis pointed to the activation and abundance of diverse classical immune and acute phase reactants, several catalytic enzymes, and varied proteins supporting the immune response. Together, this information can be used for testing and finding novel pharmacological targets to treat human intestinal inflammatory diseases.

Toxicity of spike fragments SARS-CoV-2 S protein for zebrafish: A tool to study its hazardous for human health?

Despite the significant increase in the generation of SARS-CoV-2 contaminated domestic and hospital wastewater, little is known about the ecotoxicological effects of the virus or its structural components in freshwater vertebrates. In this context, this study evaluated the deleterious effects caused by SARS-CoV-2 Spike protein on the health of Danio rerio, zebrafish. We demonstrated, for the first time, that zebrafish injected with fragment 16 to 165 (rSpike), which corresponds to the N-terminal portion of the protein, presented mortalities and adverse effects on liver, kidney, ovary and brain tissues. The conserved genetic homology between zebrafish and humans might be one of the reasons for the intense toxic effects followed inflammatory reaction from the immune system of zebrafish to rSpike which provoked damage to organs in a similar pattern as happen in severe cases of COVID-19 in humans, and, resulted in 78,6% of survival rate in female adults during the first seven days. The application of spike protein in zebrafish was highly toxic that is suitable for future studies to gather valuable information about ecotoxicological impacts, as well as vaccine responses and therapeutic approaches in human medicine. Therefore, besides representing an important tool to assess the harmful effects of SARS-CoV-2 in the aquatic environment, we present the zebrafish as an animal model for translational COVID-19 research.

COVID-19 pandemic: educational technology for post-hematopoietic stem cell transplant patients.

OBJECTIVE: to describe the experience of building the technology "Care for the prevention of COVID-19 in post-hematopoietic stem cell transplant patients". METHODS: experience report conducted in a hematopoietic stem cell transplant outpatient clinic that supported the construction of an educational technology in the form of a booklet for the prevention of COVID-19. In May 2020, a literature review in scientific databases and guidelines of health organizations were used for its development. RESULTS: printed booklet with information on the definition of coronavirus, hand hygiene, use of the mask by the patient and caregiver, isolation and social distancing and general hygiene care. FINAL CONSIDERATIONS: the use of technologies is characterized as a tool for educational actions therefore, nurses, patients and caregivers benefit from guidance processes for health care. The developed technology has the potential to minimize the impact and spread of SARS-CoV-2 among high-risk populations.

Nursing diagnosis after hematopoietic stem cell transplant due to Fanconi anemia.

OBJECTIVES: to identify nursing diagnoses in patients who underwent hematopoietic stem-cell transplants due to Fanconi anemia, according to the NANDA-I taxonomy. METHODS: exploratory study using a retrospective analysis of 85 records from patients who underwent hematopoietic stem-cell transplants due to Fanconi anemia, developed in a specialize transplant center in the South of Brazil. The results were analyzed using descriptive statistics. RESULTS: 73 different diagnoses were found in 9 out of the 13 domains from the NANDA-I taxonomy. From these, 22 were in 50% or more of the patients investigated, and most of them are related to the domain Safety/Protection. CONCLUSIONS: it was possible to identify the nursing diagnosis in the patients who underwent hematopoietic stem cell transplants due to Fanconi anemia, contributing to design a plan for the care of these patients. The same was true for those with other syndromes of chromosomal instability that need to undergo this transplant.