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Abstract Background Application of data-driven strategies may support veterinarians’ decision-making, benefitting pig disease prevention and control. However, little is known about veterinarians’ need for data utilisation to support their decision-making process. The current study used qualitative methods, specifically focus group discussions, to explore veterinarians’ views on data utilisation and their need for data tools in relation to pig health and welfare management in Spain, the Netherlands, and Ireland. Results Generally, veterinarians pointed out the potential benefits of using technology for pig health and welfare management, but data is not yet structurally available to support their decision-making. Veterinarians pointed out the challenge of collecting, recording, and accessing data in a consistent and timely manner. Besides, the reliability, standardisation, and the context of data were identified as important factors affecting the efficiency and effectiveness of data utilisation by veterinarians. A user-friendly, adaptable, and integrated data tool was regarded as potentially helpful for veterinarians’ daily work and supporting their decision-making. Specifically, veterinarians, particularly independent veterinary practitioners, noted a need for easy access to pig information. Veterinarians such as those working for integrated companies, corporate veterinarians, and independent veterinary practitioners expressed their need for data tools that provide useful information to monitor pig health and welfare in real-time, to visualise the prevalence of endemic disease based on a shared report between farmers, veterinarians, and other professional parties, to support decision-making, and to receive early warnings for disease prevention and control. Conclusions It is concluded that the management of pig health and welfare may benefit from data utilisation if the quality of data can be assured, the data tools can meet veterinarians’ needs for decision-making, and the collaboration of sharing data and using data between farmers, veterinarians, and other professional parties can be enhanced. Nevertheless, several notable technical and institutional barriers still exist, which need to be overcome.

Introduction: The introduction of CAR-T cell treatment for relapsed/refractory (r/r) mantle cell lymphoma improved survival rates of these patients. Along with its introduction in clinical routine, long-term events after CAR-T cell treatment are increasingly emerging. Case Presentation: We report the case of a patient developing acute erythroid leukemia with biallelic TP53 inactivation occurring 26 months after CAR-T therapy with brexucabtagene autoleucel (brexu-cel) for r/r mantle cell lymphoma. The patient presented with a healthy bone marrow prior to lymphoma treatments. Discussion: Secondary malignancies seem more frequent after CAR-T therapies. More studies are needed to assess potential long-term toxicities of CAR-T cell therapies including the frequency of secondary myeloid malignancies.

Abstract Currently, exchange of information between the geriatric clinic and the attending general practitioner (GP) occurs primarily through the doctor's letter after discharging from the clinic. The aim of our study was to reduce readmissions of multimorbid, geriatric patients to the clinic by establishing a new form of care via an electronic case file (ECF) and a consultation service (CS). The discharging geriatric clinic filled out an online ECF. The patient's GP should document quarterly follow-ups in the ECF. The case file was monitored by the discharging clinic due to a consultation service. The primary efficacy endpoint was the rehospitalization rate within one year. The hospitalization rate for patients managed in the project was 83.1/100 person years (PY), while the control group from insurance data had a rate of 69.0/100 PY. The primary endpoint did not show a statistically significant difference (p = 0.15). A total of 195 contacts were documented via CS for 171 participants, mostly initiated by the clinics. The clinical queries primarily concerned drug therapy. The Covid pandemic had an overall impact on hospitalizations. There are many approaches to reducing hospital readmissions after discharge of older patients. Supporting the transition from inpatient to outpatient care by different professional groups or care systems has been shown to have a positive effect. Furthermore, the utilisation of an ECF can also be beneficial in this regard.

Abstract Kagome materials are of topical interest for their diverse quantum properties linked with correlated magnetism and topology. Here, we report anomalous hydrostatic pressure (p) effect on ErMn6Sn6 through isobaric and isothermal-isobaric magnetization measurements. Magnetic field (H) suppresses antiferromagnetic T N while simultaneously enhancing the ferrimagnetic T C by exhibiting dual metamagnetic transitions, arising from the triple-spiral-nature of Er and Mn spins. Counter-intuitively, pressure enhances both T C and T N with a growth rate of 74.4 K GPa−1 and 14.4 K GPa−1 respectively. Pressure unifies the dual metamagnetic transitions as illustrated through p-H phase diagrams at 140 and 200 K. Temperature-field-pressure (T-H, T-p) phase diagrams illustrate distinct field- and pressure-induced critical points at (T cr = 246 K, H cr = 23.3 kOe) and (T cr = 435.8 K, p cr = 4.74 GPa) respectively. An unusual increase of magnetic entropy by pressure around T cr and a putative pressure-induced tricritical point pave a unique way of tuning the magnetic properties of kagome magnets through simultaneous application of H and p.

BACKGROUND: Assessment of nystagmus fixation suppression can be used as an additional diagnostic tool for patients with an acute vestibular syndrome to distinguish between a central or peripheral cause. We investigated the ability of physicians to detect fixation suppression using a nystagmus simulation model. METHODS: We used a nystagmus simulator to measure the accuracy of the nystagmus fixation suppression test. Fixation suppression was assessed randomly in 6170 trials by 20 otorhinolaryngologists and neurologists, segregated into 2 groups based on their neurootological experience, a beginner and an experienced group. The simulator presented random nystagmus slow velocity (SPV) reductions and presented 3 conditions with either changed nystagmus frequency, amplitude, or both. RESULTS: The cutoff for the discernment of fixation suppression ranged from 1.2 to 14°/s nystagmus velocity difference. The more intense the baseline nystagmus was, the more difficult was the detection of fixation suppression. There was not significant difference (P > .05) in the cutoff values in the experts group compared to the novices for all 3 different conditions. Both, novices and experts, detected frequency changes easier than differences of the nystagmus amplitude. Test sensitivity was very low (19%-65%) for discernment of small nystagmus velocity differences of ≤2°/s by experts. CONCLUSION: In our study, there was no difference between experts and novices in detection of nystagmus suppression by visual fixation. The examiners could only detect large suppression effects at low-intensity baseline nystagmus. Overall, the sensitivity and accuracy of a clinical fixation suppression test is low and the assistance with a video-oculography device is highly recommended.

Purpose Prospective, multicentric observational cohort study in Switzerland investigating measures to prevent mother-to-child transmission in pregnant women with HIV (WWH) and assessing health and development of their exposed children as well as of children with HIV (CWH) in general.Participants Between January 1986 and December 2022, a total of 1446 mother–child pairs were enrolled. During the same period, the study also registered 187 CWH and 521 HIV-exposed but uninfected children (HEU), for whom detailed maternal information was not available. Consequently, the cohort comprises a total of 2154 children.Findings to date During these 37 years, research by the Swiss Mother and Child HIV Cohort Study (MoCHiV) and its international collaborators has strongly influenced the prevention of vertical transmission of HIV (eg, introduction and discontinuation of elective caesarean section, neonatal postexposure prophylaxis and breastfeeding). Contributions have also been made to the management of diagnostics (eg, p24 antigen assay) and the effects of antiretroviral treatment (eg, prematurity, growth) in HEU and CWH.Future plans Most children present within the cohort are now HEU, highlighting the need to investigate other vertically transmitted pathogens such as hepatitis B and C viruses, cytomegalovirus or Treponema pallidum. In addition, analyses are planned on the longitudinal health status of CWH (eg, resistance and prolonged exposure to antiretroviral therapy), on social aspects including stigma in CWH and HEU, and on interventions to further optimise antenatal and postpartum care in WWH.

Novel food technologies, such as three-dimensional (3D) food printing and cellular agriculture, offer many opportunities in the field of meat and fish production, such as texture variety, food waste reduction, animal welfare, and personalized nutrition. Nevertheless, they still face resistance from consumers. Thus far, conventional meat and fish have yet to be compared simultaneously with other food alternatives. Therefore, we conducted a study to analyze acceptance of these alternatives among Swiss consumers in terms of perceived healthiness, willingness to buy, willingness to eat, and perceived environmental friendliness. In doing so, conventional meat and fish were compared on these four acceptance measures with 3D-printed plant-based, cultured, 3D-printed cultured, plant-based, and 3D-printed byproduct meat and fish alternatives. The results suggest that the plant-based alternatives perform best, whereas the 3D-printed byproduct meat or fish alternatives perform worst on all acceptance measures assessed. Moreover, perceptions of healthiness and environmental friendliness of the meat or fish alternatives appear to be the most important predictors of willingness to eat. These results indicate that future focus should be placed on communicating the health- and environment-related benefits of 3D food printing and cellular agriculture to facilitate their adoption.

Due to the discontinuation of routine smallpox vaccination after its eradication in 1980, a large part of the human population remains naïve against smallpox and other members of the orthopoxvirus genus. As a part of biosafety personnel protection programs, laboratory workers receive prophylactic vaccinations against diverse infectious agents, including smallpox. Here, we studied the levels of cross-protecting neutralizing antibodies as well as total IgG induced by either first- or third-generation smallpox vaccines against Monkeypox virus, using a clinical isolate from the 2022 outbreak. Serum neutralization tests indicated better overall neutralization capacity after vaccination with first-generation smallpox vaccines, compared to an attenuated third-generation vaccine. Results obtained from total IgG ELISA, however, did not show higher induction of orthopoxvirus-specific IgGs in first-generation vaccine recipients. Taken together, our results indicate a lower level of cross-protecting neutralizing antibodies against Monkeypox virus in recipients of third-generation smallpox vaccine compared to first-generation vaccine recipients, although total IgG levels were comparable.

IntroductionBlack American Christian church leaders are trusted community members and can be invaluable leaders and planners, listeners, and counselors for Opioid Use Disorder (OUD) sufferers in the opioid overdose crisis disproportionately affecting the Black community. This qualitative study examines the extent to which the knowledge, attitudes, practices, and beliefs of Black American church leaders support medical and harm reduction interventions for people with OUD.MethodsA semi-structured interview guide was used to conduct in-depth interviews of 30 Black Rhode Island church leaders recruited by convenience and snowball sampling.ResultsThematic analysis of the interviews identified four themes: Church leaders are empathetic and knowledgeable, believe that hopelessness and inequity are OUD risk factors, are committed to helping people flourish beyond staying alive, and welcome collaborations between church and state.ConclusionBlack American Christian church leaders are a critical resource in providing innovative and culturally sensitive strategies in the opioid overdose crisis affecting the Black American communities. As such, their views should be carefully considered in OUD policies, collaborations, and interventions in the Black American community.

Abstract Aim To describe the experiences of patients and relatives with any form of restraints in somatic acute care hospitals. Design Qualitative explorative design. Methods Qualitative research methods were used. Participants were recruited through clinical nursing specialists in participating departments of a university hospital between June and August 2020. Individual interviews were conducted and analysed using content analysis. Results Four interviews with patients and five interviews with relatives were conducted with a mean duration of 25 min. The following three topics emerged in the analysis as important: What was perceived as restraints, Assessing the experiences of restraint use on a continuum, and Lack of information about restrictive measures. Patients and relatives defined restraint very broadly and assessed the experiences of restraint on a continuum from positive to negative, with a more critical view from patients. Relatives clearly seemed to approve of the use of restraints in acute care hospitals because it provided them with a sense of security. In general, there seemed to be a lack of information about the use of restraint and its effects on patients and relatives alike. Conclusion The involvement of patients and relatives in the decision‐making process about restraint use seems to be low. Healthcare professionals need to be better educated to be able to pass on adequate information and to involve patients and their relatives adequately in all processes of restraint use. However, when relatives are involved in decision‐making as proxies for patients, it is important to consider that patients' and relatives' opinions on restraints may differ. Patient or Public Contribution Patients and relatives agreed to participate in the study and shared their experiences with us.

Background. The emergence, global spread, and persistence of SARS-CoV-2 resulted in an unprecedented need for effective antiviral drugs. Throughout the pandemic, various drug development and treatment strategies were adopted, including repurposing of antivirals designed for other viruses along with a multitude of other drugs with varying mechanisms of action (MoAs). Furthermore, multidrug treatment against COVID-19 is an ongoing topic and merits further investigation. Method/Objectives. We assessed the efficacy of multidrug treatment against SARS-CoV-2 in reconstituted human nasal epithelia, using combinations of molnupiravir and nirmatrelvir as a baseline, adding suboptimal concentrations of either GS-441524 or ivermectin, attempting to increase overall antiviral activity while lowering the overall therapeutic dose. Results. Nirmatrelvir combined with molnupiravir, GS-441524, or ivermectin at suboptimal concentrations show increased antiviral activity compared to single treatment. No triple combinations showed improved inhibition of SARS-CoV-2 replication beyond what was observed for double treatments. Conclusions. In general, we observed that the addition of a third compound is not beneficial for antiviral activity, while various double combinations exhibit increased antiviral activity over single treatment.

(1) Background: Horses infected by a tick-borne encephalitis virus (TBEV) can develop clinically apparent infections. In humans, vaccination is the most effective preventive measure, while a vaccine is not available for horses. The objective of this study was to describe the immune response in horses after a TBEV vaccination with a human vaccine. (2) Materials and Methods: Seven healthy horses were randomised to a treatment or a control group in a stratified fashion based on TBEV–IgG concentrations on day −4. The treatment group (n = 4) was intramuscularly vaccinated using an inactivated human TBEV vaccine on days 0 and 28; the control group (n = 3) did not receive an injection. A clinical examination and blood sampling were performed on day –4, 0, 2, 4, 6, 8, 10, 14, 28, 30, 32, 34, 36, 38, 43, 56, 84, and 373. A linear mixed model analysis was used to compare IgG and IgM concentrations, neutralising antibody (nAb) titres, leucocyte count, serum amyloid A (SAA), and fibrinogen and globulin concentrations between the groups and time points. (3) Results: The clinical examination was normal in all horses at all time points. There were no significant changes in SAA, globulin, and fibrinogen concentrations and leucocyte count between the groups or time points (all p > 0.05). There was no significant increase in IgG, IgM, or nAb titres in the control group over time (all p > 0.05). In the vaccination group, there was a significant increase in IgG concentration and nAb titres after the second vaccination (p < 0.0001). There was no significant increase in IgM antibodies after the TBEV vaccination (all p > 0.05). One horse in the vaccination group had an IgM concentration above the laboratory reference on day 10. (4) Conclusions: The human TBEV vaccine did not have side effects when used in healthy horses in this study. A significant rise in TBEV-specific IgG antibodies and nAbs after the second vaccination was observed. However, IgG and nAb titres have been shown to decrease within 1 year after vaccination. The results of this study indicate that a vaccination with a human vaccine only induces a mild rise in IgM antibodies and only in previously naive horses. With no significant changes to inflammatory parameters in the vaccinated horses, it remains unclear whether vaccination with the human vaccine leads to protective immunity.

With the rise of drug misuse among workers in recent years, preliminary research on potential risk factors in the workplace of single-type of drug misuse has been reported. This is the first study to examine cross-sectional associations of work stress, in terms of effort-reward imbalance, with multiple drug misuse (including any drug misuse, opioid misuse, sedatives misuse, cannabis misuse, and other drug misuse) during the past 12 months in a national sample of U.S. workers. Data of 2211 workers were derived from the nationally representative and population-based Midlife in the United States (MIDUS) study. Internal consistency reliability and factorial validity of a 17-item effort-reward imbalance measure were robust and satisfactory. After adjustment for relevant covariates, logistic regression analyses showed that workers experiencing effort-reward imbalance at work had significantly higher odds of any drug misuse (OR and 95% CI = 1.18 (1.03, 1.37)), especially opioid misuse (OR and 95% CI = 1.35 (1.07, 1.69)) and other drug misuse (OR and 95% CI = 1.36 (1.01, 1.83)). The findings suggest that a stressful work environment may act as a determinant of drug misuse, and further prospective evidence is needed.

Abstract Proper disinfection and inactivation of highly pathogenic viruses is an essential component of public health and prevention. Depending on environment, surfaces, and type of contaminant, various methods of disinfection must be both efficient and available. To test both established and novel chemical disinfectants against risk group 4 viruses in our maximum containment facility, we developed a standardized protocol and assessed the chemical inactivation of the two Ebola virus variants Mayinga and Makona suspended in two different biological soil loads. Standard chemical disinfectants ethanol and sodium hypochlorite completely inactivate both Ebola variants after 30 s in suspension at 70% and 0.5% v/v, respectively, concentrations recommended for disinfection by the World Health Organization. Additionally, peracetic acid is also inactivating at 0.2% v/v under the same conditions. Continued vigilance and optimization of current disinfection protocols is extremely important due to the continuous presence of Ebola virus on the African continent and increased zoonotic spillover of novel viral pathogens. Furthermore, to facilitate general pandemic preparedness, the establishment and sharing of standardized protocols is very important as it allows for rapid testing and evaluation of novel pathogens and chemical disinfectants.

Abstract The outer membrane insertase of Gram-negative bacteria, BAM, is a key target for urgently needed novel antibiotics. Functional reconstitutions of BAM have so far been limited to synthetic membranes and with low throughput capacity for inhibitor screening. Here, we describe a BAM functional assay in native membrane environment capable of high-throughput screening. This is achieved by employing outer membrane vesicles (OMVs) to present BAM directly in native membranes. Refolding of the model substrate OmpT by BAM was possible from the chaperones SurA and Skp, with the required SurA concentration three times higher than Skp. In the OMVs, the antibiotic darobactin had a tenfold higher potency than in synthetic membranes, highlighting the need for native conditions in antibiotics development. The assay is successfully miniaturized for 1536-well plates and upscaled using large scale fermentation, resulting in high-throughput capacities to screen large commercial compound libraries. Our OMV-based assay thus lays the basis for discovery, hit validation and lead expansion of antibiotics targeting BAM.

Abstract Background The SARS-CoV-2 (Severe Acute Respiratory Syndrome Coronavirus 2) pandemic changed the distribution of healthcare resources, leading in many cases to the suspension of all non-essential treatments and procedures and representing a challenge for medical professionals. The objective of this study was to evaluate whether clinical protocols in gynecologic oncology care were modified as a result of the pandemic and to assess surgeons’ perceptions regarding the management of gynecologic cancers". Methods Data were collected through an anonymous and voluntary survey sent via email to healthcare professionals in the field of gynecologic oncology in Spain. Results A total of 75 gynecologic oncologists completed the online survey. Of these, 93.2% (69) reported working in public hospitals and 62.5% (45) in tertiary care hospitals. 97.3% (71) were affiliated with hospitals treating patients infected with SARS-CoV-2. 85.1% (63) of the respondents expressed concern about the SARS-CoV-2 pandemic and 52.1% (38) indicated that the pandemic impacted the diagnostic and therapeutic quality of care for oncology patients. SARS-CoV-2 nasopharyngeal swab PCR (Polymerase Chain Reaction) testing was always performed before surgical interventions by 97.3% (71), being considered a best practice in triage by 94.4% (68). 87.5% (63) reported no change in the type of surgical approach during the pandemic. 62.5% (45) experienced limitations in accessing special personal protective equipment for SARS-CoV-2. An impact on the follow-up of patients with gynecologic cancers due to the pandemic was reported by 70.4% (50). Conclusions Most of the Spanish gynecologic oncologists who responded to our survey reported that the SARS-CoV-2 pandemic had affected their clinical practice. The primary measures implemented were an increase in telemedicine, restricting outpatient visits to high-risk or symptomatic patients and the use of SARS-CoV-2 screening prior to surgery. No major changes in the surgical approach or management of the treatment of ovarian, endometrial or cervical cancer during the pandemic were reported.

Abstract There is limited understanding of how the microbiota colonizing various maternal tissues contribute to the development of the neonatal gut microbiota (GM). To determine the contribution of various maternal microbiotic sites to the offspring microbiota in the upper and lower gastrointestinal tract (GIT) during early life, litters of mice were sacrificed at 7, 9, 10, 11, 12, 14, and 21 days of age, and fecal and ileal samples were collected. Dams were euthanized alongside their pups, and oral, vaginal, ileal, and fecal samples were collected. This was done in parallel using mice with either a low-richness or high-richness microbiota to assess the consistency of findings across multiple microbial compositions. Samples were analyzed using 16S rRNA amplicon sequencing. The compositional similarity between pup and dam samples were used to determine the contribution of each maternal source to the composition of the neonate fecal and ileal samples at each timepoint. As expected, similarity between neonate and maternal feces increased significantly over time. During earlier time-points however, the offspring fecal and ileal microbiotas were closer in composition to the maternal oral microbiota than other maternal sites. Prominent taxa contributed by the maternal oral microbiota to the neonate GM were supplier-dependent and included Lactobacillus spp., Streptococcus spp., and a member of the Pasteurellaceae family. These findings align with the microbial taxa reported in infant microbiotas, highlighting the translatability of mouse models in this regard, as well as the dynamic nature of the GM during early life.

Abstract Background Physical functioning is a crucial factor for independence and quality of life in old age. The aim of the "bestform—Best function of range of motion" trial is to investigate the effects of a 6 months multimodal machine-based strength, coordination and endurance training on physical function, risk of falls and health parameters in older adults. Methods Bestform is a cluster-randomised trial including older adults ≥ 65 years living in senior care facilities in Southern Germany. Senior care facilities are randomly allocated to the control group with usual care (n ≥ 10 care facilities) and to the intervention group (n ≥ 10 care facilities), overall including ≥ 400 seniors. Residents belonging to the intervention group are offered a supervised machine-based exercise training programme twice weekly over 45–60 min over six months in small groups, while those in the usual care facilities will not receive active intervention. The primary outcome is the change in Short Physical Performance Battery over six months between groups. Secondary outcomes are change in risk of falling, fear of falling, number of falls and fall-related injuries, physical exercise capacity, handgrip strength, body composition, cardiac function, blood parameters, quality of life, risk of sarcopenia, activities of daily living, and cognition over three and six months. Discussion The bestform study investigates the change in physical function between seniors performing exercise intervention versus usual care over six months. The results of the study will contribute to the development of effective physical activity concepts in senior care facilities. Trial registration ClinicalTrials.gov: NCT04207307. Registered December 2019.

BackgroundWork stress is considered as a risk factor for coronary heart disease, but its link with heart rate variability (HRV) among heart attack survivors is unknown yet. The aim of this study was to investigate associations between baseline work stress and the changes of HRV over one-year after onset of acute coronary syndrome (ACS).MethodsHundred and twenty-two patients with regular paid work before their first ACS episode were recruited into this hospital-based longitudinal cohort study. During hospitalization (baseline), all patients underwent assessments of work stress by job strain (JS) and effort-reward imbalance (ERI) models, and were assigned into low or high groups; simultaneously, sociodemographic and clinical data, as well depression, anxiety, and job burnout, were collected. Patients were followed up 1, 6, and 12 months after discharge, with HRV measurements at baseline and each follow-up point. Generalized estimating equations were used to analyze the effects of baseline work stress on HRV over the following 1 year.ResultsAfter adjusting for baseline characteristics and clinical data, anxiety, depression, and burnout scores, high JS was not associated with any HRV measures during follow-up (all p > 0.10), whereas high ERI was significantly related to slower recovery of 5 frequency domain HRV measures (TP, HF, LF, VLF, and ULF) (all p

Bisphosphonates (BP) are anti-resorptive drugs that are widely used to prevent bone loss in osteoporosis. Since inhibition of bone resorption will cause a decrease in bone formation through a process called coupling, it is hypothesized that extended treatment protocols may impair bone healing. In this study, β-tri‑calcium-phosphate (βTCP) ceramics were inserted into critical-size long bone defects in estrogen-deficient mice under BP therapy. The study assessed the benefits of coating the ceramics with Bone Morphogenetic Protein-2 (BMP2) and an engineered BMP2 analogue (L51P) that inactivates BMP antagonists on the healing process, implant resorption, and bone formation.Female NMRI mice (11–12 weeks of age) were ovariectomized (OVX) or sham operated. Eight weeks later, after the manifestation of ovariectomy-induced osteoporotic bone changes, BP therapy with Alendronate (ALN) was commenced. After another five weeks, a femoral critical-size defect was generated, rigidly fixed, and βTCP-cylinders loaded with 0.25 μg or 2.5 μg BMP2, 2.5 μg L51P, and 0.25 μg BMP2/2.5 μg L51P, respectively, were inserted. Unloaded βTCP-cylinders were used as controls. Femora were collected six and twelve weeks post-implantation.Histological and micro-computer tomography (MicroCT) evaluation revealed that insertion of cylinders coated with 2.5 μg BMP2 accelerated fracture repair and induced significant bone formation compared to controls (unloaded cylinders or coated with 2.5 μg L51P, 0.25 μg BMP2) already six weeks post-implantation, independent of estrogen-deficiency and BP therapy. The simultaneous administration of BMP2 and L51P (0.25 μg BMP2/2.5 μg L51P) did not promote fracture healing six and twelve weeks post-implantation. Moreover, new bone formation within the critical-size defect was directly linked to the removal of the βTCP-implant in all experimental groups. No evidence was found that long-term therapy with ALN impaired the resorption of the implanted graft. However, osteoclast transcriptome signature was elevated in sham and OVX animals upon treatment with BP, with transcript levels being higher at six weeks than at twelve weeks post-surgery. Furthermore, the transcriptome profile of the developing repair tissue confirmed an accelerated repair process in animals treated with 2.5 μg BMP2 implants. L51P did not increase the bioefficacy of BMP2 in the applied defect model.The present study provides evidence that continuous administration of BP does not inhibit implant resorption and does not alter the kinetics of the healing process of critical-size long bone defects. Furthermore, the BMP2 variant L51P did not enhance the bioefficacy of BMP2 when applied simultaneously to the femoral critical-size defect in sham and OVX mice.

Neuroblasts in Drosophila divide asymmetrically, sequentially expressing a series of intrinsic factors to generate a diversity of neuron types. These intrinsic factors known as temporal factors dictate timing of neuroblast transitions in response to steroid hormone signaling and specify early versus late temporal fates in neuroblast neuron progeny. After completing their temporal programs, neuroblasts differentiate or die, finalizing both neuron number and type within each neuroblast lineage. From a screen aimed at identifying genes required to terminate neuroblast divisions, we identified Notch and Notch pathway components. When Notch is knocked down, neuroblasts maintain early temporal factor expression longer, delay late temporal factor expression, and continue dividing into adulthood. We find that Delta, expressed in cortex glia, neuroblasts, and after division, their GMC progeny, regulates neuroblast Notch activity. We also find that Delta in neuroblasts is expressed high early, low late, and is controlled by the intrinsic temporal program: early factor Imp promotes Delta, late factors Syp/E93 reduce Delta. Thus, in addition to systemic steroid hormone cues, forward lineage progression is controlled by local cell-cell signaling between neuroblasts and their cortex glia/GMC neighbors: Delta transactivates Notch in neuroblasts bringing the early temporal program and early temporal factor expression to a close.

BackgroundDuring the last decade Ebola virus has caused several outbreaks in Africa. The recombinant vesicular stomatitis virus-vectored Zaire Ebola (rVSVΔG-ZEBOV-GP) vaccine has proved safe and immunogenic but is reactogenic. We previously identified the first innate plasma signature response after vaccination in Geneva as composed of five monocyte-related biomarkers peaking at day 1 post-immunization that correlates with adverse events, biological outcomes (haematological changes and viremia) and antibody titers. In this follow-up study, we sought to identify additional biomarkers in the same Geneva cohort and validate those identified markers in a US cohort.MethodsAdditional biomarkers were identified using multiplexed protein biomarker platform O-link and confirmed by Luminex. Principal component analysis (PCA) evaluated if these markers could explain a higher variability of the vaccine response (and thereby refined the initial signature). Multivariable and linear regression models evaluated the correlations of the main components with adverse events, biological outcomes, and antibody titers. External validation of the refined signature was conducted in a second cohort of US vaccinees (n=142).ResultsEleven additional biomarkers peaked at day 1 post-immunization: MCP2, MCP3, MCP4, CXCL10, OSM, CX3CL1, MCSF, CXCL11, TRAIL, RANKL and IL15. PCA analysis retained three principal components (PC) that accounted for 79% of the vaccine response variability. PC1 and PC2 were very robust and had different biomarkers that contributed to their variability. PC1 better discriminated different doses, better defined the risk of fever and myalgia, while PC2 better defined the risk of headache. We also found new biomarkers that correlated with reactogenicity, including transient arthritis (MCP-2, CXCL10, CXCL11, CX3CL1, MCSF, IL-15, OSM). Several innate biomarkers are associated with antibody levels one and six months after vaccination. Refined PC1 correlated strongly in both data sets (Geneva: r = 0.97, P < 0.001; US: r = 0.99, P< 0.001).ConclusionEleven additional biomarkers refined the previously found 5-biomarker Geneva signature. The refined signature better discriminated between different doses, was strongly associated with the risk of adverse events and with antibody responses and was validated in a separate cohort.

Abstract Objective Hospitals are frequently associated with poor working conditions that can lead to work stress and increase the risk for reduced employee well-being. Managers can shape and improve working conditions and thereby, the health of their teams. Thus, as a prerequisite, managers need to be aware of their employees’ stress levels. This study had two objectives: At first, it aimed to test the criterion validity of the Effort-Reward Imbalance (ERI) questionnaire measuring psychosocial workload in hospital employees. Secondly, mean scales of the ERI questionnaire filled in by employees were compared with mean scales of an adapted ERI questionnaire, in which managers assessed working conditions of their employees. Methods Managers (n = 141) from three hospitals located in Germany assessed working conditions of their employees with an adapted external, other-oriented questionnaire. Employees (n = 197) of the mentioned hospitals completed the short version of the ERI questionnaire to assess their working conditions. Confirmatory factor analyses (CFA) were applied to test factorial validity, using the ERI scales for the two study groups. Criterion validity was assessed with multiple linear regression analysis of associations between ERI scales and well-being among employees. Results The questionnaires demonstrated acceptable psychometric properties in terms of internal consistency of scales, although some indices of model fit resulting from CFA were of borderline significance. Concerning the first objective, effort, reward, and the ratio of effort-reward imbalance were significantly associated with well-being of employees. With regard to the second objective, first tentative findings showed that managers’ ratings of their employees’ effort at work was quite accurate, whereas their reward was overestimated. Conclusions With its documented criterion validity the ERI questionnaire can be used as a screening tool of workload among hospital employees. Moreover, in the context of work-related health promotion, managers’ perceptions of their employees’ workload deserve increased attention as first findings point to some discrepancies between their perceptions and those provided by employees.

Abstract At elevated temperatures SnSe is reported to undergo a structural transition from the low symmetry orthorhombic GeS-type to a higher symmetry orthorhombic TlI-type. Although increasing symmetry should likewise increase lattice thermal conductivity, many experiments on single crystals and polycrystalline materials indicate that this is not the case. Here we present temperature dependent analysis of time-of-flight (TOF) neutron total scattering data in combination with theoretical modeling to probe the local to long-range evolution of the structure. We report that while SnSe is well characterized on average within the high symmetry space group above the transition, over length scales of a few unit cells SnSe remains better characterized in the low symmetry GeS-type space group. Our finding from robust modeling provides further insight into the curious case of a dynamic order-disorder phase transition in SnSe, a model consistent with the soft-phonon picture of the high thermoelectric power above the phase transition.

We describe animal-to-human transmission of SARS-CoV-2 in a zoo setting in Indiana, USA. A vaccinated African lion with physical limitations requiring hand feeding tested positive for SARS-CoV-2 after onset of respiratory signs. Zoo employees were screened, monitored prospectively for onset of symptoms, then rescreened as indicated; results were confirmed by using reverse transcription PCR and whole-genome virus sequencing when possible. Traceback investigation narrowed the source of infection to 1 of 6 persons. Three exposed employees subsequently had onset of symptoms, 2 with viral genomes identical to the lion’s. Forward contact tracing investigation confirmed probable lion-to-human transmission. Close contact with large cats is a risk factor for bidirectional zoonotic SARS-CoV-2 transmission that should be considered when occupational health and biosecurity practices at zoos are designed and implemented. SARS-CoV-2 rapid testing and detection methods for big cats and other susceptible animals should be developed and validated to enable timely implementation of One Health investigations.

Summary: The vectored Ebola vaccine rVSVΔG-ZEBOV-GP elicits protection against Ebola Virus Disease (EVD). In a study of forty-eight healthy adult volunteers who received either the rVSVΔG-ZEBOV-GP vaccine or placebo, we profiled intracellular microRNAs (miRNAs) from whole blood cells (WB) and circulating miRNAs from serum-derived extracellular vesicles (EV) at baseline and longitudinally following vaccination. Further, we identified early miRNA signatures associated with ZEBOV-specific IgG antibody responses at baseline and up to one year post-vaccination, and pinpointed target mRNA transcripts and pathways correlated to miRNAs whose expression was altered after vaccination by using systems biology approaches.Several miRNAs were differentially expressed (DE) and miRNA signatures predicted high or low IgG ZEBOV-specific antibody levels with high classification performance. The top miRNA discriminators were WB-miR-6810, EV-miR-7151-3p, and EV-miR-4426. An eight-miRNA antibody predictive signature was associated with immune-related target mRNAs and pathways.These findings provide valuable insights into early blood biomarkers associated with rVSVΔG-ZEBOV-GP vaccine-induced IgG antibody responses.