Ethical challenges during critical phases of the COVID-19 pandemic: An interpretive synthesis.

BACKGROUND: During the most critical phases of COVID-19 pandemic, dramatic situations were experienced in hospitals and care centers that nurses could hardly verbalize. Especially relevant were deep challenges related to terminal illness, situations of extreme sacrifice, as well as reflections on protective measures mixed with beliefs. We intend to analyze which problems had the greatest impact on professionals. AIM: The aim is to explore the ultimate basis for action when making decisions and the orientation of their behavior in the face of moral conflicts. METHOD: The methodological strategy is an interpretive synthesis. Narrative review of academic articles that analyzed ethical dilemmas during the pandemic was carried out by searching five databases (Pubmed, Scopus, Psycinfo, CINHAL, and WOS) between January 2020 and December 2022. Finally, 43 articles were selected. ETHICAL CONSIDERATIONS: Ethical requirements were respected in all study phases. RESULTS: The reading and review of the 43 articles initiated the first phase of inductive coding which resulted in 14 initial sub-themes. Based on this structure, a second phase of coding was carried out, giving rise to six categories or emerging themes. To facilitate the process of identifying the central category, the authors agreed to carry out a phase of synthesis, grouping the six themes into three meta-themes: the identification and acceptance of human vulnerability; the discovery of positive paradigms in traumatic situations in society; the prevalence of the common good over the particular interest, as the core structure of any society. CONCLUSION: The study has shown the need to consider healthcare benevolence as a new dimension of health care upon global vulnerability. Responsibility is required to ensure the well-being of a global society, prioritizing the common good over particular interests and building solutions on solid moral structures. A new ethical landscape is essential, starting with a humanistic curricular training of all healthcare professionals.

Evaluation of relational factor in patient satisfaction with the treatment received by dental students.

INTRODUCTION: The study focused on the importance of the relational factor and empathy in the general satisfaction of patients for the treatment received by university dental students. To achieve this objective, a tool capable of evaluating the most humanistic dimensions (empathy, kindness, trust) in the development of dental treatment has been designed. MATERIALS AND METHODS: A review of the literature was carried out and, based on its findings, a questionnaire was designed to assess patient satisfaction with the dental student's empathy. It consisted of 20 questions and was completed by 80 patients. The questionnaire was subjected to a validation process using the Delphi method (content validity) and psychometric analysis (construct validity), through a principal components analysis (PCA). RESULTS: The results of the PCA showed the existence of four components that suggest grouping the 20 questions into three blocks with a sequential structure, in which the questions would describe the patient's satisfaction throughout their treatment: reception and explanation of the treatment; development and progress of treatment; and expectations and completion of treatment. In each of these blocks, satisfaction was determined by a specific humanistic dimension: communication, trust and benevolence. CONCLUSION: The validated questionnaire is an effective tool to analyse the relational factors that determine patient satisfaction in a treatment. Furthermore, the analysis of the questionnaire suggests that communication, trust and benevolence are elements that acquire singular importance throughout the care process. This analysis is essential for the acquisition of humanistic skills by future professionals and to optimize the dentist-patient relationship.

The Impact of Patients' Primary Language on Inpatient Gastrointestinal Bleeding Outcomes.

BACKGROUND: The impact of English proficiency on gastrointestinal bleeding (GIB) outcomes remains unclear. In this analysis, we compare inpatient GIB outcomes between patients with English as their primary language (EPL) and those with a primary language other than English (PLOE). METHODS: Using the 2019 State Inpatient Databases for New Jersey, Maryland, and Michigan, we created an analysis cohort of GIB hospitalizations using International Classification of Diseases, 10th Revision codes. Patients were stratified by primary language (EPL vs PLOE) and type of bleeding (variceal upper GI bleeding [VUGIB], nonvariceal upper GI bleeding [NVUGIB], and lower GI bleeding (LGIB)]. Regression analyses were used to compare mortality, 30-day readmissions, and length of stay. Adjusted odds ratios (aORs) and 95% confidence intervals (CIs) were reported. P < 0.05 was considered statistically significant. RESULTS: In the cohort, 5.5%-10% of the patients spoke a primary language other than English. Endoscopy utilization was lower among patients with PLOE vs EPL for NVUGIB (17.2% vs 21.2%, P < 0.001) and LGIB (26.3% vs 29.2%, P = 0.027). Patients with PLOE had higher odds of dying of VUGIB (aOR 1.45, 95% CI 1.16-2.48) and LGIB (aOR 1.71, 95% CI 1.22-2.12). Patients with PLOE were also more likely to be readmitted after NVUGIB (aOR 1.75, 95% CI 1.64-1.81). However, after controlling for the percentage of patients with PLOE discharged from each hospital, the disparities in mortality and readmissions were no longer detected. DISCUSSION: Disparities exist in GIB outcomes among patients with PLOE, but these gaps narrow at hospitals with higher percentages of patients with PLOE. Cultural and linguistic competence may improve outcomes in this vulnerable group.

The Yin and Yang of Breast Cancer: Ion Channels as Determinants of Left-Right Functional Differences.

Breast cancer is a complex and heterogeneous disease that displays diverse molecular subtypes and clinical outcomes. Although it is known that the location of tumors can affect their biological behavior, the underlying mechanisms are not fully understood. In our previous study, we found a differential methylation profile and membrane potential between left (L)- and right (R)-sided breast tumors. In this current study, we aimed to identify the ion channels responsible for this phenomenon and determine any associated phenotypic features. To achieve this, experiments were conducted in mammary tumors in mice, human patient samples, and with data from public datasets. The results revealed that L-sided tumors have a more depolarized state than R-sided. We identified a 6-ion channel-gene signature (CACNA1C, CACNA2D2, CACNB2, KCNJ11, SCN3A, and SCN3B) associated with the side: L-tumors exhibit lower expression levels than R-tumors. Additionally, in silico analyses show that the signature correlates inversely with DNA methylation writers and with key biological processes involved in cancer progression, such as proliferation and stemness. The signature also correlates inversely with patient survival rates. In an in vivo mouse model, we confirmed that KI67 and CD44 markers were increased in L-sided tumors and a similar tendency for KI67 was found in patient L-tumors. Overall, this study provides new insights into the potential impact of anatomical location on breast cancer biology and highlights the need for further investigation into possible differential treatment options.

When left does not seem right: epigenetic and bioelectric differences between left- and right-sided breast cancer.

BACKGROUND: During embryogenesis lateral symmetry is broken, giving rise to Left/Right (L/R) breast tissues with distinct identity. L/R-sided breast tumors exhibit consistently-biased incidence, gene expression, and DNA methylation. We postulate that a differential L/R tumor-microenvironment crosstalk generates different tumorigenesis mechanisms. METHODS: We performed in-silico analyses on breast tumors of public datasets, developed xenografted tumors, and conditioned MDA-MB-231 cells with L/R mammary extracts. RESULTS: We found L/R differential DNA methylation involved in embryogenic and neuron-like functions. Focusing on ion-channels, we discovered significant L/R epigenetic and bioelectric differences. Specifically, L-sided cells presented increased methylation of hyperpolarizing ion channel genes and increased Ca2+ concentration and depolarized membrane potential, compared to R-ones. Functional consequences were associated with increased proliferation in left tumors, assessed by KI67 expression and mitotic count. CONCLUSIONS: Our findings reveal considerable L/R asymmetry in cancer processes, and suggest specific L/R epigenetic and bioelectric differences as future targets for cancer therapeutic approaches in the breast and many other paired organs.

Analysis in the ethical decision-making of dental, nurse and physiotherapist students, through case-based learning.

INTRODUCTION: Training in ethical competencies is perceived with special interest among the objectives of health education. The dimensions of the person such as integrity, autonomy and dignity influence the choice of interventions, but the different specialties of the health sciences conceive these dimensions with different perspectives depending on the clinical setting. These divergences can be detected during the first years of undergraduate studies, and it is important to know the professional bias and its possible causes. MATERIALS AND METHODS: A procedure was developed through case-based learning (CBL) to assess various characteristics of decision-making during the early stages of student training. A semi-quantitative method was designed based on the narrative responses of a case with ethical implications in the field of gender violence. The method was applied to 294 undergraduate students in nursing (95), physiotherapy (109) and dentistry (90) from the Faculty of Health Sciences of a Spanish university. A frequency analysis of the narrative responses of the students to the proposed case was carried out, using the chi-square test to determine any association between the variables studied: gender, specialty and ethical knowledge. RESULTS: Four types of response categories were detected, as a result of combining the personal conversation, report to legal authority or require assistance of other teams. The most common option in dentists is conversation only, while physical therapists include the assistance of other teams. In nursing, a balance is observed between both possibilities. The results show that student responses differ significantly among specialties and also differ significantly according to test scores on ethical knowledge. However, no significant differences were found between the responses provided by men and women. CONCLUSION: Most of the health sciences students highly valued their own capacity for dialogue and reflection to approach situations with complex ethical dimensions. We consider that case-based learning (CBL), in combination with narrative analysis is a valid means of evaluating the professional ethical competencies of students in health sciences careers applied to a common goal.

Management of Chronic Abdominal Distension and Bloating.

Abdominal bloating and distension are 2 of the most commonly reported gastrointestinal symptoms. Abdominal bloating is characterized by symptoms of trapped gas, abdominal pressure, and fullness. Abdominal distension is defined as a measurable increase in abdominal girth. These symptoms frequently co-exist, although they can occur separately. Defined by Rome IV criteria, functional abdominal bloating and distension commonly coincide with other functional gastrointestinal disorders, such as functional dyspepsia, irritable bowel syndrome, and functional constipation. Abdominal bloating and distension can develop for multiple reasons, including food intolerances, a previous infection that perturbed the intestinal microbiota, disordered visceral sensation, delayed intestinal transit, or an abnormal viscero-somatic reflux. Treatment can be challenging to patients and providers-no regimen has been consistently successful. Successful treatment involves identifying the etiology, assessing severity, educating and reassuring patients, and setting expectations. Therapeutic options include dietary changes, probiotics, antibiotics, prokinetic agents, antispasmodics, neuromodulators, and biofeedback. We review the epidemiology and effects of chronic bloating and distension and pathophysiology, discuss appropriate diagnostic strategies, and assess available treatment options.

Gastric Emptying Scans: Poor Adherence to National Guidelines.

BACKGROUND: Accurately diagnosing gastroparesis relies upon gastric emptying scintigraphy (GES) being performed correctly. Jointly published protocol guidelines have long been available; however, the extent to which practitioners adhere to these guidelines is unknown. AIMS: This study aimed to assess national compliance with established GES protocol guidelines. METHODS: We developed a questionnaire addressing the key protocol measures outlined in the Consensus Recommendations for Gastric Emptying Scintigraphy. Survey questions addressed patient information collection (15), patient preparation and procedure protocol (16), meal content and preparation (7), imaging (3), interpretation (4), reporting (7), and institutional demographic data (7). The anonymous questionnaire was distributed electronically to members of the Society of Nuclear Medicine and Medical Imaging (SNMMI) and non-member recipients of the SNMMI daily email newsletter. One response per medical institution was permitted. RESULTS: A total of 121 out of 872 potential medical institutions (MI) responded (13.9%); 49 (40.4%) were academic/teaching medical centers. The annual number (mean) of GES procedures was 199.9 (range 5-2000 GES/year). On average, MI performed 33.5/52 (64%) of protocol measures according to guidelines while academic medical centers performed 31.5/52 (61%) of protocol measures according to guidelines. Only 4 out of 88 MI (4.5%) performed GES while adhering to three critical measures: validated study duration; controlled blood glucose levels; and proper restriction of medications. CONCLUSIONS: Low compliance with GES protocol guidelines, even among academic medical centers, raises the likely possibility of misdiagnosis and improper management of upper gastrointestinal symptoms. These results highlight a need for increased awareness of protocol guidelines for gastric scintigraphy.

Changes in Levels and Determinants of Maternal Health Service Utilization in Ethiopia: Comparative Analysis of Two Rounds Ethiopian Demographic and Health Surveys.

BACKGROUND: Antenatal care (ANC), delivery by skilled birth attendants, and postnatal care (PNC) are critical components of maternal health services for reducing maternal mortality. The study aimed to compare the utilization of maternal health services in the two most recent rounds of Ethiopia Demographic and Health Surveys (EDHS) and identify the factors influencing the utilization of these services using the 2016 EDHS. METHODS: Two rounds of EDHS data in 2011 and 2016 were used to estimate the proportion of women who had ANC, delivered by skilled birth attendants, and had a postnatal checkup and other characteristics of the surveyed population. The most recent round of data-the 2016 EDHS-was used to examine the socio-cultural and reproductive health factors associated with the three maternal health services utilization. Chi-square tests and multivariate logistic regression analyses with adjusted Odds Ratios (AOR) were conducted using Stata 15.0. RESULTS: The use of ANC services and skilled birth attendants increased significantly between 2011 and 2016 EDHS, utilization of ANC services increased from 34.0 to 65.5%, and use of skilled birth attendants increased from 11.7 to 35.9%, respectively. The use of postnatal care decreased from 9.3 to 6.9%. Utilization of maternal health service was significantly associated with urban residence, Protestant religion, Oromo ethnicity, more education, more household wealth, and less parity. Furthermore, women who had ANC visits during pregnancy were more likely to subsequently use skilled birth attendants (AOR 5.5, p < 0.001) and PNC (AOR 2.9, p < 0.001). CONCLUSION: The study highlighted the inequalities in the utilization of maternal health services between rural and urban areas, and the need of addressing the social, economic, and physical barriers that prevent women from using these services. Further, programs should be targeted at promoting the use of professional birth and postnatal services in Ethiopia.

Insomnia and sleep quality in healthcare workers fighting against COVID-19: a systematic review of the literature and meta-analysis.

The COVID-19 pandemic has the potential to significant- ly affect the mental health of healthcare workers, who stand in the frontline of this crisis. Insomnia is often related to exposure to stressful situations, such as the current health crisis, as well as other mental disorders, physical conditions and work-related problems. The objectives of this systematic review were: 1) to examine the impact of the current health pandemic produced by COVID-19 on insomnia and sleep quality of health professionals, and 2) to identify risk factors associated with insomnia. After a literature search in MEDLINE, EMBASE, and PsycINFO, 18 relevant studies were identified. The prevalence of insomnia estimated by random effects meta-analysis was 38% (95%CI= 37 to 39%), being slightly higher in women (29%, 95%CI= 27% to 30%) than in men (24%, 95%CI= 21 to 27%). The main risk factor associated with insomnia was working in a high-risk environment, followed by female sex and having a lower educational level. The high figures of self-reported insomnia and poor sleep quality observed indicate the need to develop interventions aimed at mitigating and caring for the mental health of healthcare workers fighting against this pandemic.

COVID-19 polymerase chain reaction testing before endoscopy: an economic analysis.

BACKGROUND AND AIMS: The novel coronavirus disease 2019 (COVID-19) pandemic has limited endoscopy utilization, causing significant health and economic losses. We aim to model the impact of polymerase chain reaction (PCR) testing into resuming endoscopy practice. METHODS: We performed a retrospective review of endoscopy utilization during the COVID-19 pandemic for a baseline reference. A computer model compared 3 approaches: strategy 1, endoscopy for urgent indications only; strategy 2, testing for semiurgent indications; and strategy 3, testing all patients. Analysis was made under current COVID-19 prevalence and projected prevalence of 5% and 10%. Primary outcomes were number of procedures performed and/or canceled. Secondary outcomes were direct costs, reimbursement, personal protective equipment used, and personnel infected. Disease prevalence, testing accuracy, and costs were obtained from the literature. RESULTS: During the COVID-19 pandemic, endoscopy volume was 12.7% of expected. Strategies 2 and 3 were safe and effective interventions to resume endoscopy in semiurgent and elective cases. Investing 22 U.S. dollars (USD) and 105 USD in testing per patient allowed the completion of 19.4% and 95.3% of baseline endoscopies, respectively. False-negative results were seen after testing 4700 patients (or 3 months of applying strategy 2 in our practice). Implementing PCR testing over 1 week in the United States would require 13 and 64 million USD, with a return of 165 and 767 million USD to providers, leaving 65 and 325 healthcare workers infected. CONCLUSIONS: PCR testing is an effective strategy to restart endoscopic practice in the United States. PCR screening should be implemented during the second phase of the pandemic, once the healthcare system is able to test and isolate all suspected COVID-19 cases.

Mitochondrial stress triggers a pro-survival response through epigenetic modifications of nuclear DNA.

Mitochondrial dysfunction represents an important cellular stressor and when intense and persistent cells must unleash an adaptive response to prevent their extinction. Furthermore, mitochondria can induce nuclear transcriptional changes and DNA methylation can modulate cellular responses to stress. We hypothesized that mitochondrial dysfunction could trigger an epigenetically mediated adaptive response through a distinct DNA methylation patterning. We studied cellular stress responses (i.e., apoptosis and autophagy) in mitochondrial dysfunction models. In addition, we explored nuclear DNA methylation in response to this stressor and its relevance in cell survival. Experiments in cultured human myoblasts revealed that intense mitochondrial dysfunction triggered a methylation-dependent pro-survival response. Assays done on mitochondrial disease patient tissues showed increased autophagy and enhanced DNA methylation of tumor suppressor genes and pathways involved in cell survival regulation. In conclusion, mitochondrial dysfunction leads to a "pro-survival" adaptive state that seems to be triggered by the differential methylation of nuclear genes.

Moral dilemmas involving anthropological and ethical dimensions in healthcare curriculum.

BACKGROUND: Currently a variety of novel scenarios have appeared within nursing practice such as confidentiality of a patient victim of abuse, justice in insolvent patients, poorly informed consent delivery, non-satisfactory medicine outputs, or the possibility to reject a recommended treatment. These scenarios presuppose skills that are not usually acquired during the degree. Thus, the implementation of teaching approaches that promote the acquisition of these skills in the nursing curriculum is increasingly relevant. OBJECTIVE: The article analyzes an academic model which integrates in the curriculum a series of specific theoretical concepts together with practical skills to acquire the basic ethic assessment competency. RESEARCH DESIGN: The project includes designing two subjects, General Anthropology and Ethics-Bioethics, with an applied approach in the nursing curriculum. The sequential structure of the curriculum in both subjects is constituted by three learning domains (theoretical, practical, and communicative) with different educational strategies. ETHICAL CONSIDERATIONS: No significant ethical considerations as this is a discussion paper. FINDINGS: The model was structured from the anthropology's concepts and decision-making process, applied to real situations. The structure of the three domains theoretical-practical-communicative is present in each session. DISCUSSION: It is observed that theoretical domain fosters the capacity for critical analysis and subsequent ability to judge diverse situations. The practical domain reflected two significant difficulties: students' resistance to internalizing moral problems and the tendency to superficial criticism. The communicative domain has frequently shown that the conflicting points are in the principles to be applied. CONCLUSION: We conclude that this design achieves its objectives and may provide future nursing professionals with ethical competences especially useful in healthcare practice. The three domains of the presented scheme are associated with the same process used in decision making at individual levels, where the exercise of clinical prudence acquires particular relevance.

Intratumor heterogeneity index of breast carcinomas based on DNA methylation profiles.

BACKGROUND: Cancer cells evolve and constitute heterogeneous populations that fluctuate in space and time and are subjected to selection generating intratumor heterogeneity. This phenomenon is determined by the acquisition of genetic/epigenetic alterations and their selection over time which has clinical implications on drug resistance. METHODS: DNA extracted from different tumor cell populations (breast carcinomas, cancer cell lines and cellular clones) were analyzed by MS-MLPA. Methylation profiles were used to generate a heterogeneity index to quantify the magnitude of epigenetic heterogeneity in these populations. Cellular clones were obtained from single cells derived of MDA-MB 231 cancer cell lines applying serial limiting dilution method and morphology was analyzed by optical microscopy and flow cytometry. Clones characteristics were examined through cellular proliferation, migration capacity and apoptosis. Heterogeneity index was also calculated from beta values derived from methylation profiles of TCGA tumors. RESULTS: The study of methylation profiles of 23 fresh breast carcinomas revealed heterogeneous allele populations in these tumor pieces. With the purpose to measure the magnitude of epigenetic heterogeneity, we developed an heterogeneity index based on methylation information and observed that all tumors present their own heterogeneity level. Applying the index calculation in pure cancer cell populations such as cancer cell lines (MDA-MB 231, MCF-7, T47D, HeLa and K-562), we also observed epigenetic heterogeneity. In addition, we detected that clones obtained from the MDA-MB 231 cancer cell line generated their own new heterogeneity over time. Using TCGA tumors, we determined that the heterogeneity index correlated with prognostic and predictive factors like tumor size (p = 0.0088), number of affected axillary nodes (p = 0.007), estrogen receptor expression (p < 0.0001) and HER2 positivity (p = 0.0007). When we analyzed molecular subtypes we found that they presented different heterogeneity levels. Interestingly, we also observed that all mentioned tumor cell populations shared a similar Heterogeneity index (HI) mean. CONCLUSIONS: Our results show that each tumor presents a unique epigenetic heterogeneity level, which is associated with prognostic and predictive factors. We also observe that breast tumor subtypes differ in terms of epigenetic heterogeneity, which could serve as a new contribution to understand the different prognosis of these groups.

Moral enhancement, at the peak of pharmacology and at the limit of ethics.

The debate over the improvement of moral capacity or moral enhancement through pharmacology has gained momentum in the last decade as a result of advances in neuroscience. These advances have led to the discovery and allowed the alteration of patterns of human behavior, and have permitted direct interventions on the neuronal structure of behavior. In recent years, this analysis has deepened regarding the anthropological foundations of morality and the reasons that would justify the acceptance or rejection of such technology. We present a review of proposals for pharmacological interventions directed directly towards moral enhancement. In addition, we identify the ethical dilemmas that such interventions may generate, as well as the moral assessment of the authors of these studies. There is a moderate consensus on the risks of any intervention on the intimate structure of the human condition, its autonomy and identity, but there are large differences in explaining the reasons for this concern and especially in justifying such interventions. These findings show that it is necessary to investigate the moral assessment of authors and the ethical dimension within the field of pharmacology in order to identify future trends.

A frame-shift deletion in the PURA gene associates with a new clinical finding: Hypoglycorrhachia. Is GLUT1 a new PURA target?

PURA is a DNA/RNA-binding protein known to have an important role as a transcriptional and translational regulator. Mutations in the PURA gene have been documented to cause mainly a neurologic phenotype including hypotonia, epilepsy, development delay and respiratory alterations. We report here a patient with a frame-shift deletion in the PURA gene that apart from the classical PURA deficiency phenotype had marked hypoglycorrhachia, overlapping the clinical findings with a GLUT1 deficiency syndrome. SLC2A1 (GLUT1) mutations were discarded, so we hypothesized that GLUT1 could be downregulated in this PURA deficient scenario. We confirmed reduced GLUT1 expression in the patient's peripheral blood cells compared to controls predicting that this could also be happening in the blood-brain barrier and in this way explain the hypoglycorrhachia. Based on PURA's known functions as a transcriptional and translational regulator, we propose GLUT1 as a new PURA target. Further in vitro and in vivo studies are needed to confirm this and to uncover the underlying molecular mechanisms.

[Variation analysis of the number of copies and methylene patterns in region 15q11-q13]. / Análisis de variación del número de copias y de patrones de metilación en la región 15q11-q13.

Human chromosome 15q11-q13 region is prone to suffer genetic alterations. Some genes of this region have a differential monoallelic imprinting-regulated expression pattern. Defects in imprinting regulation (IE), uniparental disomy (UPD) or copy number variation (CNV) due to chromosomal breakpoints (BP) in 15q11-q13 region, are associated with several diseases. The most frequent are Prader-Willi syndrome, Angelman syndrome and 15q11-q13 microduplication syndrome. In this work, we analyzed DNA samples from 181 patients with phenotypes which were compatible with the above-mentioned diseases, using Methyl specific-multiplex ligation-dependent probe amplification (MS-MLPA). We show that, of the 181 samples, 39 presented alterations detectable by MS-MLPA. Of those alterations, 61.5% (24/39) were deletions, 5.1% (2/39) duplications and 33.3% (13/39) UPD/IE. The CNV cases were 4 times more frequent than UPD/IE (OR= 4; IC 95%: 1.56-10.25), consistent with the literature. Among the CNVs, two atypical cases allow to postulate new possible BP sites that have not been reported previously in the literature.

Gluten-induced symptoms in diarrhea-predominant irritable bowel syndrome are associated with increased myosin light chain kinase activity and claudin-15 expression.

The mechanisms underlying diarrhea-predominant irritable bowel syndrome (IBS-D) are poorly understood, but increased intestinal permeability is thought to contribute to symptoms. A recent clinical trial of gluten-free diet (GFD) demonstrated symptomatic improvement, relative to gluten-containing diet (GCD), which was associated with reduced intestinal permeability in non-celiac disease IBS-D patients. The aim of this study was to characterize intestinal epithelial tight junction composition in IBS-D before and after dietary gluten challenge. Biopsies from 27 IBS-D patients (13 GFD and 14 GCD) were examined by H&E staining and semiquantitative immunohistochemistry for phosphorylated myosin II regulatory light chain (MLC), MLC kinase, claudin-2, claudin-8 and claudin-15. Diet-induced changes were assessed and correlated with urinary mannitol excretion (after oral administration). In the small intestine, epithelial MLC phosphorylation was increased or decreased by GCD or GFD, respectively, and this correlated with increased intestinal permeability (P<0.03). Colonocyte expression of the paracellular Na+ channel claudin-15 was also markedly augmented following GCD challenge (P<0.05). Conversely, colonic claudin-2 expression correlated with reduced intestinal permeability (P<0.03). Claudin-8 expression was not affected by dietary challenge. These data show that alterations in MLC phosphorylation and claudin-15 and claudin-2 expression are associated with gluten-induced symptomatology and intestinal permeability changes in IBS-D. The results provide new insight into IBS-D mechanisms and can explain permeability responses to gluten challenge in these patients.

Relationship of gastric emptying or accommodation with satiation, satiety, and postprandial symptoms in health.

The contributions of gastric emptying (GE) and gastric accommodation (GA) to satiation, satiety, and postprandial symptoms remain unclear. We aimed to evaluate the relationships between GA or GE with satiation, satiety, and postprandial symptoms in healthy overweight or obese volunteers (total n = 285, 73% women, mean BMI 33.5 kg/m2): 26 prospectively studied obese, otherwise healthy participants and 259 healthy subjects with previous similar GI testing. We assessed GE of solids, gastric volumes, calorie intake at buffet meal, and satiation by measuring volume to comfortable fullness (VTF) and maximum tolerated volume (MTV) by using Ensure nutrient drink test (30 ml/min) and symptoms 30 min after MTV. Relationships between GE or GA with satiety, satiation, and symptoms were analyzed using Spearman rank (rs ) and Pearson (R) linear correlation coefficients. We found a higher VTF during satiation test correlated with a higher calorie intake at ad libitum buffet meal (rs = 0.535, P < 0.001). There was a significant inverse correlation between gastric half-emptying time (GE T1/2) and VTF (rs = -0.317, P < 0.001) and the calorie intake at buffet meal (rs = -0.329, P < 0.001), and an inverse correlation between GE Tlag and GE25% emptied with VTF (rs = -0.273, P < 0.001 and rs = -0.248, P < 0.001, respectively). GE T1/2 was significantly associated with satiation (MTV, R = -0.234, P < 0.0001), nausea (R = 0.145, P = 0.023), pain (R = 0.149, P = 0.012), and higher aggregate symptom score (R = 0.132, P = 0.026). There was no significant correlation between GA and satiation, satiety, postprandial symptoms, or GE. We concluded that GE of solids, rather than GA, is associated with postprandial symptoms, satiation, and satiety in healthy participants.NEW & NOTEWORTHY A higher volume to comfortable fullness postprandially correlated with a higher calorie intake at ad libitum buffet meal. Gastric emptying of solids is correlated to satiation (volume to fullness and maximum tolerated volume) and satiety (the calorie intake at buffet meal) and symptoms of nausea, pain, and aggregate symptom score after a fully satiating meal. There was no significant correlation between gastric accommodation and either satiation or satiety indices, postprandial symptoms, or gastric emptying.