Search

This study aimed to evaluate assistant nurses' knowledge of and attitudes towards pressure injuries in a clinical setting. It employed a cross-sectional design, using two validated surveys: PUKAT 2.0 and APUP, alongside open-ended questions. A convenience sample of 88 assistant nurses from five wards across two departments at a 600-bed university hospital in Sweden participated. Participants answered the questionnaire and open-ended questions, followed by a learning seminar led by the study leader covering PUKAT 2.0 knowledge questions. The seminar ended with an evaluation of this training approach. Results revealed a significant knowledge gap in pressure injury prevention among assistant nurses, with a mean PUKAT 2.0 knowledge score of 33.8 and a standard deviation of ±11.7 (a score of 60 is deemed satisfactory). Only 3.4% (n = 3) of participants achieved a satisfactory knowledge score. However, attitudes towards pressure injury prevention, assessed by the APUP tool, were generally positive among the majority of the participants. Open-ended questions and evaluations of the seminar showed assistant nurses' desire for pressure injury prevention training and their appreciation for the seminar format. Further studies need to evaluate recurrent training procedures and departmental strategies aimed at reducing the knowledge gap among healthcare staff., (© 2024 The Author(s). International Wound Journal published by Medicalhelplines.com Inc and John Wiley & Sons Ltd.)

Background and Aims: This pilot study aimed to evaluate safety and tissue sampling from subepithelial lesions (SEL) in the upper gastrointestinal tract with a novel electric motor driven endoscopic ultrasonography (EUS)-guided 17-gauge (G) size core needle biopsy (CNB) instrument., Methods: An investigator-led prospective open label, performance and safety control study, including seven patients (female n  = 4, median 71 y, range 28-75) with a determined SEL (median size 30 mm, range 17-150 mm) in the upper digestive tract (stomach n  = 6, duodenum n  = 1) were eligible and later followed up 14 days after index procedure. All investigations were completed according to protocol with three FNB 22-G passes with four fanning strokes and two EndoDrill ® 17-G passes with three fanning strokes., Results: Quality of samples as 'visible pieces' (>5 mm): FNB ( n  = 5/7) (fragmented/blood imbibed n  = 1, poor tissue quantity n  = 1) compared with 17-G CNB ( n  = 7/7). Histological result which led to final diagnosis (leiomyoma n  = 2, adenocarcinoma n  = 1, schwannoma n  = 1, neuroendocrine tumour n  = 1, desmoid tumour n  = 1 and gastrointestinal stromal tumour (GIST) n  = 1) could be obtained with the 17-G CNB instrument in all seven patients. FNB technique reached correct diagnosis in six patients. No serious adverse event were recorded., Conclusions: By using an electric driven 17-G biopsy device, a true cylinder of core tissue can be obtained in one single puncture from the area of interest reducing the need for a second sampling. The absolute benefit of EUS-guided CNB is that the sample can be handled and histologically prepared in the same manner as standard percutaneous core needle sample, e.g., breast and prostate cancer.

Incontinence-associated dermatitis (IAD) is an irritant contact dermatitis from prolonged contact with urine or faeces, which can significantly impact patient comfort and quality of life. The identification of prognostic factors for the development of IAD has the potential to enhance management, support preventive measures and guide future research. The objective of this systematic review was to summarize the empirical evidence of prognostic factors for the development of IAD. This study included prospective and retrospective observational studies or clinical trials that described prognostic factors associated with IAD. There were no restrictions on setting, time, language, participants or geographical regions. Exclusion criteria included reviews, editorials, commentaries, methodological articles, letters to the editor, cross-sectional and case-control studies, and case reports. Searches were conducted from inception to April 2024 on MEDLINE, CINAHL, EMBASE and the Cochrane Library. The studies were assessed by two independent reviewers using the QUIPS and the CHARMS-PF for data extraction. A narrative synthesis approach was employed due to study heterogeneity and using the 'vote counting based on direction' method and the sign test. The overall certainty of evidence was assessed using adapted GRADE criteria. The review included 12 studies and identified 15 potential predictors. Moderate-quality evidence suggests that increased stool frequency, limited mobility and friction/shear problems are risk factors for IAD development. Female sex, older age, vasopressor use and loose/liquid stool are risk factors supported by low-quality evidence. Increased stool frequency, limited mobility and friction/shear problems seem to be risk factors for the development of IAD. There is insufficient evidence to support the predictive validity of female sex, older age, loose/liquid stool and vasopressor use. There is substantial methodological variability across studies, making it challenging to make comparisons. Large-scale cohort studies in different settings that incorporate our review findings should be conducted in the future., (© 2024 The Author(s). International Wound Journal published by Medicalhelplines.com Inc and John Wiley & Sons Ltd.)

Background: The ongoing global migration has led to multicultural societies, with many migrants who do not speak the official language in the host country. This could contribute to communication problems with staff in healthcare and a risk to patient safety. Research on patient safety in medication use in migrants is an under-researched area. The aim was to explore diverse foreign-born people's experiences and perceptions of self-management of medication and determine if home-based practice patterns have implications on medication safety, and what factors may support safe medication use., Methods: A qualitative explorative study, with individual semi-structured interviews and participant observations in the patients' home. Qualitative content analysis was applied., Results: A purposeful sample of 15 foreign-born persons identified by healthcare staff as having language difficulties in Swedish that may pose a safety risk in connection with medication use at home, was selected. Three categories were identified. The first category showed respondents being dependent on another person, having experiences of not receiving information about their medications due to language barriers, having difficulties getting access to the healthcare centre and feeling distrusted/misunderstood. The second category showed respondents being independent and self-motivated Although they struggled, they managed to get access/contact with the healthcare centre themselves and felt understood/listened to by the staff. The last category concerned factors that facilitating medication use; such as having a medication list in the respondents' own language and offering a choice of language on the answering machine at the healthcare centre. Although they knew it was impossible to get an interpreter at the pharmacy, they felt safe knowing there was always a solution for receiving understandable information., Conclusion: The findings highlighted that language barriers can complicate the communication between migrants and the healthcare, which can affect the medication safety. Understanding of this group is essential to improve the cooperation between patients and staff, leading to culturally congruent care. This knowledge should be used in healthcare to understand the gap in communication to increase patient safety. Further research from other angles, e.g. pharmacy/healthcare staff and relatives is needed to identify and evaluate facilitation to improve the outcome of the intended medication treatment., (© 2024. The Author(s).)

Background: Diabetic foot ulcers (DFU) pose a significant health risk in diabetic patients, with insufficient revascularization during wound healing being the primary cause. This study aimed to assess microvessel sprouting and wound healing capabilities using vascular endothelial growth factor (VEGF-A) and a modified fibroblast growth factor (FGF1)., Methods: An ex vivo aortic ring rodent model and an in vivo wound healing model in diabetic mice were employed to evaluate the microvessel sprouting and wound healing capabilities of VEGF-A and a modified FGF1 both as monotherapies and in combination., Results: The combination of VEGF-A and FGF1 demonstrated increased vascular sprouting in the ex vivo mouse aortic ring model, and topical administration of a combination of VEGF-A and FGF1 mRNAs formulated in lipid nanoparticles (LNPs) in mouse skin wounds promoted faster wound closure and increased neovascularization seven days post-surgical wound creation. RNA-sequencing analysis of skin samples at day three post-wound creation revealed a strong transcriptional response of the wound healing process, with the combined treatment showing significant enrichment of genes linked to skin growth., Conclusion: f-LNPs encapsulating VEGF-A and FGF1 mRNAs present a promising approach to improving the scarring process in DFU.

Introduction: Incontinence-associated dermatitis (IAD) is irritant contact dermatitis and skin damage associated with prolonged skin contact with urine and/or faeces. Identifying prognostic factors for the development of IAD may improve management, facilitate prevention and inform future research., Methods and Analysis: This protocol follows the guidelines of the Preferred Reporting Items for Systematic Review and Meta-Analysis Protocols. Prospective and retrospective observational studies or clinical trials in which prognostic factors associated with the development of IAD are described are eligible. There are no restrictions on study setting, time, language, participant characteristics or geographical regions. Reviews, editorials, commentaries, methodological articles, letters to the editor, cross-sectional and case-control studies, and case reports are excluded. MEDLINE, CINAHL, EMBASE and The Cochrane Library will be searched from inception until May 2023. Two independent reviewers will independently evaluate studies. The Quality in Prognostic Studies tool will be used to assess the risk of bias, and the Checklist for Critical Appraisal and Data Extraction for Systematic Reviews of Prediction Modelling Studies-Prognostic Factors checklist will be used for data extraction of the included studies. Separate analyses will be conducted for each identified prognostic factor, with adjusted and unadjusted estimated measures analysed separately. Evidence will be summarised with a meta-analysis when possible, and narratively otherwise. The Q and I 2 statistics will be calculated in order to quantify heterogeneity. The quality of the evidence obtained will be evaluated according to the Grades of Recommendation Assessment, Development and Evaluation guidance., Ethics and Dissemination: No ethical approval is needed since all data is already publicly accessible. The results of this work will be published in a peer-reviewed scientific journal., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2023. Re-use permitted under CC BY. Published by BMJ.)

Lipid nanoparticles (LNPs) are currently used to transport functional mRNAs, such as COVID-19 mRNA vaccines. The delivery of angiogenic molecules, such as therapeutic VEGF-A mRNA, to ischemic tissues for producing new blood vessels is an emerging strategy for the treatment of cardiovascular diseases. Here, the authors deliver VEGF-A mRNA via LNPs and study stoichiometric quantification of their uptake kinetics and how the transport of exogenous LNP-mRNAs between cells is functionally extended by cells' own vehicles called extracellular vesicles (EVs). The results show that cellular uptake of LNPs and their mRNA molecules occurs quickly, and that the translation of exogenously delivered mRNA begins immediately. Following the VEGF-A mRNA delivery to cells via LNPs, a fraction of internalized VEGF-A mRNA is secreted via EVs. The overexpressed VEGF-A mRNA is detected in EVs secreted from three different cell types. Additionally, RNA-Seq analysis reveals that as cells' response to LNP-VEGF-A mRNA treatment, several overexpressed proangiogenic transcripts are packaged into EVs. EVs are further deployed to deliver VEGF-A mRNA in vitro and in vivo. Upon equal amount of VEGF-A mRNA delivery via three EV types or LNPs in vitro, EVs from cardiac progenitor cells are the most efficient in promoting angiogenesis per amount of VEGF-A protein produced. Intravenous administration of luciferase mRNA shows that EVs could distribute translatable mRNA to different organs with the highest amounts of luciferase detected in the liver. Direct injections of VEGF-A mRNA (via EVs or LNPs) into mice heart result in locally produced VEGF-A protein without spillover to liver and circulation. In addition, EVs from cardiac progenitor cells cause minimal production of inflammatory cytokines in cardiac tissue compared with all other treatment types. Collectively, the data demonstrate that LNPs transform EVs as functional extensions to distribute therapeutic mRNA between cells, where EVs deliver this mRNA differently than LNPs., (© 2023 The Authors. Advanced Science published by Wiley-VCH GmbH.)

This study aimed to evaluate the feasibility of implementing an electronic version of PURPOSE T, a risk assessment instrument for pressure ulcers, in a Swedish hospital ward. A mixed-method was used. Nursing staff received training in PURPOSE T and a record review was performed (n = 30). PURPOSE T replaced the Modified Norton Scale, and after one month another record review was performed (n = 30). Individual interviews with patients (n = 15) and focus group interviews with nursing staff (n = 23) were performed after the implementation. The results of the record review and the focus group interviews showed good clinical feasibility of PURPOSE T. The record review showed that more patients were at risk of developing pressure ulcers and more nursing interventions were prescribed with PURPOSE T compared to the Modified Norton Scale. The focus group interviews showed that all nursing staff were satisfied with PURPOSE T. The instrument contributed to increased reflection and analysis as well as the opportunity for nursing staff to draw their own conclusions regarding patients´ risk status. The documentation encouraged the prescription of more preventive actions, and the nurses were more involved at bedside. However, almost all the patients expressed not receiving any information about pressure ulcers., (© 2022 The Authors. International Wound Journal published by Medicalhelplines.com Inc and John Wiley & Sons Ltd.)

Automated segmentation of human cardiac magnetic resonance datasets has been steadily improving during recent years. Similar applications would be highly useful to improve and speed up the studies of cardiac function in rodents in the preclinical context. However, the transfer of such segmentation methods to the preclinical research is compounded by the limited number of datasets and lower image resolution. In this paper we present a successful application of deep architectures 3D cardiac segmentation for rats in preclinical contexts which to our knowledge has not yet been reported. We developed segmentation models that expand on the standard U-Net architecture and evaluated models separately trained for systole and diastole phases (2MSA) and a single model trained for all phases (1MSA). Furthermore, we calibrated model outputs using a Gaussian process (GP)-based prior to improve phase selection. The resulting models approach human performance in terms of left ventricular segmentation quality and ejection fraction (EF) estimation in both 1MSA and 2MSA settings (Sørensen-Dice score 0.91 ± 0.072 and 0.93 ± 0.032, respectively). 2MSA achieved a mean absolute difference between estimated and reference EF of 3.5 ± 2.5%, while 1MSA resulted in 4.1 ± 3.0%. Applying GPs to 1MSA enabled automating systole and diastole phase selection. Both segmentation approaches (1MSA and 2MSA) were statistically equivalent. Combined with a proposed cardiac phase selection strategy, our work presents an important first step towards a fully automated segmentation pipeline in the context of rat cardiac analysis., (© 2022. The Author(s).)

Aim: To evaluate the clinical usability of PURPOSE T among registered nurses in Sweden., Background: Pressure ulcers are an adverse event and a problem worldwide. Risk assessment is a cornerstone, and a first step in pressure ulcer prevention is to identify possible risk patients and/or pressure ulcers. There are many pressure ulcer risk assessment instruments; however, they are not updated and/or evidence-based. PURPOSE T has been psychometrically evaluated in the UK and in Sweden with good inter-rater and test-retest reliability, and convergent validity was reported as moderate., Design: A descriptive study design with a qualitative approach., Methods: A total of six focus group interviews with 29 registered nurses were conducted. They were recruited from May 2018 to November 2018 from a university hospital and two nursing homes in Sweden. Data analysis was performed as described by Krueger. The study adheres to the COREQ guidelines., Results: Four categories were identified: "An efficient risk assessment instrument performed at the bedside," "Deeper understanding and awareness of risk factors," "Benefits compared to the Modified Norton Scale" and "Necessity of integration of PURPOSE T in the electronic health record and team collaboration.", Conclusion: The registered nurses acknowledged an overall positive perception of PURPOSE T´s clinical usability. Future research is needed to evaluate the feasibility of PURPOSE T., Relevance to Clinical Practice: PURPOSE T has the potential to replace outdated pressure ulcers risk assessment instruments that are used today., (© 2021 The Authors. Journal of Clinical Nursing published by John Wiley & Sons Ltd.)

Lipid nanoparticles (LNPs) are the most clinically advanced delivery system for RNA-based drugs but have predominantly been investigated for intravenous and intramuscular administration. Subcutaneous administration opens the possibility of patient self-administration and hence long-term chronic treatment that could enable messenger RNA (mRNA) to be used as a novel modality for protein replacement or regenerative therapies. In this study, we show that subcutaneous administration of mRNA formulated within LNPs can result in measurable plasma exposure of a secreted protein. However, subcutaneous administration of mRNA formulated within LNPs was observed to be associated with dose-limiting inflammatory responses. To overcome this limitation, we investigated the concept of incorporating aliphatic ester prodrugs of anti-inflammatory steroids within LNPs, i.e., functionalized LNPs to suppress the inflammatory response. We show that the effectiveness of this approach depends on the alkyl chain length of the ester prodrug, which determines its retention at the site of administration. An unexpected additional benefit to this approach is the prolongation observed in the duration of protein expression. Our results demonstrate that subcutaneous administration of mRNA formulated in functionalized LNPs is a viable approach to achieving systemic levels of therapeutic proteins, which has the added benefits of being amenable to self-administration when chronic treatment is required., Competing Interests: L.L. and T.K. are authors on the patent WO2017/194454 (A1) relating to lipid nanoparticles comprising lipophilic anti-inflammatory agents and methods of use thereof. All authors were at the time of study employees of AstraZeneca., (© 2021 AstraZeneca AB.)

Aim: To evaluate the psychometric characteristics of the Pressure Ulcer Risk Primary or Secondary Evaluation Tool (PURPOSE T); reliability (inter-rater and test-retest) and validity (convergent validity) in a Swedish context., Background: Pressure ulcers are considered as an adverse event and are a problem in healthcare worldwide. The first step in pressure ulcer prevention is to identify patients that are at risk. PURPOSE T is a new pressure ulcer risk assessment instrument that was developed in the UK using "golden standard" instrument method., Design: Observational, descriptive and comparative., Methods: A total of 235 patients and 28 registered nurses were recruited (May 2018-November 2018) from six hospital wards at a university hospital and two community nursing homes in Sweden. Blinded (ward/nursing home nurses and expert nurses) PURPOSE T assessments and follow-up retests were undertaken. Cross-tabulation and kappa statistics were used to examine the reliability, and phi correlation was used to test the convergent validity. The study followed the STROBE guideline., Results: The clinical evaluation showed "very good" (kappa) inter-rater and test-retest reliability for PURPOSE T assessment decision overall. The agreement of "at risk"/"not at risk" for both inter-rater and test-retest was also high, at least 95.5%. The convergent validity between PURPOSE T and other traditional assessment instruments was moderate., Conclusion: The evaluation of PURPOSE T demonstrated good psychometric characteristics. Further research is needed to evaluate PURPOSE T's usability among registered nurses., Relevance to Clinical Practice: There is a lack of evidence-based validated pressure ulcer risk assessment instruments for use in health care. According to our findings, the Swedish version of PURPOSE T could be used in hospitals and nursing homes to identify patients in risk or with pressure ulcers., (© 2020 The Authors. Journal of Clinical Nursing published by John Wiley & Sons Ltd.)

Muscle atrophy and cachexia are common comorbidities among patients suffering from cancer, chronic obstructive pulmonary disease, and several other chronic diseases. The peptide hormone ghrelin exerts pleiotropic effects including the stimulation of growth hormone secretion and subsequent increase of insulin-like growth factor-1 levels, an important mediator of muscle growth and repair. Ghrelin also acts on inflammation, appetite, and adipogenesis and therefore has been considered a promising therapeutic target for catabolic conditions. We previously reported on the synthesis and properties of an indane based series of ghrelin receptor full agonists which led to a sustained increase of insulin-like growth factor-1 in a dog pharmacodynamic study. Herein we report on the identification of a series of pyrrolidine or piperidine based full agonists and attempted optimization to give compounds with profiles suitable for progression as clinical candidates.

Purpose: The aim of this study was to assess the participatory capabilities of hospitalized older adults in response to the Continuous Bedside Pressure Mapping system placed on the beds to prevent pressure injuries., Design: Descriptive study., Subjects and Setting: A convenience sample of 31 orthopedic patients were recruited from an orthopedic rehabilitation unit at a university hospital in Uppsala, Sweden, that served patients aged 65 years and older., Methods: Semistructured interviews were conducted between November 2016 and February 2017, audio-recorded, and transcribed verbatim. Data were analyzed using qualitative content analysis., Result: The overall theme from 21 interviews was "A new way of understanding helped patients to recognize vulnerable pressure points and to take action in their own care" from which 2 categories, "awareness" and "action," emerged. The study showed that verbally adapted information combined with using information and communication technology increased most participants' knowledge and as they became aware of increased pressure, they started to take preventative action by changing position., Conclusions: It is possible for older participants in a rehabilitation unit who had recent orthopedic surgery to understand and use new information and communication technology and should be invited to participate in pressure injury prevention.

Background: Cerebral evoked potentials (CEP) induced by colorectal distension (CRD) in conscious rats provides a novel method in studies of visceral sensitivity. The aim of this study was to explore the pharmacological effect on CEP of compounds known to reduce the visceromotor response to CRD., Methods: Epidural electrodes were chronically implanted in eight female Sprague-Dawley rats. Evoked potentials were elicited by colorectal rapid balloon distensions (100 ms, 80 mmHg) and the effect of WIN55 (cannabinoid CB receptor agonist), clonidine (adrenergic α 2 receptor agonist), MPEP (mGluR5 receptor antagonist), pregabalin (ligand of α 2 δ subunits in voltage-gated calcium channels) and baclofen (GABA-B receptor agonist) on amplitudes and latency of CEP were determined., Results: WIN55 (0.1 μmol kg -1 ), clonidine (0.05 μmol kg -1 ), MPEP (10 μmol kg -1 ) and pregabalin (200 μmol kg -1 ) caused a significant, p < 0.05, reduction of the N2 to P2 peak-to-peak amplitude by 23 ± 8%, 25 ± 8%, 39 ± 5%, and 47 ± 6% respectively. Baclofen (9 μmol kg -1 ) induced a prolongation of the N2 peak latency of 18 ± 4% but had no significant effect on the amplitudes., Conclusion: The obtained results suggest that MPEP, WIN55, clonidine, and pregabalin reduce visceral nociceptive input to the brain, whereas the lack of effect of baclofen on CRD evoked CEP amplitudes suggest that the effect on VMR is not due to a direct analgesic effect. Brain responses to colorectal distension provide a useful tool to evaluate pharmacological effects in rats and may serve as a valuable preclinical model for understanding pharmacological mechanisms related to visceral sensitivity., (Copyright © 2018. Published by Elsevier Ltd.)

Cachexia and muscle wasting are very common among patients suffering from cancer, chronic obstructive pulmonary disease, and other chronic diseases. Ghrelin stimulates growth hormone secretion via the ghrelin receptor, which subsequently leads to increase of IGF-1 plasma levels. The activation of the GH/IGF-1 axis leads to an increase of muscle mass and functional capacity. Ghrelin further acts on inflammation, appetite, and adipogenesis and for this reason was considered an important target to address catabolic conditions. We report the synthesis and properties of an indane based series of ghrelin receptor full agonists; they have been shown to generate a sustained increase of IGF-1 levels in dog and have been thoroughly investigated with respect to their functional activity.

Protease-activated receptor-2 (PAR2) is one member of a small family of transmembrane, G-protein-coupled receptors. These receptors are activated via cleavage of their N terminus by serine proteases (e.g., tryptase), unveiling an N terminus tethered ligand which binds to the second extracellular loop of the receptor. Increasing evidence has emerged identifying key pathophysiological roles for PAR2 in both rheumatoid arthritis (RA) and osteoarthritis (OA). Importantly, this includes both pro-inflammatory and destructive roles. For example, in murine models of RA, the associated synovitis, cartilage degradation, and subsequent bone erosion are all significantly reduced in the absence of PAR2. Similarly, in experimental models of OA, PAR2 disruption confers protection against cartilage degradation, subchondral bone osteosclerosis, and osteophyte formation. This review focuses on the role of PAR2 in rheumatic disease and its potential as an important therapeutic target for treating pain and joint degradation.

A hallmark of human immunosenescence is the accumulation of late-differentiated memory CD8+ T cells with features of replicative senescence, such as inability to proliferate, absence of CD28 expression, shortened telomeres, loss of telomerase activity, enhanced activation, and increased secretion of inflammatory cytokines. Importantly, oligoclonal expansions of these cells are associated with increased morbidity and mortality risk in elderly humans. Currently, most information on the adaptive immune system is derived from studies using peripheral blood, which contains approximately only 2% of total body lymphocytes. However, most lymphocytes reside in tissues. It is not clear how representative blood changes are of the total immune status. This is especially relevant with regard to the human gastrointestinal tract (GALT), a major reservoir of total body lymphocytes (approximately 60%) and an anatomical region of high antigenic exposure. To assess how peripheral blood T cells relate to those in other locations, we compare CD8+ T cells from peripheral blood and the GALT, specifically rectosigmoid colon, in young/middle age, healthy donors, focusing on phenotypic and functional alterations previously linked to senescence in peripheral blood. Overall, our results indicate that gut CD8+ T cells show profiles suggestive of greater differentiation and activation than those in peripheral blood. Specifically, compared to blood from the same individual, the gut contains significantly greater proportions of CD8+ T cells that are CD45RA- (memory), CD28-, CD45RA-CD28+ (early memory), CD45RA-CD28- (late memory), CD25-, HLA-DR+CD38+ (activated) and Ki-67+ (proliferating); ex vivo CD3+ telomerase activity levels are greater in the gut as well. However, gut CD8+ T cells may not necessarily be more senescent, since they expressed significantly lower levels of CD57 and PD-1 on CD45RO+ memory cells, and had in vitro proliferative dynamics similar to that of blood cells. Compartment-specific age-effects in this cohort were evident as well. Blood cells showed a significant increase with age in proportion of HLA-DR+38+, Ki-67+ and CD25+ CD8+ T cells; and an increase in total CD3+ ex-vivo telomerase activity that approached significance. By contrast, the only age-effect seen in the gut was a significant increase in CD45RA- (memory) and concurrent decrease in CD45RA+CD28+ (naïve) CD8+ T cells. Overall, these results indicate dynamics of peripheral blood immune senescence may not hold true in the gut mucosa, underscoring the importance for further study of this immunologically important tissue in evaluating the human immune system, especially in the context of chronic disease and aging.

The accumulation of peripheral blood late-differentiated memory CD8 T cells with features of replicative (cellular) senescence, including inability to proliferate in vitro, has been extensively studied. Importantly, the abundance of these cells is directly correlated with increased morbidity and mortality in older persons. Of note, peripheral blood contains only 2% of the total body lymphocyte population. By contrast, the gut-associated lymphoid tissue (GALT) is the most extensive lymphoid organ, housing up to 60% of total body lymphocytes, but has never been assessed with respect to senescence profiles. We report here the development of a method for measuring and comparing proliferative capacity of peripheral blood and gut colorectal mucosa-derived CD8 T cells. The protocol involves a 5-day culture of mononuclear leukocyte populations, from blood and gut colorectal mucosa respectively, labeled with 5-(and 6)-carboxyfluorescein diacetate succinimidyl ester (CFSE) and 5-bromo-2'-deoxyuridine (BrdU) and stimulated with anti-CD2/3/28-linked microbeads. Variables tested and optimized as part of the protocol development include: mode of T cell stimulation, CFSE concentration, inclusion of a second proliferation marker, BrdU, culture duration, initial culture concentration, and inclusion of autologous irradiated feeder cells. Moving forward, this protocol demonstrates a significant advance in the ability of researchers to study compartment-specific differences of in vitro proliferative dynamics of CD8 T cells, as an indicator of replicative senescence and immunological aging. The study's two main novel contributions are (1) Optimization and adaptation of standard proliferative dynamics blood T cell protocols for T cells within the mucosal immune system. (2) Introduction of the novel technique of combining CFSE and BrdU staining to do so., (Copyright © 2017 Elsevier B.V. All rights reserved.)

Purpose: The purpose of this study was to evaluate the use of a pressure mapping system with real-time feedback of pressure points in elderly care, with specific focus on pressure injury (PI) knowledge/attitudes (staff), interface pressure, and PI prevention activities (residents)., Design: Descriptive, 1-group pretest/posttest study., Subjects and Setting: A convenience sample of 40 assistant nurses and aides participated in the study; staff members were recruited at daytime, and 1 nighttime meeting was held at the facility. A convenience sample of 12 residents with risk for PI were recruited, 4 from each ward. Inclusion criteria were participants older than 65 years, Modified Norton Scale score 20 or less, and in need of help with turning in order to prevent PI. The study setting was a care facility for the elderly in Uppsala, Sweden., Methods: A descriptive, comparative pretest/posttest study design was used. The intervention consisted of the use of a pressure mapping system, combined with theoretical and practical teaching. Theoretical and practical information related to PI prevention and the pressure mapping system was presented to the staff. The staff (n = 40) completed the Pressure Ulcer Knowledge and Assessment Tool (PUKAT) and Attitudes towards Pressure Ulcer (APuP) before and following study intervention. Residents' beds were equipped with a pressure mapping system during 7 consecutive days. Peak pressures and preventive interventions were registered 3 times a day by trained study nurses, assistant nurses, and aides., Results: Staff members' PUKAT scores increased significantly (P = .002), while their attitude scores, which were high pretest, remained unchanged. Peak interface pressures were significantly reduced (P = .016), and more preventive interventions (n = 0.012) were implemented when the staff repositioned residents after feedback from the pressure mapping system., Conclusions: A limited educational intervention, combined with the use of a pressure mapping system, was successful as it improved staff members' knowledge about PI prevention, reduced interface pressure, and increased PI prevention activities. As many of the staff members lacked formal education in PI prevention and management, opportunities for teaching sessions and reflection upon PI prevention should be incorporated into the workplace. More research is needed to evaluate the effect of continuous pressure mapping on the incidence of PI.

Pancreatic polypeptide (PP) is an anorexigenic hormone released from pancreatic F cells upon food intake. We aimed to determine the effect of PP on gastric accommodation and gastric emptying in conscious Wistar HAN rats to investigate whether effects on motor function could contribute to its anorexigenic effects. Intragastric pressure (IGP) was measured through a chronically implanted gastric fistula during the infusion of a nutrient meal (Nutridrink; 0.5 ml/min). Rats were treated with PP (0, 33 and 100 pmol·kg(-1)·min(-1)) in combination with N(G)-nitro-L-arginine methyl ester (L-NAME; 180 mg·kg(-1)·h(-1)), atropine (3 mg·kg(-1)·h(-1)), or vehicle. Furthermore, the effect of PP was tested after subdiaphragmal vagotomy of the stomach. Gastric emptying of a noncaloric and a caloric meal after treatment with 100 pmol·kg(-1)·min(-1) PP or vehicle was compared using X-rays. PP significantly increased IGP during nutrient infusion compared with vehicle (P < 0.01). L-NAME and atropine significantly increased IGP during nutrient infusion compared with vehicle treatment (P < 0.005 and 0.01, respectively). The effect of PP on IGP during nutrient infusion was abolished in the presence of L-NAME and in the presence of atropine. In vagotomized rats, PP increased IGP compared with intact controls (P < 0.05). PP significantly delayed gastric emptying of both a noncaloric (P < 0.05) and a caloric (P < 0.005) meal. PP inhibits gastric accommodation and delays gastric emptying, probably through inhibition of nitric oxide release. These results indicate that, besides the well-known centrally mediated effects, PP might decrease food intake through peripheral mechanisms., (Copyright © 2014 the American Physiological Society.)

Inconsistencies between species has stunted the progress of developing new analgesics. To increase the success of translating results between species, improved comparable models are required. Twelve rats received rectal balloon distensions on 2 different days separated by 24.3 (SD 24.6) days. Rectal balloon distensions were also performed in 18 humans (mean age: 34 yr; range: 21-56 yr; 12 men) on two separate occasions, separated by 9.3 (SD 5.5) days. In rats, cerebral evoked potentials (CEPs) were recorded by use of implanted skull-electrodes to distension pressure of 80 mmHg. In humans surface electrodes and individualized pressure, corresponding to pain detection threshold, were used. Comparison of morphology was assessed by wavelet analysis. Within- and between-day reproducibility was assessed in terms of latencies, amplitudes, and frequency content. In rats CEPs showed triphasic morphology. No differences in latencies, amplitudes, and power distribution were seen within or between days (all P ≥ 0.5). Peak-to-peak amplitude between the first positive and negative potential were the most reproducible characteristic within and between days (evaluated by intraclass correlation coefficients, ICC) (ICC = 0.99 and ICC = 9.98, respectively). In humans CEPs showed a triphasic morphology. No differences in latencies, amplitudes, or power distribution were seen within or between days (all P ≥ 0.2). Latency to the second negative potential (ICC = 0.98) and the second positive potential (ICC = 0.95) was the most reproducible characteristic within and between days. A unique and reliable translational platform was established assessing visceral sensitivity in rats and humans, which may improve the translational process of developing new drugs targeting visceral pain.

Background/aims: Our aim was to investigate whether muscarinic and nicotinic receptors mediate nitric oxide release during motor events in the rat stomach., Methods: Isolated rat stomach volume changes were monitored in an organ bath setup with an intragastric balloon coupled to a barostat and studied in basal conditions and during electrical vagal stimulation (EVS). In conscious rats, the intragastric pressure (IGP) was measured during test meal infusion., Results: In the presence of N(G)-nitro-L-arginine methyl ester (L-NAME; 0.1 mmol/l), EVS induced significant gastric contractions (mean +/- SEM = 0.27 +/- 0.04 ml; n = 6) that could be blocked by atropine (3 micromol/l) and hexamethonium (0.1 mmol/l). In the presence of atropine and/or hexamethonium, EVS-induced relaxations could not be blocked by L-NAME, while exogenous nitric oxide could still relax the stomach. In conscious rats, atropine (1 mg kg(-1)) initially decreased IGP, while during further distension it increased IGP. In the presence of L-NAME (30 mg kg(-1)) atropine consistently decreased IGP. L-NAME alone significantly increased IGP during the test meal infusion, but this effect was reduced in the presence of atropine., Conclusion: These findings indicate a role for nicotinic and muscarinic receptors in the vagal-stimulation-induced activation of nitrergic nerves in the rat stomach., (Copyright 2010 S. Karger AG, Basel.)

A novel method has been developed for simultaneous study of gastric emptying, antral motility, and gastric muscle tone in conscious mice. Intragastric pressure was measured during infusion of an X-ray-opaque, viscous meal through a chronically implanted gastric fistula (0.25 ml/min). Compared with vehicle treatment, molsidomine (nitric oxide donor) and atropine (muscarinic receptor antagonist) treatment significantly reduced the area under the intragastric pressure curve (AUC) by 37 +/- 4% and 35 +/- 3%, respectively, (mean +/- S.E.M.) whereas N (G)-nitro-L-arginine methyl ester (L-NAME; nitric oxide synthase inhibitor) significantly increased the AUC by 20 +/- 3%. Atropine also significantly reduced the frequency and amplitude of stomach contraction-induced intragastric pressure waves while molsidomine only reduced the frequency. Gastric emptying, as assessed by X-ray imaging, was significantly delayed after L-NAME and atropine treatment. This methodology is the first to enable simultaneous assessment of gastric emptying, antral motility, and gastric tone in conscious mice and confirmed the important role of nitrergic and cholinergic innervation.

Background: Computed tomography (CT) has been developed as a tool for monitoring human inflammatory bowel disease (IBD). The aim of this study was to evaluate colon wall thickness as a noninvasive marker in the dextran sodium sulfate (DSS) mouse model of colitis using micro-CT., Methods: Mice were examined by micro-CT 1, 2, or 4 times between day 0 (d0) and d26 after induction of colitis to document the kinetics of changes in colon wall thickness and its relation to colitis development., Results: DSS-treated mice displayed a significantly thicker colon wall at all timepoints (days 5, 8, 12, 19, and 26) investigated compared to healthy controls. Colon wall thickness showed a good correlation to the macroscopic grading of colitis (r = 0.81). The increase in colon wall thickness occurred mainly during the acute phase of colitis (between days 5 and 12) and did not progress much further in the chronic phase of colitis (d26). Colon wall thickness at d26 was thereby predicted by measurements at d12. All mice did not respond equally to DSS and this difference was manifest during the first 2 weeks of colitis, providing an important tool in stratifying responders from nonresponders., Conclusions: While the potential impact of handling and anesthesia should be considered on repeated micro-CT, irradiation exposure during repeated micro-CT did not affect the development of colitis. Thus, the results suggest that micro-CT can be used for monitoring and prediction of the inflammatory response in mouse colitis in future therapeutic studies.

Inhibition of gastric emptying rate can have adverse effects on the absorption of food and nutrients. The absorption phase of the plasma concentration-time profile of a compound administered orally to pre-clinical species reflects among others, the gastric and intestinal transit kinetics, and can thus assist in the early identification of delayed gastric emptying. The purpose of this article is to demonstrate the value of Physiologically Based Pharmacokinetic (PBPK) modelling in the early identification of drug induced impairment of gastric emptying from pharmacokinetic profiles. To our knowledge, this is first time that the value of a generic PBPK model for hypothesis testing has been demonstrated with examples. A PBPK model built in-house using MATLAB package and incorporating absorption, metabolism, distribution, biliary and renal elimination models has been employed for the simulation of concentration-time profiles. PBPK simulations of a few compounds that are currently in drug discovery projects show that the observed initial absorption phase of their concentration-time profiles in rat were consistent with reduced gastric emptying rates. The slow uptake of these compounds into the systemic circulation is reflected in their pharmacokinetic profiles but it is not obvious until PBPK simulations are done. Delayed gastric emptying rates of these compounds in rats were also independently observed in x-ray imaging. PBPK simulations can provide early alerts to drug discovery projects, besides aiding the understanding of complex mechanisms that determine the lineshapes of pharmacokinetic profiles. The application of PBPK simulations in the early detection of gastric emptying problems with existing data and without the need to resort to additional animal studies, is appealing both from an economic and ethical standpoint.

Objective: To simultaneously study gastric accommodation and peristaltic motility in the whole stomach of conscious rats by measuring intragastric pressure (IGP) during test-meal infusion., Material and Methods: After an overnight fast, a test-meal infusion system and a catheter to measure IGP were connected to a chronically implanted gastric fistula. IGP was measured during infusion of an X-ray-opaque, non-nutritious viscous test meal (0.25-2 ml min(-1)); gastric motility and emptying were assessed by X-ray fluoroscopy. Peristaltic motility-induced IGP waves were quantified as a motility index (wave amplitude divided by wavelength). Experiments were performed in Sprague-Dawley (SD) rats and in the high-anxiety Wistar Kyoto (WKY) rats. Moreover, the effects of 30 mg kg(-1) NG-nitro-L-arginine methyl ester (L-NAME), 1 mg kg(-1) atropine or 20 mg kg(-1) molsidomine were tested in SD rats., Results: Compared with SD rats, IGP increased significantly faster during stomach distension in WKY rats, indicating impaired accommodation in the latter strain. Motility indices did not differ between the two strains. L-NAME significantly increased IGP during stomach distension, indicating decreased gastric accommodation. However, no change in motility indices was observed with L-NAME. Treatment with atropine significantly increased IGP and decreased motility indices, indicating decreased gastric accommodation and motility. Molsidomine significantly decreased IGP during stomach distension but did not affect motility. The results correspond to X-ray observations, and confirm literature data., Conclusions: We conclude that IGP measurement during test-meal infusion represents an efficient and novel method to compare gastric accommodation and peristaltic motility in the whole stomach of conscious rats.

Purpose: To evaluate whether MRI signal and T2* measurements of lung tissue acquired at ultrashort detection times (tds) can detect emphysematous changes in lungs., Materials and Methods: MR signal intensity of in vivo mouse lungs was measured at 4.7 T at tds of 0.2 and 0.4 msec using single-point imaging (SPI). T2* was calculated from the measurements obtained at the two tds. Two groups of 8- and 30-week-old Tight Skin (TS) and aged-matched CB57BL/6 mice were examined. The TS mice spontaneously developed emphysema-like alveolar enlargement. In vivo micro-computed tomography (microCT) scanning and histology were used as reference methods., Results: MR signal and T2* were significantly lower in the lungs of TS mice than in controls. There were no significant differences between the different age groups. MR signal in lung parenchyma correlated linearly (P < 0.0001, r = 0.89) with microCT mass density, and T2* correlated linearly (P < 0.0001, r = -0.91) with the alveoli size (mean linear intercept [MLI])., Conclusion: The MR signal intensity and T2* measured at short tds can be used as imaging biomarkers to characterize parenchyma density and alveolar size, respectively.