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The controlled release of mitochondrial content into the cytosol has emerged as one of the key steps in mitochondrial signaling. In particular, the release of mitochondrial DNA (mtDNA) into the cytosol has been shown to activate interferon beta (IFN-β) gene expression to execute the innate immune response. In this report, we show that human adenovirus type 5 (HAdV-C5) infection induces the release of mtDNA into the cytosol. The release of mtDNA is mediated by the viral minor capsid protein VI (pVI), which localizes to mitochondria. The presence of the mitochondrial membrane proteins Bak and Bax are needed for the mtDNA release, whereas the viral E1B-19K protein blocked pVI-mediated mtDNA release. Surprisingly, the pVI-mediated mtDNA release did not increase but inhibited the IFN-β gene expression. Notably, the pVI expression caused mitochondrial leakage of the HSP60 protein. The latter prevented specific phosphorylation of the interferon regulatory factor 3 (IRF3) needed for IFN-β gene expression. Overall, we assign a new mitochondria and IFN-β signaling-modulating function to the HAdV-C5 minor capsid protein VI., Importance: Human adenoviruses (HAdVs) are common pathogens causing various self-limiting diseases, including conjunctivitis and the common cold. HAdVs need to interfere with multiple cellular signaling pathways during the infection to gain control over the host cell. In this study, we identified human adenovirus type 5 (HAdV-C5) minor capsid protein VI as a factor modulating mitochondrial membrane integrity and mitochondrial signaling. We show that pVI-altered mitochondrial signaling impedes the cell's innate immune response, which may benefit HAdV growth. Overall, our study provides new detailed insights into the HAdV-mitochondria interactions and signaling. This knowledge is helpful when developing new anti-viral treatments against pathogenic HAdV infections and improving HAdV-based therapeutics., Competing Interests: The authors declare no conflict of interest.

Objective: The objective of this study was 2-fold: first, to evaluate whether superb microvascular imaging (SMI) could be used to visualize neovascularization in temporal arteries, and, second, to evaluate the diagnostic performance of high frequency ultrasound with SMI using an extended protocol in patients with suspected giant cell arteritis (GCA)., Methods: This retrospective study comprised 120 patients consecutively examined with an extended CDU protocol (temporal, facial, axillary, subclavian, brachiocephalic, and carotid arteries) between 2020 and 2022. Of all patients, 107 had no previous GCA diagnosis and 13 had a previous GCA diagnosis. SMI was used to evaluate neovascularization in the temporal arteries. Arteritis were characterized as low- or medium-echogenic, homogeneous wall thickening, with or without a positive compression sign in the temporal arteries. The Halo count, i.e., the number of temporal and axillary artery segments with signs of arteritis, was evaluated. The reference was clinically diagnosed GCA confirmed after ≥6-month follow-up., Results: Of the eligible 107 patients with new suspected GCA, 33 (31%) received a clinical GCA diagnosis. Neovascularization was detected in 14 patients (43%). Patients with neovascularization displayed a higher halo count [median 6 (25th-75th percentile 4.75-7) vs. 3 (2-4-4), p = 0.005]. CDU of only the temporal arteries showed sensitivity and specificity (95% confidence intervals) of 94% (80-100%) and 100% (95-100%), respectively. The addition of extra-cranial arteries increased the sensitivity to 100%. Of the 13 patients investigated for suspected relapse, three had a clinically confirmed relapse. One of them displayed neovascularization together with other signs of inflammation., Conclusions: We show for the first time that inflammatory neovascularization of the temporal arteries can be detected by SMI. Neovascularization is associated with a more-widespread cranial disease. The value of neovascularization should be further investigated, especially for the detection of GCA relapse., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Skoog, Svensson, Eriksson, Sjöwall and Zachrisson.)

Polycystic ovary syndrome (PCOS) is associated with a low-grade inflammation, but it is unknown how hyperandrogenism, the hallmark of PCOS, affects the immune system. Using a PCOS-like mouse model, it is demonstrated that hyperandrogenism affects immune cell populations in reproductive, metabolic, and immunological tissues differently in a site-specific manner. Co-treatment with an androgen receptor antagonist prevents most of these alterations, demonstrating that these effects are mediated through androgen receptor activation. Dihydrotestosterone (DHT)-exposed mice displayed a drastically reduced eosinophil population in the uterus and visceral adipose tissue (VAT). A higher frequency of natural killer (NK) cells and elevated levels of IFN-γ and TNF-α are seen in uteri of androgen-exposed mice, while NK cells in VAT and spleen displayed a higher expression level of CD69, a marker of activation or tissue residency. Distinct alterations of macrophages in the uterus, ovaries, and VAT are also found in DHT-exposed mice and can potentially be linked to PCOS-like traits of the model. Indeed, androgen-exposed mice are insulin-resistant, albeit unaltered fat mass. Collectively, it is demonstrated that hyperandrogenism causes tissue-specific alterations of immune cells in reproductive organs and VAT, which can have considerable implications on tissue function and contribute to the reduced fertility and metabolic comorbidities associated with PCOS., (© 2024 The Authors. Advanced Science published by Wiley‐VCH GmbH.)

Transgenic mice expressing human major histocompatibility complex class II (MHCII) risk alleles are widely used in autoimmune disease research, but limitations arise due to non-physiologic expression. To address this, physiologically relevant mouse models are established via knock-in technology to explore the role of MHCII in diseases like rheumatoid arthritis. The gene sequences encoding the ectodomains are replaced with the human DRB1*04:01 and 04:02 alleles, DRA, and CD74 (invariant chain) in C57BL/6N mice. The collagen type II (Col2a1) gene is modified to mimic human COL2. Importantly, DRB1*04:01 knock-in mice display physiologic expression of human MHCII also on thymic epithelial cells, in contrast to DRB1*04:01 transgenic mice. Humanization of the invariant chain enhances MHCII expression on thymic epithelial cells, increases mature B cell numbers in spleen, and improves antigen presentation. To validate its functionality, the collagen-induced arthritis (CIA) model is used, where DRB1*04:01 expression led to a higher susceptibility to arthritis, as compared with mice expressing DRB1*04:02. In addition, the humanized T cell epitope on COL2 allows autoreactive T cell-mediated arthritis development. In conclusion, the humanized knock-in mouse faithfully expresses MHCII, confirming the DRB1*04:01 alleles role in rheumatoid arthritis and being also useful for studying MHCII-associated diseases., (© 2024 The Authors. Advanced Science published by Wiley‐VCH GmbH.)

RNA-based medicines have potential to treat a large variety of diseases, and research in the field is very dynamic. Proactively, The European Medicines Agency (EMA) organized a virtual conference on February 2, 2023 to promote the development of RNA-based medicines. The initiative addresses the goal of the EMA Regulatory Science Strategy to 2025 to "catalyse the integration of science and technology in medicines development." The conference focused on RNA technologies (excluding RNA vaccines) and involved different stakeholders, including representatives from academia, industry, regulatory authorities, and patient organizations. The conference comprised presentations and discussion sessions conducted by panels of subject matter experts. In this meeting report, we summarize the presentations and recap the main themes of the panel discussions.

Background: Nasolacrimal duct obstruction is usually treated using endoscopic or external dacryocystorhinostomy (DCR). The anatomic outcomes of both the endoscopic and external approaches are considered excellent. However, anatomic success does not translate into patient satisfaction. The current study assessed pre- and postoperative lacrimal problems using the symptom-based Lacrimal Symptom Questionnaire (Lac-Q) and investigated patient satisfaction depending on the choice of surgical technique., Methods: A total of 112 eligible patients with lacrimal problems treated using external or endonasal DCR at the ophthalmology and ear, nose, and throat clinics at Skane University Hospital, Scania, Sweden, over a four-year period, were enrolled in this retrospective study. Patients were considered eligible if they experienced preoperative epiphora and had lacrimal duct stenosis. They were offered treatment using either external or endonasal DCR and were allowed to freely choose the technique. Exclusion criteria consisted of previous ipsilateral DCR, congenital NLDO, age < 18 years, presence of cancer, previous orbital trauma, or noncompliance with postoperative follow-up. After surgery, the patients were sent the Lac-Q to evaluate their lacrimal symptoms pre- and postoperatively. Complementary questions were added pertaining to the operative scar and the patients' overall satisfaction with the operation., Results: In total, 67 (60%) patients with ages ranging from 18 to 88 years completed the questionnaire, 33 (49%) of whom underwent external DCR and 34 (51%) endonasal DCR. Of the 67 respondents, 51 (76%) were women and 16 (24%) were men. Patients scored preoperative lacrimal problems highly on the Lac-Q, reporting both symptomatic and social problems due to epiphora. Following surgery, the group that underwent external DCR remained home from work for 2 - 14 days (median, 3.5 days). However, 17 (52%) were retired. After the endonasal DCR, the patients remained home for 0 - 7 days (median, 2 days). Most patients were satisfied after DCR surgery, with both techniques significantly improving total, lacrimal symptom, and social impact scores (all P  < 0.001). No differences in postoperative satisfaction were observed between the external DCR and endonasal DCR groups ( P  > 0.05). A small number of patients expressed scar-related concerns after external DCR., Conclusions: The patients perceived lacrimal problems as a significant symptomatic and social burden. Postoperative satisfaction and symptom relief were good regardless of the surgical approach. Further prospective studies assessing patient satisfaction and its correlation with anatomical and functional success rates after external and endonasal DCR could provide robust, practical, real-world implications., Competing Interests: None., (© Author(s).)

Background: Accurate and reliable assessment of clinician integrity in the delivery of empirically supported treatments is critical to effective research and training interventions. Assessment of clinician integrity can be performed through recording simulated (SI) or real-life (RL) consultations, yet research examining the equivalence of these data is in its infancy. To explore the strength of integrity assessment between SI and RL samples in Motivational Interviewing (MI) consultations, this article examines whether Motivational Interviewing Treatment Integrity (MITI) assessments differ between SI and RL consultations and reviews the predictive validity of SI and RL MI skills categorisations for RL client response language., Methods: This study first compared MITI coding obtained in SI and RL consultations for 36 veterinary clinicians. Multilevel models of 10 MITI behaviour counts and four MITI global scores were run using MLwiN 3.02 to assess if a significant difference existed between SI and RL MITI data, with consultation within clinician within cohort (A and B) as nested random effects. Second, we investigated the effect of SI and RL MI skills groupings on rate of RL client response talk using three multivariable regression models. Two Poisson regression models, with random intercepts for farm and veterinarian and offset for number of minutes of the recordings, were estimated in the statistical software R using the package glmmTMB for the two response variables Change Talk and Sustain Talk. A logistic regression model, with the same random intercepts, with the response variable Proportion Change Talk was also estimated using the same package., Results: Veterinary clinicians were less MI consistent in RL consultations, evidenced through significantly lower global MITI Cultivating Change Talk ( p < 0.001), Partnership ( p < 0.001) and Empathy ( p = 0.003) measures. Despite lower objective MI skills groupings in RL consultations, ranking order of veterinary clinicians by MI skills was similar between contexts. The predictive validity of SI and RL MI skills groupings for RL client Change Talk was therefore similar, with significantly more RL client Change Talk associated with veterinarians categorised in the highest grouping ('moderate') in both SI ( p = 0.01) and RL ( p = 0.02) compared to untrained veterinarians in each respective context., Conclusions: Findings suggest SI and RL data may not be interchangeable. Whilst both data offer useful insights for specific research and training purposes, differing contextual MI skills thresholds may offer a more equitable assessment of clinician RL client-facing MI integrity. Further research is needed to explore the applicability of these findings across health contexts., Competing Interests: Lars Forsberg is Operations Manager at MICLab AB., (© 2023 Bard et al.)

The benefits of feeding calves more milk are increasingly being recognized by dairy farmers. However, most producers have still not implemented higher feeding plans. The aim of the present study was to gain a deeper understanding of farmer and farm staff attitudes, and the perceptions and factors considered in their decision-making regarding daily milk allowances. We collected data through focus group interviews with dairy farmers, farm managers, and calf-care workers who were selected using purposive and snowball sampling. In total, 40 persons (24 women and 16 men) joined a focus group interview (6 in all, each with 5-8 participants). Interviews were recorded, and recordings were transcribed and analyzed thematically. Participants had contrasting opinions about the minimum, maximum, and recommended daily milk allowances to their calves. Their suggested lowest daily milk allowance to sustain animal welfare ranged from 4 to 8-10 L and the maximum allowance from 6 to 15 L. We found that farmers' and farm staff's choices and recommendations of milk-feeding protocols were influenced by a large number of factors that could be grouped into 4 themes: (1) Life beyond work, (2) Farm facilities and equipment, (3) Care of the calves, and (4) Profitability and production. Participants' considerations were similar and aimed to maximize daily milk allowance based on farm conditions. However, the allowances they described as optimal for their calves often differed from what they considered practically feasible. We found that the care of the calves and the well-being of the owners and the staff was central in the participants' decision-making, but that this care perspective was challenged by the social and economic sustainability of the farm. Most participants fed their calves twice daily and did not think that increasing that number would be practically feasible. Our results indicate that the participants' viewpoints regarding calves were important for their decision-making about milk allowances. We suggest that a more holistic perspective should be used when advising farmers about milk allowances, putting particular emphasis on the caring and social sustainability aspects of the individual farm., (The Authors. Published by Elsevier Inc. and Fass Inc. on behalf of the American Dairy Science Association®. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).)

Background: We instituted Kamishibai (K-card rounding) with the goals of improving indwelling urinary catheter maintenance bundle reliability and decreasing catheter-associated urinary tract infection (CAUTI) rates., Method: In a free-standing children's hospital, we undertook a hospital-wide quality improvement project from January 2019 to June 2021 after developing a K-card based on our urinary catheter maintenance bundle. Auditors used K-cards to ask standardized questions during weekly rounds. Bundle reliability and CAUTI rates were analyzed prospectively., Results: During the study period, 826 K-card audits were performed for 657 unique patients. While overall maintenance bundle reliability remained stable at 84%, there was a statistically significant improvement in reliability to the bundle element "medical discussion of need for the urinary catheter" from 88% to 94% (P = .01). The hospital-wide CAUTI rate significantly decreased (incidence rate ratio, 0.38; 95% CI, 0.15-0.93; P = .04)., Discussion: Hospital-wide urinary catheter K-card rounding facilitated standardized data collection, discussion of reliability and real-time feedback to nurses. Maintenance bundle reliability remained stable after implementation, accompanied by a significant decrease in the CAUTI rate., Conclusions: Implementation of hospital-wide urinary catheter K-card rounding was associated with reduction in CAUTI rates. The project demonstrated likelihood of reproducibility with support of a multidisciplinary team., Competing Interests: Conflicts of interest Dr. Ana Vaughan-Malloy has disclosed stock ownership, detailed in submitted disclosure form. Other authors have no conflicts of interest., (Copyright © 2022 Association for Professionals in Infection Control and Epidemiology, Inc. Published by Elsevier Inc. All rights reserved.)

Patients with systemic lupus erythematosus (SLE) are at an increased risk of cardiovascular disease. We aimed to evaluate whether antibodies to oxidized low-density lipoprotein (anti-oxLDL) were associated with subclinical atherosclerosis in patients with different SLE phenotypes (lupus nephritis, antiphospholipid syndrome, and skin and joint involvement). Anti-oxLDL was measured by enzyme-linked immunosorbent assay in 60 patients with SLE, 60 healthy controls (HCs) and 30 subjects with anti-neutrophil cytoplasmic antibody-associated vasculitis (AAV). Intima-media thickness (IMT) assessment of vessel walls and plaque occurrence were recorded using high-frequency ultrasound. In the SLE cohort, anti-oxLDL was again assessed in 57 of the 60 individuals approximately 3 years later. The levels of anti-oxLDL in the SLE group (median 5829 U/mL) were not significantly different from those in the HCs group (median 4568 U/mL), while patients with AAV showed significantly higher levels (median 7817 U/mL). The levels did not differ between the SLE subgroups. A significant correlation was found with IMT in the common femoral artery in the SLE cohort, but no association with plaque occurrence was observed. The levels of anti-oxLDL antibodies in the SLE group were significantly higher at inclusion compared to 3 years later (median 5707 versus 1503 U/mL, p < 0.0001). Overall, we found no convincing support for strong associations between vascular affection and anti-oxLDL antibodies in SLE.

Phenotypic drug discovery (PDD) enables the target-agnostic generation of therapeutic drugs with novel mechanisms of action. However, realizing its full potential for biologics discovery requires new technologies to produce antibodies to all, a priori unknown, disease-associated biomolecules. We present a methodology that helps achieve this by integrating computational modeling, differential antibody display selection, and massive parallel sequencing. The method uses the law of mass action-based computational modeling to optimize antibody display selection and, by matching computationally modeled and experimentally selected sequence enrichment profiles, predict which antibody sequences encode specificity for disease-associated biomolecules. Applied to a phage display antibody library and cell-based antibody selection, ∼10 5 antibody sequences encoding specificity for tumor cell surface receptors expressed at 10 3 -10 6 receptors/cell were discovered. We anticipate that this approach will be broadly applicable to molecular libraries coupling genotype to phenotype and to the screening of complex antigen populations for identification of antibodies to unknown disease-associated targets., Competing Interests: J.M., C.S., and B.F. are BioInvent employees, and A.L. was employed by BioInvent. J.M., A.L., and B.F. are shareholders of BioInvent International. J.M., A.L., and B.F. are inventors on BioInvent patent applications relevant to the prediction-guided methodology for antibody discovery., (© 2023 The Author(s).)

The excited states of N=44 ^{74}Zn were investigated via γ-ray spectroscopy following ^{74}Cu β decay. By exploiting γ-γ angular correlation analysis, the 2&#95;{2}^{+}, 3&#95;{1}^{+}, 0&#95;{2}^{+}, and 2&#95;{3}^{+} states in ^{74}Zn were firmly established. The γ-ray branching and E2/M1 mixing ratios for transitions deexciting the 2&#95;{2}^{+}, 3&#95;{1}^{+}, and 2&#95;{3}^{+} states were measured, allowing for the extraction of relative B(E2) values. In particular, the 2&#95;{3}^{+}→0&#95;{2}^{+} and 2&#95;{3}^{+}→4&#95;{1}^{+} transitions were observed for the first time. The results show excellent agreement with new microscopic large-scale shell-model calculations, and are discussed in terms of underlying shapes, as well as the role of neutron excitations across the N=40 gap. Enhanced axial shape asymmetry (triaxiality) is suggested to characterize ^{74}Zn in its ground state. Furthermore, an excited K=0 band with a significantly larger softness in its shape is identified. A shore of the N=40 "island of inversion" appears to manifest above Z=26, previously thought as its northern limit in the chart of the nuclides.

Human adenoviruses (HAdVs) are widespread pathogens causing a variety of diseases. A well-controlled expression of virus capsid mRNAs originating from the major late transcription unit (MLTU) is essential for forming the infectious virus progeny. However, regulation of the MLTU mRNA metabolism has mainly remained enigmatic. In this study, we show that the cellular RNA-binding protein FXR1 controls the stability of the HAdV-5 MLTU mRNAs, as depletion of FXR1 resulted in increased steady-state levels of MLTU mRNAs. Surprisingly, the lack of FXR1 reduced viral capsid protein accumulation and formation of the infectious virus progeny, indicating an opposing function of FXR1 in HAdV-5 infection. Further, the long FXR1 isoform interfered with MLTU mRNA translation, suggesting FXR1 isoform-specific functions in virus-infected cells. We also show that the FXR1 protein interacts with N6-methyladenosine (m 6 A)-modified MLTU mRNAs, thereby acting as a novel m 6 A reader protein in HAdV-5 infected cells. Collectively, our study identifies FXR1 as a regulator of MLTU mRNA metabolism in the lytic HAdV-5 life cycle. IMPORTANCE Human adenoviruses (HAdVs) are common pathogens causing various self-limiting diseases, such as the common cold and conjunctivitis. Even though adenoviruses have been studied for more than 6 decades, there are still gaps in understanding how the virus interferes with the host cell to achieve efficient growth. In this study, we identified the cellular RNA-binding protein FXR1 as a factor manipulating the HAdV life cycle. We show that the FXR1 protein specifically interferes with mRNAs encoding essential viral capsid proteins. Since the lack of the FXR1 protein reduces virus growth, we propose that FXR1 can be considered a novel cellular proviral factor needed for efficient HAdV growth. Collectively, our study provides new detailed insights about the HAdV-host interactions, which might be helpful when developing countermeasures against pathogenic adenovirus infections and for improving adenovirus-based therapies.

Cattle veterinarians have long been encouraged to take on a role as proactive health consultants. However, the process so far has been slow in Sweden and elsewhere, and only a rather small proportion of cattle work conducted by veterinarians involves veterinary herd health management (VHHM). The aims of this exploratory study were to explore Swedish cattle veterinarians' interpretation of VHHM services and to understand the factors that might affect the extent to which cattle veterinarians perform VHHM. Six focus group discussions with cattle veterinarians complemented with 5 individual telephone interviews with clinic managers were conducted in 2020. In total, 33 cattle veterinarians participated, all employed by the largest employer of Swedish cattle veterinarians: Distriktsveterinärerna (Swedish Board of Agriculture). Participants were chosen from 6 geographical regions with the aim to present variations in gender, age, country of education, proportion of dairy cattle work at the clinic, experience in the veterinary profession, and experience in work with dairy herds and in VHHM. The focus group discussions and interviews were recorded and these recordings were transcribed and analyzed thematically. Participants interpreted VHHM as work associated with the process of advising and included both ad hoc advising and more strategic forms of services. Prebooked visits per se were not seen as VHHM. We identified 4 different themes among the factors affecting the extent of VHHM services: (1) farmer trust and demand; (2) veterinary competence; (3) time available for VHHM; and (4) the individual veterinarian's commitment and motivation. To gain farmers' trust and to create a demand for VHHM services, the results of VHHM work and the veterinarian's competence were deemed central by the participants. The veterinarians' skills in communication and relation building were considered especially important. Some farmers were perceived as having little interest in, or lacking deeper knowledge about, VHHM services. The promotion of VHHM services was mentioned as an important factor to increase farmer demand. Participants described VHHM as work demanding high skills and continuous capacity development. Veterinarians' personal commitment and motivation were also described as important for the extent to which VHHM services were performed. This was in turn affected by the psychosocial work environment (e.g., workload, interest and recognition from farmers and managers, and acceptance, priority, and support by colleagues and managers). Clinic managers had a central role in the extent to which VHHM services are offered by an individual veterinarian due to their responsibility for staff scheduling, which highly affects the conditions for capacity development, intercollegiate networking, and cooperation. Lack of time was a major barrier for VHHM. On-call duty time and subsequent compensatory leave affected the total time available, and participants described time conflicts between VHHM and emergency services; moreover, it was perceived as challenging to find sufficient time for capacity development in several different species for veterinarians working in mixed practice. The slow development toward more proactive approaches for cattle veterinarians can be explained by the numerous different factors that together constrain the veterinarian to the traditional role of diagnosing and treating sick animals., (© 2022, The Authors. Published by Elsevier Inc. and Fass Inc. on behalf of the American Dairy Science Association®. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).)

Introduction: Takayasu arteritis (TAK) is a rare inflammatory disease affecting aorta and its major branches. Ultrasound (US) can detect inflammatory features in the arterial wall, but less is known regarding skin microcirculation and vascular hemodynamics. The aim was to study if assessment of these variables could add valuable information regarding vascular affection in TAK. Methods: 17 patients diagnosed with TAK and 17 age- and sex-matched healthy controls were included. Microcirculatory peak oxygen saturation (OxyP) in the skin after induced ischemia was evaluated with laser Doppler flowmetry/diffuse reflectance spectroscopy. Cerebrovascular reserve capacity (CVR) in the brain was assessed with transcranial Doppler (TCD). Pulse waves were recorded in the radial artery by the aid of applanation tonometry, for calculation of central augmentation index (AIx75). Intima-media thickness (IMT) and stenosis/occlusions were evaluated using US in carotid and central arteries. Results: Reduced OxyP (79 ± 8% vs. 87 ± 4%, p < 0.001) was seen in patients with TAK regardless of significant arterial stenosis/occlusion or not. Increased AIx75 (22.3 ± 13.6 vs. 9.2 ± 16.3, p = 0.01) was seen in TAK patients without significant stenosis/occlusions. No differences were found in CVR, regardless of proximal stenosis. However, signs of a more high-resistance flow profile were seen in arteria cerebri media. Conclusion: Regardless of arterial stenosis or not, impaired microcirculation of the skin and preserved CVR in the brain were found in subjects with TAK. Signs of increased arterial stiffness in the brain and central arteries were observed. The value of these findings for prediction of future cardiovascular events needs to be clarified in further studies., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Svensson, Bjarnegård, Eriksson, Jonasson, Strömberg, Sjöwall and Zachrisson.)

Communication has been identified as one constraint for cattle veterinarians to act as proactive health consultants. Motivational Interviewing (MI), an evidence-based client-centered communication methodology, may therefore be a useful tool in veterinary herd health management (VHHM). The aim of this exploratory study was to investigate associations between training in MI and different measures of performance in VHHM. MI skills of 36 Swedish cattle veterinarians randomly assigned to two groups - MI veterinarians (n = 18) who had received six-months training in MI and control veterinarians (n = 18) who were not trained - were assessed using the MI Treatment Integrity coding system. Skills were categorized as untrained, trained&#95;poor, trained&#95;near moderate and trained&#95;moderate. Veterinarians each visited two to six cattle farms for VHHM consultations and revisited the same farms three to six months later to document implementation of recommendations. A gamma model and logistic or ordered logistic regression models were used to evaluate associations between MI training and performance measured as: a) proportion of consultations resulting in written herd health plans, b) proportion of recommended measures fully or partially implemented, c) Likert scores of different estimates of client satisfaction and d) total time during 6 months allocated to VHHM visits on cattle farms. We found no evidence of any significant effects of MI training on the eight performance variables analyzed. However, a pattern of numerically higher values (better performance) in trained veterinarians with poor or moderate MI skills than in untrained veterinarians was observed in most variables. Clients were highly satisfied with veterinarians' attitude, competence and time efficiency. Farms implemented a median of 66.7% (interquartile range: 50-100) of the measures partially or fully. Veterinarians allocated little time to VHHM visits (median: 2.2; interquartile range: 0.65-4.1 h per week of full-time work within cattle). Veterinarians with moderate skills spent 2.14 times more time on VHHM visits than untrained veterinarians, but the confidence interval was wide (0.88-5.21). The pattern of numerically higher values in trained veterinarians supported findings from other studies in the same project indicating a positive effect of MI training on VHHM. Our observations suggest a considerable potential to increase veterinarians' engagement in VHHM., (Copyright © 2022. Published by Elsevier B.V.)

Purpose: Sinonasal malignancies (SNM) represent a rare and complex group of cancers that includes a wide range of histopathological subtypes. Data from population-based cohorts are scarce but warranted as a basis for randomized controlled treatment trials (RCTs). Our aim was to assess overall and histology subset-specific outcomes for SNM patients treated at a tertiary referral centre., Methods: A retrospective, population-based, consecutive cohort of patients with SNMs diagnosed from 2001 through 2019 was examined. Outcome was analysed in relation to age, gender, site, stage, histopathology, and treatment., Results: Two-hundred and twenty-six patients were identified, whereof 61% presented with stage IV disease. 80% completed treatment with curative intent, which comprised surgery with neoadjuvant (29%) or adjuvant (37%) radiotherapy, monotherapy with surgery (22%), definitive chemoradiotherapy (7%), or radiotherapy (5%). Median follow-up was 106 months. The 5- and 10-year overall survival rates were 57% and 35%, respectively. Median overall survival was 76 months (esthesioneuroblastoma: 147 months; adenocarcinoma: 117; salivary carcinoma: 88; mucosal melanoma: 69; squamous cell carcinoma: 51, undifferentiated carcinoma: 42; neuroendocrine carcinoma: 9; and NUT-carcinoma 5). The 5- and 10-year disease-free survival rates were 63% and 54%, respectively, and disease-specific survival 83% and 66%. Increasing age, stage IVB, melanoma histopathology, and treatment with definitive chemoradiotherapy emerged as significant independent prognostic risk factors for disease-specific mortality (p ≤ 0.001)., Conclusion: The results indicate a seemingly good outcome in comparison to previous reports, particularly for mucosal melanoma, adenocarcinoma, and undifferentiated carcinoma. The study provides additional background for future RCTs focusing on histology subset-specific treatment for SNM., (© 2021. The Author(s).)

Chronic pain is the leading cause of life years lived with disability worldwide. The aetiology of most chronic pain conditions has remained poorly understood and there is a dearth of effective therapies. The WHO ICD-11 has categorised unexplained chronic pain states as 'chronic primary pains' (CPP), which are further defined by their association with significant distress and/or dysfunction. The new mechanistic term, 'nociplasticic pain' has been developed to illustrate their presumed generation by a structurally intact, but abnormally functioning nociceptive system. Recently, researchers have unravelled the surprising, ubiquitous presence of pain-sensitising autoantibodies in four investigated CPP indicating autoimmune causation. In persistent complex regional pain syndrome, fibromyalgia syndrome, chronic post-traumatic limb pain, and non-inflammatory joint pain associated with rheumatoid arthritis, passive transfer experiments have shown that either IgG or IgM antibodies from patient-donors cause symptoms upon injection to rodents that closely resemble those of the clinical disorders. Targets of antibody-binding and downstream effects vary between conditions, and more research is needed to elucidate the molecular and cellular details. The central nervous system appears largely unaffected by antibody binding, suggesting that the clinically evident CNS symptoms associated with CPP might arise downstream of peripheral processes. In this narrative review pertinent findings are described, and it is suggested that additional symptom-based disorders might be examined for the contribution of antibody-mediated autoimmune mechanisms., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Aim: Continuous glucose monitoring (CGM) is widely used in clinical practice and research to detect hypoglycemia. A consensus definition of CGM-recorded hypoglycemia is made by a group of international experts under the auspice of the Advanced Technologies and Treatments for Diabetes (ATTD). The purpose of this study is to compare the definition with patient-reported hypoglycemia. Methods: In a prospective, observational study of 186 patients with type 1 diabetes using blinded Medtronic iPro 2 CGM for 6 days, every patient-reported symptomatic hypoglycemic event and interstitial glucose (IG) values at the registration time were classified according to the ATTD definition of CGM-recorded hypoglycemia. For comparison between CGM and self-monitored blood glucose (SMBG) values, the International Hypoglycemia Study Group (IHSG) classification of hypoglycemia and chi-square test were used. Results: A total of 321 events of symptomatic hypoglycemia were reported by 68% of the patients, corresponding to 2.0 ± 2.3 events (mean ± standard deviation) per patient-week. A total of 206 (64%) events met the CGM consensus definition. In the remaining 115 (36%) not-confirmed events, 5 events had an IG <3.9 mmol/L, which lasted <15 min. The overall mean IG value was 3.6 ± 1.1 mmol/L (median 3.1, range 2.2-10.4). In symptomatic hypoglycemic events with both CGM and SMBG data, SMBG confirmed significantly more symptomatic hypoglycemic events than CGM ( P  < 0.001). Conclusion: CGM-recorded hypoglycemia according to the consensus definition is present at two thirds of all patient-reported events when recorded by the Medtronic iPro 2 system. The recommended minimum duration of a hypoglycemic event of 15 min is supported by the study. SMBG measurements detect significantly more symptomatic hypoglycemic events than Medtronic iPro 2 CGM.

Objective: To evaluate the diagnostic performance of an extended ultrasound protocol in patients referred under the suspicion of giant cell arteritis (GCA)., Methods: Consecutive patients with suspected GCA were examined with an extended color duplex ultrasound (CDU) protocol during a period of 2 years. The extended CDU protocol included temporal, axillary, subclavian, brachiocephalic, and carotid arteries. The reference was clinically diagnosed GCA, confirmed after ≥6-month follow-up. Hypo- or medium-echogenic, circumferential, homogenous wall thickening, and/or a positive compression sign in temporal arteries, were regarded as typical signs of arteritis., Results: Of the eligible 201 patients, 83 (41%) received a clinical GCA diagnosis at follow-up ≥6 months post CDU examination. Among these cases, 48 (58%) demonstrated inflammation solely in temporal arteries, 8 (10%) showed abnormalities restricted to extra-cranial vessels, and 23 (28%) patients displayed inflammatory changes in both temporal and extra-cranial arteries. Color duplex ultrasound of temporal arteries yielded a diagnostic sensitivity and specificity [95% confidence intervals (CI)] of 86% (76-92%) and 99% (95-99%), respectively. By adding axillary artery examination, the sensitivity increased to 92% (83-97%) while the specificity remained unchanged. Further, inclusion of subclavian artery marginally increased the sensitivity by 1%. Finally, by also including brachiocephalic and common carotid arteries resulted in a sensitivity of 95% (88-99%) and a specificity of 98% (94-99%)., Conclusions: Color duplex ultrasound examination demonstrated a high accuracy in diagnosing patients both with cranial and extra-cranial GCA. Further examination of brachiocephalic and common carotid arteries can increase the sensitivity without affecting the specificity when temporal and axillary findings are indecisive. Finally, the extended CDU protocol allows measurement of the general burden of inflammation, which could be relevant for future monitoring purposes., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Skoog, Svensson, Eriksson, Sjöwall and Zachrisson.)

Background: Immune checkpoint blockade (ICB) is a clinically proven concept to treat cancer. Still, a majority of patients with cancer including those with poorly immune infiltrated 'cold' tumors are resistant to currently available ICB therapies. Cytotoxic T lymphocyte-associated antigen-4 (CTLA-4) is one of few clinically validated targets for ICB, but toxicities linked to efficacy in approved αCTLA-4 regimens have restricted their use and precluded full therapeutic dosing. At a mechanistic level, accumulating preclinical and clinical data indicate dual mechanisms for αCTLA-4; ICB and regulatory T cell (Treg) depletion are both thought to contribute efficacy and toxicity in available, systemic, αCTLA-4 regimens. Accordingly, strategies to deliver highly effective, yet safe αCTLA-4 therapies have been lacking. Here we assess and identify spatially restricted exposure to a novel strongly Treg-depleting, checkpoint-blocking, vectorized αCTLA-4, as a highly efficacious and potentially safe strategy to target CTLA-4., Methods: A novel human IgG1 CTLA-4 antibody (4-E03) was identified using function-first screening for monoclonal antibodies (mAbs) and targets associated with superior Treg-depleting activity. A tumor-selective oncolytic vaccinia vector was then engineered to encode this novel, strongly Treg-depleting, checkpoint-blocking, αCTLA-4 antibody or a matching surrogate antibody, and Granulocyte-macrophage colony-stimulating factor (GM-CSF) (VV GM -αCTLA-4)., Results: The identified 4-E03 antibody showed significantly stronger Treg depletion, but equipotent checkpoint blockade, compared with clinically validated αCTLA-4 ipilimumab against CTLA-4-expressing Treg cells in a humanized mouse model in vivo. Intratumoral administration of VV GM -αCTLA-4 achieved tumor-restricted CTLA-4 receptor saturation and Treg depletion, which elicited antigen cross-presentation and stronger systemic expansion of tumor-specific CD8 + T cells and antitumor immunity compared with systemic αCTLA-4 antibody therapy. Efficacy correlated with FcγR-mediated intratumoral Treg depletion. Remarkably, in a clinically relevant mouse model resistant to systemic ICB, intratumoral VV GM -αCTLA-4 synergized with αPD-1 to reject cold tumors., Conclusion: Our findings demonstrate in vivo proof of concept for spatial restriction of Treg depletion-optimized immune checkpoint blocking, vectorized αCTLA-4 as a highly effective and safe strategy to target CTLA-4. A clinical trial evaluating intratumoral VV GM -αhCTLA-4 (BT-001) alone and in combination with αPD-1 in metastatic or advanced solid tumors has commenced., Competing Interests: Competing interests: MS, MR, PH, LM, CS, FJ, MB, IT, and BF are employees, MS, MR, LM, FJ, MB, IT, and BF are shareholders of BioInvent International. KLC received funding from BioInvent. J-BM, LF, CR, NS, PK, JD, JF, and EQ are employees and shareholders of Transgene., (© Author(s) (or their employer(s)) 2022. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Introduction: Systemic lupus erythematosus (SLE) is associated with premature cardiovascular disease (CVD) and mortality, unexplained by traditional risk factors. Impairment of microcirculation and vascular hemodynamics may represent early signs of vascular affection. We hypothesized that studies of microcirculation and pulse waves may provide additional information, compared to ultrasound (US) alone, for the detection of early vascular disease in SLE. Methods: Sixty well-characterized SLE-patients (52 women, eight men; mean age 43.21 ± 1.3 years) characterized by lupus nephritis (LN; n = 20), antiphospholipid syndrome (APS; n = 20) or skin and joint involvement ( n = 20) and 60 healthy controls were included. Microcirculatory peak oxygen saturation (OxyP) was evaluated using a novel combined laser Doppler flowmetry/diffuse reflectance spectroscopy method. Pulse waves were recorded in the radial artery by the aid of applanation tonometry in order to calculate central augmentation index (AIx75). Intima-media thickness (IMT) and plaque occurrence were evaluated using high frequency US, in carotid and central arteries. Results: Lower OxyP (84 ± 8 vs. 87 ± 5 %, p = 0.01) and higher AIx75 (17.3 ± 13.9 vs. 10.0 ± 14.2 %, p = 0.005) were seen in the SLE cohort. OxyP was inversely correlated with IMT in internal carotid artery (ICA), ( R = -0.32, p = 0.01). AIx75 correlated with IMT in common carotid artery (CCA), ( R = 0.36, p = 0.005), common femoral artery (CFA), ( R = 0.43, p = 0.001), and ICA ( R = 0.27, p = 0.04). AIx75 correlated negatively with OxyP ( R = -0.29, p = 0.02). SLE-patients with plaque had lower OxyP values (80 ± 8 vs. 85 ± 7 %, p < 0.001) and higher AIx75 (23.0 ± 11.6 vs. 15.5 ± 14.2 %, p < 0.001) compared to those without plaque. Conclusion: Impaired microcirculation and vessel hemodynamics were observed in SLE. These methods correlated with IMT and plaque occurrence. The importance of early macro- and micro-circulatory vascular affection for increased risk of CVD in SLE will be followed-up in future studies., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Svensson, Eriksson, Bjarnegård, Jonasson, Strömberg, Sjöwall and Zachrisson.)

We have performed the first direct measurement of the ^{83}Rb(p,γ) radiative capture reaction cross section in inverse kinematics using a radioactive beam of ^{83}Rb at incident energies of 2.4 and 2.7A  MeV. The measured cross section at an effective relative kinetic energy of E&#95;{cm}=2.393  MeV, which lies within the relevant energy window for core collapse supernovae, is smaller than the prediction of statistical model calculations. This leads to the abundance of ^{84}Sr produced in the astrophysical p process being higher than previously calculated. Moreover, the discrepancy of the present data with theoretical predictions indicates that further experimental investigation of p-process reactions involving unstable projectiles is clearly warranted.

Objective: The progress of accelerated atherosclerosis in systemic lupus erythematosus (SLE) is incompletely understood. Circulating osteopontin (OPN) is increased in autoimmune conditions, e.g. SLE, and its serum concentration was recently reported to associate with subclinical atherosclerosis in SLE, as measured by carotid intima-media thickness. The aim of this study was to investigate whether OPN may be used as a surrogate biomarker of subclinical atherosclerosis in SLE patients with different disease phenotypes., Methods: We recruited 60 well-characterised SLE cases and 60 age- and sex-matched healthy controls. The SLE cases were divided into three different disease phenotypes: SLE with antiphospholipid syndrome (APS), lupus nephritis, and isolated skin and joint involvement. Plasma OPN was detected by ELISA (Quantikine®, R&D Systems). Common carotid arteries intima media thickness was compared between the studied groups in relation to OPN levels and risk factors for vascular changes. Intima media thickness of common carotid arteries was measured by using a sensitive ultrasound technique (LOGIQ™ E9 ultrasound, GE Healthcare)., Results: OPN levels were significantly higher among the entire SLE group ( n  = 60) compared to the healthy controls ( P  = 0.03). SLE cases with concomitant APS ( n  = 20) showed higher OPN levels than the controls ( P  = 0.004), whereas none of the other two subgroups differed significantly from the healthy controls. OPN and intima media thickness were correlated to several traditional risk factors of atherosclerosis, as well as to SLE-related factors. Yet, no significant correlation was observed between OPN levels and ultrasound findings of the common carotid arteries., Conclusions: In line with previous studies, we observed increased OPN levels among SLE patients as compared to matched controls. However, the OPN concentrations did not correlate with intima media thickness of the common carotid arteries. Based on our findings, the use of OPN as a surrogate biomarker of subclinical atherosclerosis in SLE subjects, regardless of clinical phenotypes, cannot be recommended.

The ^{80}Ge structure was investigated in a high-statistics β-decay experiment of ^{80}Ga using the GRIFFIN spectrometer at TRIUMF-ISAC through γ, β-e, e-γ, and γ-γ spectroscopy. No evidence was found for the recently reported 0&#95;{2}^{+} 639-keV level suggested as evidence for low-energy shape coexistence in ^{80}Ge. Large-scale shell model calculations performed in ^{78,80,82}Ge place the 0&#95;{2}^{+} level in ^{80}Ge at 2 MeV. The new experimental evidence combined with shell model predictions indicate that low-energy shape coexistence is not present in ^{80}Ge.

Introduction: Despite improved therapies and management, patients with systemic lupus erythematosus (SLE) still have increased risks of cerebrovascular and cardiovascular disease. High-frequency ultrasound (US) provides an opportunity to distinguish atherosclerosis from inflammation in the vessels. We hypothesized that an extended US protocol may add information regarding vascular affection in SLE. Methods: Sixty patients (52 women, 8 men; mean age 43.2 ± 11.3 years) with SLE characterized by either lupus nephritis (LN; n = 20), antiphospholipid syndrome (APS; n = 20), or skin and joint involvement ( n = 20) as well as matched healthy controls ( n = 60) were included. Intima-media thickness (IMT), assessment of vessel walls, and plaque occurrence were recorded using high-frequency US (GE Logic E9) in common carotid, internal carotid, brachiocephalic, subclavian, axillary, common femoral, and proximal superficial femoral arteries as well as in the aortic arch. Results: For the entire SLE group, IMT was increased in the internal carotid artery (0.52 ± 0.17 vs. 0.45 ± 0.09 mm, p = 0.004), the common femoral artery (0.57 ± 0.23 vs. 0.49 ± 0.11 mm, p < 0.01), the subclavian artery (0.58 ± 0.19 vs. 0.53 ± 0.13 mm, p = 0.02), and the aortic arch (1.21 ± 0.63 vs. 0.98 ± 0.25 mm, p = 0.002) compared to controls. These differences were primarily observed in the APS and LN groups compared to controls. Vessels with increased IMT ≥0.9 mm had a smooth, medium echogenic appearance in areas free of atherosclerotic plaques. Atherosclerotic plaques were detected in 15/60 patients (25%) as compared to 2/60 of the controls (3%). Plaques were predominantly (67%) located in the carotid bifurcation. Multivariate analysis revealed influence of age on IMT in all vessel areas. Furthermore, in the common femoral artery, sagittal abdominal diameter, diastolic blood pressure, and cholesterol all showed association with increased IMT. In the internal carotid artery, male sex and presence of Raynaud phenomenon influenced IMT. Conclusion: Among SLE patients without presence of plaques, an extended US protocol revealed increased wall thickness with predominantly medium echogenic appearance highlighting possibly inflammation or early atherosclerosis. The appearance of vessel walls has not previously been studied in detail. An increased number of plaques were found in SLE compared to age- and sex-matched healthy controls. We found similar risk factors for increased IMT and occurrence of plaques, possibly indicating atherosclerotic mechanisms rather than inflammation., (Copyright © 2020 Svensson, Eriksson, Zachrisson and Sjöwall.)

Background: Implementing rapid molecular blood culture diagnostics in the clinical management of sepsis is essential for early pathogen identification and resistance gene testing. The GenMark ePlex blood culture panels offer a broad microbial spectrum with minimal hands-on time and approximately 1.5 h to result. Therefore, ePlex can be utilized at times when the clinical microbiology laboratory is unavailable. Methods: From 23 October 2019 to 30 December 2019, consecutive non-duplicate positive blood cultures signalling microbial growth at the 24 h/7 days-a-week available clinical chemistry laboratory between 9 pm and 7 am were analysed with ePlex. All blood cultures were transported to the microbiology laboratory the following day for conventional identification and antibiotic susceptibility testing. Results: We used ePlex to test 91 blood cultures, of which 86 had confirmed microbial growth. Eighty-one were positive for ePlex target pathogens. The ePlex results were in complete agreement with conventional methods in 72/81 (88.9%) of cases and available within a median of 10.9 h earlier. Resistance gene targets (11 mec A and 1 CTX-M) were concordant with phenotypic susceptibility in all cases. In 18/86 (20.9%) of the patient cases, there was an opportunity to optimize antimicrobial therapy based on the ePlex result. The ePlex result affected clinical decision-making in 4/86 (4.7%) of the cases and reduced the average time to effective antimicrobial therapy by 8.9 h. Conclusions: Our implementation of ePlex is a feasible option to attain around-the-clock blood culture identification in many hospitals. It can significantly reduce time-to-pathogen identification and have an impact on clinical decision-making.

Veterinarians often give advice in a persuasive form, a style that has been shown to evoke resistance to change in clients experiencing psychological ambivalence (i.e. those who see both advantages and disadvantages to changing). With this style of communication, veterinarians run the risk of counteracting their purpose to encourage clients to follow recommendations. Motivational interviewing (MI) is a client-centered communication methodology that aims to facilitate clients' internal motivation to change. In MI, Change Talk represents clients' own statements expressing consideration of, motivation for or commitment to behavior change and has been shown to be strongly correlated with behavior change. Sustain Talk is corresponding statements related to maintaining the status quo. The aim of this exploratory study was to evaluate the potential of MI to facilitate behavior change in veterinary herd health management (VHHM) by investigating the effect of dairy cattle veterinarians' MI skills on client Change and Sustain Talk. We recorded VHHM consultancies on 170 Swedish cattle farms performed by 36 veterinarians, randomly distributed into 2 groups: MI veterinarians (n = 18) had received 6-month training in MI and control veterinarians (n = 18) had not received any training. Veterinarians' MI skills were assessed using the Motivational Interviewing Treatment Integrity coding system 4.2.1 and categorized as poor&#95;untrained, poor&#95;trained, near moderate and moderate. Client communication was coded using the Client Language Easy Rating coding system. The effect of MI skills on Change Talk, Sustain Talk and Proportion of Change Talk(Change Talk divided by the sum of Sustain Talk plus Change Talk) was investigated using cross-classified regression models with random intercepts for veterinarian and client (farm). The models also included additional explanatory variables (e.g. type of veterinarian and client's satisfaction with the consultation). The veterinarian's MI skills were associated with the client's Change Talk, but results regarding Sustain Talk or Proportion of Change Talk were inconclusive. Clients of veterinarians reaching the highest (i.e. moderate) MI skills expressed 1.5 times more Change Talk than clients of untrained veterinarians. Clients of general large animal practitioners expressed less Sustain Talk than clients of animal health veterinarians and had higher Proportion of Change Talk. Results indicate that learning to practice MI may be one means to improve adherence to veterinary recommendations and to improve efficiency in VHHM services.

Background: Communication skills to promote changes in management routines are especially important in veterinary herd health management (VHHM). Motivational interviewing (MI) is a communication methodology shown to be effective in stimulating client behaviour change. This study aimed to evaluate a 6-month MI-training programme for veterinarians., Methods: Thirty-eight cattle veterinarians gathered in groups of four to eight at six workshops separated by 3-4 weeks, during which they read literature and practised their skills. MI skills were evaluated before and after training using audio recordings of role-play conversations with professional actors. Recordings were coded using the MI Treatment Integrity Code (MITI) V.4.2.1. The effect of training was evaluated by 16 regression models. Participants filled in questionnaires about their experiences., Results: All participants improved their MI skills after training in at least one parameter and significant improvements were found in all but 3 of the 16 statistically evaluated MITI variables. The mean (25th-75th percentiles) ratings of the veterinarians' perceived relevance of MI skills in their work was 4.9 (4.0-6.0) and of their satisfaction with the programme was 5.1 (5.0-6.0) on a 6-point Likert scale., Conclusions: Results show that MI training was perceived to be useful and relevant and successfully improved veterinarians' communication skills in VHHM., Competing Interests: Competing interests: LF is a partner at MIC Lab AB and HW is a partner at MeetMe Psykologkonsult AB. Research results demonstrating positive effects of MI in veterinary medicine may increase the market for codings for MIC Lab AB and the market for educational concepts in MI for MeetMe Psykologkonsult AB. CS, UE, KR and AMB have no conflict of interest to report., (© British Veterinary Association 2020. Re-use permitted under CC BY-NC. No commercial re-use. Published by BMJ.)

Background: Takayasu arteritis (TA) is a rare large-vessel arteritis that primarily affects the aorta and its major branches. The aim of this study was to describe the value of high frequency ultrasound for monitoring of inflammatory activity., Methods: Twenty-five patients, range 11-71 years, diagnosed with TA were investigated with duplex ultrasound (DUS) including follow-up studies. Twenty-five healthy controls were also investigated. Nine patients had newly diagnosed active TA. Sixteen patients had stable/inactive disease at baseline DUS, and TA was diagnosed median 4·5 years previously. Intima-media thickness (IMT), vessel and lumen diameter were measured in the carotid arteries, central neck arteries and the aortic arch. The vessel walls were studied qualitatively. The Takayasu ultrasound index was created for inflammatory activity scoring., Results: Intima-media thickness in common carotid artery (CCA) was (median and 25-75 percentile parenthetic) 2·3 mm (1·7-2·9) in clinically active TA, 1·2 mm (1·1-1·6) in clinically stable TA (P<0·001) and 0·5 mm (0·5-0·6) in healthy controls (P<0·001). Clinically active TA had prominent increase in IMT and/or increased vessel diameter, and/or intramural arteries, and/or hypoechogenic areas interpreted as oedema in the vessel wall. TA in clinical remission was characterized by increased IMT with medium to high echogenicity with or without fibrotic stripes. The Takayasu ultrasound index was higher in patients with active disease versus treated disease, 2·55 (1·60-3·05) versus 1·30 (1·00-1·58), (P = 0·003)., Conclusion: DUS is an excellent tool to monitor inflammatory changes in the vessel wall in TA. Further DUS studies in larger patient populations are warranted., (© 2019 Scandinavian Society of Clinical Physiology and Nuclear Medicine.)

Objectives: Rheumatoid arthritis (RA)-specific anti-citrullinated protein/peptide antibodies (ACPAs) might contribute to bone loss and arthralgia before the onset of joint inflammation. We aimed to dissect additional mechanisms by which ACPAs might contribute to development of joint pathology., Methods: Fibroblast-like synoviocytes (FLS) were isolated from the synovial membrane of patients with RA. The FLS cultures were stimulated with polyclonal ACPAs (anti-CCP-2 antibodies) purified from the peripheral blood of patients with RA or with monoclonal ACPAs derived from single synovial fluid B cells. We analysed how ACPAs modulate FLS by measuring cell adhesion and mobility as well as cytokine production. Expression of protein arginine deiminase (PAD) enzymes and protein citrullination were analysed by immunofluorescence, and signal transduction was studied using immunoblotting., Results: Challenge of FLS by starvation-induced stress or by exposure to the chemokine interleukin-8 was essential to sensitise the cells to ACPAs. These challenges led to an increased PAD expression and protein citrullination and an ACPA-mediated induction of FLS migration through a mechanism involving phosphoinositide 3-kinase activation. Inhibition of the PAD enzymes or competition with soluble citrullinated proteins or peptides completely abolished the ACPA-induced FLS migration. Different monoclonal ACPAs triggered distinct cellular effects in either fibroblasts or osteoclasts, suggesting unique roles for individual ACPA clones in disease pathogenesis., Conclusion: We propose that transient synovial insults in the presence of a certain pre-existing ACPA repertoire might result in an ACPA-mediated increase of FLS migration., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2019. Re-use permitted under CC BY. Published by BMJ.)

Virus infected immune cells can rapidly respond to the invader by activating the inflammasome and as a consequence release proinflammatory cytokines and eventually die by pyroptosis. In human adenovirus-5 (Ad5) infected THP-1 cells, inhibition of NLRP3 inflammasome activation was demonstrated by a decreased secretion of HMGB1 and matured forms of caspase-1and IL-1ß. An Ad5 mutant virus defective in expression of the non-coding VA RNAI failed to inhibit the NLRP3 inflammasome and in addition displayed formation of ASC specks and increased cell lysis. Importantly, in vitro synthesized VA RNAI was able to inhibit the NLRP3 inflammasome activity in THP-1 cells in the absence of an Ad5 infection, suggesting that VA RNAI binding to PKR and blocking its function is sufficient for inhibition of the NLRP3 inflammasome. Although the inhibition of NLRP3 inflammasome activation required the phylogenetically conserved base paired tetranucleotide sequence in the central stem of VA RNAI, we demonstrate that PKR binding to VA RNAI primarily protected the apical stem, but not the tetranucleotide sequence itself. VA RNAI did not influence the interaction between PKR and NLRP3. In contrast, we describe a novel interaction between PKR and ASC and further show that VA RNAI inhibited ASC phosphorylation and oligomerization. Collectively, our results indicate a novel role for Ad5 VA RNAI as an inhibitor of NLRP3 inflammasome activation by targeting the cellular pro-inflammatory protein PKR., (Copyright © 2019 Darweesh, Kamel, Gavrilin, Akusjärvi and Svensson.)

Animals used for scientific purposes are protected by EU legislation. Social animals should be kept in stable groups that enable species-typical social behavior and provide individuals with social comfort. However, when group-housing male mice, aggression within the homecage is a common husbandry and welfare problem. Excessive fighting and injuries due to aggression can cause pain and stress, resulting in individuals being euthanized or housed individually. In addition, stress can alter physiological parameters, risking scientific validity and generating larger sample sizes. Mouse aggression, and the consequences thereof, thus opposes the 3R goals of Refining the methods to minimize potential pain and suffering and Reducing the number of animals used. Animal technicians, veterinarians, and scientists using animals have valuable information on how these problems are experienced and handled in practice. We assembled these experiences from laboratory animal facilities in Sweden, mapping problems observed and identifying strategies used to prevent mouse aggression. In line with current literature, less aggression was perceived if mice were grouped before sexual maturity, re-grouping avoided and nesting material transferred at cage cleaning. Preventing aggression will minimize pain and suffering and enable housing of stable groups, leading to more reliable scientific outcomes and is thus of high 3Rs relevance., Competing Interests: The authors declare no conflict of interest.

Veterinary communication has evolved in the context of traditional veterinary tasks, such as diagnosing and treating sick animals, and this may encourage a directive communication style, in which the veterinarian acts as an expert, directing the client in what to do and how to do it. This type of communication style has been shown to evoke resistance to change in clients who are experiencing psychological ambivalence, a well-known aspect of farmers' herd health decisions. Veterinary herd health management (VHHM) constitutes an increasing proportion of the work of cattle veterinarians and often focuses on behavior change. The present study aimed to characterize communication styles of Swedish dairy cattle veterinarians involved in VHHM in relation to their skills in facilitating behavior change. A secondary aim was to investigate whether these skills differed among veterinarians depending on their experience in the veterinary profession or in VHHM. Audio-recorded role-play conversations (n = 123; reflecting VHHM telephone consultations) with 42 veterinarians involved in VHHM in Swedish dairy herds and audio-recorded on-farm consultations (n = 86) with 18 of those veterinarians were coded using a system developed to evaluate motivational interviewing (MI) skills. Motivational interviewing is a communication methodology aimed at facilitating clients' internal motivation to change. The MI Treatment Integrity (MITI) code identifies frequency counts of 10 verbal behaviors, and assesses 4 global variables on a Likert scale, based on 20 min of conversation. It also suggests 6 summary measurements of MI competency based on these 14 original variables. Of the 42 veterinarians, 39 also responded to a web questionnaire about their age, continuing education, and experience in the profession, in dairy herds and in VHHM. We analyzed associations between the 6 summary MITI variables from the role-play conversations and characteristics of the 39 veterinarians using logistic and linear multivariable regression models. Veterinarians in the role-play and on-farm conversations relied predominantly on giving information, questions, and persuasion in their consultation approaches. They generally did not explore the client's expectations or wishes regarding the agenda for the consultation, or acknowledge the client's right to make decisions about actions. Veterinarians gave advice without exploring the client's need for the advice or how the information was perceived. We found a significant reduction in so-called relational scores (Empathy plus Partnership) and an increase in MI-nonadherent behaviors (Persuasion plus Confront) as years of veterinary experience increased. Results showed that there is room for improvement in the communication style of veterinarians involved in VHHM. Wider literature suggests that training veterinarians in a client-centered communication methodology such as MI may increase the demand for and success of VHHM., (The Authors. Published by FASS Inc. and Elsevier Inc. on behalf of the American Dairy Science Association®. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).)

The problem of nonadherence to advice is recognized in several professional relationships, including the veterinarian-client relationship. A better understanding of farmer perspectives may help to improve efficiency in veterinary herd health management. This study aimed to qualitatively and quantitatively describe farmers' reasons for adherence and nonadherence with veterinary recommendations regarding preventive herd health measures. We carried out structured telephone interviews about implementation of preventive measures with owners or staff of 163 dairy farms and 6 beef farms. The farms had received an advisory visit by their veterinarian (n = 36), who had documented the preventive measures they had recommended. The interviewer noted verbatim responses to reasons for implementing preventive measures fully, partially, or not at all, and we analyzed these responses thematically. We also conducted a quantitative analysis, in which we calculated descriptive statistics of the proportions of different categories of reasons stated by the farmers. Altogether, 726 preventive measures (range per farm 1 to 17; median 3; interquartile range 2 to 6) were documented. We identified 3 organizing themes related to adherence or nonadherence with veterinary advice: trust, feasibility, and priorities. Overall, the most commonly stated reasons related to trust (in the veterinarian, in the advisory process, or in individual preventive measures). The most common reasons not to follow the recommended advice were related to feasibility. Based on the results, we recommend that, to improve adherence to their advice, veterinarians pay increased attention to farmers' needs, priorities, goals, and motives, as well as to farmers' perceptions of the effectiveness of individual preventive measures. We also recommend that veterinarians need to increase their focus on recommending preventive measures that are practically feasible to implement on farms., (The Authors. Published by FASS Inc. and Elsevier Inc. on behalf of the American Dairy Science Association®. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).)

From detailed spectroscopy of ^{110}Cd and ^{112}Cd following the β^{+}/electron-capture decay of ^{110,112}In and the β^{-} decay of ^{112}Ag, very weak decay branches from nonyrast states are observed. The transition rates determined from the measured branching ratios and level lifetimes obtained with the Doppler-shift attenuation method following inelastic neutron scattering reveal collective enhancements that are suggestive of a series of rotational bands. In ^{110}Cd, a γ band built on the shape-coexisting intruder configuration is suggested. For ^{112}Cd, the 2^{+} and 3^{+} intruder γ-band members are suggested, the 0&#95;{3}^{+} band is extended to spin 4^{+}, and the 0&#95;{4}^{+} band is identified. The results are interpreted using beyond-mean-field calculations employing the symmetry conserving configuration mixing method with the Gogny D1S energy density functional and with the suggestion that the Cd isotopes exhibit multiple shape coexistence.

The elusive β^{-}p^{+} decay was observed in ^{11}Be by directly measuring the emitted protons and their energy distribution for the first time with the prototype Active Target Time Projection Chamber in an experiment performed at ISAC-TRIUMF. The measured β^{-}p^{+} branching ratio is orders of magnitude larger than any previous theoretical model predicted. This can be explained by the presence of a narrow resonance in ^{11}B above the proton separation energy.

Phage display technology is a common approach for discovery of therapeutic antibodies. Drug candidates are typically isolated in two steps: First, a pool of antibodies is enriched through consecutive rounds of selection on a target antigen, and then individual clones are characterized in a screening procedure. When whole cells are used as targets, as in phenotypic discovery, the output phage pool typically contains thousands of antibodies, binding, in theory, hundreds of different cell surface receptors. Clonal expansion throughout the phage display enrichment process is affected by multiple factors resulting in extremely complex output phage pools where a few antibodies are highly abundant and the majority is very rare. This is a huge challenge in the screening where only a fraction of the antibodies can be tested using a conventional binding analysis, identifying mainly the most abundant clones typically binding only one or a few targets. As the expected number of antibodies and specificities in the pool is much higher, complementing methods, to reach deeper into the pool, are required, called deep mining methods. In this study, four deep mining methods were evaluated: 1) isolation of rare sub-pools of specific antibodies through selection on recombinant proteins predicted to be expressed on the target cells, 2) isolation of a sub-pool enriched for antibodies of unknown specificities through depletion of the primary phage pool on recombinant proteins corresponding to receptors known to generate many binders, 3) isolation of a sub-pool enriched for antibodies through selection on cells blocked with antibodies dominating the primary phage pool, and 4) next-generation sequencing-based analysis of isolated antibody pools followed by antibody gene synthesis and production of rare but enriched clones. We demonstrate that antibodies binding new targets and epitopes, not discovered through screening alone, can be discovered using described deep mining methods. Overall, we demonstrate the complexity of phage pools generated through selection on cells and show that a combination of conventional screening and deep mining methods are needed to fully utilize such pools. Deep mining will be important in future phenotypic antibody drug discovery efforts to increase the diversity of identified antibodies and targets.

Objective: Treatment with most antipsychotics is associated with an increased risk of weight gain and metabolic disturbances. In a randomized trial, we previously demonstrated that 16 weeks of glucagon-like peptide-1 receptor agonist liraglutide treatment vs. placebo significantly reduced glucometabolic disturbances and body weight in prediabetic, overweight/obese schizophrenia-spectrum disorder patients treated with clozapine or olanzapine. The aim of this study was to investigate whether the beneficial effects of the 16-week intervention were sustained beyond the intervention period., Method: One year after completion of the intervention, we investigated changes in body weight, fasting glucose, glycated hemoglobin, C-peptide, and lipids comparing 1-year follow-up levels to end of treatment (week 16) and baseline (week 0) levels., Results: From end of treatment to the 1-year follow-up, body weight had increased in the liraglutide-treated group. However, compared to baseline levels, the placebo-subtracted body weight loss remained significantly reduced (-3.8 kg, 95% CI: -7.3 to -0.2, P = 0.04). Fasting glucose, glycated hemoglobin, C-peptide, and lipids had each returned to baseline levels 1 year after stopping liraglutide., Conclusion: The body weight reduction during 16 weeks of liraglutide treatment was partially sustained 1 year after the intervention was completed. However, the improvements in other metabolic parameters returned to baseline levels., (© 2018 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Diarrhea is common in young calves and is often caused by Cryptosporidium parvum infection. The aim of this study was to investigate if disinfection of calf pens with hydrated lime would reduce contamination of C. parvum oocysts and improve calf health in herds with C. parvum associated diarrhea problems. Four dairy herds with ongoing C. parvum associated calf diarrhea problems each participated in the study over six to seven months. During the study period, all pens/huts for young calves were cleaned according to the usual farm routine before a new calf entered. Hydrated lime was then used to disinfect half of the pens/huts. Diarrhea incidence was recorded by the farmers and by veterinarians, who clinically examined the calves every second month. In total, 402 calves participated in the study. The farmers detected diarrhea in 214 (53%) calves, with similar proportions in calves kept in lime disinfected and control pens. Age at diarrhea onset was significantly higher in lime disinfected pens than in control pens, 9.0 days and 7.6 days, respectively. There was no difference between the groups regarding duration or severity index recorded by the farmers. The body condition score in 6-8 week old calves was significantly higher in calves that had been kept in lime disinfected pens during their first weeks of life, indicating that calves in disinfected pens/huts were less affected by their infections. Faecal samples from 5 to 21 day old calves, were collected on four occasions at each farm (n = 95). Cryptosporidium positive samples were found at all samplings in all four herds. Cryptosporidium spp. was detected in 79 (83%) samples with no difference between lime disinfected and control pens. C. parvum was the dominant species. Two different C. parvum subtypes were found; IIaA16G1R1b in three herds and IIaA16G1R1b&#95;variant in one herd. Only one subtype was found in each herd. Disinfection of calf pens with slaked lime delayed onset of diarrhea and improved the body condition in the calves, but did not affect diarrhea incidence or duration. Although lime disinfection alone will not be sufficient to control Cryptosporidium associated diarrhea in herds with extensive calf diarrhea problems, these results suggest that it can be a valuable complement to other measures., (Copyright © 2018 The Authors. Published by Elsevier B.V. All rights reserved.)

The aim was to assess the activation and association of the NF-κB system across synovial membrane (SM) and articular cartilage (AC) in patients with knee osteoarthritis (OA) and ascertain its potential effects on catabolic mediator expression in advanced OA. SM and AC were obtained from 40 OA patients undergoing total knee arthroplasty and from 19 postmortem control subjects. NF-κB subunit RelA in nuclear and cytosolic fractions and NF-κB1-DNA binding in nuclear extracts was assessed by ELISA, whereas NFKB1 , RELA , IL-8 , IL-6 , and MMP3 gene expression were analyzed by reverse transcriptase-quantitative PCR in tissues. We observed higher SM nuclear RelA protein levels and upregulated NF-κB1-DNA binding in OA patients compared with postmortem controls. However, in AC, lower nuclear RelA levels were observed compared with cytosolic extracts in patients. Nuclear RelA levels correlated positively with NF-κB1-DNA binding in SM and AC in patients. SM RELA and MMP3 mRNA levels were upregulated, whereas IL-8 and IL-6 as well as AC RELA were downregulated in patients compared with controls. In SM, nuclear RelA levels correlated positively with MMP3 gene expression in patients. A negative correlation was observed between SM nuclear RelA levels and AC NF-κB1-DNA binding, and SM nuclear NF-κB1-DNA binding correlated negatively with AC MMP3 and NFKB1 mRNA levels in patients. These findings highlight NF-κB-triggered cross-talk and feedback mechanisms between SM and AC in OA. Further, our findings strongly support a role for an activated NF-κB system in the transcriptional mechanism of inflammatory processes, especially in SM of patients with advanced OA., (Copyright © 2018 by The American Association of Immunologists, Inc.)

The primary aim was to identify cytokines involved in blood borne, neuroimmune joint-to-CNS signalling in knee osteoarthritis (OA) patients. Monocyte chemoattractant protein 1 (MCP1) and Interleukin-8 (IL-8) were elevated in the cerebrospinal fluid (CSF) in patients indicating neuroinflammation. Significant positive correlations were found for MCP1 across CSF, serum and synovial fluid (SF), in female, but not male patients. The results revealed sex differences in neuroimmune signalling and implicated MCP1 in blood borne joint-to-CNS signalling in female patients. Symptom severity correlated with IL-6 and IL-8 levels in SF, but was inversely associated with IL-6 and IL-8 levels in CSF, indicating that neuroinflammation in OA may be an adaptive, possibly neuroprotective mechanism promoting symptom reduction., (Copyright © 2018 The Authors. Published by Elsevier B.V. All rights reserved.)

A preventive herd health approach will most likely reduce incidences of clinical and subclinical disease. Swedish veterinary organizations offer specific veterinary herd health management (HHM) programs, but these services are not used to a large extent. The aim of this study was to investigate dairy farmers' experience of HHM and the conditions for collaboration with veterinarians in HHM. Six focus group discussions were conducted in March 2015 in West Sweden. In total, 33 dairy farmers participated. The recordings were transcribed and coded using thematic analysis, and the transcripts were reviewed to identify potential factors indicating barriers for farmers to engage a veterinarian in HHM. The participants reported HHM to be important, but they had difficulty defining the actions included in the concept. They described a wide range of their work duties as preventive. The farmers' list of potential contributions by the veterinarians in HHM was strikingly short compared to the considerable number of preventive measures they performed themselves. Four main obstacles for farmers and farm managers to engage a veterinarian in HHM on their farm were identified in the analysis: "costs", "veterinary knowledge, skills, and organization", "farmer attitudes", and "veterinarian-farmer relationships". Costs were proposed as the main reason against engaging a veterinarian in HHM and included a high veterinary bill, low cost-benefit of veterinary services, and high costs to implement advice. Poor veterinary competence in HHM and poor knowledge about effective measures, practical farming, and farm economics were other important obstacles. Veterinarians were perceived to insufficiently describe their services and their benefits, and several participants felt they had never been offered veterinary HHM. Although veterinary HHM may be initiated by the farmer, the participants expected the veterinarian to have special responsibility for the initiation. A firm trust between farmer, staff, and veterinarian was considered crucial for veterinary HHM, but such trust takes a long time to build and can easily be disrupted by, for example, a veterinarian's poor communication skills or lack of time. Our findings suggest that Swedish dairy farmers and herd managers find disease prevention important and that they perform a wide range of tasks to prevent disease in their animals. However, they do not see what role the veterinarian can play, and veterinarians were mainly associated with treating unhealthy cows. In order to increase the use of veterinary HHM programs the services and potential benefits of such programs need to be communicated more proactively., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Objective: The aim of this study was to evaluate an extended protocol of the large vessels using high-frequency duplex ultrasound (DUS) for detection of vessel wall inflammation., Methods: Fifty-eight patients performed a DUS examination where arteritis could not be excluded. All DUS examinations were performed using ACUSON S2000 TM ultrasound system (Siemens Medical Solutions USA, Inc.). High-frequency linear transducers were used (18L6 MHz, 9L4MHz) or curve linear for the aortic arch (6C2 MHz). Carotid, vertebral, central neck arteries (subclavian, axillary, innominate) arteries, aortic arch and femoral arteries were studied. Circumferential, homogenous wall thickening, with or without a hyperechogenic stripe lining the innermost layer, were regarded as typical signs of arteritis. Intima-media thickness (IMT) was measured in the patients and a normal control group. The latest clinical updated diagnosis was assessed at least 6 months after DUS., Results: The DUS findings showed normal vessels (n = 14), arteritis and atherosclerosis (n = 13), atherosclerosis (n = 15) and arteritis (n = 16). The latter group had a significant increased IMT in the common femoral artery and the common carotid artery (mean 1·0 ±  SD 0·3 mm versus 0·6 ± 0·2 mm in the normal group (n = 37), P<0·00001, 1·2 ± 0·5 mm versus 0·8 ± 0·2 mm in the normal group (n = 40), P<0·00001). In the groups with sonographic signs implying arteritis (n = 29), 20 patients had a clinical diagnosis of arteritis, whereas eight patients had another main diagnosis such as malignancy/other inflammatory or infectious disease complicated by inflammation of the vessel wall. One patient had multiple diagnoses and was not possible to classify., Conclusion: An extended ultrasound protocol for central neck and leg arteries could be of value for diagnosis of arteritis. In case of atypical vessel wall inflammation, other main diagnoses should be considered., (© 2017 Scandinavian Society of Clinical Physiology and Nuclear Medicine. Published by John Wiley & Sons Ltd.)

A method for computer-aided assessment of blood vessel geometries based on shape-fitting algorithms from metric vision was evaluated. Acoustic images of cross sections of the radial artery and cephalic vein were acquired, and medical practitioners used a computer application to measure the wall thickness and nominal diameter of these blood vessels with a caliper method and the shape-fitting method. The methods performed equally well for wall thickness measurements. The shape-fitting method was preferable for measuring the diameter, since it reduced systematic errors by up to 63% in the case of the cephalic vein because of its eccentricity., (© 2017 by the American Institute of Ultrasound in Medicine.)

Background: A study of herd-level risk factors for calf mortality in large Swedish dairy herds showed low serum concentrations of α-tocopherol and β-carotene in 1-7 day old calves to be more common in high mortality herds. Therefore, we aimed to investigate if calf mortality risk at herd level is associated with concentrations of α-tocopherol and/or β-carotene at individual level in feed, colostrum, cow and calf serum, while controlling for herd level covariates. Inclusion criteria were affiliation to the Swedish official milk recording scheme, herd size of ≥ 120 milking cows/year, calf mortality risk (day 1-90) of at least 6% (high mortality; HM) or less than 1% (low mortality; LM) and located within one of two regions in southern Sweden. This cross-sectional study was performed in 2010 in 19 (n HM  = 9; n LM  = 10) dairy herds. Questionnaires were used to collect information about feed and routines for colostrum feeding. Feed (n = 57), colostrum (n = 162), cow serum (n = 189) and calf serum samples (n = 187) were collected and analysed for α-tocopherol and β-carotene. Other analyses e.g. total serum protein, fat content, and total solids in colostrum were also performed. Linear regression models with vitamin concentrations in feed, colostrum, cow and calf serum as outcome were performed., Results: Calves in HM herds had lower concentrations of α-tocopherol in serum than calves in LM herds, but the effect depended on total protein status in serum of the calf (P = 0.036). Calves from herds that fed transition milk for 3 days or more had higher α-tocopherol concentrations in serum than calves from herds feeding transition milk up to 2 days (P = 0.013). Fat percentage in colostrum was positively associated with α-tocopherol (P < 0.001) and β-carotene concentrations in colostrum (P < 0.001). A diet containing ≥ 20% (in kg dry matter) maize silage of the total ration was negatively associated with β-carotene concentration in cow serum (P = 0.001)., Conclusions: High calf mortality risks were associated with lower concentrations of α-tocopherol in calf serum for calves with failure of passive transfer. Feeding transition milk longer was associated with higher concentrations of α-tocopherol in calf serum. In HM herds, evaluation of the calves' α-tocopherol status is recommended.

Objective: Endoscopic pituitary surgery has shown favorable clinical outcomes. Less is known about the impact of surgical approaches on health-related quality of life (HRQoL) and work capacity. The present study was undertaken to compare transsphenoidal microscope-assisted surgery with endoscopic transsphenoidal surgery regarding preoperative and surgical factors for the final outcome of HRQoL and work capacity., Methods: In a retrospective study of patients operated on for pituitary adenoma, outcome was compared between those operated on before and after transition with endoscopic surgery at our department. Data were gathered via patient questionnaires and patients' files., Results: After exclusions, 235 patients were included (99 microsurgical and 136 endoscopic). Frequency of complications was similar but tumor size was significantly larger in the endoscopic group. Complications did not affect HRQoL or work capacity. HRQoL was not affected by surgical technique but showed an overall trend toward lower values compared with the general population. Sick leave, return to work frequency, and permanent sick leave were not affected by surgical technique. Female gender was a factor for lower ratings in all outcome variables., Conclusions: Surgical technique does not influence HRQoL or work capacity in this long-term follow-up although both are decreased compared with the general population. We conclude that fully endoscopic pituitary surgery, despite including larger tumors, bears the same risk for complications as microsurgery. In addition, females have a greater risk for decrease in HRQoL and work ability. This factor should be taken into account when informing patients and appreciating expectations of treatment., (Copyright © 2017 Elsevier Inc. All rights reserved.)