Pain and discomfort in children with gastrostomy tubes - In the context of hematopoietic stem cell transplantation.

BACKGROUND: In children with malignant and severe non-malignant disorders undergoing hematopoietic stem cell transplantation (HSCT), treatment related pain and discomfort are common. Food consumption may become troublesome, making the use of a gastrostomy tube (G-tube) necessary and resulting in complications, why the purpose was to explore pain and discomfort during the transplantation and post-transplantation time. METHODS: This was a mixed methods study where data were collected along the child's total health-care process between 2018 and 2021. Questions with fixed answer options were used, simultaneously, semi-structured interviews were performed. In total, sixteen families participated. Descriptive statistics and content analysis were used to describe analysed data. FINDINGS: Intense pain was common during the post-surgery phase, especially in conjunction with G-tube care, which is why the children needed support to manage the situation. After the post-surgery phase when the skin has healed, most of the children experienced minor to no pain or bodily discomfort, why the G-tube became a well-functioning and supportive tool in daily life. CONCLUSIONS: This study describes variations in and experiences of pain and bodily discomfort in conjunction with G-tube insertion in a unique sample of children who had undergone HSCT. In conclusion, the children's comfort in daily life after the post-surgery phase seemed to be only marginally affected by G-tube insertion. Children with severe non-malignant disorders seemed to experience a higher frequency and intensity of pain and bodily discomfort due to the G-tube than children with malignant disorders. PRACTICE IMPLICATIONS: The paediatric care team need competence in assessing G-tube related pain and awareness that experiences may differ depending on the child's disorder.

Experiences before and after nasogastric and gastrostomy tube insertion with emphasis on mealtimes: a case study of an adolescent with cerebral palsy.

Purpose: Adolescents with cerebral palsy may need a feeding tube due to feeding challenges, since nutritional intake and mealtimes may be negatively affected. The purpose of the study was to describe and better understand how one adolescent with cerebral palsy and her parents experienced mealtimes before and after a nasogastric and gastrostomy tube insertion and how the use of these feeding tubes was experienced in daily life.Methods: Individual interviews were performed with one adolescent and each of her parents. In total, six interviews were conducted on two separate occasions. The qualitative approach known as Interpretive Description was used during the analysis.Results: Four thematic patterns were identified within the data: (i) struggling with nutritional intake, (ii) the paradox of using an aid, (iii) being different, and (iv) challenges of public mealtimes.Conclusions: The results showed that four themes influenced daily mealtimes in adolescents with cerebral palsy and a gastrostomy tube. Nutritional intake and mealtimes may be difficult, which is why using a gastrostomy tube can be a relief. However, the gastrostomy tube can also pose a challenge and a paradox. Time of change and acceptance seems necessary in order to meet these challenges.

The five aspect meal model as a conceptual framework for children with a gastrostomy tube in paediatric care.

BACKGROUND: Cancer treatments may induce side effects and cause eating problems. A gastrostomy tube may be required in order to maintain and optimise the child's nutritional needs. Despite the use of a gastrostomy tube, it is important to maintain a natural and attractive mealtime for the child. The Five Aspect Meal Model is age neutral and originally designed to improve restaurant visits. Its five aspects conceptualise what is necessary to ensure a complete meal experience. To date, there is lack of knowledge to guided model development about mealtimes adapted to children and limited knowledge regarding mealtime experiences for children with a gastrostomy tube. AIM: The aim was to investigate whether the Five Aspect Meal Model could be appropriate to be used for children with a gastrostomy tube in caring science and paediatric care. METHODS: The design followed steps retrieved from Renjith and colleagues. Seven interviews were performed with the Five Aspect Meal Model as a base in the interview guide. The transcripts were analysed by using a qualitative directed content analysis with a deductive approach, which finally passed into a more inductive one. FINDINGS: All aspects of the Five Aspect Meal Model were represented in the interviews. There were also experiences related to the gastrostomy tube and the mealtimes that did not fit into any of the five predetermined categories. As a result, the modified version was developed, an adapted prescribing practice model that includes seven aspects, whereof bodily discomfort and time for change and acceptance are specific to children with a gastrostomy tube. CONCLUSION: Based on children and their parent's experiences, the Five Aspect Meal Model has been developed and adapted into a modified version, which includes seven aspects. The modified version seems to be appropriate to use within caring science and paediatric care.

G protein-coupled estrogen receptor 1/G protein-coupled receptor 30 localizes in the plasma membrane and traffics intracellularly on cytokeratin intermediate filaments.

G protein-coupled receptor 30 [G protein-coupled estrogen receptor 1 (GPER1)], has been introduced as a membrane estrogen receptor and a candidate cancer biomarker and therapeutic target. However, several questions surround the subcellular localization and signaling of this receptor. In native cells, including mouse myoblast C(2)C(12) cells, Madin-Darby canine kidney epithelial cells, and human ductal breast epithelial tumor T47-D cells, G-1, a GPER1 agonist, and 17ß-estradiol stimulated GPER1-dependent cAMP production, a defined plasma membrane (PM) event, and recruitment of ß-arrestin2 to the PM. Staining of fixed and live cells showed that GPER1 was localized both in the PM and on intracellular structures. One such intracellular structure was identified as cytokeratin (CK) intermediate filaments, including those composed of CK7 and CK8, but apparently not endoplasmic reticulum, Golgi, or microtubules. Reciprocal coimmunoprecipitation of GPER1 and CKs confirmed an association of these proteins. Live staining also showed that the PM receptors constitutively internalize apparently to reach CK filaments. Receptor localization was supported using FLAG- and hemagglutinin-tagged GPER1. We conclude that GPER1-mediated stimulation of cAMP production and ß-arrestin2 recruitment occur in the PM. Furthermore, the PM receptors constitutively internalize and localize intracellularly on CK. This is the first observation that a G protein-coupled receptor is capable of associating with intermediate filaments, which may be important for GPER1 regulation in epithelial cells and the relationship of this receptor to cancer.

Deletion of the G protein-coupled receptor 30 impairs glucose tolerance, reduces bone growth, increases blood pressure, and eliminates estradiol-stimulated insulin release in female mice.

In vitro studies suggest that the G protein-coupled receptor (GPR) 30 is a functional estrogen receptor. However, the physiological role of GPR30 in vivo is unknown, and it remains to be determined whether GPR30 is an estrogen receptor also in vivo. To this end, we studied the effects of disrupting the GPR30 gene in female and male mice. Female GPR30((-/-)) mice had hyperglycemia and impaired glucose tolerance, reduced body growth, increased blood pressure, and reduced serum IGF-I levels. The reduced growth correlated with a proportional decrease in skeletal development. The elevated blood pressure was associated with an increased vascular resistance manifested as an increased media to lumen ratio of the resistance arteries. The hyperglycemia and impaired glucose tolerance in vivo were associated with decreased insulin expression and release in vivo and in vitro in isolated pancreatic islets. GPR30 is expressed in islets, and GPR30 deletion abolished estradiol-stimulated insulin release both in vivo in ovariectomized adult mice and in vitro in isolated islets. Our findings show that GPR30 is important for several metabolic functions in female mice, including estradiol-stimulated insulin release.

Characterization of the human chemerin receptor--ChemR23/CMKLR1--as co-receptor for human and simian immunodeficiency virus infection, and identification of virus-binding receptor domains.

Studies were conducted to elucidate co-receptor spectrum and function of the inflammatory receptor, CMKLR1/ChemR23, which was recently identified as the receptor for the cystatin-like chemoattractant, TIG2, also named chemerin. An infection model was applied based on stably transfected NP-2.CD4 host cells expressing various co-receptor constructs and exposed to panels of HIV-1, HIV-2 and SIV primary isolates. In a panel of 27 HIV-1 isolates tested, 12 isolates could use CMKLR1/ChemR23. As expected from a relatively high sequence homology with the extracellular domains of CCR3, HIV-1 isolates showing R3 tropism were particularly efficient in using CMKLR1/ChemR23. In addition, 5 out of 7 HIV-2 isolates and 13 out of 15 SIV (SMM-3 origin) used CMKLR1/ChemR23, in accordance with the previously documented ability of these isolates to use several co-receptors. In order to define important extracellular epitopes for the viral interaction, a hybrid receptor model was applied. This was based on the fact that the rat receptor, although structurally very similar to the human orthologue, was inefficient as viral co-receptor. When the rat receptor was "humanized" to include regions unique to the human receptor (N-terminus or second extracellular loop), exposure to HIV-1, HIV-2 and SIV isolates resulted in infection. The relative importance of the two critical receptor regions differed between HIV-1/HIV-2 on the one hand and SIV on the other. The results strongly support that the chemerin receptor, in the presence of CD4, functions as a "minor co-receptor" promoting infection by these classes of viruses.

The mouse chemerin receptor gene, mcmklr1, utilizes alternative promoters for transcription and is regulated by all-trans retinoic acid.

CMKLR1 (chemoattractant-like receptor 1) is a G-protein-coupled receptor implicated in cartilage and bone development and is expressed in organs like the parathyroid gland, brain, and lung. The receptor is also expressed in dendritic cells and in macrophages where it acts as a co-receptor for entry of HIV/SIV isolates into human CD4(+) cells. Recently, a protein named "chemerin" (also known as TIG2) was isolated from human inflammatory fluids and hemofiltrate and found to be the endogenous ligand for CMKLR1. We have previously described the genomic organization of the cmklr1 gene and characterized its promoter in mouse neuroblastoma NB4 1A3 cells. In the present study we identify a second transcript, cmklr1b, in mouse microglia BV2 cells. Cmklr1b is transcribed from an alternative promoter with a transcription start site located 6780 bp downstream of the previously identified exon 1 (cmklr1a). The cmklr1b promoter lacks a TATA box but contains two CCAAT boxes in opposite directions. 5' Deletion analysis of the promoter region in BV2 cells using a luciferase reporter gene assay indicates two regions, between 623-755 bp and 56-125 bp upstream of transcription start site, to be important for promoter function. The proximal promoter region includes both CCAAT boxes, and site-directed mutagenesis separately within these elements revealed that only the forward CCAAT element was important for transcription. Although the forward CCAAT element is essential for transcription electrophoretic mobility shift and super-shift assays demonstrated that both CCAAT elements actually bind nuclear proteins from BV2 cells and identified the binding factor as NFY. Real-time reverse transcriptase-PCR experiments of cmklr1b expression in all-trans retinoic acid (ATRA)- stimulated BV2 cells showed strong up-regulation of receptor transcript. Luciferase reporter gene assay of the promoter in ATRA-stimulated BV2 cells confirmed that transcriptional activity of the cmklr1b promoter is increased by ATRA. However, deletion analysis could not identify an ATRA-responsive element within the promoter region suggesting that gene activation is likely to occur through alternative mechanisms. The results emphasise a possible role of cmklr1 in bone modelling.

Genomic organization and promoter analysis of the gene encoding the mouse chemoattractant-like receptor, CMKLR1.

Chemoattractant-like receptor 1 (CMKLR1) is a functionally unknown ("orphan") G-protein coupled receptor. It has been implicated in osseous and cartilage development, and it also has a pathophysiological role as one of the minor coreceptors involved in human immunodeficiency virus type I (HIV-1)/simian immunodeficiency virus (SIV) infection of CD4(+) immune cells. Here we report the cloning of the mouse cmklr1 gene, the characterization of its genomic structure for comparison with the human gene, and the mapping and functional analysis of its 5' flanking sequence. The gene was found to contain three exons intercepted by one larger and one smaller intron. The overall structure resembles the human orthologue. The promoter lacks classical TATA and CCAAT boxes but contains several GC-rich regions as well as AP-4 elements, C/EBP motifs, and GATA-1 and GATA-2 binding sites. Promoter function was analyzed in mouse neuroblastoma (NB4 1A3) cells, endogenously expressing CMKLR1, as well as in mouse embryonic fibroblastic (3T3 clone A31) cells not expressing CMKLR1. 5' Deletion analysis and luciferase reporter gene assays of the promoter indicated that a 280-bp sequence adjacent to the transcription start site (established through 5'-RACE) is essential for initiating transcription. Within this region it was possible to identify four potential Sp1-binding sites that may be active in the transcription of the gene. Thus, we show that the mcmklr1 gene has several conserved features in common with its human counterpart, which suggests that they are regulated in a similar manner. The promoter does not seem to be tissue specific but other elements or enhancers may be missing. The results provide a necessary basis for further studies of the gene regulation and function of this chemoattractant-like receptor and will be useful when manipulating the gene in the development of transgenic animal models.