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Abstract Background Premature newborns admitted to neonatal intensive care units (NICUs) undergo numerous painful interventions during care and treatment. The purpose of this study was to compare the effects of using sucrose and kangaroo mother care by on selected physiological variables and pain resulting from venipuncture in premature infants admitted to NICUs affiliated with Shiraz University of Medical Sciences. Methods This clinical trial included premature infants admitted to 2 NICUs. The sample size consisted of 66 neonates, with 22 newborns in each group. Randomization was performed using the block allocation method. Data collection involved a demographic questionnaire, the neonatal infant pain scale, and a pulse oximetry device. Friedman, Kruskal–Wallis, and Dunn’s post hoc tests employed for data analysis, with a significance level of P

Oxygen deprivation and excess are both toxic. Thus, the bodys ability to adapt to varying oxygen tensions is critical for survival. While the hypoxia transcriptional response has been well studied, the post-translational effects of oxygen have been underexplored. In this study, we systematically investigate protein turnover rates in mouse heart, lung, and brain under different inhaled oxygen tensions. We find that the lung proteome is the most responsive to varying oxygen tensions. In particular, several extracellular matrix (ECM) proteins are stabilized in the lung under both hypoxia and hyperoxia. Furthermore, we show that complex 1 of the electron transport chain is destabilized in hyperoxia, in accordance with the exacerbation of associated disease models by hyperoxia and rescue by hypoxia. Moreover, we nominate MYBBP1A as a hyperoxia transcriptional regulator, particularly in the context of rRNA homeostasis. Overall, our study highlights the importance of varying oxygen tensions on protein turnover rates and identifies tissue-specific mediators of oxygen-dependent responses.

SUMMARY: This experiment aimed to assess the effects of combining early or late feeding programs with prebiotics on the growth performance, carcass characteristics, blood metabolites, mucin-2 gene expression, and intestinal morphology of broiler chickens. A total of 720 day-old male and female (50:50) broiler chicks were randomly assigned to a 2 × 3 factorial arrangement with 24 experimental units (pens) and 30 birds/pen for 6 wk. Six treatments consisted of 2 feeding programs (early: fed at hatchery; or late: 48 h feed deprivation) and 3 levels of prebiotic supplementation (none, recommended dosage, or 3 times the recommended dosage). Late access to feed during the starter phase resulted in decreased feed intake (FI) and weight gain (WG), as well as increased feed conversion ratio (FCR) (P < 0.05). During the entire rearing period, broilers in the early feeding program, fed diets without prebiotics had higher mortality rates compared to other treatment groups (P < 0.05). Also, the feeding programs and inclusion of prebiotics in the diets did not have a significant effect on FI, WG, or FCR. In both feeding programs, the supplementation of prebiotic resulted in improved ileal morphology indicators and increased mucin-2 gene expression (P < 0.05). The use of prebiotic in both the early and late access to feed groups led to decreased serum levels of triglycerides and uric acid (P < 0.05). In conclusion, late access to feed negatively affected the early growth performance of broiler chicks. Prebiotic supplementation positively influenced mucin-2 gene expression, especially in early feeding programs. Early feed access combined with prebiotics improved intestinal health compared to late access. While prebiotic did not affect overall growth performance, it reduced mortality rates. Further studies are recommended.

Background: Aromatherapy is a modality within the realm of alternative medicine to manage pain and alleviate anxiety in high-stress circumstances. The primary objective of this study was to examine the impact of damask rose on the levels of anxiety and pain experienced by patients under endoscopic lithotripsy. Methods: The present double-blind randomized clinical trial was conducted at hospitals in Shiraz, Iran, in 2022, involving 120 patients undergoing endoscopic lithotripsy. These patients were randomly allocated into control and intervention groups using a permuted block design. The data collection was done using the Spielberger and the Visual Analog Scale questionnaires at three stages: the baseline period, the pre-operative holding area, and six hours following the surgical procedure. The intervention group was exposed to a cotton swab infused with three drops of damask rose for a duration of 30 minutes. The data analysis included descriptive statistics, repeated measure analysis of variance, and pairwise comparisons utilizing the Bonferroni post hoc test. Results: The mean levels of overt anxiety in the intervention group during the first and second phases of the intervention were 46.17±7.18 (P

Objective: Compiling and designing short and practical psychometric tools are among the benefits and strengths of a good standard test. The Delirium-O-Meter questionnaire measures patients' delirium status. Accordingly, the main aim of this research was to check the reliability and validity of the Persian version of this questionnaire. Method: This exploratory psychometric study was conducted from 2021 to 2022 at the therapeutic research training centers of Tabriz University of Medical Sciences. The study population included patients diagnosed with delirium. Content and construct validity were assessed using exploratory factor analysis and confirmatory factor analysis. Exploratory factor analysis was performed using SPSS 18, which helped identify the underlying factor structure, while confirmatory factor analysis in Smart PLS was employed to confirm the structure's fit. Pearson correlation was used to evaluate the consistency between different raters, and Cronbach's alpha was calculated to assess internal consistency. These methods were selected for their robustness in evaluating the instrument's psychometric properties, ensuring the reliability and validity of the Persian version of the Delirium-O-Meter questionnaire. Results: The Persian version of the Delirium-O-Meter questionnaire, consisting of 11 items, demonstrated strong psychometric properties. The average impact factor was 3.24, indicating a high relevance of the items. The content validity ratio was 0.78, and the content validity index was 0.87, both above the acceptable thresholds, confirming the content validity of the questionnaire. Cronbach's alpha coefficient for the entire questionnaire was 0.77, reflecting good internal consistency. The Kaiser-Meyer-Olkin index was 0.88, and Bartlett's sphericity test was significant (χ² = 278.45, P < 0.001), indicating the appropriateness of the data for factor analysis. Exploratory factor analysis revealed two factors that explained 76.09% of the total variance, supporting the questionnaire's construct validity. Additionally, Pearson’s correlation coefficient between the assessments of two nurses was 0.91, signifying inter-rater solid reliability. Conclusion: The Persian version of the Delirium-O-Meter questionnaire demonstrates acceptable reliability and validity, as confirmed by the comprehensive psychometric evaluation conducted in this study. The strong internal consistency, significant content and construct validity, and high inter-rater reliability underscore its effectiveness in assessing delirium in Persian-speaking patients. These findings highlight the questionnaire's suitability for clinical use, providing a reliable and valid instrument for accurately diagnosing and managing delirium in diverse healthcare settings.

Author(s): Rita T. Amiel Castro [sup.1] , Nora K. Schaal [sup.2] , Hannah Meyerhoff [sup.1] , Heidi Preis [sup.3] [sup.4] , Brittain Mahaffey [sup.3] , Marci Lobel [sup.3] [sup.4] , [...], Objectives Pregnant women are likely to experience high levels of stress during the COVID-19 pandemic. However, the factors that might influence the extent of experienced emotional distress are poorly understood. Therefore, we aimed to investigate potential correlates of prenatal emotional distress during the COVID-19 pandemic. Methods In total, N = 1437 pregnant women from Germany and Switzerland participated in an online study during the first wave of the COVID-19 pandemic (May-August 2020). The survey assessed prenatal distress, pandemic-related pregnancy stress, general anxiety, fear of childbirth, and several socio-demographic, pregnancy- and COVID-19-related factors. Linear multivariate regression models were the main analytical strategy. Results The results highlight that several factors such as full-time employment, nulliparity, high-risk pregnancy, emotional problems, cancelled prenatal appointments, and stating that COVID-19 affected the choice of birth mode were significantly associated with elevated prenatal distress, anxiety, pandemic-related pregnancy stress, and fear of childbirth. Conversely, access to an outdoor space was a protective factor for pandemic-related pregnancy stress and prenatal distress. Conclusions for Practice Overall, the study highlights significant correlates influencing the levels of emotional distress pregnant women experienced during the COVID-19 pandemic. These findings may contribute to the improvement of maternal prenatal medical and psychological care during a public health crisis of international concern, such as the COVID-19 pandemic.

Abstract Background The aim of the current study is to assess the prevalence of different categories of thyroid dysfunction and their associated risk factors among the modern urban population of Tehran, the capital of Iran. Methods The present investigation is a sub-study of the HAMRAH study, a population-based prospective study designed to assess the prevalence of traditional cardiovascular risk factors and their changes through a 10-year follow-up. 2228 (61% female) adults aged between 30 and 75 years old and with no overt cardiovascular diseases were selected through a multistage cluster randomized sampling. Blood levels of thyroid-stimulating hormone (TSH), thyroxin (T4), and triiodothyronine (T3) were measured with the aim of assessing the prevalence of abnormal thyroid function status among the modern urban Iranian population, and in order to report the total prevalence of participants with clinical hypo- or hyperthyroidism, the number of individuals taking thyroid-related drugs were added to the ones with overt thyroid dysfunction. A subgroup analysis was also performed to determine the associated risk factors of thyroid dysfunction. Results The prevalence of thyroid dysfunction among the total population was 7% (95%CI: 5.9 − 8%) and 0.4% (95% CI: 0.1 − 0.6%) for subclinical and overt hypothyroidism, and 1.6% (95% CI: 1 − 2%) and 0.2% (95% CI: 0 − 0.3%) for subclinical and overt hyperthyroidism, respectively. Clinical thyroid dysfunction was detected in 10.3% of the study population (9.4% had clinical hypo- and 0.9% had clinical hyperthyroidism). In the subgroup analysis, thyroid dysfunction was significantly more prevalent among the female participants (P-value = 0.029). Conclusions In the current study, the prevalence of different categories of abnormal thyroid status, and also the rate of clinical hypo- and hyperthyroidism was assessed using the data collected from the first phase of the HAMRAH Study. In this study, we detected a higher prevalence of clinical and subclinical hypothyroidism among the Iranian population compared to the previous studies.

Background & Aims Some studies have reported a high risk of metabolic syndrome among women and night shift workers. This study aims to determine the status of metabolic syndrome laboratory indicators and thyroid function tests in nurses working in Rajaei Cardiovascular, Medical, & Research Center (RCMRC) in Tehran, Iran, in 2020-2021. Materials & Methods This is a descriptive cross-sectional study on the health records of nurses working in RCMRC. The sampling was done using a census method. Records with incomplete information were excluded. A form containing demographic characteristics, thyroid function indicators, and metabolic syndrome laboratory indicators was used to collect data from the health records. Data analysis was performed in SPSS software, version 26. Results Out of 401 reviewed records, 339 cases (84.5%) were for female nurses. The mean age of nurses was 37.47±8.68 years, and their mean work experience was 13.17±8.07 years. According to the criteria of the American Heart Association and the National Heart, Lung, and Blood Institute, the prevalence of abnormalities in metabolic syndrome laboratory tests was 5.21%, while according to the National Cholesterol Education Program III criteria, it was 2.99%. The prevalence of clinical hypothyroidism was 0.2%; subclinical hypothyroidism, 12.0%; and subclinical hyperthyroidism, 1.5%. Conclusion The prevalence of metabolic syndrome and thyroid disorders among nurses working in RCMRC is not considerable. Further large-scale studies (cohort or longitudinal) are recommended.

Liver fibrosis is a complex, dynamic process associated with a broad spectrum of chronic liver diseases and acute liver failure, characterised by the dysregulated intrahepatic production of extracellular matrix proteins replacing functional liver cells with scar tissue. Fibrosis progresses due to an interrelated cycle of hepatocellular injury, triggering a persistent wound-healing response. The accumulation of scar tissue and chronic inflammation can eventually lead to cirrhosis and hepatocellular carcinoma. Currently, no therapies exist to directly treat or reverse liver fibrosis; hence, it remains a substantial global disease burden. A better understanding of the intricate inflammatory network that drives the initiation and maintenance of liver fibrosis to enable the rationale design of new intervention strategies is required. This review clarifies the most current understanding of the hepatic fibrosis cellular network with a focus on the role of regulatory T cells, and a possible trajectory for T cell immunotherapy in fibrosis treatment. Despite good progress in elucidating the role of the immune system in liver fibrosis, future work to better define the function of different immune cells and their mediators at different fibrotic stages is needed, which will enhance the development of new therapies.

Abstract Introduction All businesses that deal directly with clients need to observe ethics, but in the nursing profession due to its nature, compliance with professional ethics becomes more necessary. On the other hand, nurses face tensions and difficult conditions in their daily work environment. Resilience is one of the most important abilities of human beings, which in difficult conditions causes effective adaptation to stress-causing factors. Therefore, the relationship between resilience and professional ethics becomes important. The aim of the study The present study was conducted to investigate the relationship between resilience and professional ethics in nurses of Shahid Ganji Hospital, Borazjan 2022–2023. Methods The current study is a cross-sectional descriptive-analytical study. The study environment was Shahid Ganji Hospital in Borazjan, Bushehr, Iran. The research method of the current study was census, so all 400 nurses of this hospital were invited to participate in the study. Finally, 340 of them were included in the study based on the inclusion criteria. Data collection tools included a demographic information form, Connor-Davidson questionnaire, and Cadozier professional ethics questionnaire. Data analysis was done using SPSS version 22 software. Results Most of the participants were between 25 and 30 years old. The average overall score of resilience and professional ethics of nurses participating in the study was 64.1 ± 16.3 and 34.3 ± 9.4, respectively. No significant difference was observed between the demographic characteristics of nurses with resilience and professional ethics. The Spearman correlation coefficient indicated a statistically significant and inverse relationship between professional ethics and resilience levels (r = -0.265, P

Abstract Objective Otitis media with effusion is common in children with cleft palates. This study aimed to investigate the link between palatal closure techniques and audiological outcomes. Methods In this retrospective‐prospective cohort study, we examined the relationship between palate repair techniques and hearing outcomes in children with cleft palates. From 2017 to 2022, 190 ears of 95 cleft patients were studied at the Cleft Lip and Palate Department of Shiraz University of Medical Sciences. Variables assessed included the surgical technique, cleft severity, auditory brainstem response (ABR) threshold, and tympanometry configuration. Results The mean ABR improved from a prepalatoplasty value of 39.51(11.62) decibels (dB) to a postpalatoplasty mean of 26.61(11.60) dB (Cohen's d: 1.12 [95% CI; 0.90–1.34]). Initially, 87.9% of the studied ears exhibited abnormal tympanometry, but this significantly decreased to 47% postsurgery (risk ratio: 4.43 [95% CI; 1.20–16.43]). When compared with Sommerlad intravelar veloplasty, the Nadjmi modified Furlow palatoplasty was associated with a notably lower mean ABR (β: −6.58 [95% CI: −10.43 to −2.73], p‐value = .001) and a reduced frequency of abnormal tympanometry (odds ratio [OR]: −1.10; 95% CI: −1.85 to −0.36, p‐value = .004). Factors like prepalatoplasty ABR, cleft palate severity, gender, and syndromic did not confound these findings. Conclusions Although the Nadjmi modified Furlow palatoplasty showed better results, our findings indicate a significant improvement in ABR and tympanometry outcomes for both techniques. Future randomized controlled trials are suggested to confirm the influence of palatal closure techniques on audiological outcomes. Level of Evidence 3b.

Abstract A key goal for implanted medical devices is that they do not elicit a detrimental immune response. Macrophages play critical roles in the modulation of the host immune response and are the cells responsible for persistent inflammatory reactions to implanted biomaterials. Two novel immune‐instructive polymers that stimulate pro‐ or anti‐inflammatory responses from macrophages in vitro are investigated. These also modulate in vivo foreign body responses (FBR) when implanted subcutaneously in mice. Immunofluorescent staining of tissue abutting the polymer reveals responses consistent with pro‐ or anti‐inflammatory responses previously described for these polymers. Three Dimensional OrbiTrap Secondary Ion Mass Spectrometry (3D OrbiSIMS) analysis to spatially characterize the metabolites in the tissue surrounding the implant, providing molecular histology insight into the metabolite response in the host is applied. For the pro‐inflammatory polymer, monoacylglycerols (MG) and diacylglycerols (DG) are observed at increased intensity, while for the anti‐inflammatory coating, the number of phospholipid species detected decreased, and pyridine and pyrimidine levels are elevated. Small molecule signatures from single‐cell studies of M2 macrophages in vitro correlate with the in vivo observations, suggesting potential for prediction. Metabolite characterization by the 3D OrbiSIMS is shown to provide insight into the mechanism of bio‐instructive materials as medical devices and to inform on the FBR to biomaterials.

Abstract Dendritic cells (DCs) are part of the innate immune system with a key role in initiating and modulating T cell mediated immune responses. Coeliac disease is caused by inappropriate activation of such a response leading to small intestinal inflammation when gluten is ingested. Tissue transglutaminase, an extracellular matrix (ECM) protein, has an established role in coeliac disease; however, little work to date has examined its impact on DCs. The aim of this study was to investigate the effect of small intestinal ECM proteins, fibronectin (FN) and tissue transglutaminase 2 (TG-2), on human DCs by including these proteins in DC cultures. The study used flow cytometry and scanning electron microscopy to determine the effect of FN and TG-2 on phenotype, endocytic ability and and morphology of DCs. Furthermore, DCs treated with FN and TG-2 were cultured with T cells and subsequent T cell proliferation and cytokine profile was determined. The data indicate that transglutaminase affected DCs in a concentration-dependent manner. High concentrations were associated with a more mature phenotype and increased ability to stimulate T cells, while lower concentrations led to maintenance of an immature phenotype. These data provide support for an additional role for transglutaminase in coeliac disease and demonstrate the potential of in vitro modelling of coeliac disease pathogenesis.

Abstract Objective This study aimed to evaluate the inflammatory effect of diet using the dietary Inflammatory Index (DII) on the odds of periodontitis. We hypothesized that a diet with high DII scores (a pro-inflammatory diet) is associated with high chronic and systematic inflammation resulting in periodontitis. Periodontitis is one of the most common inflammatory diseases that affect the tissues around the tooth and results from the interaction of bacterial infection and the host immune response. The DII shows the association between different food components and the level of specific inflammatory biomarkers. Method The food intake of 87 cases with diagnosed periodontitis and 87 control was assessed using a 163-item valid food frequency questionnaire (FFQ). The DII was calculated based on the FFQ data. Logistic and linear regression models adjusting for multivariable confounders were used to investigate the odds ratio (OR) and 95% confidence intervals (CI) of developing periodontitis. Results There was a significant difference between the mean intake of micronutrients and food groups, including saturated fatty acids (SFAs), iron, magnesium, manganese, vitamin C, crude fiber, selenium, chromium, whole fiber, caffeine, dairy, and meat, between patients with periodontitis and the control group (p-value˂0.05). DII scores in this study ranged from -3.13 to + 0.99. However, the periodontitis OR in the raw and multivariable-adjusted models was not statistically significant (multivariable-adjusted OR tertiles 1 vs. tertiles 3 = 2.00, 95%CI: 0.4–90.42, p-value = 0.08). A similar result was also observed in the continuous model of DII (multivariable-adjusted OR DII continuous = 1.93, 95%CI: 0.30–98.79, p-value = 0.05). Conclusion Although the OR was not statistically significant in crude models, a significant trend was found in multivariable-adjusted models. The results were promising since this is the first study to examine the association between diet-induced inflammation and dental disease. It is advisable to conduct additional studies with high sample sizes and other designs, such as prospective studies.

Biomaterials are designed to interact with biological systems to replace, support, enhance, or monitor their function. However, there are challenges associated with traditional biomaterials’ development due to the lack of underlying theory governing cell response to materials’ chemistry. This leads to the time-consuming process of testing different materials plus the adverse reactions in the body such as cytotoxicity and foreign body response. High-throughput screening (HTS) offers a solution to these challenges by enabling rapid and simultaneous testing of a large number of materials to determine their bio-interactions and biocompatibility. Secreted proteins regulate many physiological functions and determine the success of implanted biomaterials through directing cell behaviour. However, the majority of biomaterials’ HTS platforms are suitable for microscopic analyses of cell behaviour and not for investigating non-adherent cells or measuring cell secretions. Here, we describe a multi-well platform adaptable to robotic printing of polymers and suitable for secretome profiling of both adherent and non-adherent cells. We detail the platform's development steps, encompassing the preparation of individual cell culture chambers, polymer printing, and the culture environment, as well as examples to demonstrate surface chemical characterisation and biological assessments of secreted mediators. Such platforms will no doubt facilitate the discovery of novel biomaterials and broaden their scope by adapting wider arrays of cell types and incorporating assessments of both secretome and cell-bound interactions.Key features• Detailed protocols for preparation of substrate for contact printing of acrylate-based polymers including O2 plasma etching, functionalisation process, and Poly(2-hydroxyethyl methacrylate) (pHEMA) dip coating.• Preparations of 7 mm × 7 mm polymers employing pin printing system.• Provision of confined area for each polymer using ProPlate® multi-well chambers.• Compatibility of this platform was validated using adherent cells [primary human monocyte–derived macrophages (MDMs)) and non-adherent cells (primary human monocyte–derived dendritic cells (moDCs)].• Examples of the adaptability of the platform for secretome analysis including five different cytokines using enzyme-linked immunosorbent assay (ELISA, DuoSet®).Graphical overview

Jessel et al. ("Behavior Analysis & Practice," 13(1), 205-216, 2020a) conducted a review of the functional analysis literature between the years 1965 and 2016. The authors found an increasing trend in analyses replicating the components of Iwata et al. ("Journal of Applied Behavior Analysis," 27, 197-209, 1982/1994a) and determined that those components have come to represent a standard format. Since the inception of the standard, other functional analysis formats (e.g., brief, latency-based, trial-based) have been developed to improve analysis efficiency and control, with most retaining fundamental components of the standard and some omitting all (e.g., interview-informed, synthesized contingency analysis; IISCA). We conducted a review of functional analyses in this two-part evaluation to determine the levels of efficiency and control afforded by functional analysis variations and formats.

Abstract The lifespans of proteins range from minutes to years within mammalian tissues. Protein lifespan is relevant to organismal aging, as long‐lived proteins accrue damage over time. It is unclear how protein lifetime is shaped by tissue context, where both cell turnover and proteolytic degradation contribute to protein turnover. We develop turnover and replication analysis by 15N isotope labeling (TRAIL) to quantify protein and cell lifetimes with high precision and demonstrate that cell turnover, sequence‐encoded features, and environmental factors modulate protein lifespan across tissues. Cell and protein turnover flux are comparable in proliferative tissues, while protein turnover outpaces cell turnover in slowly proliferative tissues. Physicochemical features such as hydrophobicity, charge, and disorder influence protein turnover in slowly proliferative tissues, but protein turnover is much less sequence‐selective in highly proliferative tissues. Protein lifetimes vary nonrandomly across tissues after correcting for cell turnover. Multiprotein complexes such as the ribosome have consistent lifetimes across tissues, while mitochondria, peroxisomes, and lipid droplets have variable lifetimes. TRAIL can be used to explore how environment, aging, and disease affect tissue homeostasis.

Background: One of the factors effective in controlling acute coronary syndrome (ACS) symptoms, such as heart failure, is sufficient knowledge of the disease, factors effective on its occurrence, and its prevention. Moreover, the improvement of self-efficacy, which is a predictor of important life factors in these patients, such as treatment process and quality of life (QOL), must be considered as one of the main goals of nursing care for these patients. The aim of this study was to determine the effect of the family-centered self-care program on the health literacy level and self-efficacy of patients with ACS during hospital discharge. Materials and Methods: The present study was a quasi-experimental study performed with a pretest-posttest design. The statistical population of the study consisted of all patients with ACS hospitalized at Shahid Chamran Hospital in Isfahan in 2020. Through the convenience sampling method, 50 patients were selected and randomly divided into intervention and control groups. For the intervention group, 6 sessions of 45–60 minutes of family-centered self-care intervention were held. The subjects completed the Health Literacy for Iranian Adults (HELIA) questionnaire before and after the intervention. Data were analyzed using Chi-square test, independent t-test, and paired t-test in the SPSS statistical software. Results: The mean score of health literacy did not significantly differ between the intervention and control groups before the intervention (p > 0.050). However, after the intervention, this rate was equal to 82.16 (7.94) and 60.85 (15.71) in the intervention and control groups, respectively, which was significantly higher in the intervention group compared to the control group (p < 0.001). Furthermore, there was no significant difference between the two groups in terms of the mean self-efficacy score before the intervention (p > 0.05). However, after the intervention, this score was significantly higher in the intervention group 34.71 (10.11) compared to the control group 35.22 (13.30). Conclusions: Family-centered self-care program after discharge, as a simple, applicable, and efficient method can improve the health literacy level and self-efficacy of patients with ACS.

Key Clinical Message In patients presenting with aortic ectasia and myxomatous valve diseases at young ages, possible underlying acromegaly should be in mind. Abstract Acromegaly is a chronic systemic disease mainly caused by the benign pituitary adenoma secreting growth hormone (GH) in excess. Acromegaly is associated with various complications such as cardiovascular diseases. In this regard, timely diagnosis, and management of these patients could be life‐saving. Herein, a case of aneurysmal dilation of the sinus of Valsalva with severe aortic and mitral regurgitation in a patient with undiagnosed acromegaly is presented.

The Three-dimensional OrbiTrap Secondary Ion Mass Spectrometry (3D OrbiSIMS) is a secondary ion mass spectrometry instrument, a combination of a Time of Flight (ToF) instrument with an Orbitrap analyzer. The 3D OrbiSIMS technique is a powerful tool for metabolic profiling in biological samples. This can be achieved at subcellular spatial resolution, high sensitivity, and high mass-resolving power coupled with MS/MS analysis. Characterizing the metabolic signature of macrophage subsets within tissue sections offers great potential to understand the response of the human immune system to implanted biomaterials. Here, we describe a protocol for direct analysis of individual cells after in vitro differentiation of naïve monocytes into M1 and M2 phenotypes using cytokines. As a first step in vivo, we investigate explanted silicon catheter sections as a medical device in a rodent model of foreign body response. Protocols are presented to allow the host response to different immune instructive materials to be compared. The first demonstration of this capability illustrates the great potential of direct cell and tissue section analysis for in situ metabolite profiling to probe functional phenotypes using molecular signatures. Details of the in vitro cell approach, materials, sample preparation, and explant handling are presented, in addition to the data acquisition approaches and the data analysis pipelines required to achieve useful interpretation of these complex spectra. This method is useful for in situ characterization of both in vitro single cells and ex vivo tissue sections. This will aid the understanding of the immune response to medical implants by informing the design of immune-instructive biomaterials with positive interactions. It can also be used to investigate a broad range of other clinically relevant therapeutics and immune dysregulations.Graphical overview