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Abstract Background Sepsis, defined as a dysregulated inflammatory response to infection inducing organ dysfunction, is a common cause of mortality in both humans and animals. Early detection and treatment is essential for survival, but accurate diagnosis is challenging due to the lack of specific biomarkers for sepsis. This study explored the potential of the keratinocyte-derived chemokine (KC)-like protein in dogs as a biomarker of sepsis in dogs with bacterial uterine infection (pyometra). The aim was to compare KC-like concentrations in dogs with pyometra with or without sepsis and to assess associations between KC-like and clinical variables, including days of hospitalization as an outcome. Results A mouse KC ELISA was validated and used to determine the concentrations of KC-like in serum from 34 dogs with pyometra and 18 healthy controls. Dogs with pyometra were classified as having sepsis based on two different criteria for systemic inflammatory response syndrome (SIRS), resulting in 74% and 30% sepsis-positive, respectively. The concentration of KC-like protein was higher in pyometra dogs with sepsis than in pyometra dogs without sepsis (p

Purpose: Although speech-language pathologists have provided gender-affirming voice training for trans women since the 1970s, evidence for this training's effectiveness remains weak. Our study aimed to redress limitations of earlier studies and evaluate voice training effects on outcomes important to trans women. Method: Seventy-four trans women (19-54 years old) who wanted a more female-sounding voice were recruited through two health facilities and provided with an eight- to 12-session voice training program based on contemporary literature, usual clinical practice, and client-centered care principles. Self-reported outcomes and an audio-recorded reading sample were collected 3 months before, immediately before and after, and 3 months after training. Forty cisgender speakers were audio-recorded reading the same sample material as comparison voices. Seventy-nine naive listeners made gender-related voice ratings of an extract from these audio recordings. Training effectiveness was evaluated using group-level analyses (linear mixed-effects models) and individual-level analyses to establish what proportion of participants improved to a predetermined relevant degree. Results: Group-level analyses demonstrated positive training effects, maintained 3 months posttraining, for trans women's vocal satisfaction, perceptions of voice-related social participation, and self- and listener perceptions of their voices. Individual-level analyses also demonstrated positive effects. Two thirds of trans women increased vocal satisfaction to a relevant degree, one third who reported restricted social participation before training reduced this restriction to a relevant degree, and all were rated more female-sounding after training (although not all to a relevant degree). Conclusions: All trans women participants made progress toward their voice goals and maintained those gains at follow-up. These findings provide evidence that gender-affirming speech-language pathology services warrant prioritization. Further research is warranted to investigate factors predicting outcomes of voice training for trans women.

Abstract Background A 3D printed self-locking device made of polydioxanone (PDO) was developed to facilitate a standardized ligation technique. The subcutaneous tissue reaction to the device was evaluated after implantation in ten horses of mixed age, sex and breed and compared to loops of poly(lactic-co-glycolic acid) (PLGA). In two of the horses, the implants were removed before closing the skin. The appearance of the implants and surrounding tissue was followed over time using ultrasonography. Implants were removed after 10 and 27 (± 1) days for histologic examination. Results On macroscopic inspection at day 10, the PDO-device was fragmented and the surrounding tissue was oedematous. On ultrasonographic examination, the device was seen as a hyperechoic structure with strong acoustic shadowing that could be detected 4 months post-implantation, but not at 7 months. Histology revealed a transient granulomatous inflammation, i.e., a foreign body reaction, which surrounded both PDO and PLGA implants. The type and intensity of the inflammation varied between individuals and tissue category. Conclusions The 3D printed PDO-device caused a transient inflammatory reaction in the subcutaneous tissue and complete resorption occurred between 4 and 7 months. Considering the intended use as a ligation device the early fragmentation warrants further adjustments of both material and the 3D printing process before the device can be used in a clinical setting.

Abstract Background Speed of eating, an important aspect of eating behaviour, has recently been related to loss of control of food intake and obesity. Very little time is allocated for lunch at school and thus children may consume food more quickly and food intake may therefore be affected. Study 1 measured the time spent eating lunch in a large group of students eating together for school meals. Study 2 measured the speed of eating and the amount of food eaten in individual school children during normal school lunches and then examined the effect of experimentally increasing or decreasing the speed of eating on total food intake. Methods The time spent eating lunch was measured with a stop watch in 100 children in secondary school. A more detailed study of eating behaviour was then undertaken in 30 secondary school children (18 girls). The amount of food eaten at lunch was recorded by a hidden scale when the children ate amongst their peers and by a scale connected to a computer when they ate individually. When eating individually, feedback on how quickly to eat was visible on the computer screen. The speed of eating could therefore be increased or decreased experimentally using this visual feedback and the total amount of food eaten measured. Results In general, the children spent very little time eating their lunch. The 100 children in Study 1 spent on average (SD) just 7 (0.8) minutes eating lunch. The girls in Study 2 consumed their lunch in 5.6 (1.2) minutes and the boys ate theirs in only 6.8 (1.3) minutes. Eating with peers markedly distorted the amount of food eaten for lunch; only two girls and one boy maintained their food intake at the level observed when the children ate individually without external influences (258 (38) g in girls and 289 (73) g in boys). Nine girls ate on average 33% less food and seven girls ate 23% more food whilst the remaining boys ate 26% more food. The average speed of eating during school lunches amongst groups increased to 183 (53)% in the girls and to 166 (47)% in the boys compared to the speed of eating in the unrestricted condition. These apparent changes in food intake during school lunches could be replicated by experimentally increasing the speed of eating when the children were eating individually. Conclusions If insufficient time is allocated for consuming school lunches, compensatory increased speed of eating puts children at risk of losing control over food intake and in many cases over-eating. Public health initiatives to increase the time available for school meals might prove a relatively easy way to reduce excess food intake at school and enable children to eat more healthily.

BackgroundEating disorders and obesity are serious health problems with poor treatment outcomes and high relapse rates despite well-established treatments. Several studies have suggested that virtual reality technology could enhance the current treatment outcomes and could be used as an adjunctive tool in their treatment. ObjectiveThis study aims to investigate the differences between eating virtual and real-life meals and test the hypothesis that eating a virtual meal can reduce hunger among healthy women. MethodsThe study included 20 healthy women and used a randomized crossover design. The participants were asked to eat 1 introduction meal, 2 real meals, and 2 virtual meals, all containing real or virtual meatballs and potatoes. The real meals were eaten on a plate that had been placed on a scale that communicated with analytical software on a computer. The virtual meals were eaten in a room where participants were seated on a real chair in front of a real table and fitted with the virtual reality equipment. The eating behavior for both the real and virtual meals was filmed. Hunger was measured before and after the meals using questionnaires. ResultsThere was a significant difference in hunger from baseline to after the real meal (mean difference=61.8, P

Abstract Objectives A novel 3-gene host transcriptional signature (GBP5, DUSP3 and KLF2) has been validated for tuberculosis (TB) treatment monitoring using laboratory-based RNA sequencing platforms. The signature was recently translated by Cepheid into a prototype cartridge-based test that can be run on the GeneXpert instrument. In this study, we prospectively evaluated the change in the expression of the cartridge-based 3-gene signature following treatment initiation among pulmonary TB patients who were microbiologically cured at the end of treatment. Results The 3-gene signature expression level (TB score) changed significantly over time with respect to baseline among 31 pulmonary TB patients. The greatest increase in TB score occurred within the first month of treatment (median fold-increase in TB score: 1.08 [IQR 0.54–1.52]) and plateaued after 4 months of treatment (median TB score: 1.97 [IQR: 1.03–2.33]). The rapid and substantial increase of the TB score in the first month of treatment holds promise for the early identification of patients that respond to TB treatment. The plateau in TB score at 4 months may indicate early clearance of disease and could direct treatment to be shortened. These hypotheses need to be further explored with larger prospective treatment monitoring studies.

Purpose: The purpose of this work was to study how voice use in daily life is impacted by Parkinson's disease (PD), specifically if there is a difference in voice sound level and phonation ratio during everyday activities for individuals with PD and matched healthy controls. A further aim was to study how variations in environmental noise impact voice use. Method: Long-term registration of voice use during 1 week in daily life was performed for 21 participants with PD (11 male, 10 female) and 21 matched healthy controls using the portable voice accumulator VoxLog. Voice use was assessed through registrations of spontaneous speech in different ranges of environmental noise in daily life and in a controlled studio recording setting. Results: Individuals with PD use their voice 50%-60% less than their matched healthy controls in daily life. The difference increases in high levels of environmental noise. Individuals with PD used an average voice sound level in daily life that was 8.11 dB (female) and 6.7 dB (male) lower than their matched healthy controls. Difference in mean voice sound level for individuals with PD and controls during spontaneous speech during a controlled studio registration was 3.0 dB for the female group and 4.1 dB for the male group. Conclusions: The observed difference in voice use in daily life between individuals with PD and matched healthy controls is a 1st step to objectively quantify the impact of PD on communicative participation. The variations in voice use in different levels of environmental noise and when comparing controlled and variable environments support the idea that the study of voice use should include methods to assess function in less controlled situations outside the clinical setting.

Multi-resolution techniques are essential for the performance of large-scale simulations of computational fluid dynamics with particle methods. In this study, a novel adaptive multi-resolution scheme has been developed for the least squares moving particle semi-implicit (LSMPS) method. With the proposed technique, particles are dynamically resized based on a local error estimate. The error estimate is defined by how well the velocity of a particle can be approximated by the Taylor-series expansions of its fluid neighbours, and vice versa for wall neighbours. Due to the adaptiveness of the multi-resolution technique, time-consuming optimization of predefined particle size targets is avoided. The adaptiveness also enables particle resizing which tracks transient resolution changes of the flow. Therefore, the adaptiveness should improve the computational efficiency of the multi-resolution method. In this study, the multi-resolution technique was tested for a two-dimensional eccentric rotating cylinder problem with a small clearance and a known steady-state solution. As expected, initially uniform particle sizes quickly decreased around the clearance. The particle size distribution evolution was smooth in both time and space throughout the simulations. Consequently, the multi-resolution method gave significantly more accurate results than a single resolution method with the same number of particles and time-step length. A drawback with the multi-resolution scheme is that the restrictions on time-step lengths become tighter. This issue is considered by ongoing development of a multi-time stepping scheme.

BackgroundAnorexia nervosa is one of the more severe eating disorders, which is characterized by reduced food intake, leading to emaciation and psychological maladjustment. Treatment outcomes are often discouraging, with most interventions displaying a recovery rate below 50%, a dropout rate from 20% to 50%, and a high risk of relapse. Patients with anorexia nervosa often display anxiety and aversive behaviors toward food. Virtual reality has been successful in treating vertigo, anxiety disorder, and posttraumatic stress syndrome, and could potentially be used as an aid in treating eating disorders. ObjectiveThe aim of this study was to evaluate the feasibility and usability of an immersive virtual reality technology administered through an app for use by patients with eating disorders. MethodsTwenty-six participants, including 19 eating disorder clinic personnel and 5 information technology personnel, were recruited through emails and personal invitations. Participants handled virtual food and utensils on an app using immersive virtual reality technology comprising a headset and two hand controllers. In the app, the participants learned about the available actions through a tutorial and they were introduced to a food challenge. The challenge consisted of a meal type (meatballs, potatoes, sauce, and lingonberries) that is typically difficult for patients with anorexia nervosa to eat in real life. Participants were instructed, via visual feedback from the app, to eat at a healthy rate, which is also a challenge for patients. Participants rated the feasibility and usability of the app by responding to the mHealth Evidence Reporting and Assessment checklist, the 10-item System Usability Scale, and the 20-point heuristic evaluation questionnaire. A cognitive walkthrough was performed using video recordings of participant interactions in the virtual environment. ResultsThe mean age of participants was 37.9 (SD 9.7) years. Half of the participants had previous experience with virtual reality. Answers to the mHealth Evidence Reporting and Assessment checklist suggested that implementation of the app would face minor infrastructural, technological, interoperability, financial, and adoption problems. There was some disagreement on intervention delivery, specifically regarding frequency of use; however, most of the participants agreed that the app should be used at least once per week. The app received a mean score of 73.4 (range 55-90), earning an overall “good” rating. The mean score of single items of the heuristic evaluation questionnaire was 3.6 out of 5. The lowest score (2.6) was given to the “accuracy” item. During the cognitive walkthrough, 32% of the participants displayed difficulty in understanding what to do at the initial selection screen. However, after passing the selection screen, all participants understood how to progress through the tasks. ConclusionsParticipants found the app to be usable and eating disorder personnel were positive regarding its fit with current treatment methods. Along with the food item challenges in the current app, participants considered that the app requires improvement to offer environmental and social (eg, crowded room vs eating alone) challenges.

Background: There is a need to identify scalable tuberculosis screening strategies among high burden populations. The WHO has identified a non-sputum-based triage test as a development priority. Methods: We performed a diagnostic case-control study of point-of-care C-reactive protein (CRP) and Prototype-Xpert-MTB-Host-Response (Xpert-MTB-HR) assays in the context of a mass screening program for tuberculosis in two prisons in Brazil. All incarcerated individuals irrespective of symptoms were screened by sputum Xpert MTB/RIF and sputum culture. Among consecutive, Xpert MTB/RIF or culture-confirmed cases and Xpert MTB/RIF and culture-negative controls, CRP was quantified in serum by a point-of-care assay (iChroma-II) and a 3-gene expression score was quantified from whole blood using the Xpert-MTB-HR cartridge. We evaluated receiver operating characteristic area under the curve (AUC) and assessed specificity at 90% sensitivity and sensitivity at 70% specificity, consistent with WHO target product profile (TPP) benchmarks. Findings: Two hundred controls (no TB) and 100 culture- or Xpert MTB/RIF-positive tuberculosis cases were included. Half of tuberculosis cases and 11% of controls reported any tuberculosis symptoms. AUC for CRP was 0·79 (95% CI: 0·73–0·84) and for Xpert-MTB-HR was 0·84 (95% CI: 0·79–0·89). At 90% sensitivity, Xpert-MTB-HR had significantly higher specificity (53·0%, 95% CI: 45·0–69·0%) than CRP (28·1%, 95% CI: 20·2–41·8%) (p = 0·003), both well below the TPP benchmark of 70%. Among individuals with medium or high sputum Xpert MTB/RIF semi-quantitative load, sensitivity (at 70% specificity) of CRP (90·3%, 95% CI: 74·2–98·0) and Xpert-MTB-HR (96·8%, 95% CI: 83·3–99·9%) was higher. Interpretation: For active case finding in this high tuberculosis-burden setting, CRP and Xpert-MTB-HR did not meet TPP benchmarks for a triage test. However, Xpert-MTB-HR was highly sensitive in detecting individuals with medium or high sputum bacillary burden. Funding: National Institutes of Health (R01 AI130058 and R01 AI149620) and Brazilian National Council for Scientific and Technological Development (CNPq-404182/2019-4).

Background Individuals with Anorexia Nervosa are often described as restless, hyperactive and having disturbed sleep. The result reproducibility and generalisability of these results are low due to the use of unreliable methods, different measurement methods and outcome measures. A reliable method to measure both physical activity and sleep is through accelerometry. The main purpose of the study was to quantify the physical activity and sleeping behaviour of anorexia nervosa patients. Another purpose was to increase result reproducibility and generalisability of the study. Material and methods Accelerometer data were collected from the first week of treatment of anorexia nervosa at an inpatient ward. Raw data from the Axivity AX3© accelerometer was used with the open-source package GGIR for analysis, in the free statistical software R. Accelerometer measurements were transformed into euclidean norm minus one with negative values rounded to zero (ENMO). Physical activity measurements of interest were 24h average ENMO, daytime average ENMO, inactivity, light activity, moderate activity, and vigorous activity. Sleep parameters of interest were sleep duration, sleep efficiency, awakenings, and wake after sleep onset. The sleep duration of different age groups was compared to recommendations by the National Sleep Foundation using a Fisher’s exact test. Results Of 67 patients, due to data quality 58 (93% female) were included in the analysis. Average age of participants was 17.8 (±6.9) years and body mass index was 15.5 (±1.9) kg/m2. Daytime average ENMO was 17.4 (±5.1) mg. Participants spent 862.6 (±66.2) min per day inactive, 88.4 (±22.6) min with light activities, 25.8 (±16.7) min with moderate activities and 0.5 (±1.8) min with vigorous activities. Participants slept for 461.0 (±68.4) min, waking up 1.45 (±1.25) times per night for 54.6 (±35.8) min, having an average sleep quality of 0.88 (±0.10). 31% of participants met sleep recommendations, with a significantly higher number of 6–13 year old patients failing to reach recommendations compared to 14–25 year old patients. Conclusion The patient group spent most of their time inactive at the beginning of treatment. Most patients failed to reach sleep recommendations. The use of raw data and opensource software should ensure result reproducibility, enable comparison across points in treatment and comparison with healthy individuals.

The limited size of some neuronal types and their entangled environment renders it difficult to study their transcription regulation. Here the authors present a comparative analysis of histone modifications and transcription in dopaminergic and serotonergic neurons and embryonic neural progenitors.

In the originally published version of this Article, financial support was not fully acknowledged. The PDF and HTML versions of the Article have now been corrected to include support to Thomas Perlmann provided by Knut and Alice Wallenberg Foundation (grant 2013.0075) and Swedish Research Council (VR; grant 2016-02506).

To develop a self-efficacy questionnaire for voice modification related to gender affirmation and to examine the internal consistency and test-retest reliability of the questionnaire among a cohort of trans women. This study was undertaken in two phases. In phase I, four Speech- Language Pathologists (SLPs) and four trans women informed the development of the Self-Efficacy Scale for Voice Modification in Trans Women (SES-VMTW). In phase II, using classical test theory, data from 31 Australian and 27 Swedish trans women who completed the SES-VMTW twice with an interim period of 3-6 weeks were analyzed for internal consistency and test-retest reliability. During this second phase, the 19 items of the SES-VMTW were subcategorized by consensus among the authors into like groups. Phase I resulted in the 19-item SES-VMTW and four subcategories were identified: 1) Change (items related to changing voice); 2) Perception (items related to the ability to perceive changes in voice; 3) Psychological (items related to engaging in voice practice despite psychological barriers; 4) Logistical (items related to engaging in voice practice despite logistical barriers). In Phase II, initial psychometric analysis was applied to the full questionnaire as well as to the subcategories. The Cronbach's alpha for the full questionnaire (α = 0.86) at both the test and retest timepoints indicates a high level of internal consistency. Item-total correlation analysis indicated that individual items correlated with the questionnaire total score, but that they generally correlated more strongly with the total score for the relevant subcategory. The Cronbach's alpha for the four subcategories of the SES-VMTW were variable but all coefficients exceeded 0.6, thus supporting the reliability of the new scale. Good test-retest reliability was demonstrated for the full questionnaire (intraclass correlation coefficient = 0.84; 95% confidence interval, 0.73-0.90, P < 0.001) and was moderate to good for the four subcategories. The findings of the current study are promising, suggesting that both the full SES-VMTW and the four subcategories can provide consistent and reliable insight into self-efficacy for trans women aiming to modify their voice as part of their gender affirmation. [ABSTRACT FROM AUTHOR]

At the beginning of the coronavirus crisis, the EU was fiercely criticized for doing too little. The lack of action was often explained bythe EU's limited competence in the policy area of public health. As this is certainly true, the article shows that in fact, the EU'scompetence has evolved overthe yearsasa resultof different health crises. Due to this evolution, the EU is in a much better position to deal with the crisis than just a few years ago. In light of the EU's evolving competence, the article also discusses the prospects for the establishment of a Health Union as well as the expansion of EU competence as a result of this crisis. It argues that this time, we cannot take further integration for granted. [ABSTRACT FROM AUTHOR]

The purpose of this study was to assess the outcome following continuous tactile biofeedback of voice sound level administered, with a portable voice accumulator to individuals with Parkinson's disease (PD). Nine out of 16 participants with PD completed a 4-week intervention program where biofeedback of voice sound level was administered with the portable voice accumulator VoxLog during speech in daily life. The feedback, a tactile vibration signal from the device, was activated when the wearer used a voice sound level below an individually predetermined threshold level, reminding the wearer to increase voice sound level during speech. Voice use was registered in daily life with the VoxLog during the intervention period as well as during one baseline week, one follow-up week post intervention and 1 week 3 months post intervention. Self-to-other ratio (SOR), which is the difference between voice sound level and environmental noise, was studied in multiple noise ranges. A significant increase in SOR across all noise ranges of 2.28 dB (SD: 0.55) was seen for participants with scores above the cut-off for normal function (>26 points) on the cognitive screening test Montreal Cognitive Assessment (MoCA) (n = 5). No significant increase was seen for the group of participants with MoCA scores below 26 (n = 4). Forty-four percent ended their participation early, all which scored below 26 on MoCA (n = 7). Biofeedback administered in daily life regarding voice level may help individuals with PD to increase their voice sound level in relation to environmental noise in daily life, but only for a limited subset. Only participants with normal cognitive function as screened by MoCA improved their voice sound level in relation to environmental noise. [ABSTRACT FROM AUTHOR]