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Solid organ transplantation (SOT) is considered the optimal treatment for children with end-stage organ failure; however, increased efforts are needed to understand the gap surrounding equitable access to and health outcomes of SOT for Indigenous children. This scoping review summarizes the literature on the characteristics of access to and health outcomes of pediatric SOT among Indigenous children in the settler-colonial states of Canada, Aotearoa New Zealand, Australia, and the United States. A search was performed on MEDLINE, EMBASE, PsycINFO, and CINAHL for studies matching preestablished eligibility criteria from inception to November 2021. A preliminary gray literature search was also conducted. Twenty-four studies published between 1996 and 2021 were included. Studies addressed Indigenous pediatric populations within the United States (n = 7), Canada (n = 6), Aotearoa New Zealand (n = 5), Australia (n = 5), and Aotearoa New Zealand and Australia combined (n = 1). Findings showed that Indigenous children experienced longer time on dialysis, lower rates of preemptive and living donor kidney transplantation, and disparities in patient and graft outcomes after kidney transplantation. There were mixed findings about access to liver transplantation for Indigenous children and comparable findings for graft and patient outcomes after liver transplantation. Social determinants of health, such as geographic remoteness, lack of living donors, and traditional spiritual beliefs, may affect SOT access and outcomes for Indigenous children. Evidence gaps emphasize the need for action-based initiatives within SOT that prioritize research with and for Indigenous pediatric populations. Future research should include community-engaged methodologies, situated within local community contexts, to inform culturally safe care for Indigenous children., Competing Interests: The authors declare no conflicts of interest., (Copyright © 2024 The Author(s). Published by Wolters Kluwer Health, Inc.)

Thin films of the solid solution Nd1-xLaxNiO 3 are grown in order to study the expected 0 K phase transitions at a specific composition. We experimentally map out the structural, electronic and magnetic properties as a function of x and a discontinuous, possibly first order, insulator-metal transition is observed at low temperature when x = 0.2. Raman spectroscopy and scanning transmission electron microscopy show that this is not associated with a correspondingly discontinuous global structural change. On the other hand, results from density functional theory (DFT) and combined DFT and dynamical mean field theory calculations produce a 0 K first order transition at around this composition. We further estimate the temperature-dependence of the transition from thermodynamic considerations and find that a discontinuous insulator-metal transition can be reproduced theoretically and implies a narrow insulator-metal phase coexistence with x . Finally, muon spin rotation ( µ SR) measurements suggest that there are non-static magnetic moments in the system that may be understood in the context of the first order nature of the 0 K transition and its associated phase coexistence regime., (Creative Commons Attribution license.)

Immunoglobulin E (IgE)-mediated food allergy is a real public health problem worldwide. The prevalence of food allergy is particularly high in children. Patients with food allergy experience high morbidity with a change in quality of life due to the risk of severe anaphylaxis. Current treatment options are poor. Allergen avoidance is widely recommended but exposes patients to accidental ingestion. Oral immunotherapy is also used in patients with food allergies to the most common allergens. Oral immunotherapy consists of a daily administration of small, gradually increasing amounts of allergens to induce desensitisation. This procedure aims at inducing immune tolerance to the ingested food allergens. However, some patients experience adverse reactions and discontinue oral immunotherapy.Given that IgE plays a crucial role in food allergy and anti-IgE are effective in allergic asthma, the use of anti-IgE therapeutic monoclonal antibodies (mAbs) such as omalizumab has been assessed in food allergy patients. The use of omalizumab as a monotherapy in food allergy has not been extensively studied but looks promising. There is more published evidence regarding the effect of omalizumab and oral immunotherapy in food allergy. Given the promising results of oral immunotherapy regarding sustained tolerance in clinical trials and the potential capacity of omalizumab to reduce symptoms in case of accidental exposure, a strategy combining oral immunotherapy with omalizumab pre-treatment has been suggested as a safer option in patients with severe food allergy compared to isolated therapy. Omalizumab seems useful in ensuring safer administration of oral immunotherapy with the oral immunotherapy maintenance dose being reached more rapidly. Quality-of-life improvement is greater with oral immunotherapy + omalizumab compared to oral immunotherapy alone. Moreover, sustained unresponsiveness is achieved more frequently with omalizumab. Considering that precision medicine and personalised therapy are major goals for allergic diseases, predictive biomarkers are crucial in order to identify food allergy patients more likely to benefit from anti-IgE therapies., (© 2021. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Many material properties such as superconductivity, magnetoresistance or magnetoelectricity emerge from the non-linear interactions of spins and lattice/phonons. Hence, an in-depth understanding of spin-phonon coupling is at the heart of these properties. While most examples deal with one magnetic lattice only, the simultaneous presence of multiple magnetic orderings yield potentially unknown properties. We demonstrate a strong spin-phonon coupling in SmFeO 3 that emerges from the interaction of both, iron and samarium spins. We probe this coupling as a remarkably large shift of phonon frequencies and the appearance of new phonons. The spin-phonon coupling is absent for the magnetic ordering of iron alone but emerges with the additional ordering of the samarium spins. Intriguingly, this ordering is not spontaneous but induced by the iron magnetism. Our findings show an emergent phenomenon from the non-linear interaction by multiple orders, which do not need to occur spontaneously. This allows for a conceptually different approach in the search for yet unknown properties., (© 2022. The Author(s).)

The systemic treatment of hepatocellular carcinoma is changing rapidly. Three main classes of treatment are now available. Historically, multi-targeted tyrosine kinase inhibitors (TKIs) (sorafenib and lenvatinib as first-line; regorafenib and cabozantinib as second-line) were the first to show an improvement in overall survival (OS). Anti-vascular endothelial growth factor (anti-VEGF) antibodies can be used in first-line (bevacizumab) or second-line (ramucirumab) combination therapy. More recently, immuno-oncology (IO) has profoundly changed therapeutic algorithms, and the combination of atezolizumab-bevacizumab is now the first-line standard of care. Therefore, the place of TKIs needs to be redefined. The objective of this review was to define the place of TKIs in the therapeutic algorithm at the time of IO treatment in first-line therapy, with a special focus on lenvatinib that exhibits one of the higher anti-tumoral activity among TKI in HCC. We will discuss the place of lenvatinib in first line (especially if there is a contra-indication to IO) but also after failure of atezolizumab and bevacizumab. New opportunities for lenvatinib will also be presented, including the use at an earlier stage of the disease and combination with IOs.

Competing Interests: The authors have no funding or conflicts of interest to declare.

Background: The Canadian Transplant games ("Games") were created to increase awareness of organ donation and highlight the importance of staying active and healthy post-transplant. It is unclear what motivates solid organ transplant (SOT) recipients to participate and whether the games serve as an incentive for SOT recipients to increase their physical activity (PA) levels., Objectives: 1. To describe the characteristics of participants from past games and their motivation for attending and 2. to determine whether there was an interest in participating in goal-based, pre-games exercise training programs., Methods: A web-based questionnaire was sent to adult SOT recipients who were members of the Canadian Transplant Association. The survey included questions about why participants attended, their PA levels, and their interest in a pre-games training program., Results: Of the 157 participants, more were male than female; the 35-54-year-old age group was the most common; and 62% of respondents received a liver or kidney transplant. The most common reasons for participating in the games were to showcase health post-transplant, promote awareness of organ donation, sports competition, and social reasons. Sixty-five percent of respondents reported that they would be interested in an exercise program to be more physically prepared for the competition., Conclusion: Pre-games training programs could be developed to motivate participation and help participants achieve higher training intensities and foster social interaction. Directing resources to individuals who do not attend the games and to those who are not physically active should be considered., (Copyright © 2020 Elsevier Inc. All rights reserved.)

In stressful situations, catecholamines modulate mammalian immune function, and in addition, they can be sensed by many bacteria. Catecholamine sensing was also found in the zoonotic gut pathogen Salmonella Typhimurium, probably contributing to the stress-induced increased risk of salmonellosis. Virulence traits such as proliferation and invasiveness are promoted upon bacterial catecholamine sensing, but it is unknown whether S. Typhimurium may also inhibit mammalian immune function in stressful situations. We thus investigated whether supernatants from S. Typhimurium grown in the presence of catecholamines modulate porcine mitogen-induced lymphocyte proliferation. Lymphocyte proliferation was reduced by supernatants from catecholamine-exposed Salmonella in a dose-dependent manner. We further examined whether adrenaline oxidation to adrenochrome, which is promoted by bacteria, could be responsible for the observed effect, but this molecule either enhanced lymphocyte functionality or had no effect. We could thereby exclude adrenochrome as a potential immunomodulating agent produced by S. Typhimurium. This study is the first to demonstrate that bacteria grown in the presence of catecholamine stress hormones alter their growth environment, probably by producing immunomodulating substances, in a way that host immune response is suppressed. These findings add a new dimension to interkingdom signaling and provide novel clues to explain the increased susceptibility of a stressed host to Salmonella infection., (Copyright © 2020 Reiske, Schmucker, Steuber, Toulouse, Pfaffinger and Stefanski.)

Background: The benefits of online education are well known and include increased access and flexibility. Despite the increased acceptance and availability of online courses, challenges exist related to increasing connectedness within the triad of students, course content, and faculty., Method: Screen capture recordings (SCRs) are web-based audiovisual recordings that were used to deliver course materials in several nurse practitioner courses in two different educational settings. SCRs allow for meaningful feedback to be given in a warm and caring voice and were used to provide individual student feedback on assignments., Results: Fifty students at a public university and 75 students at a private university received SCR course materials and faculty feedback. At both university settings, student response to SCR course materials and faculty feedback was overwhelmingly positive., Conclusion: SCRs enhance connectedness by conveying faculty tone, caring, and authentic human presence to students, thereby improving the student learning experience. [J Nurs Educ. 2020;59(9):531-535.]., (Copyright 2020, SLACK Incorporated.)

Objective: Compelling evidence supports a treat-to-target (T2T) strategy for optimal outcomes in rheumatoid arthritis (RA). There is limited knowledge regarding the factors that impede implementation of T2T, particularly in a setting where adherence to T2T is protocol-specified. We aimed to assess clinical factors that associate with failure to adhere to T2T., Methods: Patients with RA from 10 countries who were starting or changing conventional synthetic disease-modifying antirheumatic drugs and/or starting tumor necrosis factor inhibitors were followed for 2 years. Participating physicians were required per protocol to adhere to the T2T strategy. Factors influencing adherence to T2T low disease activity (T2T-LDA; 44-joint count Disease Activity Score ≤ 2.4) were analyzed in 2 types of binomial generalized estimating equations models: (1) including only baseline features (baseline model); and (2) modeling variables that inherently vary over time as such (longitudinal model)., Results: A total of 571 patients were recruited and 439 (76.9%) completed 2-year followup. Failure of adherence to T2T-LDA was noted in 1765 visits (40.5%). In the baseline multivariable model, a high number of comorbidities (OR 1.10, 95% CI 1.02-1.19), smoking (OR 1.32, 95% CI 1.08-1.63) and high number of tender joints (OR 1.03, 95% CI 1.02-1.04) were independently associated with failure to implement T2T, while anticitrullinated protein antibody/rheumatoid factor positivity (OR 0.63, 95% CI 0.50-0.80) was a significant facilitator of T2T. Results were similar in the longitudinal model., Conclusion: Lack of adherence to T2T in the RA BIODAM cohort was evident in a substantial proportion despite being a protocol requirement, and this could be predicted by clinical features. [Rheumatoid Arthritis (RA) BIODAM cohort; ClinicalTrials.gov: NCT01476956].

Objective: The Outcome Measures in Rheumatology Soluble Biomarker Working Group initiated an international, multicenter, prospective study, the Rheumatoid Arthritis (RA) BIODAM cohort, to generate resources for the clinical validation of candidate biomarkers predictive of radiographic progression. This first report describes the cohort, clinical outcomes, and radiographic findings., Methods: Patients with RA from 38 sites in 10 countries starting or changing conventional synthetic disease-modifying antirheumatic drugs and/or starting tumor necrosis factor inhibitors were followed for 2 years. Participating physicians were required to adhere to a treat-to-target strategy. Biosamples (serum, urine) were acquired every 3 months, radiography of hands and feet every 6 months, and ultrasound of hands and feet every 3 months in a subset. Primary endpoint was radiographic progression by the Sharp/van der Heijde score., Results: A total of 571 patients were recruited and 439 (76.9%) completed 2-year followup. At baseline, the majority was female (76%), mean age 55.7 years, and mean disease duration 6.5 years. Patients had a mean of 8.4 swollen and 13.6 tender joints, 44-joint count Disease Activity Score (DAS44) 3.8, 77.7% rheumatoid factor-positive or anticitrullinated protein antibody-positive. Percentage of patients in DAS and American College of Rheumatology remission at 2 years was 52.2% and 27.1%, respectively. Percentage of patients with radiographic progression (> 0.5) at 1 and 2 years was 38.2% and 59.9%, respectively., Conclusion: The RA BIODAM prospective study succeeded in generating an extensive list of clinical, imaging (2343 radiographs), and biosample (4638 sera) resources that will be made available to expedite the identification and validation of biomarkers for radiographic damage endpoints. (Clinicaltrials.gov: NCT01476956, clinicaltrials.gov/ct2/show/NCT01476956).

Model materials are precious test cases for elementary theories and provide building blocks for the understanding of more complex cases. Here, we describe the lattice dynamics of the structural phase transition in francisite Cu_{3}Bi(SeO_{3})_{2}O_{2}Cl at 115 K and show that it provides a rare archetype of a transition driven by a soft antipolar phonon mode. In the high-symmetry phase at high temperatures, the soft mode is found at (0,0,0.5) at the Brillouin zone boundary and is measured by inelastic x-ray scattering and thermal diffuse scattering. In the low-symmetry phase, this soft-mode is folded back onto the center of the Brillouin zone as a result of the doubling of the unit cell, and appears as a fully symmetric mode that can be tracked by Raman spectroscopy. On both sides of the transition, the mode energy squared follows a linear behavior over a large temperature range. First-principles calculations reveal that, surprisingly, the flat phonon band calculated for the high-symmetry phase seems incompatible with the displacive character found experimentally. We discuss this unusual behavior in the context of an ideal Kittel model of an antiferroelectric transition.

Background: Prurigo nodularis is a chronic pruritic skin disease with multiple nodular skin lesions. Nemolizumab is a monoclonal antibody targeting the interleukin-31 receptor, which is involved in the pathogenesis of prurigo nodularis., Methods: We conducted a 12-week, randomized, double-blind, phase 2 trial of nemolizumab (at a dose of 0.5 mg per kilogram of body weight) administered subcutaneously at baseline, week 4, and week 8, as compared with placebo, in patients with moderate-to-severe prurigo nodularis and severe pruritus. Moderate-to-severe prurigo nodularis was defined as 20 or more nodules, and severe pruritus was defined as a mean score of at least 7 for the worst daily intensity of pruritus on the numerical rating scale (scores range from 0 [no itch] to 10 [worst itch imaginable]). The primary outcome was the percent change from baseline in the mean peak score for pruritus on the numerical rating scale at week 4. Secondary outcomes included additional measures of itching and disease severity. Safety assessments were performed through week 18., Results: A total of 70 patients were randomly assigned in a 1:1 ratio to receive nemolizumab (34 patients) or placebo (36). The initial pruritus score on the numerical rating scale was 8.4 in each group. At week 4, the peak pruritus score on the numerical rating scale was reduced from baseline by 4.5 points (change, -53.0%) in the nemolizumab group, as compared with a reduction of 1.7 points (change, -20.2%) in the placebo group (difference, -32.8 percentage points; 95% confidence interval, -46.8 to -18.8; P<0.001). Results for secondary outcomes were in the same direction as for the primary outcome. Nemolizumab was associated with gastrointestinal symptoms (abdominal pain and diarrhea) and musculoskeletal symptoms., Conclusions: Nemolizumab resulted in a greater reduction in pruritus and severity of skin lesions than placebo in patients with prurigo nodularis but was associated with adverse events. Larger and longer trials are needed to determine the durability and safety of nemolizumab for the treatment of prurigo nodularis. (Funded by Galderma; ClinicalTrials.gov number, NCT03181503.)., (Copyright © 2020 Massachusetts Medical Society.)

The Na + ion-translocating NADH:quinone oxidoreductase (NQR) from Vibrio cholerae is a membrane-bound respiratory enzyme which harbors flavins and Fe-S clusters as redox centers. The NQR is the main producer of the sodium motive force (SMF) and drives energy-dissipating processes such as flagellar rotation, substrate uptake, ATP synthesis, and cation-proton antiport. The NQR requires for its maturation, in addition to the six structural genes nqrABCDEF , a flavin attachment gene, apbE , and the nqrM gene, presumably encoding a Fe delivery protein. We here describe growth studies and quantitative real-time PCR for the V. cholerae O395N1 wild-type (wt) strain and its mutant Δ nqr and Δ ubiC strains, impaired in respiration. In a comparative proteome analysis, FeoB, the membrane subunit of the uptake system for Fe 2+ (Feo), was increased in V. cholerae Δnqr In this study, the upregulation was confirmed on the mRNA level and resulted in improved growth rates of V. cholerae Δnqr with Fe 2+ as an iron source. We studied the expression of feoB on other respiratory enzyme deletion mutants such as the ΔubiC mutant to determine whether iron transport is specific to the absence of NQR resulting from impaired respiration. We show that the nqr operon comprises, in addition to the structural nqrABCDEF genes, the downstream apbE and nqrM genes on the same operon and demonstrate induction of the nqr operon by iron in V. cholerae wt. In contrast, expression of the nqrM gene in V. cholerae Δnqr is repressed by iron. The lack of functional NQR has a strong impact on iron homeostasis in V. cholerae and demonstrates that central respiratory metabolism is interwoven with iron uptake and regulation. IMPORTANCE Investigating strategies of iron acquisition, storage, and delivery in Vibrio cholerae is a prerequisite to understand how this pathogen thrives in hostile, iron-limited environments such as the human host. In addition to highlighting the maturation of the respiratory complex NQR, this study points out the influence of NQR on iron metabolism, thereby making it a potential drug target for antibiotics., (Copyright © 2020 American Society for Microbiology.)

Bacterial pathogens are influenced by signaling molecules including the catecholamines adrenaline and noradrenaline which are host-derived hormones and neurotransmitters. Adrenaline and noradrenaline modulate growth, motility and virulence of bacteria. We show that adrenaline is converted by the pathogen Vibrio cholerae to adrenochrome in the course of respiration, and demonstrate that superoxide produced by the respiratory, Na +  - translocating NADH:quinone oxidoreductase (NQR) acts as electron acceptor in the oxidative conversion of adrenaline to adrenochrome. Adrenochrome stimulates growth of V. cholerae, and triggers specific responses in V. cholerae and in immune cells. We performed a quantitative proteome analysis of V. cholerae grown in minimal medium with glucose as carbon source without catecholamines, or with adrenaline, noradrenaline or adrenochrome. Significant regulation of proteins participating in iron transport and iron homeostasis, in energy metabolism, and in signaling was observed upon exposure to adrenaline, noradrenaline or adrenochrome. On the host side, adrenochrome inhibited lipopolysaccharide-triggered formation of TNF-α by THP-1 monocytes, though to a lesser extent than adrenaline. It is proposed that adrenochrome produced from adrenaline by respiring V. cholerae functions as effector molecule in pathogen-host interaction., (Copyright © 2019 Elsevier B.V. All rights reserved.)

The invention of a biological membrane which is used as energy storage system to drive the metabolism of a primordial, unicellular organism represents a key event in the evolution of life. The innovative, underlying principle of this key event is respiration. In respiration, a lipid bilayer with insulating properties is chosen as the site for catalysis of an exergonic redox reaction converting substrates offered from the environment, using the liberated Gibbs free energy (ΔG) for the build-up of an electrochemical H + (proton motive force, PMF) or Na + gradient (sodium motive force, SMF) across the lipid bilayer. Very frequently , several redox reactions are performed in a consecutive manner, with the first reaction delivering a product which is used as substrate for the second redox reaction, resulting in a respiratory chain. From today's perspective, the (mostly) unicellular bacteria and archaea seem to be much simpler and less evolved when compared to multicellular eukaryotes. However, they are overwhelmingly complex with regard to the various respiratory chains which permit survival in very different habitats of our planet, utilizing a plethora of substances to drive metabolism. This includes nitrogen, sulfur and carbon compounds which are oxidized or reduced by specialized, respiratory enzymes of bacteria and archaea which lie at the heart of the geochemical N, S and C-cycles. This chapter gives an overview of general principles of microbial respiration considering thermodynamic aspects, chemical reactions and kinetic restraints. The respiratory chains of Escherichia coli and Vibrio cholerae are discussed as models for PMF- versus SMF-generating processes, respectively. We introduce main redox cofactors of microbial respiratory enzymes, and the concept of intra-and interelectron transfer. Since oxygen is an electron acceptor used by many respiratory chains, the formation and removal of toxic oxygen radicals is described. Promising directions of future research are respiratory enzymes as novel bacterial targets, and biotechnological applications relying on respiratory complexes.

Objective: To assess the incidence and the risk factors for zoster in patients exposed to intravenous cyclophosphamide (CYC) for systemic vasculitis or systemic lupus erythematosus (SLE), as well as the protective effect of prophylaxis by valacyclovir (VCV)., Methods: This retrospective study included all adults treated by intravenous CYC for SLE or systemic vasculitis between 2011 and 2015 at Toulouse University Hospital, France. Zoster occurrence was recorded using medical chart review, laboratory data, and patient interviews. Univariate Cox models were computed to assess the risk factors for zoster and the protective effect of prophylaxis by VCV., Results: The cohort consisted of 110 patients (81 systemic vasculitis and 29 SLE). During a mean followup of 3.4 years after CYC initiation, 10 cases of zoster occurred, leading to an overall incidence of 27.9/1000 patient-years (95% CI 15.2-50.6); it was 59.4/1000 patients (95% CI 27.5-123.6) during the year after CYC initiation. Four patients experienced persistent postherpetic neuralgia. Probable risk factors were lymphopenia < 500/ µ l at CYC initiation (HR 5.11, 95% CI 0.94-27.93) and female sex (HR 4.36, 95% CI 0.51-37.31). The incidence was higher in patients with SLE (HR as compared with systemic vasculitis patients = 2.68, 95% CI 0.54-13.26). None of the 19 patients exposed to VCV during the followup developed zoster., Conclusion: The incidence of zoster is high in systemic vasculitis and in patients with SLE exposed to intravenous CYC. CYC may favor postherpetic neuralgia. Prophylaxis by VCV should be considered, particularly in cases of lymphopenia < 500/ µ l at CYC initiation and during the year after.

The electrogenic, sodium ion-translocating NADH:quinone oxidoreductase (NQR) from Vibrio cholerae is frequent in pathogenic bacteria and a potential target for antibiotics. NQR couples the oxidation of NADH to the formation of a sodium motive force (SMF) and therefore drives important processes, such as flagellar rotation, substrate uptake, and energy-dissipating cation-proton antiport. We performed a quantitative proteome analysis of V. cholerae O395N1 compared to its variant lacking the NQR using minimal medium with glucose as the carbon source. We found 84 proteins (regulation factor of ≥2) to be changed in abundance. The loss of NQR resulted in a decrease in the abundance of enzymes of the oxidative branch of the tricarboxylic acid (TCA) cycle and an increase in abundance of virulence factors AcfC and TcpA. Most unexpected, the copper resistance proteins CopA, CopG, and CueR were decreased in the nqr deletion strain. As a consequence, the mutant exhibited diminished resistance to copper compared to the reference strain, as confirmed in growth studies using either glucose or mixed amino acids as carbon sources. We propose that the observed adaptations of the nqr deletion strain represent a coordinated response which counteracts a drop in transmembrane voltage that challenges V. cholerae in its different habitats. IMPORTANCE The importance of the central metabolism for bacterial virulence has raised interest in studying catabolic enzymes not present in the host, such as NQR, as putative targets for antibiotics. Vibrio cholerae lacking the NQR, which is studied here, is a model to estimate the impact of specific NQR inhibitors on the phenotype of a pathogen. Our comparative proteomic study provides a framework to evaluate the chances of success of compounds directed against NQR with respect to their bacteriostatic or bactericidal action., (Copyright © 2018 American Society for Microbiology.)

LacZ (β-galactosidase) is used to monitor the transcription of genes in reporter strains carrying the lacZ gene under the control of a promotor of interest. This protocol for LacZ activity determinations in Vibrio cholerae following detergent lysis results in 2.5-fold increase of LacZ activities compared to lysis with chloroform., (Copyright © 2017 Elsevier B.V. All rights reserved.)

The Na+-translocating NADH:quinone oxidoreductase (NQR) is the entry site for electrons into the respiratory chain of Vibrio cholerae, the causative agent of cholera disease. NQR couples the electron transfer from NADH to ubiquinone to the translocation of sodium ions across the membrane. We investigated the pH dependence of electron transfer and generation of a transmembrane voltage (ΔΨ) by NQR reconstituted in liposomes with Na+ or Li+ as coupling cation. ΔΨ formation was followed with the voltage-sensitive dye oxonol. With Na+, ΔΨ was barely influenced by pH (6.5-8.5), while Q reduction activity exhibited a maximum at pH 7.5-8.0. With Li+, ΔΨ was generally lower, and the pH profile of electron transfer activity did not reveal a pronounced maximum. We conclude that the coupling efficiency of NQR is influenced by the nature of the transported cation, and by the concentration of protons. The 3D structure of NQR reveals a transmembrane channel in subunit NqrB. It is proposed that partial uncoupling of the NQR observed with the smaller Li+, or with Na+ at pH 7.5-8.0, is caused by the backflow of the coupling cation through the channel in NqrB.

Background and Purpose: Achievement of recommended targets for HbA1c, low-density lipoproteins (LDLs), and blood pressure (BP) improves outcomes in adults with diabetes. To meet targets, access to an affordable and consistent supply of medication is necessary, which can be challenging for the medically underserved. The Social Determinants of Health (SDOH) framework guided variable selection in this study, which explored the relationship between continuous access to medication and HbA1c, LDL, and BP in adults with type 2 diabetes who are uninsured and of low socioeconomic status., Methods: This study was conducted using archived medical record data and a convenience sample of adults (n = 65) who received health care on a mobile health van and medications from a pharmaceutical procurement program. Pre-post data were analyzed using dependent t-tests., Conclusions: Continuous access to medication was related to improved HbA1c (p = .003), LDL (p = .004), and systolic BP (p = .025). Access to a consistent source of medications for chronic disease is related to improved health outcomes., Practice Implications: Knowledge was gained about the effect of improved access, nontraditional healthcare delivery systems, and improved outcomes related to collaboration among community partners. Interventions aimed at the wider SDOH may reduce disparities of the medically underserved., (©2015 American Association of Nurse Practitioners.)

Inadequate nutritional intake is an important modifiable risk factor for frailty. Existing evidence supports the importance of adequate dietary quantity and especially quality to ensure sufficient intakes of energy, protein and micronutrients. However, to date no nutritional intervention or supplementation concept has emerged as being effective for the prevention or treatment of frailty. Further research, including specifically the group of frail older persons and those at risk of frailty, and focussing on functional benefits as an outcome, is needed to allow definite recommendations for optimal diet, i.e. food and nutrient intakes, for this population. This article aims to give a short overview on current knowledge concerning the role of nutrition for the prevention and treatment of frailty, while providing readers with references giving an overview for further reading.

Unlabelled: In Escherichia coli or Salmonella enterica, the stress-associated mammalian hormones epinephrine (E) and norepinephrine (NE) trigger a signaling cascade by interacting with the QseC sensor protein. Here we show that Vibrio cholerae, the causative agent of cholera, exhibits a specific response to E and NE. These catecholates (0.1 mM) enhanced the growth and swimming motility of V. cholerae strain O395 on soft agar in a medium containing calf serum, which simulated the environment within the host. During growth, the hormones were converted to degradation products, including adrenochrome formed by autooxidation with O2 or superoxide. In E. coli, the QseC sensor kinase, which detects the autoinducer AI-3, also senses E or NE. The genome of V. cholerae O395 comprises an open reading frame coding for a putative protein with 29% identity to E. coli QseC. Quantitative reverse transcriptase PCR (qRT-PCR) experiments revealed increased transcript levels of the qseC-like gene and of pomB, a gene encoding a structural component of the flagellar motor complex, under the influence of E or NE. Phentolamine blocks the response of E. coli QseC to E or NE. A V. cholerae mutant devoid of the qseC-like gene retained the phentolamine-sensitive motility in the presence of E, whereas NE-stimulated motility was no longer inhibited by phentolamine. Our study demonstrates that V. cholerae senses the stress hormones E and NE. A sensor related to the histidine kinase QseC from E. coli is identified and is proposed to participate in the sensing of NE., Importance: Vibrio cholerae is a Gram-negative bacterium that may cause cholera, a severe illness with high mortality due to acute dehydration caused by diarrhea and vomiting. Pathogenic V. cholerae strains possess virulence factors like the cholera toxin (CTX) and the toxin-coregulated pilus (TCP) produced in response to signals provided by the host. In pathogenic enterobacteria, the stress-associated hormones epinephrine (E) and norepinephrine (NE) of the human host act as signal molecules for the production of virulence factors and promote bacterial growth by the sequestration of iron from the host. Here we show that V. cholerae, like some enterobacteria, benefits from these stress hormones and possesses a sensor to recognize them., (Copyright © 2015, American Society for Microbiology. All Rights Reserved.)

The Na⁺-translocating NADH:ubiquinone oxidoreductase (Na⁺-NQR) of Vibrio cholerae is a respiratory complex that couples the exergonic oxidation of NADH to the transport of Na⁺ across the cytoplasmic membrane. It is composed of six different subunits, NqrA, NqrB, NqrC, NqrD, NqrE, and NqrF, which harbor FAD, FMN, riboflavin, quinone, and two FeS centers as redox co-factors. We recently determined the X-ray structure of the entire Na⁺-NQR complex at 3.5-Å resolution and complemented the analysis by high-resolution structures of NqrA, NqrC, and NqrF. The position of flavin and FeS co-factors both at the cytoplasmic and the periplasmic side revealed an electron transfer pathway from cytoplasmic subunit NqrF across the membrane to the periplasmic NqrC, and via NqrB back to the quinone reduction site on cytoplasmic NqrA. A so far unknown Fe site located in the midst of membrane-embedded subunits NqrD and NqrE shuttles the electrons over the membrane. Some distances observed between redox centers appear to be too large for effective electron transfer and require conformational changes that are most likely involved in Na⁺ transport. Based on the structure, we propose a mechanism where redox induced conformational changes critically couple electron transfer to Na⁺ translocation from the cytoplasm to the periplasm through a channel in subunit NqrB.

A novel technique is described to determine Delta'(17)O(TFL) with high accuracy and precision by using infrared (IR) laser fluorination with F(2) as the reaction gas. The technique includes precise monitoring of the intensity ratio of the (14)NF(2)+ (m/z 52) to O(2) signals. The correlation between the intensity of (14)NF(2) + and positive error in delta(17)O(VSMOW) allows correction of measured data to obtain reliable Delta'(17)O(TFL) values. The resultant error in Delta'(17)O(TFL) of a single measurement after correction is in the range of +/-0.06 per thousand, i.e. sufficiently small to permit the technique to be useful for meteorite classification. Our data for technical O(2), in combination with literature data, suggest a negative anomaly of tropospheric air O(2) with Delta'(17)O(TFL) = -0.344 +/- 0.015 per thousand (1sigma)., (Copyright 2007 John Wiley & Sons, Ltd.)

Traumatic aortic valve regurgitation is a rare complication of non-penetrating thoracic trauma. The most frequent lesion is the isolated injury of the non-coronary cusp. Actually, the transoesophageal echocardiography is the procedure of choice to confirm the diagnosis and to reveal the associated cardiovascular lesions. Surgical management with early operation is the best policy, however this surgery can be delayed for treatment of other life-threatening injuries. Up today, aortic valve replacement (AVR) was recommended to repair traumatic aortic valve regurgitation; nevertheless, in the recent international literature, the number of cases reports with conservative surgery (CS) is increasing: 10 AVR (group I) and 10 CS (group II). Analysis of the post-operative and long term periods shows good results: it confirms the excellent clinical evolution in the group I (mean time of follow-up: 18.2 +/- 16.3 months), and reveals satisfactory results in the group II for patients with isolated lesion (mean time of follow-up: 29.1 +/- 30.7 months). In conclusion, each time the traumatic aortic regurgitation is due to an isolated lesion, the conservative surgery should be performed in order to avoid aortic valve replacement and its potential complications especially in young patients with healthy valves. However, the aortic valve replacement is the safest technique for complex or multiple injuries of the aortic valve.

Objective: We assessed the effects of glucose-insulin-potassium (GIK) by echocardiography in stable patients with ischemic dysfunction., Methods: Twelve male patients with stable coronary disease (SCD) and ejection fraction (EF) <45% were studied for systolic function. GIK (glucose 30%, 300 insulin units and KCl 6 g/l) was infused at 1 ml/kg per h over 20 min. Hemodynamic and echocardiographic measurements were recorded at rest (T(0)), at the end (20 min) of GIK infusion (T+20), 20 and 40 min after the end of the infusion (T+40 and T+60)., Results: At T+20, a significant decrease in WMSI (wall motion score index) was observed compared with T(0) (2.16+/-0.14 vs. 2.30+/-0.16: P<0.05). An increase in EF was reported at T+40 and T+60 compared with T(0) (44.1+/-7.8% and 53.3+/-11.6% vs. 35.6+/-4.5%, respectively: P<0.01). A decrease in WMSI was observed at T+40 and T+60 compared with rest (2.02+/-0.17 and 1.93+/-0.11 vs. 2.30+/-0.16, respectively: P<0.01)., Conclusion: Our present work suggests that GIK infusion improves systolic function in patients with SCD and ejection fraction <45%. Further studies are needed to determine if short-term GIK infusion could be useful for therapeutic or diagnostic strategies in these patients.

The modified Duromedics-Tekna bileaflet pyrolitic carbon mechanical prosthesis was reintroduced by Baxter in 1990. This report details the first case of sudden leaflet fracture of a Tekna mitral valve five years after implantation, which was managed successfully by replacement with a St. Jude Medical mechanical prosthesis. The fracture had occurred transversely, with the fragments embolizing to the terminal aortic bifurcation and the left common femoral artery. These were localized by computed tomography and removed two days after valve replacement.

Unlabelled: The objective of this phase II study was to determine the efficacy and toxicity of a combination of carboplatin and etoposide as salvage treatment, in previously treated patients with persistent or recurrent ovarian cancer following first-line cisplatin-based chemotherapy., Patients and Methods: From July 1990 to August 1994, 58 patients were treated with 3-week cycles of chemotherapy consisting of carboplatin (200 mg/m2, D1) and etoposide (120 mg/m2, D1, D2). Criteria for evaluating previous response to cisplatin were strictly defined., Results: The overall response rate was 36%, with five complete responses (CR, 9%), 16 partial responses (PR, 27%) and the median duration of response was 10 months (range: 4 to 38). In the group of patients who progressed during the first year following the diagnosis, the response was 1 CR and 2 PR (12%) and in the group of patients who progressed from the second year after diagnosis, 4 CR and 14 PR (56%), with a median survival of 8.5 and 21 months respectively (p = 0.0013). The response rate was 59% in the potentially platinum sensitive group versus 8.7% in the primary resistant group (0.02 < p < 0.05). Myelotoxicity was the main side-effect but did not appear to be cumulative. Grade 3 and grade 4 anemia were observed in 26% and 3% of the patients respectively, neutropenia in 14% and 2% and thrombocytopenia in 14% and 8.5%. One patient died of sepsis associated with neutropenia., Conclusion: Treatment was easily manageable and well tolerated. The advantage of carboplatin and etoposide combination in potentially responsive patients is represented by the reduced nephrotoxicity, neurotoxicity and ototoxicity as compared with cisplatin containing regimen, with durable feasibility in outpatients. This second-line chemotherapy for ovarian cancer is effective as salvage treatment in potentially responsive patients with late recurrent tumors, while paclitaxel is the drug of choice for patients who have developped primary or secondary resistance to platin therapy.

Purpose: The purpose of this study is to evaluate the toxicity and the results of abdominopelvic irradiation with a four orthogonal field's technique in patients with ovarian carcinoma., Methods and Materials: Between May 1981 and December 1990, 167 patients with ovarian carcinoma have been treated with whole abdominal irradiation: 62 patients with no or minimal residual disease < 2 cm after initial surgery (group 1) and 105 patients with no residual disease or macroscopic residual disease < 2 cm assessed by second-look surgery after incomplete debulking surgery and cisplatin-based polychemotherapy (group 2). Irradiation was performed by a four orthogonal field's technique. Thirty grays were given with a 25 MV photon beam (1.5 Gy/fraction/day, 20 fractions over 30 days). Boosts were performed in 50 cases (median dose of 15 Gy)., Results: With a median follow-up of 68 months, the 5-year actuarial survival rate was 50% in the entire group, 67% in group 1, 40% in group 2, and 84% in T1, 61.5% in T2, 38% in T3. Five-year actuarial survival was analyzed according to the residuum: (a) after initial surgery (no residual disease: 70%, residual disease: 36.5%), (b) after second-look surgery: 76% in patients with a negative second look, 66% in patients with microscopic residual disease, 22% in patients with macroscopic residual disease and secondary surgical reduction, and 10% in patients with small unresectable nodules. Nine percent of the patients failed to complete irradiation acute side effects related. Five percent required surgery for bowel obstruction., Conclusion: The abdominopelvic irradiation with this four orthogonal field's technique was associated with tolerable acute toxicity and a low risk of serious late complications. Similar late results to have been reported whole abdominal irradiation with chemotherapy in patients with negative or microscopic residual disease after surgery. Randomized trials comparing these two adjuvant treatments are warranted.

From May 1981 through December 1990, 167 patients with ovarian carcinoma were treated with whole abdominal irradiation. All patients of the first group (n = 62) presented with no or minimal (< 2 cm) residual disease at the time of irradiation. They received whole abdominal irradiation after initial surgery. Residual disease was left after initial surgery for patients of the second group (n = 105). They underwent a cisplatin polychemotherapy regimen followed by second-look laparotomy and abdominopelvic irradiation. The irradiation was performed by a four orthogonal field's technique. Thirty grays were given with a 25 MV photon beam. Boosts were performed in 50 cases (mean dose of 15 Gy); 91% have completed irradiation at the prescribed dose level; 5% had severe intestinal toxicity requiring surgery. The median follow-up was 68 months. The 5-year actuarial survival rate was 50%, 67% group 1.40% group 2. Five-year actuarial survival was 84% for T1, 61.5% for T2, 38% for T3. Five-year survival depended on tumor rest after initial surgery (residual disease 36.5%, no residual disease 70%). For patients in group 2, the size of residual disease at second-look laparotomy was a significant prognostic factor: five-year actuarial survival 76% with negative second-look, microscopic residual disease (positive cytology or random biopsies) 60%, microscopic disease after cytoreductive surgery at second-look 22%, macroscopic residual disease (small nodules) 10%. These results indicate that abdominopelvic irradiation is valuable in the treatment of ovarian carcinoma when there is no macroscopic residual disease after initial surgery or second look laparotomy. To assess the place of radiotherapy, randomized trials comparing whole abdominal irradiation with chemotherapy, watch policy for staged patients is warranted.

Sixty patients with advanced carcinoma of the cervix were treated with 3-week cycles of chemotherapy consisting of bleomycin (10 mg/m2, D1, 2, 3), mitomycin (10 mg/m2, D1), cisplatin (80 mg/m2, D3), etoposide (100 mg/m2, D1, 2, 3). Twenty-six patients had prior therapy. Toxicities noted were primarily nausea, vomiting, asthenia, fever and myelosuppression, especially in the pre-treated patients. One patient died of pulmonary toxicity. Of the 34 untreated patients, 25 objective responses (74%) were observed, with two complete responses (6%) and among the 26 pre-treated patients, ten objective responses (39%) with only one complete response. The mean duration of response was 3.8 months [2-14]. These data indicate that combination chemotherapy regimen is active against advanced and recurrent cervical cancer but caution is required for administration and continuation of treatment after four cycles. This method of chemotherapy has significant potential for primary treatment in patients with locally advanced disease.

A sentinel health information system using telematics and a network of general practitioners was set up in Aquitaine in south western France in 1986. Among the health problems under surveillance was acute diarrhoea. Data for each patient who fulfilled the usual case definition for acute diarrhoea were reported by general practitioners using home terminals (Minitels) connected to a central computer by telephone. Over one year 2234 cases of diarrhoea were reported, the incidence varying from 0.8 to 1.5 cases per doctor per week. Seasonal variations in incidence were observed, with peaks in the winter and in the summer. Only 379 (17%) episodes of diarrhoea were classified as severe, and these patients consulted their general practitioners earlier than patients whose diarrhoea was less severe. Foreign travel was rarely found in the patients' histories, but clusters of cases were found in communities (4.6%) and in families (22.3%). The advantages of this system were easy reporting and immediate feedback, but it was difficult to extrapolate the data, and the system was inadequate for intervening in outbreaks of diarrhoeal disease. Our knowledge of diarrhoeal diseases in south west France improved.

In June 1982, the Direction of the French Hospitals introduced the project for the medicalisation of the system of information (PMSI) derived from the American Fetter system. The aim of this project was the collection of basic data necessary to the establishment of a national minimum data set base (MDS). Since 1985, a french regional cancer center, the Foundation Bergonié, has collected MDS by computer. Now, we give the results of the analysis concerning 28,379 MDS collected from 1986 to 1988. However, 11,127 (39%) MDS have not yet been analyzed by PMSI as they are connected with external activity or ambulatory care. It is possible to form a diagnosis related group (DRG) from the MDS to analyze the management of hospitals and utilization of means. 279 DRG were formed from 12,252 MDS, in our Institute. In fact, only 30 DRG with a sufficient number of MDS (over 100) were studied. This descriptive study shows that a few DRG maintain homogeneity in terms of length of hospitalisation especially in the surgical sector. It seems necessary to incorporate new criteria for MDS in order to improve the study of DRG; however groups sufficiently large for statistical analysis must be maintained.