Co-Occurrence of Sarcopenia and Frailty in Acutely Admitted Older Medical Patients: Results from the Copenhagen PROTECT Study.

BACKGROUND: Sarcopenia and frailty are often used interchangeably in clinical practice yet represent two distinct conditions and require different therapeutic approaches. The literature regarding the co-occurrence of both conditions in older patients is scarce as most studies have investigated the prevalence of sarcopenia and frailty separately. OBJECTIVES: We aim to evaluate the prevalence and co-occurrence of sarcopenia and frailty in a large sample of acutely admitted older medical patients. DESIGN: Secondary analyses using cross-sectional data from the Copenhagen PROTECT study. SETTING: Patients were included from the acute medical ward at Copenhagen University Hospital, Bispebjerg and Frederiksberg, Copenhagen, Denmark, between November 2019 and November 2021. PARTICIPANTS: Acutely admitted older medical patients (≥65 years). MEASUREMENTS: Handgrip strength (HGS) was investigated using a handheld dynamometer. Lean mass (SMI) was investigated using direct-segmental multifrequency bioelectrical impedance analyses (DSM-BIA). Low HGS, low SMI, and sarcopenia were defined according to the recent definitions from the European Working Group on Sarcopenia in Older People (EWGSOP2). The Clinical Frailty Scale (CFS) was used to evaluate frailty, with a value > 5 indicating the presence of frailty. Patients were enrolled and tested within 24 hours of admission. RESULTS: This study included 638 patients (mean age: 78.2±7.6, 55% female) with complete records of SMI, HGS, and the CFS. The prevalence of low HGS, low SMI, sarcopenia, and frailty were 39.0%, 33.1%, 19.7%, and 39.0%, respectively. Sarcopenia and frailty co-occurred in 12.1% of the patients. CONCLUSIONS: It is well-known that sarcopenia and frailty represent clinical manifestations of ageing and overlap in terms of the impairment in physical function observed in both conditions. Our results demonstrate that sarcopenia and frailty do not necessarily co-occur within the older acutely admitted patient, highlighting the need for separate assessments of frailty and sarcopenia to ensure the accurate characterization of the health status of older patients.

Plasmoid Formation and Strong Radiative Cooling in a Driven Magnetic Reconnection Experiment.

We present the first experimental study of plasmoid formation in a magnetic reconnection layer undergoing rapid radiative cooling, a regime relevant to extreme astrophysical plasmas. Two exploding aluminum wire arrays, driven by the Z machine, generate a reconnection layer (S_{L}≈120) in which the cooling rate far exceeds the hydrodynamic transit rate (τ_{hydro}/τ_{cool}>100). The reconnection layer generates a transient burst of >1 keV x-ray emission, consistent with the formation and subsequent rapid cooling of the layer. Time-gated x-ray images show fast-moving (up to 50 km s^{-1}) hotspots in the layer, consistent with the presence of plasmoids in 3D resistive magnetohydrodynamic simulations. X-ray spectroscopy shows that these hotspots generate the majority of Al K-shell emission (around 1.6 keV) prior to the onset of cooling, and exhibit temperatures (170 eV) much greater than that of the plasma inflows and the rest of the reconnection layer, thus providing insight into the generation of high-energy radiation in radiatively cooled reconnection events.

Exploring nurses' emotional reactions to and reporting of patient-on-nurse workplace violence: A mixed-methods study.

BACKGROUND: Workplace violence, including violent, intimidating, and disruptive acts, commonly occurs in healthcare settings. Type 2 workplace violence in nursing refers to patient/visitor behaviors directed toward clinicians, contributing to physical and psychological harm. Nurse victims often do not report these events to employers or law enforcement, making it challenging to address workplace violence. OBJECTIVES: Our research examined nurse reactions to Type 2 workplace violence by identifying what behaviors they perceived as aggressive and reportable. Specific aims included: 1) developing and testing video vignettes to portray realistic patient aggression scenarios; 2) identifying nurse understandings of aggressive events that prompt affective reactions, and; 3) examining clinical characteristics related to the nurse victim's likelihood to report. DESIGN: Through a sequential mixed-methods design, we qualitatively developed novel video vignettes portraying Type 2 workplace violence to experimentally examine how nurses interpreted them within a quantitative repeated measures survey. METHODS: Two expert nurse research panels (n = 10) created five vignettes, from which nurses (n = 282) completed a survey with 1382 unique responses. Analyses included descriptive statistics and repeated measures ANOVA/regression models. RESULTS: Video vignettes realistically portrayed workplace violence events, eliciting negative emotional responses among nurses that increased in magnitude with statistical significance as the level of displayed aggression escalated. Statistically significant factors influencing nurse reporting of workplace violence included; 1) the level of aggression displayed by the patient; 2) the level of harm received by the nurse; 3) whether the nurse felt the patient's actions were intentional, and; 4) the nurse's perceived frequency of exposure to workplace violence. CONCLUSIONS: Results suggested that nurse victims of Type 2 workplace violence experience depression, anger, fear, and anxiety, which may contribute to long-term mental health consequences. Findings also identified factors related to nurse reporting behaviors, which may help mitigate workplace violence in healthcare settings by informing research and promoting workplace practices that encourage reporting and safety. REGISTRATION: Not registered. TWEETABLE ABSTRACT: Nurse reactions to workplace violence: Video vignettes reveal escalating aggression's impact on reporting. #EndNurseAbuse #WorkplaceViolence.

Vancomycin-resistant Enterococcus faecium: impact of ending screening and isolation in a Danish University hospital.

BACKGROUND: Substantial resources are used in hospitals worldwide to counteract the ever-increasing incidence of vancomycin-resistant and vancomycin-variable Enterococcus faecium (VREfm and VVEfm), but it is important to balance patient safety, infection prevention, and hospital costs. AIM: To investigate the impact of ending VREfm/VVEfm screening and isolation at Odense University Hospital (OUH), Denmark, on patient and clinical characteristics, risk of bacteraemia, and mortality of VREfm/VVEfm disease at OUH. The burden of VREfm/VVEfm bacteraemia at OUH and the three collaborative hospitals in the Region of Southern Denmark (RSD) was also investigated. METHODS: A retrospective cohort study was conducted including first-time VREfm/VVEfm clinical isolates (index isolates) detected at OUH and collaborative hospitals in the period 2015-2022. The intervention period with screening and isolation was from 2015 to 2021, and the post-intervention period was 2022. Information about clinical isolates was retrieved from microbiological databases. Patient data were obtained from hospital records. FINDINGS: At OUH, 436 patients were included in the study, with 285 in the intervention period and 151 in the post-intervention period. Ending screening and isolation was followed by an increased number of index isolates. Besides a change in van genes, only minor non-significant changes were detected in all the other investigated parameters. Mortality within 30 days did not reflect the VREfm/VVEfm-attributable deaths, and in only four cases was VREfm/VVEfm infection the likely cause of death. CONCLUSION: Despite an increasing number of index isolates, nothing in the short follow-up period supported a reintroduction of screening and isolation.

Evaluation of Genetic or Cellular Impairments in Type I IFN Immunity in a Cohort of Young Adults with Critical COVID-19.

Several genetic and immunological risk factors for severe COVID-19 have been identified, with monogenic conditions relating to 13 genes of type I interferon (IFN) immunity proposed to explain 4.8% of critical cases. However, previous cohorts have been clinically heterogeneous and were not subjected to thorough genetic and immunological analyses. We therefore aimed to systematically investigate the prevalence of rare genetic variants causing inborn errors of immunity (IEI) and functionally interrogate the type I IFN pathway in young adults that suffered from critical COVID-19 yet lacked comorbidities. We selected and clinically characterized a cohort of 38 previously healthy individuals under 50 years of age who were treated in intensive care units due to critical COVID-19. Blood samples were collected after convalescence. Two patients had IFN-α autoantibodies. Genome sequencing revealed very rare variants in the type I IFN pathway in 31.6% of the patients, which was similar to controls. Analyses of cryopreserved leukocytes did not indicate any defect in plasmacytoid dendritic cell sensing of TLR7 and TLR9 agonists in patients carrying variants in these pathways. However, lymphocyte STAT phosphorylation and protein upregulation upon IFN-α stimulation revealed three possible cases of impaired type I IFN signaling in carriers of rare variants. Together, our results suggest a strategy of functional screening followed by genome analyses and biochemical validation to uncover undiagnosed causes of critical COVID-19.

Gemcitabine and Cisplatin Versus Methotrexate, Vinblastine, Doxorubicin, and Cisplatin in Advanced or Metastatic Bladder Cancer: Results of a Large, Randomized, Multinational, Multicenter, Phase III Study.

PURPOSE: Gemcitabine plus cisplatin (GC) and methotrexate, vinblastine, doxorubicin, and cisplatin (MVAC) were compared in patients with locally advanced or metastatic transitional-cell carcinoma (TCC) of the urothelium. PATIENTS AND METHODS: Patients with stage IV TCC and no prior systemic chemotherapy were randomized to GC (gemcitabine 1,000 mg/m2 days 1, 8, and 15; cisplatin 70 mg/m2 day 2) or standard MVAC every 28 days for a maximum of six cycles. RESULTS: Four hundred five patients were randomized (GC, n = 203; MVAC, n = 202). The groups were well-balanced with respect to prognostic factors. Overall survival was similar on both arms (hazards ratio [HR], 1.04; 95% confidence interval [CI], 0.82 to 1.32; P = .75), as were time to progressive disease (HR, 1.05; 95% CI, 0.85 to 1.30), time to treatment failure (HR, 0.89; 95% CI, 0.72 to 1.10), and response rate (GC, 49%; MVAC, 46%). More GC patients completed six cycles of therapy, with fewer dose adjustments. The toxic death rate was 1% on the GC arm and 3% on the MVAC arm. More GC than MVAC patients had grade 3/4 anemia (27% v 18%, respectively) and thrombocytopenia (57% v 21%, respectively). On both arms, the RBC transfusion rate was 13 of 100 cycles and grade 3/4 hemorrhage or hematuria was 2%; the platelet transfusion rate was four patients per 100 cycles and two patients per 100 cycles on GC and MVAC, respectively. More MVAC patients, compared with GC patients, had grade 3/4 neutropenia (82% v 71%, respectively), neutropenic fever (14% v 2%, respectively), neutropenic sepsis (12% v 1%, respectively), and grade 3/4 mucositis (22% v 1%, respectively) and alopecia (55% v 11%, respectively). Quality of life was maintained during treatment on both arms; however, more patients on GC fared better regarding weight, performance status, and fatigue. CONCLUSION: GC provides a similar survival advantage to MVAC with a better safety profile and tolerability. This better-risk benefit ratio should change the standard of care for patients with locally advanced and metastatic TCC from MVAC to GC.

Prevalence of and risk factors for self-reported menstrual changes following COVID-19 vaccination: a Danish cohort study.

STUDY QUESTION: Are there some characteristics that render individuals more susceptible to report menstrual changes following the Coronavirus disease 2019 (COVID-19) vaccination? SUMMARY ANSWER: We found that 30% of menstruating women reported menstrual changes following COVID-19 vaccination and several potential risk factors including stress, vaccine concerns, severe COVID-19 infection, and immediate vaccine symptoms were associated with these reports. WHAT IS KNOWN ALREADY: Studies suggest that COVID-19 vaccination might temporarily prolong menstrual cycle length by less than 1 day. Specific characteristics may trigger menstrual changes in temporal relation to the vaccination simply by chance or render women more vigilant to potential menstrual changes after being vaccinated. However, research investigating potential risk factors for reporting menstrual changes following COVID-19 vaccination is limited. STUDY DESIGN, SIZE, DURATION: A population-based Danish cohort study. Data were collected from May 2021 to December 2021 as a part of the BiCoVac Cohort with the aim of examining non-specific effects following COVID-19 vaccination. The main study population included 13 648 menstruating women aged 16-65 years who completed all surveys, received their first dose of a COVID-19 vaccine during the data collection period, and completed questions related to their menstrual cycle. PARTICIPANTS/MATERIALS, SETTING, METHODS: Potential risk factors included 14 biological, physical, or psychological measures. Information on most potential risk factors was self-reported and collected before the participants' first COVID-19 vaccination. Information about any menstrual change following COVID-19 vaccination was self-reported at the end of the data collection period. Logistic regression analyses were used to estimate crude and adjusted odds ratios (ORs) with 95% CIs for the association between each potential risk factor and reporting menstrual changes following COVID-19 vaccination. MAIN RESULTS AND THE ROLE OF CHANCE: Any menstrual change following COVID-19 vaccination was reported by 30% of menstruating women. Most of the potential risk factors were associated with reports of menstrual changes following COVID-19 vaccination. In particular, higher odds were found among women who reported ≥5 immediate vaccine symptoms; OR 1.67 [1.50-1.86], had had a prior severe COVID-19 infection; OR 2.17 [1.40-3.35], had a high-stress level at baseline; OR 1.67 [1.32-2.10], or were concerned about COVID-19 vaccines prior to vaccination; OR 1.92 [1.50-2.45]. Lower odds were found among women with regular menstrual cycles using hormonal contraception; OR 0.71 [0.65-0.78]. LIMITATIONS, REASONS FOR CAUTION: We were unable to address the causal effect of COVID-19 vaccination on the reported menstrual changes, as information about menstrual changes was not available among non-vaccinated women. WIDER IMPLICATIONS OF THE FINDINGS: The study identified several potential risk factors for reporting menstrual changes following COVID-19 vaccination. Further studies are needed to establish causal associations and the clinical impact of self-reported menstrual changes. STUDY FUNDING/COMPETING INTEREST(S): The BiCoVac data collection was funded by TrygFonden (id-number: 153678). No competing interests are declared. TRIAL REGISTRATION NUMBER: N/A.

Self-consistent and detailed opacities from a non-equilibrium average-atom model.

Modern density functional theory (DFT) is a powerful tool for accurately predicting self-consistent material properties such as equations of state, transport coefficients and opacities in high energy density plasmas, but it is generally restricted to conditions of local thermodynamic equilibrium (LTE) and produces only averaged electronic states instead of detailed configurations. We propose a simple modification to the bound-state occupation factor of a DFT-based average-atom model that captures essential non-LTE effects in plasmas-including autoionization and dielectronic recombination-thus extending DFT-based models to new regimes. We then expand the self-consistent electronic orbitals of the non-LTE DFT-AA model to generate multi-configuration electronic structure and detailed opacity spectra. This article is part of the theme issue 'Dynamic and transient processes in warm dense matter'.

Immediate adverse reactions following COVID-19 vaccination among 16-65-year-old Danish citizens.

INTRODUCTION: There is sparse knowledge of immediate adverse reactions following COVID-19 vaccination. OBJECTIVE: This study aimed to estimate the frequency and number of immediate adverse reactions following COVID-19 vaccination in a Danish population. METHODS: The study used data from the Danish population-based cohort study BiCoVac. The frequencies of 20 self-reported adverse reactions were estimated for each vaccine dose stratified by sex, age, and vaccine type. Also, the distributions of number of adverse reactions following each dose were estimated stratified by sex, age, vaccine type, and prior COVID-19 infection. RESULTS: A total of 889,503 citizens were invited and 171,008 (19 %) vaccinated individuals were included in the analysis. The most frequently reported adverse reaction following the first dose of COVID-19 vaccine was redness and/or pain at the injection site (20 %) while following the second and third dose, tiredness was the most frequently reported adverse reaction (22 % and 14 %, respectively). Individuals aged 26-35 years, females, and those with a prior COVID-19 infection were more likely to report adverse reactions compared with older individuals, males, and those with no prior COVID-19 infection, respectively. Following the first dose, individuals vaccinated with ChAdOx1-2 (AstraZeneca) reported more adverse reactions compared with individuals vaccinated with other vaccine types. Individuals vaccinated with mRNA-1273 (Moderna) reported more adverse reactions following the second and third dose compared with individuals vaccinated with BNT162b2 (Pfizer-BioNTech). CONCLUSION: The frequency of immediate adverse reactions was highest among females and younger persons, however, most of the Danish citizens did not experience immediate adverse reactions following COVID-19 vaccination.

Demonstration of improved laser preheat with a cryogenically cooled magnetized liner inertial fusion platform.

We report on progress implementing and testing cryogenically cooled platforms for Magnetized Liner Inertial Fusion (MagLIF) experiments. Two cryogenically cooled experimental platforms were developed: an integrated platform fielded on the Z pulsed power generator that combines magnetization, laser preheat, and pulsed-power-driven fuel compression and a laser-only platform in a separate chamber that enables measurements of the laser preheat energy using shadowgraphy measurements. The laser-only experiments suggest that ∼89% ± 10% of the incident energy is coupled to the fuel in cooled targets across the energy range tested, significantly higher than previous warm experiments that achieved at most 67% coupling and in line with simulation predictions. The laser preheat configuration was applied to a cryogenically cooled integrated experiment that used a novel cryostat configuration that cooled the MagLIF liner from both ends. The integrated experiment, z3576, coupled 2.32 ± 0.25 kJ preheat energy to the fuel, the highest to-date, demonstrated excellent temperature control and nominal current delivery, and produced one of the highest pressure stagnations as determined by a Bayesian analysis of the data.

A generalized approach to x-ray data modeling for high-energy-density plasma experiments.

Accurate understanding of x-ray diagnostics is crucial for both interpreting high-energy-density experiments and testing simulations through quantitative comparisons. X-ray diagnostic models are complex. Past treatments of individual x-ray diagnostics on a case-by-case basis have hindered universal diagnostic understanding. Here, we derive a general formula for modeling the absolute response of non-focusing x-ray diagnostics, such as x-ray imagers, one-dimensional space-resolved spectrometers, and x-ray power diagnostics. The present model is useful for both data modeling and data processing. It naturally accounts for the x-ray crystal broadening. The new model verifies that standard approaches for a crystal response can be good approximations, but they can underestimate the total reflectivity and overestimate spectral resolving power by more than a factor of 2 in some cases near reflectivity edge features. We also find that a frequently used, simplified-crystal-response approximation for processing spectral data can introduce an absolute error of more than an order of magnitude and the relative spectral radiance error of a factor of 3. The present model is derived with straightforward geometric arguments. It is more general and is recommended for developing a unified picture and providing consistent treatment over multiple x-ray diagnostics. Such consistency is crucial for reliable multi-objective data analyses.

Reducing urinary catheter use in geriatric patients - results of a single-center champion-led intervention.

BACKGROUND: Indwelling urinary tract catheters (UTC) are a well-known risk factor for urinary tract infections (UTI). Because geriatric patients are at high risk of infection, an intervention with a focus on appropriate and minimal UTC use was introduced in 4 acute care geriatric wards. METHODS: Between 11/2018 and 1/2020, unit-based data on UTC use and nosocomial UTI was collected in accordance with the methods of the German national surveillance system KISS. From 6/2019 to 1/2020, a champion-led intervention was implemented which focused on: (i) feedback of surveillance data, (ii) education and training in aseptic UTC insertion and maintenance, (iii) HCW's daily assessment of UTC necessity based on a checklist and (iv) timely removal of unnecessary UTCs. UTC use, incidence, and incidence densities for catheter-associated UTI (CAUTI) were calculated before and during the intervention. In addition, we analyzed adherence to a scheduled daily assessment of UTC necessity. Rate ratios (RR) with 95% confidence intervals (95%CI) were calculated. Differences based on the quality of checklist completion were evaluated using the Kruskal Wallis test. RESULTS: We analyzed the data of 3,564 patients with a total 53,954 patient days, 9,208 UTC days, and 61 CAUTI. Surveillance data showed a significant decrease in the pooled UTC utilization rate from 19.1/100 patient days to 15.2/100 patient days (RR = 0.80, 95%CI 0.77-0.83, p < 0.001). CAUTI per 100 patients dropped from 2.07 to 1.40 (RR = 0.68, 95%CI 0.41-1.12, p = 0.1279). Overall, 373 patients received a UTC during the intervention. Of those patients 351 patients had an UTC ≥ 2 days. The analysis of these patients showed that 186 patients (53%) received a checklist as part of their chart for daily evaluation of UTC necessity. 43 (23.1%) of the completed checklists were of good quality; 143 (76.9%) were of poor quality. Patients in the group whose checklists were of good quality had fewer UTC days (median 7 UTC days IQR (3-11)) than patients whose checklists were of poor quality (11 UTC days IQR (6-16), p = 0.001). CONCLUSION: We conclude that a champion-led, surveillance-based intervention reduces the use of UTC among geriatric patients. Further research is needed to determine to what extent the use of checklists in daily medical UTC assessment affects the prevention of CAUTI. The fact that patients whose checklists were completed well had fewer UTC days should encourage a conscientious and thorough daily review of the need for UTC.

Do bone turnover markers reflect changes in bone microarchitecture during treatment of patients with thyroid dysfunction?

PURPOSE: This study aimed to compare changes in the bone turnover markers (BTMs)-C-terminal telopeptide of type I collagen (CTX-I) and procollagen I N-terminal peptide (PINP)-with changes in the bone microarchitecture, assessed by high-resolution peripheral quantitative computed tomography (HR-pQCT), during treatment of patients with thyroid dysfunction. METHODS: In women with newly diagnosed hypo- or hyperthyroidism, HR-pQCT variables, obtained from the tibia and the radius, were compared with BTMs. Data were collected at diagnosis and after at least 12 months of euthyroidism. RESULTS: 73 women completed the study (hypothyroidism, n = 27; hyperthyroidism, n = 46). Among hyperthyroid patients, correlations were found between changes in BTMs and HR-pQCT variables, primarily for cortical variables in the tibia, i.e. cortical thickness (CTX-I, p < 0.001; PINP, p < 0.001), and volumetric bone mass density (vBMD) (CTX-I, p < 0.001; PINP, p < 0.001). Moreover, correlations between BTMs and estimated bone strength were found. In the hypothyroid subgroup, no significant findings existed after adjustment. Following treatment, less decrease in tibial vBMD was seen among patients with increasing CTX-I compared to those with a decreasing CTX-I level (p = 0.009). Opposite findings applied to PINP, as patients with decreasing PINP showed an increase in tibial vBMD, in contrast to a decline in this parameter among patients with increasing PINP (p < 0.001). CONCLUSION: Changes in CTX-I and PINP correlated with HR-pQCT variables during the treatment of women with thyroid dysfunction. To some extent, these BTMs reflected the restoration of bone microarchitecture. CTX-I seems to be the most sensitive BTM in treatment-naïve thyroid diseases, while PINP is more useful for monitoring during treatment. TRIAL REGISTRATION NUMBER: NCT02005250. Date: December 9, 2013.

Abdominal ultrasound in head and neck squamous cell carcinoma staging: yes or no?

PURPOSE: Abdominal ultrasound is a diagnostic staging procedure for distant metastases in head and neck squamous cell carcinoma (HNSCC). However, currently performed abdominal staging procedures do not follow consistent standards. Therefore, this retrospective study on 498 patients aimed at investigating on abdominal ultrasound as a staging procedure in HNSCC. MATERIALS AND METHODS: A retrospective analysis of 498 head and neck cancer patients treated in our Department of Head and Neck Surgery between 2008 and 2015 was performed. Disease-related data were collected over a mean follow-up time of 30.3 months, and results of abdominal ultrasound were analyzed. RESULTS: 426 patients received abdominal ultrasound as a staging procedure. 7% (29) were suspicious for metastases. In 19 cases (66%), the detected abnormalities were masses of the liver. In four patients, abdominal metastases were confirmed at the time of initial diagnosis. 16 patients developed abdominal metastases in the course of the disease (on average 623 days after initial diagnosis). 19 out of 20 patients with abdominal metastases had an N2/N3 cervical lymph node status. In this study, the negative predictive value of abdominal ultrasound for HNSCC staging was 99.03%, while the positive predictive value yielded 5.88% (N2/N3-patients). CONCLUSION: Only in patients with locally advanced lymph-node-status (N2/N3), abdominal ultrasound can be useful as a staging investigation to exclude abdominal metastasis in HNSCC patients. For N0/N1 patients, abdominal ultrasound might be dispensed. Of note, in case of a positive result, further diagnostic procedures are mandatory.

How, where and when to screen for porcine cytomegalovirus (PCMV) in donor pigs for xenotransplantation.

Porcine cytomegalovirus (PCMV), that is actually a porcine roseolovirus (PRV), is a common herpesvirus in domestic pigs and wild boars. In xenotransplantation, PCMV/PRV has been shown to significantly reduce the survival time of pig kidneys and hearts in preclinical trials with different non-human primates. Furthermore, PCMV/PRV has been transmitted in the first pig to human heart xenotransplantation and contributed to the death of the patient. Although transmitted to the recipient, there is no evidence that PCMV/PRV can infect primate cells including human cells. PCMV/PRV is closely related to the human herpesviruses 6 and 7, and only distantly related to the human CMV (HCMV). Antiviral drugs used for the treatment of HCMV are less effective against PCMV/PRV. However, there are well described strategies to eliminate the virus from pig facilities. In order to detect the virus and to eliminate it, highly sensitive detection methods and the knowledge of how, where and when to screen the donor pigs is required. Here, a comparative testing of organs from pigs of different ages using polymerase chain reaction (PCR)-based and immunological methods was performed. Testing young piglets, PCMV/PRV was detected effectively by PCR in blood, bronchoalveolar lavage fluid, tonsils and heart. In adult animals, detection by PCR was not successful in most cases, because the virus load was below the detection limit or the virus was in its latent stage. Therefore, detection of antibodies against selected recombinant proteins corresponding to epitopes detected by nearly all infected animals in a Western blot assay is advantageous. By contrast, immunological testing is not beneficial in young animals as piglets might have PCMV/PRV-specific antibodies obtained from their infected mother via the colostrum. Using a thoughtful combination of PCR-based and immunological methods, detection of PCMV/PRV in donor pigs for xenotransplantation is feasible and a controlled elimination of the virus by early weaning or other methods is possible.

Homogeneous, Micron-Scale High-Energy-Density Matter Generated by Relativistic Laser-Solid Interactions.

Short-pulse, laser-solid interactions provide a unique platform for studying complex high-energy-density matter. We present the first demonstration of solid-density, micron-scale keV plasmas uniformly heated by a high-contrast, 400 nm wavelength laser at intensities up to 2×10^{21} W/cm^{2}. High-resolution spectral analysis of x-ray emission reveals uniform heating up to 3.0 keV over 1 µm depths. Particle-in-cell simulations indicate the production of a uniformly heated keV plasma to depths of 2 µm. The significant bulk heating and presence of highly ionized ions deep within the target are attributed to the few MeV hot electrons that become trapped and undergo refluxing within the target sheath fields. These conditions enabled the differentiation of atomic physics models of ionization potential depression in high-energy-density environments.

Long-distance transit alters liver and skeletal muscle physiology of beef cattle.

Transportation of cattle is necessary but negatively impacts animal health and production efficiency. To gain a better understanding of the physiological responses to long-distance road transit, 36 crossbred beef steers (324 ±â€¯36 kg) were randomly assigned to treatments (n = 12 steers/treatment): no transit and ad libitum access to feed and water (CON), no transit but deprived of feed and water for 18 h (DEPR), or road transit and no access to feed or water for 18 h (1 790 km; TRANS). Blood, liver, and muscle (longissimus dorsi) samples were collected pre- and post-treatment for analysis of blood metabolites, blood leukocyte profiles, blood markers of oxidative stress, and tissue antioxidant enzyme activity. Additionally, discovery-based metabolomics and proteomics analyses were performed on tissue samples collected immediately post-treatment (d 1). Data (except for omics) were analyzed using ProcMixed of SAS 9.4 with the fixed effect of treatment and steer as the experimental unit. Omics data were analyzed using MetaboAnalyst; metabolites and proteins of interest were identified based on a fold change threshold of 1.20 and t-test P-value of 0.10. On d 1, percent of pretreatment BW and DM intake were least for TRANS steers (P ≤ 0.06). Percent of pretreatment BW remained lesser for TRANS steers on d 8 (P = 0.05). Serum haptoglobin was greatest for TRANS steers immediately post-treatment (P = 0.02). Additionally, TRANS steers exhibited the greatest increase in the neutrophil to lymphocyte ratio and serum non-esterified fatty acids during the treatment period (P < 0.01), indicating TRANS steers experienced a more robust inflammatory and neuroendocrine response. Immediately post-treatment, liver superoxide dismutase activity tended to be greatest for both DEPR and TRANS (P = 0.07) while muscle superoxide dismutase activity was only greatest for TRANS (P = 0.02), suggesting TRANS steers may have experienced more oxidative stress due to the additional physical effort required to stand and maintain balance during transit. The abundance of several proteins (alpha-2-HS-glycoprotein) and metabolites (lactate, citrate, tri-hydroxybutyric acid, and leucine) associated with energy metabolism were altered in the liver and muscle of TRANS. The differential responses for DEPR versus TRANS steers indicate muscle plays an important role in how cattle respond to and recover from transportation stress.

Global airways â€" a novel Standard Tests for Asthma, allergic Rhinitis, and chronic Rhinosinusitis (STARR-15).

BACKGROUND: Global airway disease, with symptoms from both upper and lower airways, is a challenging problem for clinicians. Our goal is to design one single standard test for the awareness of global airway diseases to be used in clinical setting. MATERIAL AND METHODS: During 2019, rhinologists and pulmonologists generated a pool of items based on literature, patient-reported outcome measures and clinical experience. The items were administered to 206 patients with known asthma, CRS, allergic rhinitis, or a combination thereof. The patients also completed the Asthma Control Questionnaire (ACQ-5) and the Sino-Nasal Outcome Test (SNOT-22). Using a mix of clinical knowledge and data-driven methods a global airways questionnaire was developed. RESULTS: Mean ACQ score was highest in patients with all three, whereas the highest SNOT-22 score was observed in patients with CRS and asthma. After the development process, analysis of responses from 206 patients to 44 items on a new global airway’s questionnaire led to identification of 15 items that form the STARR-15 questionnaire with three underlying domains (an allergic rhinitis sub-factor, a CRS sub-factor and an asthma sub-factor). CONCLUSION: STARR-15 represents the first global airways questionnaire, to be used when examining patients with upper and lower airways symptoms. Future analyses are warranted to evaluate the clinical and psychometric properties of STARR-15.

Association of the Kynurenine Pathway of Tryptophan Metabolism With Human Immunodeficiency Virus-Related Gut Microbiota Alterations and Visceral Adipose Tissue Accumulation.

BACKGROUND: The aim of the study was to investigate the association between human immunodeficiency virus (HIV)-related gut microbiota changes, alterations in the kynurenine (Kyn) pathway of tryptophan (Trp) metabolism, and visceral adipose tissue in the context of HIV infection. METHODS: Three hundred eighty-three people with HIV (PWH) were included from the Copenhagen comorbidity in HIV infection (COCOMO) study. Gut microbiota composition was analyzed by 16S ribosomal ribonucleic acid sequencing. Plasma metabolites were analyzed by liquid chromatography-tandem mass spectrometry. Visceral adipose tissue (VAT) and subcutaneous adipose tissue (SAT) areas were measured by single-slice computed tomography (CT) scan (4th lumbar vertebra). RESULTS: The HIV-related gut microbiota alterations were associated with lower Trp (ß -.01; 95% confidence interval [CI], -0.03 to -0.00) and higher Kyn-to-Trp ratio (ß 0.03; 95% CI, 0.01-0.05), which in turn was associated with higher VAT-to-SAT ratio (ß 0.50; 95% CI, 0.10-0.90) and larger VAT area (ß 30.85; 95% CI, 4.43-57.28). In mediation analysis, the Kyn-to-Trp ratio mediated 10% (P = .023) of the association between the VAT-to-SAT ratio and HIV-related gut microbiota. CONCLUSIONS: Our data suggest HIV-related gut microbiota compositional changes and gut microbial translocation as potential drivers of high Kyn-to-Trp ratio in PWH. In turn, increased activity in the Kyn pathway of Trp metabolism was associated with larger visceral adipose tissue area. Taken together, our findings suggest a possible role for this pathway in the gut-adipose tissue axis in the context of HIV infection.