Compromised intestinal integrity in older adults during daily activities:a pilot study

Abstract Background Malnutrition is a common and significant problem in older adults. Insight into factors underlying malnutrition is needed to develop strategies that can improve the nutritional status. Compromised intestinal integrity caused by gut wall hypoperfusion due to atherosclerosis of the mesenteric arteries in the aging gastrointestinal tract may adversely affect nutrient uptake. The presence of compromised intestinal integrity in older adults is not known. The aim of this study is to provide a proof-of-concept that intestinal integrity is compromised in older adults during daily activities. Methods Adults aged ≥75 years living independently without previous gastrointestinal disease or abdominal surgery were asked to complete a standardized walking test and to consume a standardized meal directly afterwards to challenge the mesenteric blood flow. Intestinal fatty acid-binding protein (I-FABP) was measured as a plasma marker of intestinal integrity, in blood samples collected before (baseline) and after the walking test, directly after the meal, and every 15 min thereafter to 75 min postprandially. Results Thirty-four participants (median age 81 years; 56% female) were included. Of the participants, 18% were malnourished (PG-SGA score ≥ 4), and 32% were at risk of malnutrition (PG-SGA score, 2 or 3). An I-FABP increase of ≥50% from baseline was considered a meaningful loss of intestinal integrity and was observed in 12 participants (35%; 8 females; median age 80 years). No significant differences were observed in either baseline characteristics, walking test scores, or calorie/macronutrient intake between the groups with and without a ≥ 50% I-FABP peak. Conclusion This study is first to indicate that intestinal integrity is compromised during daily activities in a considerable part of older adults living independently

Agreement of 2D transthoracic echocardiography with cardiovascular magnetic resonance imaging after ST-elevation myocardial infarction

Background: This study was designed to investigate the agreement of 2D transthoracic echocardiography (2D TTE) with cardiovascular magnetic resonance imaging (CMR) in a contemporary population of ST-elevation myocardial infarction (STEMI) patients. Methods: In this subanalysis of the GIPS-III trial, a randomized controlled trial investigating the administration of metformin in STEMI patients to prevent reperfusion injury, we studied 259 patients who underwent same-day CMR and 2D TTE assessments four months after hospitalization for a first STEMI. Bland-Altman analyses were performed to assess agreement between LV end-diastolic volume (LVEDV), LV end-systolic volume (LVESV), LV ejection fraction (LVEF), and LV mass measurements. Sensitivity and specificity of 2D TTE to detect categories of LVEF (≤35%, 35–50%, ≥50%) was determined. Linear regression of absolute differences in measurements between imaging modalities was used to investigate whether patient characteristics impact measurement bias. Results: Pairwise difference (bias) and 95% limits of agreement between CMR and 2D TTE measurements were +84 (37, 147) ml for LVEDV, +39 (6, 85) ml for LVESV, -1.1 ± 13.5% for LVEF, and -75 (-154, -14) g for LV mass. Sensitivity and specificity of 2D TTE to detect subjects with moderately depressed LVEF (35–50%) as measured by CMR were 52% and 88% respectively. We observed a significant effect of enzymatic infarct size on bias between 2D TTE and CMR in measuring LVESV and LVEF (P = 0.029, P = 0.001 respectively), of age and sex on bias between 2D TTE and CMR in measuring LV mass (P = 0.027, P < 0.001) and LVEDV (P = 0.001, P = 0.039), and of heart rate on bias between 2D TTE and CMR in LV volume measurements (P = 0.004, P = 0.016). Conclusions: Wide limits of agreement, underestimation of LV volumes and overestimation of LV mass was observed when comparing 2D TTE to CMR. Enzymatic infarct size, age, sex, and heart rate are potential sources of bias between imaging modalities

Phenotype Frequencies of Autosomal Minor Histocompatibility Antigens Display Significant Differences among Populations

Minor histocompatibility (H) antigens are allogeneic target molecules having significant roles in alloimmune responses after human leukocyte antigen–matched solid organ and stem cell transplantation (SCT). Minor H antigens are instrumental in the processes of transplant rejection, graft-versus-host disease, and in the curative graft-versus-tumor effect of SCT. The latter characteristic enabled the current application of selected minor H antigens in clinical immunotherapeutic SCT protocols. No information exists on the global phenotypic distribution of the currently identified minor H antigens. Therefore, an estimation of their overall impact in human leukocyte antigen–matched solid organ and SCT in the major ethnic populations is still lacking. For the first time, a worldwide phenotype frequency analysis of ten autosomal minor H antigens was executed by 31 laboratories and comprised 2,685 randomly selected individuals from six major ethnic populations. Significant differences in minor H antigen frequencies were observed between the ethnic populations, some of which appeared to be geographically correlated

A Uniform Genomic Minor Histocompatibility Antigen Typing Methodology and Database Designed to Facilitate Clinical Applications

BACKGROUND: Minor Histocompatibility (H) antigen mismatches significantly influence the outcome of HLA-matched allogeneic stem cell transplantation. The molecular identification of human H antigens is increasing rapidly. In parallel, clinical application of minor H antigen typing has gained interest. So far, relevant and simple tools to analyze the minor H antigens in a quick and reliable way are lacking. METHODOLOGY AND FINDINGS: We developed a uniform PCR with sequence-specific primers (PCR-SSP) for 10 different autosomal minor H antigens and H-Y. This genomic minor H antigen typing methodology allows easy incorporation in the routine HLA typing procedures. DNA from previously typed EBV-LCL was used to validate the methodology. To facilitate easy interpretation for clinical purposes, a minor H database named dbMinor (http://www.lumc.nl/dbminor) was developed. Input of the minor H antigen typing results subsequently provides all relevant information for a given patient/donor pair and additional information on the putative graft-versus-host, graft-versus-tumor and host-versus-graft reactivities. SIGNIFICANCE: A simple, uniform and rapid methodology was developed enabling determination of minor H antigen genotypes of all currently identified minor H antigens. A dbMinor database was developed to interpret the genomic typing for its potential clinical relevance. The combination of the minor H antigen genomic typing methodology with the online dbMinor database and applications facilitates the clinical application of minor H antigens anti-tumor targets after stem cell transplantation

A critical evaluation of topology optimization results for strut‐and‐tie modeling of reinforced concrete

Defining a suitable truss model is one of the most important steps of applying the strut‐and‐tie modeling (STM) method to design D‐regions in reinforced concrete (RC) structures. The truss model is a discrete representation of the stress field developed within a region of a concrete element. Topology optimization (TO) methods have been investigated by researchers for about two decades to generate suitable models for the STM method. Several truss models and numerous continuum TO results that could serve as an inspiration for suitable truss models have been proposed. However, limited attention has been paid to the evaluation of various TO results in the perspective of the STM method. As a result, it is at present unclear to what extent TO results offer a benefit for STM modeling, and which method should be preferred. In order to address this gap, an automatic and objective evaluation procedure is proposed in this paper. First, a TO result extraction method is proposed to systematically convert optimized topologies to truss‐like structures. Next, based on the extracted structures, three evaluation measures are formulated to evaluate TO results. These measures indicate whether an analyzable truss model could be extracted, to which extent tensile stress regions are covered by tensile ties and how economical the design will be. The effectiveness of the proposed evaluation procedure is validated using known STM solutions. Subsequently, the evaluation procedure is applied to 23 TO results from the literature, covering three different design problems. Most TO results show a good performance in covering tensile regions and would result in economical designs, and some undesired topologies are also identified by the evaluation method. Nevertheless, the use of continuum TO is most hampered by difficulties in identifying a suitable truss from the TO results

Optimization-based three-dimensional strut-and-tie model generation for reinforced concrete

Strut-and-tie modelling (STM) is an effective and widely used method to design disturbed regions (D-regions) of reinforced concrete structures. Among the various steps of STM, finding a suitable truss-analogy model is the most challenging part. Even for experienced engineers it is difficult to find representative models for complex D-regions, and this task is even harder for three-dimensional (3D) D-regions. To date, only a few 3D STM models have been proposed by researchers for several complex D-regions, which leaves practitioners with little guidance. In order to solve this problem, a method is proposed to automatically generate 3D optimization-based STM (3D-OPT-STM) models. The generation method comprises a compliance-based topology optimization process that generates optimized structural forms by maximizing stiffness, a topology extraction method, and a shape optimization method. In this study, three 3D-OPT-STM models are generated for typical 3D D-regions, and their performances are compared to manually created STM models. The generated 3D-OPT-STM models result in more economical designs. Moreover, geometrical and loading parameter studies demonstrate the applicability and robustness of the proposed method

Mode of death in Shapiro syndrome: A case report

Background Shapiro syndrome is extremely rare and is characterized by the triad of spontaneous periodic hypothermia, hyperhidrosis and agenesis of the corpus callosum, resulting in neurological and psychological disorders. The exact mechanism of this syndrome is unknown and treatment consists of controlling the periodic attacks. This case report describes a case of Shapiro syndrome presenting with ventricular fibrillation (VF) who was treated with dual chamber implantable cardioverter defibrillator (ICD) therapy. Case summary A 45-year-old man, suffering from Shapiro syndrome with frequent hypothermic attacks, was admitted to the emergency department with an out of hospital cardiac arrest caused by VF due to hypothermia. To prevent cardiac death during future hypothermic attacks with VF, the patient was treated with a dual chamber ICD. Within 1 month after ICD implantation the patient had two events of ventricular tachycardia/VF during hypothermia, which were both successfully terminated by an ICD shock. One year after ICD implantation the patient suffered from an uncontrolled urinary tract infection and the patient passed away. Post-mortem interrogation of the ICD did not reveal further episodes of VF and showed a higher supraventricular heartrate in the last days before his death, probably due to a sinus tachycardia driven by the infection. It was concluded that the most likely cause of death was an uncontrolled sepsis. Discussion The current case showed that ICD therapy can be successful in treating VF episodes in patients with unexpected periods of hypothermia