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BackgroundSeveral European countries recently developed international diagnostic and management guidelines for pemphigus, which have been instrumental in the standardization of pemphigus management.ObjectiveWe now present results from a subsequent Delphi consensus to broaden the generalizability of the recommendations.MethodsA preliminary survey, based on the European Dermatology Forum and the European Academy of Dermatology and Venereology guidelines, was sent to a panel of international experts to determine the level of consensus. The results were discussed at the International Bullous Diseases Consensus Group in March 2016 during the annual American Academy of Dermatology conference. Following the meeting, a second survey was sent to more experts to achieve greater international consensus.ResultsThe 39 experts participated in the first round of the Delphi survey, and 54 experts from 21 countries completed the second round. The number of statements in the survey was reduced from 175 topics in Delphi I to 24 topics in Delphi II on the basis of Delphi results and meeting discussion.LimitationsEach recommendation represents the majority opinion and therefore may not reflect all possible treatment options available.ConclusionsWe present here the recommendations resulting from this Delphi process. This international consensus includes intravenous CD20 inhibitors as a first-line therapy option for moderate-to-severe pemphigus.

Howard J Korman,1 David Baunoch,2 Natalie Luke,2 Dakun Wang,3 Xihua Zhao,4 Michael Levin,1 David L Wenzler,1 Mohit Mathur5 1Comprehensive Urology Division, Michigan Healthcare Professionals, Royal Oak, MI, USA; 2Department of Research and Development, Pathnostics, Irvine, CA, USA; 3Department of Writing, Stat4Ward, Pittsburgh, PA, USA; 4Department of Statistical Analysis, Stat4Ward, Pittsburgh, PA, USA; 5Department of Medical Affairs, Pathnostics, Irvine, CA, USACorrespondence: Mohit Mathur, Pathnostics, 15545 Sand Canyon Suite 100, Irvine, CA, 92618, USA, Email mmathur@pathnostics.comPurpose: Complicated UTIs (cUTIs) cause significant morbidity and healthcare resource utilization and cost. Standard urine culture has limitations in detecting polymicrobial and non-E. coli infections, resulting in the under-diagnosis and under-treatment of cUTIs. In this study, patient-reported outcomes were compared between treated and untreated patients when an advanced diagnostic test combining multiplex-polymerase chain reaction (M-PCR) with a pooled antibiotic susceptibility method (P-AST) was incorporated into the patients’ clinical management.Methods: Patients who had symptoms typical of cUTI and positive M-PCR/P-AST test results were recruited from urology clinics. Symptom reduction and clinical cure rates were measured from day 0 through day 14 using the American English Acute Cystitis Symptom Score (ACSS) Questionnaire. Clinical cure was defined based on the sum of the scores of four US Food and Drug Administration (FDA) symptoms and the absence of visible blood in the urine.Results: Of 264 patients with suspected cUTI, 146 (55.4%) had exclusively non-E. coli infections (115 treated and 31 untreated) and 190 (72%) had polymicrobial infections (162 treated and 28 untreated). Treated patients exhibited greater symptom reduction compared to untreated ones on day 14 for those with exclusively non-E. coli organisms (3.18 vs 1.64, p = 0.006) and polymicrobial infections (3.52 vs 1.41, p = 0.002), respectively. A higher percentage of treated patients than of untreated patients achieved clinical cure for polymicrobial infections on day 14 (58.7% vs 36.4%, p = 0.049).Conclusion: Patients with cUTIs treated based on the M-PCR/P-AST diagnostic test had significantly improved symptom reduction and clinical cure rates compared to untreated patients among those with non-E. coli or polymicrobial infections.Keywords: urinary tract infection, complicated urinary tract infection, antibiotic, clinical outcome, diagnostic testing, polymerase chain reaction

Howard J Korman,1 Mohit Mathur,2 Natalie Luke,2 Dakun Wang,3 Xihua Zhao,4 Michael Levin,1 David L Wenzler,1 David Baunoch5 1Comprehensive Urology Division, Michigan Healthcare Professionals, Royal Oak, MI, USA; 2Department of Medical Affairs, Pathnostics, Irvine, CA, USA; 3Department of Writing, Stat4Ward, Pittsburgh, PA, USA; 4Department of Statistical Analysis, Stat4Ward, Pittsburgh, PA, USA; 5Department of Research and Development, Pathnostics, Irvine, CA, USACorrespondence: Mohit Mathur, Pathnostics, 15545 Sand Canyon Suite 100, Irvine, CA, 92618, USA, Email mmathur@pathnostics.comObjective: To compare antibiotic resistance results at different time points in patients with urinary tract infections (UTIs), who were either treated based upon a combined multiplex polymerase chain reaction (M-PCR) and pooled antibiotic susceptibility test (P-AST) or were not treated.Methods: The M-PCR/P-AST test utilized here detects 30 UTI pathogens or group of pathogens, 32 antibiotic resistance (ABR) genes, and phenotypic susceptibility to 19 antibiotics. We compared the presence or absence of ABR genes and the number of resistant antibiotics, at baseline (Day 0) and 5– 28 days (Day 5– 28) after clinical management in the antibiotic-treated (n = 52) and untreated groups (n = 12).Results: Our results demonstrated that higher percentage of patients had a reduction in ABR gene detection in the treated compared to the untreated group (38.5% reduction vs 0%, p = 0.01). Similarly, significantly more patients had reduced numbers of resistant antibiotics, as measured by the phenotypic P-AST component of the test, in the treated than in the untreated group (42.3% reduction vs 8.3%, p = 0.04).Conclusion: Our results with both resistance gene and phenotypic antibiotic susceptibility results demonstrated that treatment based upon rapid and sensitive M-PCR/P-AST resulted in reduction rather than induction of antibiotic resistance in symptomatic patients with suspected complicated UTI (cUTI) in an urology setting, indicating this type of test is valuable in the management of these types of patients. Further studies of the causes of gene reduction, including elimination of ABR gene-carrying bacteria and loss of ABR gene(s), are warranted.Keywords: urinary tract infection, complicated urinary tract infection, antibiotic resistance, antibiotic resistance genes, diagnostic testing, polymerase chain reaction

Objective: This study aims to investigate the impact of slow embryo development on the subsequent live birth rate and birthweight outcomes following a fresh day 5 transfer. Study design: This retrospective multicenter cohort study included 1,213 consecutive patients undergoing autologous oocyte in vitro fertilization (IVF) treatment at four associated private clinics during 2016–2019. Only fresh single day 5 transfers were included for analysis. Results: No implantation was achieved by embryos that failed to reach the early blastocyst stage on day 5 ([Formula: see text]). After adjusting for potential confounding factors, multivariate logistic regression (expressed as adjusted odds ratio or aOR and [Formula: see text] confidence interval) showed a significantly reduced live birth rate in early blastocysts ([Formula: see text]) in reference to those at the expanding (aOR = 0.584, [Formula: see text], [Formula: see text], [Formula: see text]), expanded (aOR = 0.322, [Formula: see text], [Formula: see text], [Formula: see text]), or hatching/hatched stages (aOR = 0.255, [Formula: see text], [Formula: see text], [Formula: see text]). However, early blastocysts led to similar birthweights ([Formula: see text], [Formula: see text]) in comparison to those at the expanding ([Formula: see text], [Formula: see text], [Formula: see text]), expanded ([Formula: see text], [Formula: see text], [Formula: see text]), or hatching/hatched stages ([Formula: see text], [Formula: see text], [Formula: see text]). This was further confirmed by linear regression analysis using either birthweight or [Formula: see text] score (gestation-adjusted birthweight). Conclusion: Slow day 5 development is associated with reduced live birth rate when transferred fresh, however, subsequent birthweight is not impacted once pregnancy is initiated.

Objectives: To address the knowledge gap in the practice of compassionate healthcare by elucidating patient perspectives on compassion, empathy, and sympathy.Methods: Semi-structured telephone interviews were conducted at two time points with patients undergoing head and neck cancer treatment. Questions explored participants’ understanding of compassion, sympathy, and empathy, as they relate to each other and to healthcare. Interviewers manually recorded responses. Qualitative exploratory methods were used to analyze data; inductive line-by-line coding was conducted to develop primary codes. Themes emerged through categorization of codes.Results: Ninety-five interviews conducted with 63 participants across two time points revealed four major themes – Compassion-vs-Empathy-vs-Sympathy, Coping Methods, Showing Care, and Nature of Interaction – encompassing seven categories, with a total of 24 codes. Codes were consistent across time points, except for two new codes, “positivity” and “personalized” emerging during follow-up interviews.Conclusions: Patient narrative from this study supported the concept that compassion is multidimensional and enabled several dimensions to be identified, highlighting the importance of patient perspectives in improving the provision of compassionate healthcare. Findings should be considered in future training and practice.

Objectifs : Améliorer les connaissances sur la pratique des soins compatissants en mettant en lumière le point de vue des patients sur la compassion, l’empathie et la sympathie.Méthodes : Des entretiens téléphoniques semi-structurés ont été menés à deux moments précis avec des patients suivant un traitement contre le cancer de la tête et du cou. Les questions visaient à explorer la compréhension qu’ont les participants de la compassion, de la sympathie, de l’empathie et des relations mutuelles entre ces notions dans un contexte de soins de santé. Les chercheurs ont consigné manuellement les réponses. Des méthodes exploratoires qualitatives ont été utilisées pour analyser les données et un codage inductif ligne par ligne a été effectué pour développer des codes primaires. Une catégorisation des codes a ensuite permis de faire ressortir des thèmes récurrents.Résultats : Quatre-vingt-quinze entretiens menés avec 63 participants à deux moments différents ont fait ressortir quatre thèmes principaux : 1) manifestations de bienveillance; 2) nature des interactions; 3) compassion, empathie et sympathie; 4) méthodes d’adaptation. Ces thèmes se subdivisaient en sept catégories, conduisant à un total de 24 codes. Les codes étaient cohérents d’un point de vue temporel, à l’exception de deux nouveaux codes, « positivité » et « personnalisé », apparus lors des entretiens de suivi.Conclusions : Les témoignages des patients de cette étude ont conforté le concept selon lequel la compassion est multidimensionnelle et ont permis de définir plusieurs dimensions de ce sentiment, soulignant l’importance de tenir compte du point de vue des patients pour améliorer la prestation de soins compatissants. Les conclusions devraient être intégrées dans les formations et les pratiques futures.

Urska Arnautovska,1,2 James P Kesby,3,4 Nicole Korman,1,2 Amanda L Rebar,5 Justin Chapman,2,3 Nicola Warren,1,2 Susan L Rossell,6,7 Frances L Dark,1,2 Dan Siskind1,2,4 1Faculty of Medicine, The University of Queensland, Woolloongabba, QLD, Australia; 2Metro South Addictions and Mental Health Service, Woolloongabba, QLD, Australia; 3Centre for Mental Health, Griffith University, Nathan, QLD, Australia; 4Queensland Centre for Mental Health Research, Wacol, QLD, 4076, Australia; 5Motivation of Health Behaviours Lab, Appleton Institute, School of Health, Medical, and Applied Sciences; Central Queensland University, Rockhampton, QLD, Australia; 6Centre for Mental Health, School of Health Sciences, Swinburne University of Technology, Hawthorn, VIC, Australia; 7Psychiatry, St Vincent’s Hospital Melbourne, Fitzroy, VIC, AustraliaCorrespondence: Urska Arnautovska, Faculty of Medicine, The University of Queensland, Princess Alexandra Hospital, Building 19 (Room 1MH.44.0), 199 Ipswich Road, Woolloongabba, QLD, 4102, Australia, Tel +61 7 3176 5813, Fax +61 7 3176 2821, Email u.arnautovska@uq.edu.auAbstract: People with severe mental illness such as schizophrenia experience high physical comorbidity, leading to a 15– 20-year mortality gap compared with the general population. Lifestyle behaviours such as physical activity (PA) play important roles in the quest to bridge this gap. Interventions to increase PA engagement in this population have potential to be efficacious; however, their effectiveness can be hindered by low participant engagement, including low adherence and high drop-out, and by implementation of interventions that are not designed to compensate for the cognitive and motivational impairments characteristic for this group. Moreover, and importantly, the negative symptoms of schizophrenia are associated with neurobiological changes in the brain, which—based on principles of biopsychology—can contribute to poor motivation and impaired decision-making processes and behavioural maintenance. To increase PA levels in people with schizophrenia, better understanding of these neurological changes that impact PA engagement is needed. This has the potential to inform the design of interventions that, through enhancement of motivation, could effectively increase PA levels in this specific population. Incorporating strategies that address the dopamine dysregulation associated with schizophrenia, such as boosting the role of reward and self-determined motivation, may improve long-term PA maintenance, leading to habitual PA. Consideration of motivation and behavioural maintenance is also needed to impart health benefits such as prevention of chronic disease, which is associated with currently low PA levels in this high metabolic risk population. Taking a biopsychological perspective, we outline the neural pathways involved in motivation that are impacted by schizophrenia and propose strategies for promoting motivation for and PA engagement from adoption to habit formation.Keywords: exercise, psychosis, autonomous motivation, behaviour change, lifestyle interventions, behavioural maintenance

Abstract We have investigated the elimination of inert gases in the lung during the elimination of nitrous oxide (N2O) using a two‐step mathematical model that allows the contribution from net gas volume expansion, which occurs in Step 2, to be separated from other factors. When a second inert gas is used in addition to N2O, the effect on that gas appears as an extra volume of the gas eliminated in association with the dilution produced by N2O washout in Step 2. We first considered the effect of elimination in a single gas‐exchanging unit under steady‐state conditions and then extended our analysis to a lung having a log‐normal distribution of ventilation and perfusion. A further increase in inert gas elimination was demonstrated with gases of low solubility in the presence of the increased ventilation‐perfusion mismatch that is known to occur during anesthesia. These effects are transient because N2O elimination depletes the input of that gas from mixed venous blood to the lung, thereby rapidly reducing the magnitude of the diluting action.

This paper shows that, on average, populism in power produces a decrease in state capture. However, (unconstrained) populism in power that reduces existing levels of rule of law generates greater state capture than (contained) populism that has no negative effects on rule of law. The moderating effect we theorize is that the strength of the rule of law on state capture will show decreased effects at controlling state capture when a country is populist relative to non-populist. Populist leaders may seek to rid the old corruption networks, but once they aggrandize their power and weaken the rule of law, they have incentives to establish corrupt linkages with opportunistic economic elites who are willing to work with them, increasing state capture as a result. To test this theory, the paper employs a random effects model with 6 different specifications across 18 different Latin American countries, throughout the time period 1996-2017.

Fluorescent glucose derivatives are valuable tools as glucose analogs in plant research to explore metabolic pathways, study enzyme activity, and investigate cellular processes related to glucose metabolism and sugar transport. They allow visualization and tracking of glucose uptake, its utilization, and distribution within plant cells and tissues. This study investigates the phenotypic and metabolic impact of the exogenously fed glucose derivative, 2-(N-(7-nitrobenz-2-oxa-1,3-diazol-4-yl)amino)-2-deoxyglucose) (2-NBDG) on the fibers of Gossypium hirsutum (Upland cotton) ovule in vitro cultures. The presence of 2-NBDG in the culture medium did not lead to macroscopic morphological alterations in ovule and fiber development or to the acquisition of fluorescence or yellow coloration. Confocal laser scanning microscope imaging and chromatographic analysis of cotton ovules’ outer rim cross-sections showed that the 2-NBDG is transported from the extracellular space and accumulated inside some outer integument cells, epidermal cells, and fertilized epidermal cells (fibers), but is not incorporated into the cell walls. Untargeted metabolic profiling of the fibers revealed significant changes in the relative levels of metabolites involved in glycolysis and upregulation of alternative energy-related pathways. To provide biochemical and structural evidence for the observed downregulation of glycolysis pathways in the fibers containing 2-NBDG, kinetics analysis and docking simulations were performed on hexokinase from G. hirsutum (GhHxk). Notably, the catalytic activity of heterologously expressed recombinant active GhHxk exhibited a five-fold decrease in reaction rates compared to D-glucose. Furthermore, GhHxk exhibited a linear kinetic behavior in the presence of 2-NBDG instead of the Michaelis-Menten kinetics found for D-glucose. Docking simulations suggested that 2-NBDG interacts with a distinct binding site of GhHxk9, possibly inducing a conformational change. These results highlight the importance of considering fluorescent glucose derivatives as ready-to-use analogs for tracking glucose-related biological processes. However, a direct comparison between their mode of action and its extrapolation into biochemical considerations should go beyond microscopic inspection and include complementary analytical techniques.