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Aims: Pharmacologic blockade of neurohormonal pathways in patients with acute myocardial infarction (MI) can result in acute changes in biomarkers of kidney function. We evaluated the effect of sacubitril/valsartan versus ramipril on initial changes in serum creatinine and the association of these changes with longer‐term outcomes among participants in PARADISE‐MI. Methods and results: In this randomized, double‐blind, active‐controlled, event‐driven trial, 5661 patients with an acute MI were assigned to receive sacubitril/valsartan or ramipril, with no run‐in. The frequency of an initial pre‐specified increase in serum creatinine (≥26.5 or ≥44 μmol/L) from baseline to week 1 was compared between arms. Multivariable Cox regression models were fit to examine the association of acute changes in serum creatinine with the primary cardiovascular composite outcome (cardiovascular death, first heart failure hospitalization, or outpatient heart failure), all‐cause mortality, and longer‐term changes in estimated glomerular filtration rate (eGFR). An initial increase in serum creatinine ≥26.5 μmol/L occurred in 155 of 2604 (6.0%) patients assigned to sacubitril/valsartan and 120 of 2603 (4.6%) patients assigned to ramipril (odds ratio [OR] 1.32; 95% confidence interval [CI] 1.03–1.68). The corresponding numbers for an increase ≥44 μmol/L were 57 (2.2%) and 42 (1.6%), respectively (OR 1.37; 95% CI 0.92–2.05). A higher odds of increased serum creatinine ≥26.5 and ≥44 μmol/L for sacubitril/valsartan versus ramipril appeared to be restricted to patients who had a greater decline in systolic blood pressure over the same period (p‐interaction = 0.05 and 0.001, respectively). In multivariable analyses, neither an acute increase in serum creatinine ≥26.5 or ≥44 μmol/L was associated with a higher risk of cardiovascular outcomes, all‐cause mortality, or differences in longer‐term eGFR slope. Findings were similar across the randomized treatment arms (p‐interaction >0.6 for all). Conclusions: Following acute MI, patients assigned to sacubitril/valsartan had a higher frequency of initial increases in serum creatinine at 1 week, compared with ramipril. In adjusted models, initial increases in serum creatinine with either treatment were not associated with adverse cardiovascular outcomes or changes in longer‐term kidney function. [ABSTRACT FROM AUTHOR]

Introduction Biologic and small-molecule therapies have revolutionised the treatment of moderate-to-severe inflammatory bowel disease (IBD). A significant proportion of patients experience early or delayed treatment failure. Patients with IBD with greater visceral obesity are less likely to respond to biologics. Sarcopenia has been identified as a predictor of disease severity and need for rescue therapy in acute severe ulcerative colitis. The aim of this study is to assess the feasibility of a physician-derived exercise programme in patients with IBD commencing biologic or small-molecule therapy in addition to the effect on physical fitness, body composition and objective measures of quality of life, fatigue scores and disease activity.Methods and analysis This is a randomised controlled feasibility study comparing the effects of a physician-derived exercise programme and standard medical care (biologic/small-molecule therapy) with standard care alone in patients with moderate to severe IBD. Patients with IBD in the intervention group will undergo a structured exercise programme for 20 weeks. Both IBD groups will carry out body composition, disease activity and quality-of-life assessments at baseline, week 12 and week 26. The primary objective is to assess the feasibility of the physician-derived exercise programme in patients with IBD commencing disease-modifying therapies. Secondary endpoints include a change in cardiorespiratory fitness, disease activity/inflammation, fatigue, health-related quality of life outcomes and body composition between the two IBD groups. Exploratory endpoints include validation of anterior thigh ultrasound for sarcopenia screening, assessment of proinflammatory cytokines and markers of immunometabolism.Ethics and dissemination This study has received ethical approval from the Beaumont Hospital Ethics committee on 22 October 2021 (reference number 21/21). Data generated or analysed during this study will be published as an article and supplementary appendix in relevant medical journals. The data will also be presented at national and international conferences.Trial registration number NCT05174754.

BackgroundPeriprosthetic joint infection (PJI) is one of the most common causes of revision total hip arthroplasty (THA) and associated with higher costs, prolonged pain, and worse clinical outcomes. Many factors have been linked to increased infection rates, one being the operative equipment and instrumentation used during the surgical procedure. With few arthroplasty instruments designed for complete disassembly and increasingly complex instrument designs, this study seeks to understand the effect that instrument disassembly plays on infection using disassembled and assembled standard femoral broach handles (BHs).MethodsTwo BHs, not designed for disassembly, were modified and then contaminated in the disassembled state with Geobacillus stearothermophilus vegetative-form bacteria and spores. Using both flash and standard sterilization cycles, the BHs were steam sterilized in the disassembled or assembled state and then analyzed for remaining bacteria and spores.ResultsAt all target locations after either a flash sterilization cycle or a standard sterilization cycle, complete eradication of both the vegetative-form and spore-form of G stearothermophilus was achieved.ConclusionThis study demonstrates that adequate decontamination of the tested BHs can be achieved after steam sterilization in either the disassembled or assembled state, without an increased risk of infection transmission.

Novel environmentally friendly alternatives for packaging materials such as bioplastics are being developed to mitigate problems with petrochemical plastics but low acceptance of these bioplastics among consumers and others have delayed their adoption. Through a mixed method approach, this work aims to assess the factors contributing to the low adoption rates of bioplastics as a way to inform development of more highly accepted bioplastics. Stakeholders with a variety of links with the packaging/plastic industries were interviewed using a semi-structured interview approach and the results were analysed to discover recurrent themes and perceptions regarding packaging. From this thematic analysis, a survey was conducted to explore consumer opinion. The findings indicate that although the population is aware and interested in changing to environmentally friendly packaging, confusion exists as to what that means and what are the best ways to effect that change. The teenager group was identified as the most susceptible to be involved in the change. Frequently cited barriers to acceptance centred on separation of waste and access to correct waste bins. The characteristics likely to lead to a higher acceptance of novel bioplastics by composters were time of decomposition, small thickness, and possibility of being introduced in current processes of packaging preparation, among others.

The efficiency with which ribosomes shift reading frames when decoding viral RNA may change over the course of an infection.

Although the immune response within draining lymph nodes (DLNs) has been studied for decades, how their stromal compartment contributes to this process remains to be fully explored. Here, we show that donor mast cells were prominent activators of collagen I deposition by fibroblastic reticular cells (FRCs) in DLNs shortly following transplantation. Serial analysis of the DLN indicated that the LN stroma did not return to its baseline microarchitecture following organ rejection and that the DLN contained significant fibrosis following repetitive organ transplants. Using several FRC conditional-knockout mice, we show that induction of senescence in the FRCs of the DLN resulted in massive production of collagen I and a proinflammatory milieu within the DLN. Stimulation of herpes virus entry mediator (HVEM) on FRCs by its ligand LIGHT contributed chiefly to the induction of senescence in FRCs and overproduction of collagen I. Systemic administration of ex vivo-expanded FRCs to mice decreased DLN fibrosis and strengthened the effect of anti-CD40L in prolonging heart allograft survival. These data demonstrate that the transformation of FRCs into proinflammatory myofibroblasts is critically important for the maintenance of a proinflammatory milieu within a fibrotic DLN., Introduction Lymph nodes (LNs) are the quintessential organs of alloimmunity following transplantation. Recent advances in elucidating the function of specific cellular and stromal compartments in the LN have broadened our [...]

Abstract Background: Previously we reported the discovery of stop codon readthrough in AMD1 mRNA followed by ribosome stalling at the end of a conserved Open Reading Frame (ORF) that we termed AMD1. To explain the severe suppression of reporters fused to AMD1 tail we proposed a mechanism invoking ribosome queueing. In the original study, we tested this hypothesis, by placing the reporter stop codon in the context of readthrough permissive sequences in a dual reporter vector with downstream reporter expression driven by the EMCV IRES. In accordance with our hypothesis, we observed a striking disproportional reduction of upstream reporter activity in response to increased readthrough levels. Methods: Here we employ dual luciferase assays, western blotting and RT-qPCR to explore the effects of test sequences downstream to the reporter stop codon on its expression in dual and monocistronic reporter vectors. Results: With the dual reporter system, the disproportionate reduction of upstream reporter activity is not specific to AMD1 tail and occurs as long as the readthrough stop codon context is present at the end of the reporter’s ORF. In a monocistronic vector without an IRES, the test sequences had distinct effects which were reflective of their properties e.g., AMD1 tail inhibitory effect. We further show by employing RT-qPCR that in the IRES vectors, the Fluc activity levels measured by the luciferase assay are an accurate proxy of RNA levels. Conclusions: While our findings provide little new information regarding the functional role of AMD1 tail, they raise caution for the use of viral IRES elements in expression vectors for studying mechanisms of mRNA translation. These findings may also be pertinent to the natural properties of readthrough permissive sequences and of IRES elements, though these require a separate investigation.

Free-living amoebae (FLA) are gaining attention due to the increasing number of related grave central nervous system (CNS) and sight-threatening eye infections and their role as Trojan horses for many bacteria and viruses. This study was conducted in Assiut City, Egypt to detect the presence of FLA in different water sources using morphological and molecular approaches and determine their potential pathogenicity. A total of 188 water samples (100 tap, 80 tank, and 8 swimming pool samples) were collected, cultivated on non-nutrient agar seeded with Escherichia coli, and inspected for FLA. Thermo- and osmo-tolerance assays were performed to determine their pathogenicity. Polymerase chain reaction and sequence analysis were performed to confirm the identification and analyze the genotype. Overall, 52 samples (27.7%) were positive for FLA. Of these, 20.7% were identified as Acanthamoeba, 1.6% as Vahlkampfiidae, and 5.3% as mixed Acanthamoeba and Vahlkampfiidae. Seven species of Acanthamoeba were recognized, of which A. triangularis, A. polyphaga, A. lenticulata, and A. culbertsoni are thermo- and osmo-tolerant, and A. astronyxis, A. comandoni, and A. echinulata are non-thermo- and non-osmo-tolerant. The phylogeny analysis revealed T4 and T7 genotypes. Among Vahlkampfiids, 61.5% were identified as thermo- and osmo-tolerant Vahlkampfia, and 30.8% were identified as non-pathogenic Naegleria. One isolate (7.7%) was identified as potentially pathogenic Allovahlkampfia, as confirmed by sequencing. This is the first report documenting the occurrence and phylogeny of waterborne FLA (Acanthamoeba/Vahlkampfiidae) in Assiut, Egypt. The presence of potentially pathogenic FLA highlights the possible health hazards and the need for preventive measures.

Additions to the popular evaporation rate determination laboratory of alcohol-based hand-rub sanitizers are described here. Significantly, inquiry-driven protocols for formulating hand-rub sanitizers, falling-ball viscometry, and sanitizer efficacy are included. Incorporation of familiar substances ("molecular relevance") enables students to assimilate knowledge and connect to and recognize interrelated disciplines. To stimulate engagement and project ownership, students were given the opportunity to alter sanitizer formulations by varying the amount and molecular weight of the gelling agent. Viscosities were determined using a falling-ball viscometer to integrate physics and fluid dynamics concepts into these experiments. Lastly, to stress microbiological applications and determine the efficacy of their hand sanitizers, students tested the formulated hand sanitizers for qualitative efficacy using agar plating of skin secretions and comparing colonies formed from sanitized versus nonsanitized hands. Chemistry students with diverse interests recognized links across disciplinary boundaries (e.g., increased their awareness of physical properties of hand sanitizers and the relationship of molecular-scale phenomena to these properties). This three-hour laboratory provides an interdisciplinary supplement directly designed for freshman chemistry and engineering chemistry undergraduates and increases integration among biology, chemistry, engineering, and physics.

In the past 50 years, the electronic and communication industries have grown exponentially, which has caused major concerns about electromagnetic (EM) pollution. In recent years, more thrust has been given to development of polymer composites to lessen electromagnetic interference (EMI) pollution. In the present work, porous polydimethylsiloxane (PDMS) composite foams based on cobalt ferrite (CoFe2O4) and reduced graphene oxide (rGO) are produced through the ammonium bicarbonate template approach. The resulting foams possess increased EMI shielding effectiveness via the absorption‐dominated mechanism due to the fact that PDMS foam functions as a three‐dimensional (3D) network, rGO offers the requisite conductive channel, and CoFe2O4 produces the necessary magnetic loss. The total EMI shielding effectiveness (SE) of PDMS/rGO composite foams without CoFe2O4 is 24 dB, however, with different weight percentages of CoFe2O4 added (3%, 6%, and 9%), the EMI SE increases to 41 dB for 3 mm thickness. The heat insulation performance of the material is also studied, and the measured thermal conductivity is 0.0391 Wm−1 K−1, which is very low value. The attributes of the composite foam underscore its excellent thermal insulation performance and its capacity for EMI shielding, rendering it highly suitable for diverse applications across various fields. [ABSTRACT FROM AUTHOR]

The present study presents an investigation of family functioning in the families of adolescents with severe restrictive eating disorders (REDs) assessed before and 6 months after a multidisciplinary family treatment program that combined psychodynamic psychotherapy, parental role intervention, and triadic or family-centered interventions. Nutritional counseling and neuropsychiatric monitoring of the overall treatment and care process were also provided. Family functioning was assessed using the clinical version of the Lausanne Trilogue Play (LTPc), a semi-structured procedure for observing family dynamics, previously validated for this patient population. The LTPc is divided into four phases. In phase 1, the mother interacts with the patient while the father assumes the role of observer. In phase 2, the father plans an activity with the patient while the mother observes. In phase 3, all the family members interact. Finally, in phase 4, the parents talk while the adolescent observes. A significant change emerged in family functioning after the treatment, but only for the interactive phase 2, when the father is required to interact with the daughter while the mother silently observes. The results of this study suggest that a relatively brief multidisciplinary treatment program may significantly improve family functioning in the families of patients diagnosed with severe REDs. Although appropriate clinical trials are needed to further test the efficacy of this treatment, the results also reinforce the concept that treatment programs targeting the individual patient and both the parents should be a first-line approach in adolescents with severe REDs.

Spexin (SPX), a neuropeptide with diverse functions, is a novel satiety factor in fish models and its role in feeding control has been recently confirmed in mammals. In mouse, food intake was shown to trigger SPX expression in glandular stomach with parallel rise in serum SPX and these SPX signals could inhibit feeding via central actions within the hypothalamus. However, the mechanisms for SPX regulation by food intake are still unclear. To examine the role of insulin signal caused by glucose uptake in SPX regulation, the mice were IP injected with glucose and insulin, respectively. In this case, serum SPX was elevated by glucose but not altered by insulin. Meanwhile, SPX transcript expression in the glandular stomach was up-regulated by glucose but the opposite was true for insulin treatment. Using in situ hybridization, the differential effects on SPX gene expression were located in the gastric mucosa of glandular stomach. Co-injection experiments also revealed that glucose stimulation on serum SPX and SPX mRNA expressed in glandular stomach could be blocked by insulin. In gastric mucosal cells prepared from glandular stomach, the opposite effects on SPX transcript expression by glucose and insulin could still be noted with similar blockade of the stimulatory effects of glucose by insulin. In this cell model, SPX gene expression induced by glucose was mediated by glucose uptake via GLUT, ATP synthesis by glycolysis/respiratory chain, and subsequent modulation of KATP channel activity, but the voltage-sensitive Ca2+ channels were not involved. The corresponding inhibition by insulin, however, was mediated by PI3K/Akt, MEK1/2/ERK1/2, and P38MAPK cascades coupled to insulin receptor but not IGF-1 receptor. Apparently, glucose uptake in mice can induce SPX expression in the glandular stomach through ATP synthesis via glucose metabolism and subsequent modification of KATP channel activity, which may contribute to SPX release into circulation to act as the satiety signal after food intake. The insulin rise caused by glucose uptake, presumably originated from the pancreas, may serve as a negative feedback to inhibit the SPX response by activating MAPK and PI3K/Akt pathways in the stomach.

This article describes the development of the Design Evaluation and Feedback Tool (DEFT), a custom-built web-based system that collects and reports data to support teaching, learning, and research in project-based engineering design education. The DEFT system collects data through short weekly questionnaires for students and instructors in engineering design classes, and uses these data to produce weekly reports for both types of user. The system is intended to engage students in reflective reporting on their experiential learning, to support educators in coaching student designers, and to serve as a data collection tool for education researchers. DEFT was developed through an iterative design and evaluation process, involving 185 students and 18 instructors at two universities. The system was evaluated using a combination of participation observation, user interviews, and anonymous questionnaires, and the results guided subsequent improvements to the system. This article describes the development and evaluation process, provides an overview of the resulting system, and ends by discussing the potential for DEFT to be used in evaluating and improving project-based design classes.

Objectives: This retrospective, observational experiential study aimed to examine the utility of Minimally Invasive Parfasicular Surgery (MIPS) with Brainpath® and/or Myriad™ in a large, diverse patient cohort and to compare observational characteristics with those in the existing MIPS-BrainPath/Myriad medical literature. Patients and methods: Demographic and surgical data from June 2, 2012 to April 30, 2019 were retrospectively extracted from a secure MIPS case summary database. Descriptive statistics were performed. Results: 1826 cases were extracted for analysis: 668 vascular; 1109 tumor; 47 unclassified and 2 “other.” Predominate vascular locations were subcortical and intraventricular. The average age for the vascular and tumor groups were 57.1 and 53.3 years respectively with a greater number of pediatric patients in the tumor group. Mean operating times were 176.0 min (tumor group) and 120.6 (vascular group). Hemorrhages and malformations averaged 5.27 cm3 vs. 2.76 cm in the tumor cohort. There were more male patients. Of the vascular cases, most were intracranial hemorrhages (n = 563, 84.5%); most tumor cases were primary brain tumors (n = 522, 47.7%) with 335 secondary tumors or metastatic brain tumors. Thirty-four percent of the entire cohort experienced at least one presurgical deficit related to the brain defect; headaches were the most commonly observed symptom. Deaths or infections directly related to MIPS were not captured within the database. Conclusion: These data support current, yet limited, medical literature observations demonstrating the versatility and utility of MIPS-BrainPath and/or Myriad for reaching and removing tumors and vascular anomalies located in eloquent brain regions in a variety of patient types.