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By crossing septin7-floxed mice with Lyz2-Cre mice carrying the Cre recombinase inserted in the Lysozyme-M (Lyz2) gene locus we aimed the specific deletion of septin7 in myeloid cells, such as monocytes, macrophages and granulocytes. Septin7flox/flox:Lyz2-Cre mice show no alterations in the myeloid compartment. Septin7-deleted macrophages (BMDMs) were isolated and analyzed. The lack of Septin7 expression was confirmed and a constitutive double-nucleation was detected in Septin7-deficient BMDMs indicating a defect in macrophage cytokinesis. However, phagocytic function of macrophages as judged by uptake of labelled E. coli particles and LPS-stimulated macrophage activation as judged by induction of TNF mRNA expression and TNF secretion were not compromised. In addition to myeloid cells, Lyz2-Cre is also active in type II pneumocytes (AT2 cells). We monitored lung adenocarcinoma formation in these mice by crossing them with the conditional knock-in Kras-LSL-G12D allele. Interestingly, we found that control mice without septin7 depletion die after 3–5 weeks, while the Septin7-deficient animals survived 11 weeks or even longer. Control mice sacrificed in the age of 4 weeks display a bronchiolo-alveolar hyperplasia with multiple adenomas, whereas the Septin7-deficient animals of the same age are normal or show only a weak multifocal brochiolo-alveolar hyperplasia. Our findings indicate an essential role of Septin7 in macrophage cytokinesis but not in macrophage function. Furthermore, septin7 seems absolutely essential for oncogenic Kras-driven lung tumorigenesis making it a potential target for anti-tumor interventions.

With the change in the location of school education from the classroom to the home during the COVID-19 outbreak, there should be more educational caregiving from children’s parents when children learn online. Parental involvement in children’s online learning including study guide and psychological counseling is the specific content of educational caregiving, which is different from face-to-face learning. More attention should be paid to parental involvement and parents’ satisfaction with the online learning effect. This study therefore conducted a survey on middle school students’ parents to establish a moderating model, exploring the influence of parental involvement on parent satisfaction, and the number of children and parental education level as the moderator variables influencing parental involvement. The results show that there is a significant positive correlation between parental involvement and satisfaction, while the parental education level and the number of children both have a moderating effect on the relationship between parental involvement and parent satisfaction. The moderating effect of the education level of parents shows negative, while the moderating effect of the number of children is positive. An interesting finding is that the number of children has a very low influence on parental involvement.

Canine distemper and canine parvoviral enteritis are infections caused by the canine distemper virus (CDV) and canine parvovirus type 2 (CPV-2), respectively. They are two common infectious diseases that cause high morbidity and mortality in affected dogs. Combination vaccines have been broadly used to protect dogs from infections of CDV, CPV-2, and other viruses. VP2 is the most abundant protein of the CPV-2 capsid. It elicits potent immunity in animals and, therefore, is widely used for designing subunit antigen-based vaccines. In this study, we rescued a recombinant CDV (QN vaccine strain) using reverse genetics. The recombinant CDV (rCDV-VP2) was demonstrated to express stably the VP2 in cells for at least 33 serial passages in vitro. Unfortunately, a nonsense mutation was initially identified in the VP2 open reading frame (ORF) at passage-34 (P34) and gradually became predominant in rCDV-VP2 quasispecies with passaging. Neither test strip detection nor indirect immunofluorescence assay demonstrated the expression of the VP2 at P50. The P50 rCDV-VP2 was subjected to next-generation sequencing, which totally identified 17 single-nucleotide variations (SNVs), consisting of 11 transitions and 6 transversions. Out of the 17 SNVs, 1 and 9 were identified as nonsense and missense mutations, respectively. Since the nonsense mutation arose in the VP2 ORF as early as P34, an earlier rCDV-VP2 progeny should be selected for the vaccination of animals in future experiments.

Flipped learning could improve the learning effectiveness of students. However, some studies have pointed out the limitations related to flipped classrooms because the content of the flipped course does not vary according to the needs of the students. On the other hand, adaptive teaching, which customizes the learning mode according to the individual needs of students, can make up for some of the shortcomings of flipped teaching. This study combines adaptive teaching with flipped teaching and applies it to face-to-face classroom activities. The purpose of this research is to explore whether the implementation of flipping and adaptive learning in a computer programming course can improve the learning effectiveness of students. The experimental subjects of this study are the sophomore students in the Department of Information Management. The flipped classroom with adaptive instruction has been realized in the limited course time. This study uses questionnaires to collect pre- and post-test data on the “learning motivation” of students. The learning effectiveness was evaluated based on the students' previous programming course (C language) and the semester scores of this course. Research results show that the post-test “learning motivation” has improved overall compared with the pre-test, and the learning effect is significant. The results of this research not only prove the effectiveness of modern teaching theories in programming courses but also lay the foundation for future teaching design.

Women remain under-represented in leadership positions in many countries. Since executive search consultants (also known as headhunters) act as gatekeepers in the hiring process, headhunters' biases might influence the female under-representation. There is preliminary evidence that suggests headhunters favor men, but direct evidence is missing. Thus, this study directly tested this assumption using implicit and explicit measures (an implicit association test and a gender role attitudes survey), completed by 123 German executive search consultants. Although neither measure showed an anti-women bias (with the explicit measure being compared to a match sample from a representative survey using propensity score matching), the implicit association test showed an in-group bias (i.e., male headhunter had a stronger association of men and competence than of women and competence). The latter is worrisome because the majority of consultants in this business are men. Thus, organizations interested in more female managers need to carefully consider who they hire as their executive search consultants.

Understanding key socio-demographic variables of 2019 coronavirus disease (COVID-19) vaccine recipients is crucial to improving its acceptance and Nigeria's COVID-19 control strategy. The survey was conducted as a non-probability cross-sectional survey of 2,936 COVID-19 vaccine recipients in Kwara State. Our findings revealed that 74% (n = 2,161) of the vaccine recipients were older than 40 years. Forty percent (n = 1,180) of the vaccine recipients earned a monthly income >100,000 Naira (equivalent to US $200). Most of the vaccine recipients (64%, n = 1,880) had tertiary education, while 15% (n = 440) of them had no formal education. Almost half of the recipients (47%, n = 1,262) were government employees and 28.8% (n = 846) of them had health-related backgrounds. Only 17% (n = 499) of the vaccine recipients have been screened for the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), of which 21% (n = 105/499) of them were tested positive. Only 47% (n = 1,378) had been fully immunized. The prevalence of confirmed COVID-19 cases among COVID-19 vaccine recipients in Kwara State was 3.6% (n = 105/2,936). The most recurrent adverse events following immunization (AEFIs) among vaccine recipients were fever (14%, n = 411), pain at injection site (47%, n = 1,409), headache (19%, n = 558), and body weakness (9%, n = 264). The need to protect themselves from the deadly virus was the main reason that prompted people to voluntarily accept the COVID-19 vaccine. There is a high level of COVID-19 vaccine acceptance among respondents across all social classes including those with no formal education, those with very low monthly income (< US $2 per day), and in untested population. Hence, vaccine donors should prioritize equitable distribution to Low-and-Middle-income Countries (LMICs) such as Nigeria, and health authorities should improve vaccine advocacy to focus on vaccine safety and efficacy.

Doxorubicin (DOX) is a successful chemotherapeutic widely used for the treatment of a range of cancers. However, DOX can have serious side-effects, with cardiotoxicity and hepatotoxicity being the most common events. Oxidative stress and changes in metabolism and bioenergetics are thought to be at the core of these toxicities. We have previously shown in a clinically-relevant rat model that a low DOX dose of 2 mg kg–1 week–1 for 6 weeks does not lead to cardiac functional decline or changes in cardiac carbohydrate metabolism, assessed with hyperpolarized [1-13C]pyruvate magnetic resonance spectroscopy (MRS). We now set out to assess whether there are any signs of liver damage or altered liver metabolism using this subclinical model. We found no increase in plasma alanine aminotransferase (ALT) activity, a measure of liver damage, following DOX treatment in rats at any time point. We also saw no changes in liver carbohydrate metabolism, using hyperpolarized [1-13C]pyruvate MRS. However, using metabolomic analysis of liver metabolite extracts at the final time point, we found an increase in most acyl-carnitine species as well as increases in high energy phosphates, citrate and markers of oxidative stress. This may indicate early signs of steatohepatitis, with increased and decompensated fatty acid uptake and oxidation, leading to oxidative stress.

BackgroundAcinetobacter baumannii is a leading cause of healthcare-associated infections worldwide, due to both its persistence in the hospital setting and ability to acquire high levels of antibiotic resistance. Carbapenem-resistant A. baumannii isolates (CRAB) limit the activity of current antimicrobial regimens and new alternatives or adjuncts to traditional antibiotics are urgently needed. Durlobactam is a novel broad-spectrum inhibitor of serine-type β-lactamases that restores sulbactam (SUL) activity against A. baumannii. The sulbactam-durlobactam (SD) combination has recently completed Phase 3 testing in the global ATTACK trial.ObjectivesThe aim of this study is to evaluate the in vitro activity of SD versus comparators against a representative nationwide collection of CRAB isolates.MethodsOne hundred ninety CRAB isolates were collected from clinical samples of patients hospitalized in 11 hospitals throughout Greece during 2015. In vitro activities of SD and comparators (SUL alone, amikacin, minocycline, imipenem, meropenem, colistin, SD and imipenem combined with SD) were determined by broth microdilution.ResultsDurlobactam restored sulbactam activity against the majority of the strains tested, with SD exhibiting the lowest MIC90 (8 μg/ml) relative to the other single comparators tested; 87.9% of the isolates had SD MICs ≤4/4 µg/ml. The most active comparator was colistin (MIC90 = 16 μg/ml). The addition of imipenem further lowered the MIC90 of SD by one two-fold dilution.ConclusionsThis study demonstrated the potential utility of SD for the treatment of infections caused by A. baumannii. If its clinical efficacy is confirmed, SD may be an important therapeutic option for CRAB infections.

Rabies has been listed as a priority zoonotic disease in many African countries and the countdown to reach the goal of eliminating dog-mediated human rabies deaths by 2030 means that disease control measures need to be applied fast. In this context, an essential pillar of any national plan to control rabies is the implementation of reliable diagnostic techniques to ensure the success of field surveillance systems. Although many African countries have received international support for the control of rabies–some countries, like Benin, have not received a similar level of support. Indeed, until 2018, Benin was not able to diagnose rabies and rabies diagnosis in animals as well as humans relied solely on observed clinical symptoms. Although the Central Veterinary Laboratory (CVL) of Parakou had the equipment to implement two recommended tests, the lack of specific reagents and skills prevented the implementation of a rabies diagnostic service. Here we present the joint efforts of the national authorities in Benin, intergovernmental agencies, and non-governmental organizations to assess the strengths and weaknesses of the government's rabies control efforts. We have applied the Stepwise Approach toward Rabies Elimination (SARE) analysis, implemented rabies diagnostic capacities at the CVL of Parakou, characterized strains of rabies virus circulating in Benin, and finally integrated an inter-laboratory comparison program.

Aim: Liver fibrosis monitoring is essential in patients with chronic hepatitis B (CHB). However, less robust, noninvasive diagnostic methods for staging liver fibrosis, other than liver biopsy, are available. Our previous study demonstrated a panel of cellular proteins recognized by autoantibodies that may have potential value in discrimination of CHB and liver cirrhosis. We aim to assess the diagnostic value of these serum autoantibodies for staging liver fibrosis.Methods: Candidate autoantigens were screened and assessed by microarray analysis in 96 healthy controls and 227 CHB patients with pre-treatment biopsy-proven METAVIR fibrosis score, comprising 69, 115, and 43 cases with S0-1, S2-3, and S4 stages, respectively. Autoantibodies with potential diagnostic value for staging liver fibrosis were verified by enzyme-linked immunosorbent assays (ELISA). Receiver operating characteristic curve was conducted to evaluate autoantibody performance.Results: Microarray analysis identified autoantigens CENPF, ACY1, HSPA6, and ENO1 with potential diagnostic value for liver fibrosis staging, among which CENPF and ACY1 were validated using ELISA. CENPF and ACY1 autoantibodies had area under the curve values of 0.746 and 0.685, 58.14 and 74.42% sensitivity, and 88.41 and 60.87% specificity, respectively, for discriminating liver fibrosis stages S4 and S0-1. The prevalence of CENPF and ACY1 autoantibodies was not correlated with age, sex or level of inflammation.Conclusions: Autoimmune responses may be elicited during progression of liver fibrosis, and serum autoantibodies may be a valuable biomarker for staging liver fibrosis deserving of further study.

AimsTo explore changes in alcohol purchase and consumption during the first few months of the Covid-19 pandemic, and assess associations between increased alcohol purchase/use and socioeconomic and environmental factors.DesignSecondary data from a cross-sectional online survey conducted from 17 April to 25 June 2020.SettingThirty-eight countries from all continents of the world.ParticipantsA total of 37,206 adults (mean age:36.7, SD:14.8, 77% female) reporting alcohol purchasing and drinking habit before and during the pandemic.MeasurementsChanges in alcohol stock-up and frequency of alcohol use during the pandemic and increased alcohol stock-up and use were stratified by gender, age, education, household structure, working status, income loss, psychological distress, and country based on alcohol consumption per capita. The associations between increased alcohol stock-up/use and living with children, working from home, income loss and distress were examined using multivariate logistic regression, controlling for demographic factors.FindingsThe majority of respondents reported no change in their alcohol purchasing and drinking habits during the early pandemic period. Increased drinking was reported by 20.2% of respondents, while 17.6% reported decreased alcohol use. More than half (53.3%) of respondents experienced psychological distress, with one in five (20.7%) having severe distress. Female gender, being aged under 50, higher educational attainment, living with children, working from home, and psychological distress were all independently associated with increased alcohol drinking during lockdown. Limitations of the study were the non-representative sample, the data collection early in the pandemic, and the non-standard measurement of alcohol consumption.ConclusionIncreased psychological distress among people during the early pandemic period, resulted in increased alcohol consumption, especially among women with children working from home during lockdown.

Mannitol, a natural alcoholic-sugar, was recently suggested as a potential disease-modifying agent in Parkinson's disease. In animal models of the disease, mannitol interferes with the formation of α-synuclein fibrils, inhibits the formation of α-synuclein oligomers and leads to phenotypic recovery of impaired motor functions. Parkinson's patients who consume mannitol report improvements of both motor and non-motor symptoms. Safety of long-term use of oral mannitol, tolerable dose and possible benefit, however, were never clinically studied. We studied the safety of oral mannitol in Parkinson's disease and assessed the maximal tolerable oral dose by conducting a phase IIa, randomized, double-blind, placebo-controlled, single-center, dose-escalating study (ClinicalTrials.gov Identifier: NCT03823638). The study lasted 36 weeks and included four dose escalations of oral mannitol or dextrose to a maximal dose of 18 g per day. The primary outcome was the safety of oral mannitol, as assessed by the number of adverse events and abnormal laboratory results. Clinical and biochemical efficacy measures were collected but were not statistically-powered. Fourteen patients receiving mannitol completed the trial (in addition to eight patients on placebo). Mannitol-related severe adverse events were not observed. Gastrointestinal symptoms limited dose escalation in 6/14 participants on mannitol. None of the clinical or biochemical efficacy secondary outcome measures significantly differed between groups. We concluded that long-term use of 18 g per day of oral mannitol is safe in Parkinson's disease patients but only two third of patients tolerate this maximal dose. These findings should be considered in the design of future efficacy trials.

Although previous work has linked parent autonomy support to the development of children’s executive function (EF) skills, the role of specific autonomy-supportive behaviors has not been thoroughly investigated. We compiled data from four preschool-age samples in the Midwestern United States (N = 366; M age = 44.26 months; 72% non-Hispanic White, 19% Black/African American, 5% Multiracial) to examine three relevant autonomy-supportive behaviors (supporting competence, positive verbalizations, and offering choice) and their associations with child EF. We coded parent autonomy-supportive behaviors from a 10-min interaction between parent and child dyads working on challenging jigsaw puzzles together. Children completed a battery of EF. Overall, child EF was most consistently correlated with the offering choice subscale. Additionally, only the offering choice subscale predicted child EF while controlling for the other autonomy support subscales and child age. These results suggest that parent provision of choice is an especially relevant aspect of autonomy-supportive parenting and may be important to the development of EF in early childhood. Future research should directly measure children’s experience with choice and how it relates to emerging EF.

Epileptic seizures/post-traumatic epilepsy (ES/PTE) are frequent in persons with brain injuries, particularly for patients with more severe injuries including ones that result in disorders of consciousness (DoC). Surprisingly, there are currently no best practice guidelines for assessment or management of ES in persons with DoC. This study aimed to identify clinician attitudes toward epilepsy prophylaxis, diagnosis and treatment in patients with DoC as well as current practice in regards to the use of amantadine in these individuals. A cross-sectional online survey was sent to members of the International Brain Injury Association (IBIA). Fifty physician responses were included in the final analysis. Withdrawal of antiepileptic drug/anti-seizure medications (AED/ASM) therapy was guided by the absence of evidence of clinical seizure whether or not the AED/ASM was given prophylactically or for actual seizure/epilepsy treatment. Standard EEG was the most frequent diagnostic method utilized. The majority of respondents ordered an EEG if there were concerns regarding lack of neurological progress. AED/ASM prescription was reported to be triggered by the first clinically evident seizure with levetiracetam being the AED/ASM of choice. Amantadine was frequently prescribed although less so in patients with epilepsy and/or EEG based epileptic abnormalities. A minority of respondents reported an association between amantadine and seizure. Longitudinal studies on epilepsy management, epilepsy impact on neurologic prognosis, as well as potential drug effects on seizure risk in persons with DoC appear warranted with the goal of pushing guideline development forward and improving clinical assessment and management of seizures in this unique, albeit challenging, population.

Corona virus disease 2019 (COVID-19) pathogenesis is intimately linked to the severe acute respiratory syndrome corona virus 2 (SARS-CoV-2) and disease severity has been associated with compromised induction of type I interferon (IFN-I) cytokines which coordinate the innate immune response to virus infections. Here we identified the SARS-CoV-2 encoded protein, Spike, as an inhibitor of IFN-I that antagonizes viral RNA pattern recognition receptor RIG-I signaling. Ectopic expression of SARS-CoV-2 Spike blocked RIG-I mediated activation of IFNβ and downstream induction of interferon stimulated genes. Consequently, SARS-CoV-2 Spike expressing cells harbored increased RNA viral burden compared to control cells. Co-immunoprecipitation experiments revealed SARS-CoV-2 Spike associated with interferon regulatory factor 3 (IRF3), a key transcription factor that governs IFN-I activation. Co-expression analysis via immunoassays further indicated Spike specifically suppressed IRF3 expression as NF-κB and STAT1 transcription factor levels remained intact. Further biochemical experiments uncovered SARS-CoV-2 Spike potentiated proteasomal degradation of IRF3, implicating a novel mechanism by which SARS-CoV-2 evades the host innate antiviral immune response to facilitate COVID-19 pathogenesis.

Introduction: Following resident requests, we created a public metrics dashboard to inform residents of their daily productivity. Our goal was to iteratively improve the dashboard based on resident feedback and to measure the impact of reviewing aggregate data on self-perceived productivity. Methods: A 10-question anonymous survey was completed by our postgraduate year 1-3 residents. Residents answered questions on the dashboard and rated their own productivity before and after reviewing aggregate peer-comparison data. Using the Wilcoxon signed-rank test we calculated summary statistics for survey questions and compared distributions of pre- and post-test, self-rated productivity scores. Results: All 43 eligible residents completed the survey (response rate 100%). Thirteen (30%) residents “rarely” or “never” reviewed the dashboard. No respondents felt the dashboard measured their productivity or quality of care “extremely accurately” or “very accurately.” Seven (16%) residents felt “very” or “extremely pressured” to change their practice patterns based on the metrics provided, and 28 (65%) would have preferred private over public feedback. Fifteen residents (35%) changed their self-perceived rank after viewing peer-comparison data, although not significantly in a particular direction (z = 0.71, P = 0.48). Conclusion: Residents did not view the presented metrics as reflective of their productivity or quality of care. Viewing the dashboard did not lead to statistically significant changes in resident self-perception of productivity. This finding highlights the need for expanding the resident conversation and education on metrics, given their frequent inclusion in attending physician workforce payment and incentive models.

Children with cystic fibrosis (CF) (cwCF) suffer from inadequate weight gain, failure to thrive, and muscle weakness. The latter may be secondary to disuse atrophy (muscle wasting or reduction in muscle size associated with reduced physical activity and inflammation). Handgrip strength (HGS) is a reliable surrogate for muscle strength and lean body mass. Data from our CF center have shown an association between low HGS and forced expiratory volume in 1 s (FEV1) in cwCF. High-intensity interval training (HIIT) improves physical strength. Therefore, we devised a project to assess implementing a HIIT exercise program in the home setting, in order to improve physical strength in cwCF with HGS ≤ 50th percentile. Patients were instructed to complete 3–5 sessions of HIIT exercises per week. Wilcoxon matched-pairs signed-rank tests were used to compare HGS, FEV1, and body mass index (BMI) percentile at baseline and at a follow-up clinic visit. Follow-up was limited due to the COVID pandemic. Adherence to the HIIT regimen was poor. A total of twenty-nine cwCF participated in the program. However, a total of 13 individuals reported some form of moderate activity at follow-up and therefore constituted our final study population. There was a statistically significant increase in absolute grip strength (AGS) and FEV1 for these individuals. Even though the home HIIT protocol was not followed, the project demonstrated that moderate physical activity in cwCF can lead to significant improvement in HGS and overall physical strength.

In this study we replicated the explanatory effect of a label which had been found byGiffin et al. (2017). In their experiments, they used vignettes describing an odd behavior of a person based on culturally specific disorders that were unfamiliar to respondents. It turned out that explanations which explain an odd behavior through a person’s tendency to behave that way (circulus vitiosus) seemed more persuasive if the disorder was given a label that was used in the explanation. We replicated these results in Experiment 1, and in a follow-up Experiment 2 we examined the familiarity with category information and the evaluation of that category over time (the delay lasted one week). We realized that the label effect persists even when people make judgments based on their recollections about a category. Furthermore, according to a content analysis of the recollections, participants in the label condition remembered more information from the vignettes but tended to forget an artificial label; however, they used other words from the disorder domain instead (like “disease” or “kleptomania”). This allowed us to suggest a new interpretation of this effect: we suppose that in theGiffin et al. (2017)experiments the label did not bring any new features to a category itself, but pointed to a relevant domain instead, so the effect appeared from the activation of areas of knowledge in semantic memory and the application of relevant schema for learning a new phenomenon.

Introduction: This study examined the role of individual characteristics in predicting short- and long-term benefits of the Italian version of Cognitive Stimulation Therapy (CST-IT), an evidence-based intervention for people with mild-to-moderate dementia.Materials and Methods: Data were drawn from a sample (N = 123) of people with dementia (PwD) who took part in a multicenter controlled clinical trial of CST-IT. Assessments at pre-test, immediately after completing the treatment, and 3 months later investigated the following outcomes: general cognitive functioning and language, mood and behavior, everyday functioning, and quality of life. Age, education and baseline (pre-test) cognitive functioning, mood (depression) and behavioral and neuropsychiatric symptoms were considered as predictors of any short- and long-term benefits.Results: Linear mixed-effects models showed that different individual characteristics -particularly education and age- influenced the benefits of CST-IT, depending on the outcome measures considered. Higher education predicted larger gains in general cognitive functioning and, along with less severe depressive symptoms, in language (magnification effects). Older age was associated with positive changes in mood (compensation effects). Albeit very modestly, older age was also associated with larger gains in everyday functioning (compensation effects). Gains in quality of life were predicted by older age and lower education (compensation effects). Baseline cognitive functioning, mood and/or behavioral symptoms broadly influenced performance too, but their role again depended on the outcomes considered.Discussion: These findings underscore the importance of considering and further exploring how psychosocial interventions like CST are affected by individual characteristics in order to maximize their efficacy for PwD.

Refugees are often exposed to a variety of stressors and traumatic events, posing a significant risk for the development of mental disorders. Young refugees may be particularly at risk because adverse life events affect identity formation, a developmental task that is typically expected in adolescence and emerging adulthood. Trauma and cultural changes may alter identity development, potentially leading to identity diffusion, a core concept of personality disorders. However, previous research on personality pathology among refugees is scarce. In this study, we examine identity development and maladaptive personality traits in young refugees and migrants. Refugees from 22 countries of origin were recruited in a German reception center (n = 120) and a group of adults with a migration background in first- or second generation was obtained via web-based recruitment (n = 281). Identity development was measured using the Assessment of Identity Development in Adolescence – Short Form. Maladaptive personality traits were assessed with the Personality Inventory for DSM-5-Brief Form. Group differences between refugees and migrants regarding identity development and trait expression were investigated using t-tests. The relationship between the two measures and their corresponding subscales was examined by means of correlation analyses. Refugees reported significantly higher levels of identity diffusion, negative affectivity, detachment, antagonism, and disinhibition compared to migrants. No significant differences were found for psychoticism. Correlation analyses revealed low to moderate positive associations between identity diffusion and maladaptive trait expression. Possible implications for early phase of resettlement, preventive psychiatric care and further research questions are discussed.

There has been increased concern regarding the potential human health risks associated with exposure to phthalates. Research indicates that food intake is the most critical exposure pathway for phthalates. This study aimed to investigate packaged beef samples for the presence of dimethyl terephthalate (DMTP), di-n-butyl phthalate (DnBP), and diisooctyl phthalate (DiOP) and to assess their translocation from the common form of food packaging procured from various Saint-Petersburg and Leningrad region shops. The packaging samples include paper and different types of plastic. Phthalates were extracted by dichloromethane and analyzed by gas chromatography coupled with mass spectrometry (GC-MS). While DnBP had the highest mean values in beef from 34.5 to 378.5 μg·kg−1, DiOP displayed the lowest mean values from LOD to 37 μg·kg−1. The larger contact area and the presence of distributed fat on the surface of the minced meat resulted in significantly higher phthalate translocation than beef slices. Further, DMTP was not detected in any samples. However, the examined food packages do not meet the requirements of Russian, EU and USA legislation, as DnBP migrates to meat. Calculated maximum DnBP daily intake of 0.167 μg·kg−1·day−1 for chilled minced beef in vacuum packaging did not exceed tolerable daily intake (TDI) level. The most alarming results are concerning the phthalates presence in beef farmed in the Leningrad region and not subjected to any plastic packaging. A full-scale study is warranted to determine the pathways and sources of phthalates migration in the food chain.

Background: Knowledge and beliefs about health and health care are part of the general concept of health literacy. Studies demonstrated that large parts of the population report inadequate health literacy. There are only few studies specifically addressing public knowledge and beliefs about emergency care. We examine magnitude and social variations of public knowledge about emergency care in Germany.Methods: Analyses make use of a telephone survey conducted in Hamburg, Germany. Random sample consisted of 1,207 adult respondents. We asked whether the respondents know various emergency care services. Moreover, capabilities of dealing with an emergency case were assessed. Sex, age, education, and migration background were introduced as predictors into regression models.Results: 98% of the respondents stated to know the rescue service, while 74% knew the medical on call service and 49% were aware of an emergency practice nearby. About 71% of the interviewees said it was easy for them to find out whom to turn to in a case of a medical emergency. Fewer respondents found it easy to evaluate when to use emergency medical services and to evaluate whether a health problem is a medical emergency. Knowledge and capabilities were positively associated with education and negatively related to migration background.Conclusions: This study indicates a lack of public knowledge about emergency care and social inequalities in public knowledge according to education and migration status. Findings suggest that interventions are needed to improve public knowledge and that considering social inequalities should be a basic principle for such interventions.

Pain has not only sensory, but also emotional and cognitive, components. Some studies have explored the effect of pain on time perception, but the results remain controversial. Whether individual pain-related emotional and cognitive factors play roles in this process should also be explored. In this study, we investigated the effect of electrical stimulation–induced pain on interval timing using a temporal bisection task. During each task session, subjects received one of five types of stimulation randomly: no stimulus and 100 and 300 ms of non-painful and painful stimulation. Pain-related emotional and cognitive factors were measured using a series of questionnaires. The proportion of “long” judgments of a 1,200-ms visual stimulus duration was significantly smaller with 300 ms painful stimulation than with no stimulus (P < 0.0001) and 100 ms (P < 0.0001) and 300 ms (P = 0.021) non-painful stimulation. The point of subjective equality (PSE) did not differ among sessions, but the average Weber fraction (WF) was higher for painful sessions than for no-stimulus session (P = 0.022). The pain fear score correlated positively with the PSE under 100 ms non-painful (P = 0.031) and painful (P = 0.002) and 300 ms painful (P = 0.006) stimulation. Pain catastrophizing and pain anxiety scores correlated significantly with the WF under no stimulus (P = 0.005) and 100 ms non-painful stimulation (P = 0.027), respectively. These results suggest that electrical stimulation–induced pain affects temporal sensitivity, and that pain-related emotional and cognitive factors are associated with the processing of time perception.

Heat stress (HS) alters the rumen fermentation of dairy cows thereby affecting the metabolism of rumen papillae and thus the epithelial barrier function. The aim of the present study was to investigate if HS damages the barrier function of ruminal epithelia. Eight multiparous Holstein dairy cows with rumen cannula were randomly equally allocated to two replicates (n = 4), with each replicate being subjected to heat stress or thermal neutrality and pair-feeding in four environmental chambers. Micromorphological observation showed HS aggravated the shedding of the corneum and destroyed the physical barrier of the ruminal epithelium to a certain extent. Transcriptomics analysis of the rumen papillae revealed pathways associated with DNA replication and repair and amino acid metabolism were perturbated, the biological processes including sister chromatid segregation, etc. were up-regulated by HS, while the MAPK and NF-kB cell signaling pathways were downregulated. However, no heat stress-specific change in the expression of tight junction protein or TLR4 signaling was found, suggesting that HS negatively affected the physical barrier of the ruminal epithelium to some extent but did not break the ruminal epithelium. Heat stress invoked mechanisms to maintain the integrity of the rumen epithelial barrier by upregulating the expression of heat shock protein and repairments in rumen papillae. The increase in amino acid metabolism in rumen papillae might affect the nutrient utilization of the whole body. The findings of this study may inform future research to better understand how heat stress affects the physiology and productivity of lactating cows and the development of mitigation strategies.

Purpose: This study aimed to assess the prevalence, incidence, and associated factors of possible sarcopenia in a nationwide representative sample of the community-dwelling older Chinese population.Methods:This study used the data of participants aged 60 years and over from the China Health and Retirement Longitudinal Study (CHARLS). Data on participants from three waves (2011–2015) of CHARLS were extracted. Possible sarcopenia was defined as low muscle strength or low physical performance, based on the Asian Working Group for Sarcopenia 2019 consensus. We first described baseline prevalence and four-year incidence of possible sarcopenia. Then multiple logistic regression and multivariable parametric proportional hazard model with Weibull distribution were used to examine the association of risk factors with baseline prevalence and four-year incidence of possible sarcopenia, respectively.Results:The prevalence of possible sarcopenia was 46.0%. The four-year incidence of possible sarcopenia was 11.9 per 100 person-years. Multivariable analysis revealed that advanced age and depressive symptoms were associated with increased prevalence of possible sarcopenia, while receiving education and moderate or high physical activity were associated with a lower risk of possible sarcopenia prevalence. For incidence, only advanced age was associated with an increased risk of possible sarcopenia incidence.Conclusion:Our study revealed the substantial burden of possible sarcopenia and related risk factors in community-dwelling settings in China. It highlighted the importance of early detection and intervention in this subclinical group for the prevention of sarcopenia.

The world of work has been severely affected by the COVID-19 pandemic due to the high instability observed in the labor market, bringing several new challenges for leaders and employees. The present study aims to analyze the role of organizational and job resources in predicting employees' job insecurity during the first wave of the COVID-19 outbreak, through the mediating role of work engagement. A sample of 207 Portuguese employees participated (Mean age = 45 years old, SD = 9.92), of which 64.7% were women. Data was collected using an online survey, including self-report measures of organizational resources (perceived organizational support), job resources (performance feedback and job autonomy), job insecurity, and work engagement. Data showed that job and organizational resources negatively influenced job insecurity. Moreover, work engagement was a significant mediator of the relation between performance feedback (facet of job resources) and job insecurity. Findings suggest that investing in job and organizational resources can act as protective factors to minimize feelings of job insecurity. Likewise, leaders should foster work engagement among employees to help them balance the relation between these resources and job insecurity, especially in crisis situations. Overall, this study takes a new, underexplored perspective, theoretically bridging organizational and job resources with job insecurity and work engagement during a time of great uncertainty, such as the COVID-19 pandemic. info:eu-repo/semantics/publishedVersion

Background: Agarwood, a type of herbal medicine widely used in Asian countries, is noted in traditional medicine for its intelligence-enhancing effects. Agarwood incense is traditionally administered by oral and nasal inhalation. To verify whether agarwood incense can exert its intelligence-enhancing effects in this way to rescue learning and memory impairment, typical clinical manifestations of dementia, we conducted a set of behavioral tests related to learning and memory.Methods: C57BL/6 mice were divided into six groups. In addition to the control and model groups, we added a donepezil treatment group to evaluate the effect of three different agarwood administration doses. After a week of administration, scopolamine was injected 30 min before each behavioral test to create a learning and memory impairment model. A series of behavioral tests [the Morris water maze test (MWM), the novel object recognition test (NOR), and the step-down test (SDT)] were used to assess their learning ability, as well as their spatial and recognition memory.Results: After scopolamine injection, the model group showed significant learning and memory impairment (i.e., longer latencies, lower crossing times, and lesser distance travelled in the target quadrant in MWM; a lower recognition index in NOR; and longer latencies and higher error times in SDT). The other four treatment groups all showed improvements in these indicators, and the overall therapeutic effect of agarwood was superior.Conclusion: The inhalation administration of agarwood can significantly improve the learning and memory impairment caused by scopolamine in mice, and the therapeutic effect varied between doses.

Background: Real-world data regarding outcomes of idiopathic pulmonary fibrosis (IPF) are scarce, outside of registries. The claims data from the French National Health System (SNDS) were used to describe outcomes in patients diagnosed with IPF in 2015–2016 but who did not receive antifibrotic therapies.Method: Patients aged Results: A total of 5,360 patients (43.2%) not treated with antifibrotic therapies were included. The mean age was 75.5 years, and 57.9% were males. In the year before inclusion, 47.3% of patients had a Charlson score ≥5. During follow-up, 41.2% of patients died. The unadjusted incidence rate was 29.9 per 100 person-years (95%CI = [28.7–31.2]), and the cumulative incidence of death at 3 years was 50.2% (95% CI = [48.3–52.1%]). In the study population, 35.3% of patients experienced an acute respiratory-related hospitalization. The unadjusted incidence rate was 32.1 per 100 person-years (95%CI = [30.6–33.5]) and the cumulative incidence of the event at 3 years was 41.5% (95% CI = [39.7–43.2%]).Interpretation: This observational study showed that, if untreated with antifibrotics, IPF is associated with a 50% all-cause mortality at 3 years. These figures can serve as a historical control of the natural course of the disease.

Iron acquisition through siderophores, a class of small, potent iron-chelating organic molecules, is a widely spread strategy among pathogens to survive in the iron-restricted environment found in the host. Although these molecules have been implicated in the pathogenesis of several species, there is currently no comprehensive study addressing siderophore production in Staphylococcus epidermidis. Staphylococcus epidermidis is an innocuous skin commensal bacterium. The species, though, has emerged as a leading cause of implant-associated infections, significantly supported by an inherent ability to form biofilms. The process of adaptation from skin niche environments to the hostile conditions during invasion is yet not fully understood. Herein, we addressed the possible role of siderophore production in S. epidermidis virulence. We first identified and deleted a siderophore homolog locus, sfaABCD, and provided evidence for its involvement in iron acquisition. Our findings further suggested the involvement of siderophores in the protection against oxidative stress-induced damage and demonstrated the in vivo relevance of a siderophore-mediated iron acquisition during S. epidermidis infections. Conclusively, this study addressed, for the first time in this species, the underlying mechanisms of siderophore production, highlighting the importance of a siderophore-mediated iron acquisition under host relevant conditions and, most importantly, its contribution to survival within the host., This study was supported by the Portuguese Foundation for Science and Technology (FCT) through the funded project PTDC/BIAMOL/29553/2017, under the scope of COMPETE2020 (POCI-01-0145-FEDER-029553), and the strategic funding of UID/BIO/04469/2019 unit. This study was also supported through funds from the German Research Council (DFG) and the Damp Foundation. FO was supported by an individual Ph.D. scholarship (SFRH/BD/101399/2014)., The authors acknowledge the support of the i3S Scientific Platform HEMS, member of the PPBI (PPBIPOCI-01-0145-FEDER-022122)., info:eu-repo/semantics/publishedVersion

Src homology 3-domain growth factor receptor-bound 2-like interacting protein 1 (SGIP1), originally known as a regulator of energy homeostasis, was later found to be an ortholog of Fer/Cip4 homology domain-only (FCHo) proteins and to function during endocytosis. SGIP1α is a longer splicing variant in mouse brains that contains additional regions in the membrane phospholipid-binding domain (MP) and C-terminal region, but functional consequences with or without additional regions between SGIP1 and SGIP1α remain elusive. Moreover, many previous studies have either inadvertently used SGIP1 instead of SGIP1α or used the different isoforms with or without additional regions indiscriminately, resulting in further confusion. Here, we report that the additional region in the MP is essential for SGIP1α to deform membrane into tubules and for homo-oligomerization, and SGIP1, which lacks this region, fails to perform these functions. Moreover, only SGIP1α rescued endocytic defects caused by FCHo knock-down. Thus, our results indicate that SGIP1α, but not SGIP1, is the functional ortholog of FCHos, and SGIP1 and SGIP1α are not functionally redundant. These findings suggest that caution should be taken in interpreting the role of SGIP1 in endocytosis.

Background: There are scarce and controversial data on whether human immunodeficiency virus (HIV) infection is associated with changes in aortic pressure (aoBP) and waveform-derived indexes. Moreover, it remains unknown whether potential differences in aoBP and waveform indexes between people living with HIV (PLWHIV) and subjects without HIV (HIV-) would be affected by the calibration method of the pressure waveform.Aims: To determine: (i) whether PLWHIV present differences in aoBP and waveform-derived indexes compared to HIV- subjects; (ii) the relative impact of both HIV infection and cardiovascular risk factors (CRFs) on aoBP and waveform-derived indexes; (iii) whether the results of the first and second aims are affected by the calibration method.Methods: Three groups were included: (i) PLWHIV (n = 86), (ii) HIV- subjects (general population; n = 1,000) and (iii) a Reference Group (healthy, non-exposed to CRFs; n = 398). Haemodynamic parameters, brachial pressure (baBP; systolic: baSBP; diastolic: baDBP; mean oscillometric: baMBPosc) and aoBP and waveform-derived indexes were obtained. Brachial mean calculated (baMBPcalc=baDBP+[baSBP-baDBP]/3) pressure was quantified. Three waveform calibration schemes were used: systolic-diastolic, calculated (baMBPcalc/baDBP) and oscillometric mean (baMBPosc/baDBP).Results: Regardless of CRFs and baBP, PLWHIV presented a tendency of having lower aoBP and waveform-derived indexes which clearly reached statistical significance when using the baMBPosc/baDBP or baMBPcalc/baDBP calibration. HIV status exceeded the relative weight of other CRFs as explanatory variables, being the main explanatory variable for variations in central hemodynamics when using the baMBPosc/baDBP, followed by the baMBPcalc/baDBP calibration.Conclusions: The peripheral waveform calibration approach is an important determinant to reveal differences in central hemodynamics in PLWHIV.

How listeners handle prosodic cues of linguistic and paralinguistic origin is a central question for spoken communication. In the present EEG study, we addressed this question by examining neural responses to variations in pitch accent (linguistic) and affective (paralinguistic) prosody in Swedish words, using a passive auditory oddball paradigm. The results indicated that changes in pitch accent and affective prosody elicited mismatch negativity (MMN) responses at around 200 ms, confirming the brain’s pre-attentive response to any prosodic modulation. The MMN amplitude was, however, statistically larger to the deviation in affective prosody in comparison to the deviation in pitch accent and affective prosody combined, which is in line with previous research indicating not only a larger MMN response to affective prosody in comparison to neutral prosody but also a smaller MMN response to multidimensional deviants than unidimensional ones. The results, further, showed a significant P3a response to the affective prosody change in comparison to the pitch accent change at around 300 ms, in accordance with previous findings showing an enhanced positive response to emotional stimuli. The present findings provide evidence for distinct neural processing of different prosodic cues, and statistically confirm the intrinsic perceptual and motivational salience of paralinguistic information in spoken communication.

Few studies have explored outdoor therapy when facilitated by clinical psychologists within an inpatient mental health service. In the present study, outdoor psychology sessions were introduced after service users (SUs) expressed a desire to return to face-to-face working during the COVID-19 pandemic. This study aimed to explore SUs’ and clinical psychologists’ perspectives on the feasibility of conducting outdoor therapy within the service. A mixed-method approach was underpinned by critical realist philosophy. Three psychologists maintained reflective diaries following outdoor therapy sessions with 16 SUs. A subsample of 14 SUs completed scales measuring therapeutic alliance and comfort during outdoor sessions. A subsample of eight SUs participated in semi-structured interviews. Data was analysed using descriptive statistics and thematic analysis. Quantitative and qualitative data demonstrated high SU satisfaction with therapeutic alliance and comfort outdoors. Six themes were identified: utilising a person-centred approach; the value of multi-disciplinary team support; enhancing therapeutic engagement; the benefits of time away from the ward; managing confidentiality; physical health and safety. This feasibility study demonstrated the introduction of outdoor psychology sessions within an inpatient mental health service to be a viable response to COVID-19. The findings suggest outdoor therapy can be an effective and safe mode of therapy, and can offset the challenges of indoor working, providing certain risk factors are considered and managed. The limitations of this study and implications for clinical practice are discussed. Further research is now required to support future integration into clinical practice.

Purpose: Pathologic studies suggest that unstable plaque morphology and inflammation are associated with cerebrovascular events. 18F-fluorodeoxyglucose positron emission tomography (18FDG-PET) is a validated technique for non-invasive imaging of inflammation-related plaque metabolism, and MRI can identify morphologic features of plaque instability. The aim of this study was to investigate the association of selected imaging characteristics of plaque vulnerability measured with MRI and PET in patients with symptomatic carotid stenosis.Methods: Patients from the BIOVASC study were selected based on the following inclusion criteria: (1) age ≥ 50 years; (2) recent (max).Results: Twenty-five patients met inclusion criteria (72% men, mean age 65 years). MRI-measured plaque volume was greater in men (1,708–1,286 mm3, p = 0.03), patients who qualified with stroke (1,856–1,440 mm3, p = 0.05), and non-statin users (1,325–1,797 mm3, p = 0.03). SUVmax was associated with MRI-measured plaque lipid-rich necrotic core (LRNC) in the corresponding axial slice (rs = 0.64, p < 0.001) and was inversely associated with whole-plaque fibrous cap thickness (rs = −0.4, p = 0.02) and calcium volume (rs = −0.4, p = 0.03).Conclusion: This study demonstrated novel correlations of non-invasive imaging biomarkers of inflammation-related plaque metabolism with morphological MRI markers of plaque instability. If replicated, our findings may support the application of combined MRI and PET to detect vulnerable plaque in future clinical practise and randomised trials.

Muscle activities of the elbow flexors, especially the brachialis muscle (BR), have been measured with intramuscular electromyography (EMG) using the fine-wire electrodes. It remains unclear whether BR activity can be assessed using surface EMG. The purpose of this study was to compare the EMG patterns of the BR activity recorded during elbow flexion using surface and fine-wire electrodes and to determine whether surface EMG can accurately measure the BR activity. Six healthy men were asked to perform two tasks—a maximum isometric voluntary contractions (MVICs) task and an isotonic elbow-flexion task without lifting any weight. The surface and intramuscular EMG were simultaneously recorded from the BR and the long and short heads of the biceps brachii muscle (BBLH and BBSH, respectively). The locations of the muscles were identified and marked under ultrasonographic guidance. The peak cross-correlation coefficients between the EMG signals during the MVICs task were calculated. For the isotonic elbow-flexion task, the EMG patterns for activities of each muscle were compared between the surface and the fine-wire electrodes. All cross-correlation coefficients between the surface EMG signals from the muscles were lower than 0.3. Furthermore, the EMG patterns of the BR activity were not significantly different between the surface and the fine-wire electrodes. The BR has different EMG pattern from the BBLH and the BBSH. The BR activity, conventionally measured with intramuscular EMG, can be accurately accessed with surface EMG during elbow flexion performed without lifting any weight, independent from the BBLH and BBSH activities.

Unlike most neuronal nicotinic acetylcholine receptor (nAChR) subunits, α7, α9, and α10 subunits are able to form functional homo- or heteromeric receptors without any β subunits. While the α7 subtype is widely distributed in the mammalian brain and several peripheral tissues, α9 and α9α10 nAChRs are mainly found in the cochlea and immune cells. α-Conotoxins that specifically block the α9α10 receptor showed anti-nociceptive and anti-hyperalgesic effects in animal models. Hence, this subtype is considered a drug target for analgesics. In contrast to the α9α10-selective α-conotoxins, the three-finger toxin α-bungarotoxin inhibits muscle-type and α7 nAChRs in addition to α9α10 nAChRs. However, the selectivity of α-neurotoxins at the α9α10 subtype was less intensively investigated. Here, we compared the potencies of α-conotoxins and α-neurotoxins at the human α9α10 nAChR by two-electrode voltage clamp analysis upon expression in Xenopus oocytes. In addition, we analyzed effects of several α9α10-selective α-conotoxins on mouse granulocytes from bone marrow to identify possible physiological functions of the α9α10 nAChR subtype in these cells. The α-conotoxin-induced IL-10 release was measured upon LPS-stimulation. We found that α-conotoxins RgIA, PeIA, and Vc1.1 enhance the IL-10 expression in granulocytes which might explain the known anti-inflammatory and associated analgesic activities of α9α10-selective α-conotoxins. Furthermore, we show that two long-chain α-neurotoxins from the cobra Naja melanoleuca venom that were earlier shown to bind to muscle-type and α7 nAChRs, also inhibit the α9α10 subtype at nanomolar concentrations with one of them showing a significantly slower dissociation from this receptor than α-bungarotoxin.

Introduction: Laparoscopic surgery for Upper Urinary Tract Urothelial Cell Carcinoma (UTUC) is still debated for its possible seeding risk and thus consequent oncological recurrences, especially for atypical ones. The aim of the study is to compare recurrence and survival after Laparoscopic vs. Open Radical Nephroureterectomy (RNU) for Upper Urinary Tract Urothelial Cancer (UTUC).Method: A retrospective evaluation of UTUC consecutive surgeries from 2008 to 2019 was conducted, including pT ≥ 2, High Grade UTUC who underwent RNU with bladder cuff excision without concomitant lymphadenectomy in three urological tertiary centers. Statistical analyses compared recurrence and cancer specific survival, based on surgical approach, while logistic multivariate analyses and Kaplan Meyer survival curve analyzed possible risk factors for recurrence and survival.Results: One hundred seven cases of RNU, 47 (43.9%) laparoscopic and 60 (56.1%) open, were included in this report. Preoperative characteristics were comparable between groups. However, tumor stage was higher in the Open arm [T3–T4 in 44 (73.3%) vs. 20 (43.4%) in Laparoscopic]. Mean follow-up was 91.6 months in laparoscopy RNU vs. 93.5 months in open RNU. Recurrence rate (RR) was comparable between groups (p = 0.594), and so was the site, although 3 (6.3%) peritoneal recurrences were found only in laparoscopic group (p = 0.057). At multivariate logistic regression, tumor stage and surgical approach were independent predictors of recurrence (p < 0.05), while only tumor stage was predictor of cancer specific death (p = 0.029).Conclusion: Surgical approach has no impact on recurrence site, overall survival, and RR. Still, according to our data peritoneal carcinomatosis was present only in laparoscopic arm, despite how it didn't reach statistical significance.

The sophistication of artificial intelligence (AI) technologies has significantly advanced in the past decade. However, the observed unpredictability and variability of AI behavior in noisy signals is still underexplored and represents a challenge when trying to generalize AI behavior to real-life environments, especially for people with a speech disorder, who already experience reduced speech intelligibility. In the context of developing assistive technology for people with Parkinson's disease using automatic speech recognition (ASR), this pilot study reports on the performance of Google Cloud speech-to-text technology with dysarthric and healthy speech in the presence of multi-talker babble noise at different intensity levels. Despite sensitivities and shortcomings, it is possible to control the performance of these systems with current tools in order to measure speech intelligibility in real-life conditions.

While electroencephalogram (EEG) burst-suppression is often induced therapeutically using sedatives in the intensive care unit (ICU), there is hitherto no evidence with respect to its association to outcome in moderate-to-severe neurological patients. We examined the relationship between sedation-induced burst-suppression (SIBS) and outcome at hospital discharge and at 6-month follow up in patients surviving moderate-to-severe traumatic brain injury (TBI). For each of 32 patients recovering from coma after moderate-to-severe TBI, we measured the EEG burst suppression ratio (BSR) during periods of low responsiveness as assessed with the Glasgow Coma Scale (GCS). The maximum BSR was then used to predict the Glasgow Outcome Scale extended (GOSe) at discharge and at 6 months post-injury. A multi-model inference approach was used to assess the combination of predictors that best fit the outcome data. We found that BSR was positively associated with outcomes at 6 months (P = 0.022) but did not predict outcomes at discharge. A mediation analysis found no evidence that BSR mediates the effects of barbiturates or propofol on outcomes. Our results provide initial observational evidence that burst suppression may be neuroprotective in acute patients with TBI etiologies. SIBS may thus be useful in the ICU as a prognostic biomarker.

Post-implantation localization of deep brain stimulation (DBS) lead based on a magnetic resonance (MR) image is widely used. Existing localization methods use artifact center method or template registration method, which may lead to a considerable deviation of > 2 mm, and result in severe side effects or even surgical failure. Accurate measurement of lead position can instantly inform surgeons of the imprecise implantation. This study aimed to identify the influencing factors in DBS lead post-implantation localization approach, analyze their influence, and describe a localization approach that uses the individual template method to reduce the deviation. We verified that reconstructing direction should be parallel or perpendicular to lead direction, instead of the magnetic field. Besides, we used simplified relationship between magnetic field angle and deviation error to correct the localization results. The mean localization error can be reduced after correction and favors the feasibility of direct localization of DBS lead using MR images. We also discussed influence of in vivo noise on localization frequency and the possibility of using only MR images to localize the contacts.

Introduction: The best way to titrate the positive end-expiratory pressure (PEEP) in patients suffering from acute respiratory distress syndrome is still matter of debate. Electrical impedance tomography (EIT) is a non-invasive technique that could guide PEEP setting based on an optimized ventilation homogeneity.Methods: For this study, we enrolled the patients with 2019 coronavirus disease (COVID-19)-related acute respiratory distress syndrome (ARDS), who required mechanical ventilation and were admitted to the ICU in March 2021. Patients were monitored by an esophageal catheter and a 32-electrode EIT device. Within 48 h after the start of mechanical ventilation, different levels of PEEP were applied based upon PEEP/FiO2 tables, positive end-expiratory transpulmonary (PL)/ FiO2 table, and EIT. Respiratory mechanics variables were recorded.Results: Seventeen patients were enrolled. PEEP values derived from EIT (PEEPEIT) were different from those based upon other techniques and has poor in-between agreement. The PEEPEIT was associated with lower plateau pressure, mechanical power, transpulmonary pressures, and with a higher static compliance (Crs) and homogeneity of ventilation.Conclusion: Personalized PEEP setting derived from EIT may help to achieve a more homogenous distribution of ventilation. Whether this approach may translate in outcome improvement remains to be investigated.

Cystic fibrosis (CF), the most common inherited disease in Caucasians, is caused by mutations in CFTR, the most frequent of which is F508del. F508del causes ER retention and degradation of the mutant CFTR protein, but also defective channel gating and decreased half-life at the plasma membrane. Despite the recent successes with small molecule CFTR modulator drugs, the folding-corrector/gating-potentiator drug combinations approved for CF individuals carrying F508del-CFTR have sometimes produced severe side effects. Previously, we showed that a prolonged, 15-days treatment of polarized bronchial epithelial monolayers with the VX-809+VX-770 combination resulted in epithelial dedifferentiation effects that we found were caused specifically by VX-809. Moreover, prolonged VX-770 exposure also led to the destabilization of VX-809-rescued F508del-CFTR. Notably, co-treatment with the physiological factor HGF prevented VX-809-mediated epithelial differentiation and reverted the destabilizing effect of VX-770 on VX-809-rescued CFTR. Here, we show that prolonged treatment with VX-661, a second-generation corrector developed based on VX-809 structure, does not perturb epithelial integrity of polarized bronchial epithelial monolayers. Yet, its efficacy is still affected by co-exposure to VX-770, the potentiator present in all VX-661-containing combination therapies approved in the United States and Europe for treatment of F508del-CFTR carriers. Importantly, we found that co-treatment with HGF still ameliorated the impact of VX-770 in F508del-CFTR functional rescue by VX-661, without increasing cell proliferation (Ki-67) or altering the overall expression of epithelial markers (ZO-1, E-cadherin, CK8, CK18). Our findings highlight the importance of evaluating the cellular effects of prolonged exposure to CFTR modulators and suggest that the benefits of adding HGF to current combination therapies should be further investigated. This work was supported by the Grant PTDC/BIA-CEL/28408/2017 (to PJ and PM) and Center Grant UID/MULTI/04046/2019 to BioISI, both from the Portuguese Fundação para a Ciência e a Tecnologia. info:eu-repo/semantics/publishedVersion

Gram-positive anaerobic cocci (GPAC) are a commensal part of human flora but are also opportunistic pathogens. This is possibly the first study to report a case of Peptoniphilus harei bacteremia in an abdominal aortic aneurysm (AAA) patient. Matrix-assisted laser desorption ionization time-of-flight mass spectrometry (MALDI-TOF MS) failed to identify the isolate and molecular analysis confirmed it as P. harei. A comprehensive literature review revealed that P. harei is an emergent pathogen. This study serves as a reminder for practicing clinicians to include anaerobic blood cultures as part of their blood culture procedures; this is particularly important situations with a high level of suspicion of infection factors in some noninfectious diseases, as mentioned in this publication. Clinical microbiologists should be aware that the pathogenic potential of GPAC can be greatly underestimated leading to incorrect diagnosis on using only one method for pathogen identification. Upgradation and correction of the MALDI-TOF MS databases is recommended to provide reliable and rapid identification of GPAC at species level in medical diagnostic microbiology laboratories.

Purpose: We investigated the persistence of the vaccine-induced immunoglobulin G (IgG) antibodies against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) among healthcare workers (HCWs) in Odisha who received a complete dose of either Covaxin or Covishield vaccine.Methods: This 24-week longitudinal cohort study was conducted from January to July 2021 with participants from 6 healthcare and research facilities of Odisha to understand the dynamicity of the vaccine-induced IgG antibodies against SARS-CoV-2 after the complete dose of vaccines.Results: Serum samples were collected from 614 participants during each follow-up and were tested in two chemiluminescent microparticle immunoassay (CLIA)-based platforms to detect SARS-CoV-2 antibodies both qualitatively and quantitatively. Among these participants, 308 (50.2%) participants were Covishield recipients and the rest 306 (49.8%) participants took Covaxin. A total of 81 breakthrough cases were recorded and the rest 533 HCWs without any history of postvaccination infection showed significant antibody waning either from T3 (Covaxin recipient) or T4 (Covishield recipient). The production of vaccine-induced IgG antibodies is significantly higher (p < 0.001) in Covishield compared with Covaxin. Covishield recipients produced higher median anti-S IgG titer than Covaxin. No statistically significant differences in antibody titers were observed based on age, gender, comorbidities, and blood groups.Conclusion: This 6-month follow-up study documents a 2-fold and 4-fold decrease in spike antibody titer among Covishield and Covaxin recipients, respectively. The clinical implications of antibody waning after vaccination are not well understood. It also highlights the need for further data to understand the long-term persistence of vaccine-induced antibody and threshold antibody titer required for protection against reinfection.

Cardiolipin is a tetra-acylated di-phosphatidylglycerol lipid enriched in the matrix-facing (inner) leaflet of the mitochondrial inner membrane. Cardiolipin plays an important role in regulating mitochondria function and dynamics. Yet, the mechanisms connecting cardiolipin distribution and mitochondrial protein function remain indirect. In our previous work, we established an in vitro system reconstituting mitochondrial inner membrane fusion mediated by Opa1. We found that the long form of Opa1 (l-Opa1) works together with the proteolytically processed short form (s-Opa1) to mediate fast and efficient membrane fusion. Here, we extend our reconstitution system to generate supported lipid bilayers with asymmetric cardiolipin distribution. Using this system, we find the presence of cardiolipin on the inter-membrane space-facing (outer) leaflet is important for membrane tethering and fusion. We discuss how the presence of cardiolipin in this leaflet may influence protein and membrane properties, and future applications for this approach.

Dairy products can act as a dietary source of lithium (Li), and a recent study in university-aged males demonstrated that Greek yogurt (GY) supplementation augmented gains in fat free mass, strength and bone formation after 12 weeks of resistance exercise training compared to carbohydrate (CHO) pudding supplementation. Here, we performed secondary analyses to explore whether GY would alter serum Li levels and whether changes in serum Li would associate with changes in body composition, strength, and bone turnover markers. Results show that the GY group maintained serum Li levels after exercise training, whereas the CHO group did not. Maintaining/elevating serum Li levels was also associated with greater gains in strength and reductions in bone resorption. However, controlling for other dietary factors in GY such as protein and calcium weakened these associations. Thus, future studies should assess the causative role, if any, of dietary Li alone on strength and bone resorption in humans.

Clinical and basic research suggests that exercise is a safe behavioral intervention and is effective for improving cognitive function in cerebrovascular diseases, including subcortical ischemic vascular dementia (SIVD). However, most of the basic research uses young animals to assess the effects of exercise, although SIVD is an age-related disease. In this study, therefore, we used middle-aged mice to examine how treadmill exercise changes the cognitive function of SIVD mice. As a mouse model of SIVD, prolonged cerebral hypoperfusion was induced in 8-month-old male C57BL/6J mice by bilateral common carotid artery stenosis. A week later, the mice were randomly divided into two groups: a group that received 6-week treadmill exercise and a sedentary group for observation. After subjecting the mice to multiple behavioral tests (Y-maze, novel object recognition, and Morris water maze tests), the treadmill exercise training was shown to only be effective in ameliorating cognitive decline in the Y-maze test. We previously demonstrated that the same regimen of treadmill exercise was effective in young hypoperfused-SIVD mice for all three cognitive tests. Therefore, our study may indicate that treadmill exercise during cerebral hypoperfusion has only limited effects on cognitive function in aging populations.

G-protein signaling pathways are central in the regulation of cardiac function in physiological and pathophysiological conditions. Their functional analysis through optogenetic techniques with selective expression of opsin proteins and activation by specific wavelengths allows high spatial and temporal precision. Here, we present the application of long wavelength-sensitive cone opsin (LWO) in cardiomyocytes for activation of the Gi signaling pathway by red light. Murine embryonic stem (ES) cells expressing LWO were generated and differentiated into beating cardiomyocytes in embryoid bodies (EBs). Illumination with red light (625 nm) led to an instantaneous decrease up to complete inhibition (84–99% effectivity) of spontaneous beating, but had no effect on control EBs. By using increasing light intensities with 10 s pulses, we determined a half maximal effective light intensity of 2.4 μW/mm2 and a maximum effect at 100 μW/mm2. Pre-incubation of LWO EBs with pertussis toxin completely inhibited the light effect proving the specificity for Gi signaling. Frequency reduction was mainly due to the activation of GIRK channels because the specific channel blocker tertiapin reduced the light effect by ~80%. Compared with pharmacological stimulation of M2 receptors with carbachol with slow kinetics (>30 s), illumination of LWO had an identical efficacy, but much faster kinetics (i signaling cascade in cardiomyocytes with red light, providing high temporal precision.

Vesicular stomatitis virus (VSV) causes a disease in susceptible livestock that is clinically indistinguishable from foot-and-mouth disease. Rapid testing is therefore critical to identify VSV and rule out FMD. We previously developed and validated a multiplex real-time reverse transcription polymerase chain reaction assay (mRRT-PCR) for detection of both VS New Jersey virus (VSNJV) and VS Indiana virus (VSIV). However, it was subsequently apparent that this assay failed to detect some VSNJV isolates in Mexico, especially in genetic group II, lineage 2.1. In order to enhance the sensitivity of the mRRT-PCR for VSNJV, parts of the assay were redesigned and revalidated using new and improved PCR chemistries. The redesign markedly improved the assay by increasing the VSNJV detection sensitivity of lineage 2.1 and thereby allowing detection of all VSNJV clades. The new assay showed an increased capability to detect VSNJV. Specifically, the new mRRT-PCR detected VSNJV in 100% (87/87) of samples from Mexico in 2006-2007 compared to 74% for the previous mRRT-PCR. Furthermore, the analytical sensitivity of the new mRRT-PCR was enhanced for VSNJV. Importantly, the modified assay had the same sensitivity and specificity for VSIV as the previously published assay. Our results highlight the challenges the large genetic variability of VSV pose for virus detection by mRRT-PCR and show the importance of frequent re-evaluation and validation of diagnostic assays for VSV to ensure high sensitivity and specificity.

Introduction: Despite the advantages of umbilical cord blood culture (UCBC) use for diagnosis of early onset sepsis (EOS), contamination rates have deterred neonatologists from its widespread use. We aimed to implement UCBC collection in a level III neonatal intensive care unit (NICU) and apply quality improvement (QI) methods to reduce contamination in the diagnosis of early onset sepsis.Methods: Single-center implementation study utilizing quality improvement methodology to achieve 0% contamination rate in UCBC samples using the Plan-Do-Study-Act (PDSA) model for improvement. UCBC was obtained in conjunction with peripheral blood cultures (PBC) in neonates admitted to the NICU due to maternal chorioamnionitis. Maternal and neonatal characteristics between clinical sepsis and asymptomatic groups were compared. Process, outcome, and balancing measures were monitored.Results: Eighty-two UCBC samples were collected in addition to peripheral blood culture from neonates admitted due to maternal chorioamnionitis. Ten (12%) neonates had a diagnosis of clinical sepsis. All PBCs were negative and 5 UCBCs were positive in the study period. After 2 PDSA cycles, there was special cause variation with improvement in the percent of contaminated samples from 7.3 to 0%. There was no change in antibiotic duration among asymptomatic neonates.Conclusions: Implementation of UCBC for the diagnosis of EOS in term infants is feasible and contamination can be minimized with the implementation of a core team of trained providers and a proper sterile technique without increasing antibiotic duration.