Mercury Concentrations in Two Populations of the most Endangered Dolphin (Pontoporia blainvillei) from the Southwestern Atlantic Ocean.

Mercury contamination has been aggravated by emerging environmental issues, such as climate change. Top predators present concerning Hg concentrations once this metal bioaccumulates and biomagnifies. This study evaluated total mercury (THg) concentrations in tissues of 43 franciscanas (Pontoporia blainvillei) from two populations: the Franciscana Management Area (FMA) IIb and FMA IIIa. Animals from FMA IIIa showed mean concentration 5-times and 2.5-times higher in the liver and kidney (4.73 ± 6.84 and 0.52 ± 0.51 µg.g-1, w.w., respectively) than individuals from FMA IIb (0.89 ± 1.04 and 0.22 ± 0.15 µg.g-1, w.w., respectively). This might be due to: (I) individuals sampled from FMA IIIa being larger and older, and/or (II) the area near FMA IIIa presents environmental features leading to higher THg availability. Coastal contamination can affect franciscanas' health and population maintenance at different levels depending on their life history and, therefore, it should be considered to guide specific conservation actions.

"Catheter replacement in catheter-associated urinary tract infection: current state of evidence ".

PURPOSE: Catheter associated urinary tract infection (CAUTI) is the most common healthcare associated infection. A significant knowledge gap exists regarding the necessity of catheter replacement as part of CAUTI treatment. Current guidelines recommend replacement for faster recovery and to prevent recurrences, but adherence is low. In this systematic review, we aimed to assess the available evidence regarding catheter replacement for CAUTI. MATERIALS AND METHODS: Eligible studies investigated the effect of catheter replacement in CAUTI on clinical outcomes and/or recurrence rates, irrespective of catheter type or setting. We searched electronic literature databases from inception to October 15th, 2023. Information was extracted regarding setting, eligibility criteria, definition of CAUTI, timing of replacement, and outcomes. RESULTS: Of the 257 identified studies, four were considered relevant and included. Two were randomized controlled trials (RCT) and two were observational studies. One RCT showed higher rates of clinical recovery and lower recurrence rates in the replacement group, while results of the other RCT favoured retainment, with a lower recurrence rate in the retainment group, although longer antimicrobial treatment in this group. Two observational studies were inconclusive. CONCLUSIONS: Current guidelines rely heavily on recommendations from a single study, emphasizing the need for further research. The burden of catheter replacement, including patient discomfort and resource impact, warrants careful consideration. A randomized trial is essential to provide more evidence on the effect of catheter replacement on clinical outcomes including CAUTI recurrence.

Cognitive and physical fatigue: the experience and consequences of 'brain fog' after Spontaneous Coronary Artery Dissection (SCAD), a qualitative study.

AIMS: Brain fog and fatigue are common issues after acute coronary syndrome. However, little is known about the nature and impact of these experiences in spontaneous coronary artery dissection (SCAD) survivors. The aims of this study were to understand the experiences of brain fog and the coping strategies used after SCAD. METHODS AND RESULTS: Participants were recruited from the Victor Chang Cardiac Research Institute Genetics Study database and were considered eligible if their event occurred within 12-months. Seven semi-structured online focus groups were conducted between December to January 2021-2022, with this study reporting findings related to brain fog and fatigue. Interviews were transcribed and thematically analysed using an iterative approach. Participants (N=30) were a mean age of 52.2 ((9.5) and mostly female (n=27, 90%). The overarching theme of brain fog after SCAD included four main themes: how brain fog is experienced, perceived causes, impacts, and how people cope. Experiences included memory lapses, difficulty concentrating and impaired judgement, and perceived causes included medication, fatigue and tiredness, and menopause and hormonal changes. Impacts of brain fog included rumination, changes in self-perception, disruption to hobbies/pastimes, and limitations at work. Coping mechanisms included setting reminders and expectations, being one's own advocate, lifestyle and self-determined medication adjustments, and support from peers. CONCLUSION: Brain fog is experienced by SCAD survivors and the impacts are varied and numerous, including capacity to work. SCAD survivors reported difficulty understanding causes and found their own path to coping. Recommendations for clinicians are provided.

Comparison of the Effects of Hydralazine and Labetalol on Intracranial Pressure When Used for Blood Pressure Control in Patients With Intracranial Hemorrhage: A Retrospective Study.

Background Recommendations on optimal agents to manage blood pressure (BP) in patients with an intracranial hemorrhage (ICH) are lacking. A case series suggests that hydralazine can cause intracranial pressure (ICP) elevation in an ICH. The purpose of this study was to compare the effects of intravenous (IV) hydralazine to IV labetalol on ICP in patients with ICH. Materials and methods A retrospective chart review from September 2015 to September 2021 on adults admitted to a level I trauma center with ICH, requiring an external ventricular drain or ICP monitor, and pharmacologic intervention with IV hydralazine or IV labetalol. ICP measurements and clinical interventions 0-80 minutes prior to and after medication administration were compared. Data points were excluded if multiple antihypertensive agents were administered. Results A total of 27 patients were included (three received only hydralazine, 13 only labetalol, and 11 both). Twenty-seven doses of hydralazine and 115 doses of labetalol were compared. There was no significant difference in mean ICP 0-80 minutes following hydralazine and labetalol administration (p = 0.283). Of the hydralazine doses, 29.6% received intervention for elevated ICP, while 25.2% of labetalol doses received intervention (p = 0.633). Hydralazine patients received m = 0.56 interventions for ICP, and labetalol patients received m = 0.36 interventions (p = 0.223). Of the patients that required intervention for ICP management, hydralazine patients required m = 1.88 interventions, while labetalol patients required m = 1.41 interventions (p = 0.115).  Conclusion There was no significant difference in mean ICP at 0-80 minutes following administration of hydralazine or labetalol. There was also no significant difference in interventions required for elevated ICP management between groups. Larger studies are needed to confirm these findings.

TP53 somatic evolution in cervical liquid-based cytology and blood from individuals with and without ovarian cancer and BRCA1 or BRCA2 germline mutations.

Somatic TP53 mutations are prevalent in normal tissue but little is known about their association with cancer risk. Cervical liquid-based cytology (LBC), commonly known as Pap test, provides an accessible gynecological sample to test the value of TP53 somatic mutations as a biomarker for high-grade serous ovarian cancer (HGSC), a cancer type mostly driven by TP53 mutations. We used ultra-deep duplex sequencing to analyze TP53 mutations in LBC and blood samples from 70 individuals (30 with and 40 without HGSC) undergoing gynecologic surgery, 30 carrying BRCA1 or BRCA2 germline pathogenic variants (BRCApv). Only 30% of the tumor mutations were found in LBC samples. However, TP53 pathogenic mutations were identified in nearly all LBC and blood samples, with only 5.4% of mutations in LBC (20/368) also found in the corresponding blood sample. TP53 mutations were more abundant in LBC than in blood and increased with age in both sample types. BRCApv carriers with HGSC had more TP53 clonal expansions in LBC than BRCApv carriers without cancer. Our results show that, while not useful for direct cancer detection, LBC samples capture TP53 mutation burden in the gynecological tract, presenting potential value for cancer risk assessment in individuals at higher hereditary risk for ovarian cancer.

Clinical Implementation of DIGEST as an Evidence-Based Practice Tool for Videofluoroscopy in Oncology: A Six-Year Single Institution Implementation Evaluation.

Clinical implementation of evidence-based practice (EBP) tools is a healthcare priority. The Dynamic Grade of Swallowing Toxicity (DIGEST) is an EBP tool developed in 2016 for videofluoroscopy in head and neck (H&N) oncology with clinical implementation as a goal. We sought to examine: (1) feasibility of clinical implementation of DIGEST in a national comprehensive cancer center, and (2) fidelity of DIGEST adoption in real-world practice. A retrospective implementation evaluation was conducted in accordance with the STARI framework. Electronic health record (EHR) databases were queried for all consecutive modified barium swallow (MBS) studies conducted at MD Anderson Cancer Center from 2016 to 2021. Implementation outcomes included: feasibility as measured by DIGEST reporting in EHR (as a marker of clinical use) and fidelity as measured by accuracy of DIGEST reporting relative to the decision-tree logic (penetration-aspiration scale [PAS], residue, and Safety [S] and Efficiency [E] grades). Contextual factors examined included year, setting, cancer type, MBS indication, and provider. 13,055 MBS were conducted by 29 providers in 7,842 unique patients across the lifespan in diverse oncology populations (69% M; age 1-96 years; 58% H&N cancer; 10% inpatient, 90% outpatient). DIGEST was reported in 12,137/13,088 exams over the 6-year implementation period representing 93% (95% CI: 93-94%) adoption in all exams and 99% (95% CI: 98-99%) of exams excluding the total laryngectomy population (n = 730). DIGEST reporting varied modestly by year, cancer type, and setting/provider (> 91% in all subgroups, p < 0.001). Accuracy of DIGEST reporting was high for overall DIGEST (incorrect SE profile 1.6%, 200/12,137), DIGEST-safety (incorrect PAS 0.4% 51/12,137) and DIGEST-efficiency (incorrect residue 1.2%, 148/12,137). Clinical implementation of DIGEST was feasible with high fidelity in a busy oncology practice across a large number of providers. Adoption of the tool across the lifespan in diverse cancer diagnoses may motivate validation beyond H&N oncology.

The extracellular serine protease from Staphylococcus epidermidis elicits a type 2-biased immune response in atopic dermatitis patients.

Background: Atopic dermatitis (AD) is a chronic, relapsing inflammatory skin disease with skin barrier defects and a misdirected type 2 immune response against harmless antigens. The skin microbiome in AD is characterized by a reduction in microbial diversity with a dominance of staphylococci, including Staphylococcus epidermidis (S. epidermidis). Objective: To assess whether S. epidermidis antigens play a role in AD, we screened for candidate allergens and studied the T cell and humoral immune response against the extracellular serine protease (Esp). Methods: To identify candidate allergens, we analyzed the binding of human serum IgG4, as a surrogate of IgE, to S. epidermidis extracellular proteins using 2-dimensional immunoblotting and mass spectrometry. We then measured serum IgE and IgG1 binding to recombinant Esp by ELISA in healthy and AD individuals. We also stimulated T cells from AD patients and control subjects with Esp and measured the secreted cytokines. Finally, we analyzed the proteolytic activity of Esp against IL-33 and determined the cleavage sites by mass spectrometry. Results: We identified Esp as the dominant candidate allergen of S. epidermidis. Esp-specific IgE was present in human serum; AD patients had higher concentrations than controls. T cells reacting to Esp were detectable in both AD patients and healthy controls. The T cell response in healthy adults was characterized by IL-17, IL-22, IFN-γ, and IL-10, whereas the AD patients' T cells lacked IL-17 production and released only low amounts of IL-22, IFN-γ, and IL-10. In contrast, Th2 cytokine release was higher in T cells from AD patients than from healthy controls. Mature Esp cleaved and activated the alarmin IL-33. Conclusion: The extracellular serine protease Esp of S. epidermidis can activate IL-33. As an antigen, Esp elicits a type 2-biased antibody and T cell response in AD patients. This suggests that S. epidermidis can aggravate AD through the allergenic properties of Esp.

Pharmacotherapy for older people with obesity.

Rates of obesity continue to rise, including in older adults. Use of medication for obesity in the elderly has been considered controversial, due to concerns around potential progression of age-related sarcopenia and a general lack of evidence for its use in this age group. Within this review, we describe the general considerations when prescribing obesity pharmacotherapy for older adults living with obesity. We evaluate in detail the anti-obesity medications currently licenced in Europe, with emphasis on the available efficacy, safety and cardiovascular outcome data gathered from study of older people. Finally, we discuss future directions and avenues of research.

Genetic relationships between behavioral traits and feed efficiency traits in lactating Holstein cows.

The evaluation of dairy cow feed efficiency using residual feed intake accounts for known energy sinks. However, behavioral traits may also contribute to the variation in feed efficiency. Our objective was to estimate the heritability and repeatability of behavioral traits and their genetic correlations with feed efficiency and its components in lactating Holstein cows. The first data set consisted of 36,075 daily rumination and lying time records collected using a SMARTBOW ear tag accelerometer (Zoetis, Parsippany, NJ) and 6,371 weekly feed efficiency records of 728 cows from the University of Wisconsin-Madison. The second data set consisted of 59,155 daily activity records, measured as number of steps, recorded by pedometers (AfiAct; S.A.E. Afikim, Kibbutz Afikim, Israel), and 8,626 weekly feed efficiency records of 635 cows from the University of Florida. Feed efficiency and its components included dry matter intake, change in body weight, metabolic body weight, secreted milk energy, and residual feed intake. The statistical models included the fixed effect of cohort, lactation number, and days in milk, and the random effects of animal and permanent environment. Heritability estimates for behavioral traits using daily records were 0.19 ± 0.06 for rumination and activity, and 0.37 ± 0.07 for lying time. Repeatability estimates for behavioral traits using daily data ranged from 0.56 ± 0.02 for activity to 0.62 ± 0.01 for lying time. Both heritability and repeatability estimates were larger when weekly records instead of daily records were used. Rumination and activity had positive genetic correlations with residual feed intake (0.40 ± 0.19 and 0.31 ± 0.22, respectively) while lying time had a negative genetic correlation with this residual feed intake (-0.27 ± 0.11). These results indicate that more efficient cows tend to spend more time lying and less time active. Additionally, less efficient cows tend to eat more and therefore also tend to ruminate longer. Overall, sensor-based behavioral traits are heritable and genetically correlated with feed efficiency and its components and, therefore, they could be used as indicators to identify feed efficient cows within the herd.

Healthy tissue metabolism assessed by [18F]FDG PET/CT as a marker of prognosis and adverse events in advanced Hodgkin lymphoma patients.

The aim of the study was to assess healthy tissue metabolism (HTM) using 2-deoxy-2-[18F]fluoro-D-glucose ([18F]FDG) positron emission tomography/computed tomography (PET/CT) during chemotherapy in Hodgkin lymphoma (HL) and the association of HTM with baseline metabolic tumour volume (MTV), haematological parameters, adverse events (AEs), early response and progression-free survival (PFS). We retrospectively identified 200 patients with advanced HL from the RATHL trial with [18F]FDG-PET/CT before (PET0) and following 2 cycles of chemotherapy (PET2). [18F]FDG-uptake was measured in bone marrow (BM), spleen, liver and mediastinal blood pool (MBP). Deauville score (DS) 1-3 was used to classify responders and DS 4-5, non-responders. [18F]FDG-uptake decreased significantly in BM and spleen and increased in liver and MBP at PET2 (all p < 0.0001), but was not associated with MTV. Higher BM uptake at PET0 was associated with lower baseline haemoglobin and higher absolute neutrophil counts, platelets, and white blood cells. High BM, spleen, and liver uptake at PET0 was associated with neutropenia after cycles 1-2. BM uptake at PET0 was associated with treatment failure at PET2 and non-responders with higher BM uptake at PET2 had significantly inferior PFS (p = 0.023; hazard ratio = 2.31). Based on these results, we concluded that the change in HTM during chemotherapy was most likely a direct impact of chemotherapy rather than a change in MTV. BM uptake has prognostic value in HL.

Healthcare cost expenditure for robotic versus laparoscopic liver resection: a bottom-up economic evaluation.

BACKGROUND: Minimally invasive liver surgery (MILS) is increasingly performed via the robot-assisted approach but may be associated with increased costs. This study is a post-hoc comparison of healthcare cost expenditure for robotic liver resection (RLR) and laparoscopic liver resection (LLR) in a high-volume center. METHODS: In-hospital and 30-day postoperative healthcare costs were calculated per patient in a retrospective series (October 2015-December 2022). RESULTS: Overall, 298 patients were included (143 RLR and 155 LLR). Benefits of RLR were lower conversion rate (2.8% vs 12.3%, p = 0.002), shorter operating time (167 min vs 198 min, p = 0.044), and less blood loss (50 mL vs 200 mL, p < 0.001). Total per-procedure costs of RLR (€10260) and LLR (€9931) were not significantly different (mean difference €329 [95% bootstrapped confidence interval (BCI) €-1179-€2120]). Lower costs with RLR due to shorter surgical and operating room time were offset by higher disposable instrumentation costs resulting in comparable intraoperative costs (€5559 vs €5247, mean difference €312 [95% BCI €-25-€648]). Postoperative costs were similar for RLR (€4701) and LLR (€4684), mean difference €17 [95% BCI €-1357-€1727]. When also considering purchase and maintenance costs, RLR resulted in higher total per-procedure costs. DISCUSSION: In a high-volume center, RLR can have similar per-procedure cost expenditure as LLR when disregarding capital investment.

Clinical effectiveness and cost-effectiveness of Structured Psychological Support for people with probable personality disorder in mental health services in England: study protocol for a randomised controlled trial.

INTRODUCTION: Evidence-based psychological treatments for people with personality disorder usually involve attending group-based sessions over many months. Low-intensity psychological interventions of less than 6 months duration have been developed, but their clinical effectiveness and cost-effectiveness are unclear. METHODS AND ANALYSIS: This is a multicentre, randomised, parallel-group, researcher-masked, superiority trial. Study participants will be aged 18 and over, have probable personality disorder and be treated by mental health staff in seven centres in England. We will exclude people who are: unwilling or unable to provide written informed consent, have a coexisting organic or psychotic mental disorder, or are already receiving psychological treatment for personality disorder or on a waiting list for such treatment. In the intervention group, participants will be offered up to 10 individual sessions of Structured Psychological Support. In the control group, participants will be offered treatment as usual plus a single session of personalised crisis planning. The primary outcome is social functioning measured over 12 months using total score on the Work and Social Adjustment Scale (WSAS). Secondary outcomes include mental health, suicidal behaviour, health-related quality of life, patient-rated global improvement and satisfaction, and resource use and costs. The primary analysis will compare WSAS scores across the 12-month period using a general linear mixed model adjusting for baseline scores, allocation group and study centre on an intention-to-treat basis. In a parallel process evaluation, we will analyse qualitative data from interviews with study participants, clinical staff and researchers to examine mechanisms of impact and contextual factors. ETHICS AND DISSEMINATION: The study complies with the Helsinki Declaration II and is approved by the London-Bromley Research Ethics Committee (IRAS ID 315951). Study findings will be published in an open access peer-reviewed journal; and disseminated at national and international conferences. TRIAL REGISTRATION NUMBER: ISRCTN13918289.

Cost-Effectiveness of Unselected Multigene Germline and Somatic Genetic Testing for Epithelial Ovarian Cancer.

BACKGROUND: Parallel panel germline and somatic genetic testing of all patients with ovarian cancer (OC) can identify more pathogenic variants (PVs) that would benefit from PARP inhibitor (PARPi) therapy, and allow for precision prevention in unaffected relatives with PVs. In this study, we estimate the cost-effectiveness and population impact of parallel panel germline and somatic BRCA testing of all patients with OC incorporating PARPi therapy in the United Kingdom and the United States compared with clinical criteria/family history (FH)-based germline BRCA testing. We also evaluate the cost-effectiveness of multigene panel germline testing alone. METHODS: Microsimulation cost-effectiveness modeling using data from 2,391 (UK: n=1,483; US: n=908) unselected, population-based patients with OC was used to compare lifetime costs and effects of panel germline and somatic BRCA testing of all OC cases (with PARPi therapy) (strategy A) versus clinical criteria/FH-based germline BRCA testing (strategy B). Unaffected relatives with germline BRCA1/BRCA2/RAD51C/RAD51D/BRIP1 PVs identified through cascade testing underwent appropriate OC and breast cancer (BC) risk-reduction interventions. We also compared the cost-effectiveness of multigene panel germline testing alone (without PARPi therapy) versus strategy B. Unaffected relatives with PVs could undergo risk-reducing interventions. Lifetime horizon with payer/societal perspectives, along with probabilistic/one-way sensitivity analyses, are presented. Incremental cost-effectiveness ratio (ICER) and incremental cost per quality-adjusted life year (QALY) gained were compared with £30,000/QALY (UK) and $100,000/QALY (US) thresholds. OC incidence, BC incidence, and prevented deaths were estimated. RESULTS: Compared with clinical criteria/FH-based BRCA testing, BRCA1/BRCA2/RAD51C/RAD51D/BRIP1 germline testing and BRCA1/BRCA2 somatic testing of all patients with OC incorporating PARPi therapy had a UK ICER of £51,175/QALY (payer perspective) and £50,202/QALY (societal perspective) and a US ICER of $175,232/QALY (payer perspective) and $174,667/QALY (societal perspective), above UK/NICE and US cost-effectiveness thresholds in the base case. However, strategy A becomes cost-effective if PARPi costs decrease by 45% to 46% or if overall survival with PARPi reaches a hazard ratio of 0.28. Unselected panel germline testing alone (without PARPi therapy) is cost-effective, with payer-perspective ICERs of £11,291/QALY or $68,808/QALY and societal-perspective ICERs of £6,923/QALY or $65,786/QALY. One year's testing could prevent 209 UK BC/OC cases and 192 deaths, and 560 US BC/OC cases and 460 deaths. CONCLUSIONS: Unselected panel germline and somatic BRCA testing can become cost-effective, with a 45% to 46% reduction in PARPi costs. Regarding germline testing, unselected panel germline testing is highly cost-effective and should replace BRCA testing alone.

'Yeah, this is my donation': An application of psychological ownership in blood donation.

To meet the priority healthcare needs of any population there must be a consistently available blood supply donated by willing donors. Due to this universal need for blood, retaining blood donors remains an ongoing challenge for blood services internationally. Encouraging psychological ownership, or the feeling of ownership one experiences over a possession, provides a potential novel solution to donor retention. This study, based on semi-structured interviews with blood donors, investigates how donors perceive and develop psychological ownership in the context of blood donation. Interviews were conducted in Australia with 20 current blood donors (10 men, 10 women; Mage = 41.95). Through thematic analysis, six themes were identified based primarily on the theoretical framework of psychological ownership. This research offers a novel perspective on donor retention, suggesting that donors' ownership over their individual donation practices, and not the blood service, may contribute to maintaining a stable blood supply.

Extraction of uranyl from spent nuclear fuel wastewater via complexation-a local vibrational mode study.

CONTEXT: The efficient extraction of uranyl from spent nuclear fuel wastewater for subsequent reprocessing and reuse is an essential effort toward minimization of long-lived radioactive waste. N-substituted amides and Schiff base ligands are propitious candidates, where extraction occurs via complexation with the uranyl moiety. In this study, we extensively probed chemical bonding in various uranyl complexes, utilizing the local vibrational modes theory alongside QTAIM and NBO analyses. We focused on (i) the assessment of the equatorial O-U and N-U bonding, including the question of chelation, and (ii) how the strength of the axial U = O bonds of the uranyl moiety changes upon complexation. Our results reveal that the strength of the equatorial uranium-ligand interactions correlates with their covalent character and with charge donation from O and N lone pairs into the vacant uranium orbitals. We also found an inverse relationship between the covalent character of the equatorial ligand bonds and the strength of the axial uranium-oxygen bond. In summary, our study provides valuable data for a strategic modulation of N-substituted amide and Schiff base ligands towards the maximization of uranyl extraction. METHOD: Quantum chemistry calculations were performed under the PBE0 level of theory, paired with the relativistic NESCau Hamiltonian, currently implemented in Cologne2020 (interfaced with Gaussian16). Wave functions were expanded in the cc-pwCVTZ-X2C basis set for uranium and Dunning's cc-pVTZ for the remaining atoms. For the bonding properties, we utilized the package LModeA in the local modes analyses, AIMALL in the QTAIM calculations, and NBO 7.0 for the NBO analyses.

Characterization of Unique Pathological Features of COVID-Associated Coagulopathy: Studies with AC70 hACE2 Transgenic Mice Highly Permissive to SARS-CoV-2 Infection.

COVID-associated coagulopathy seemly plays a key role in post-acute sequelae of SARS- CoV-2 infection. However, the underlying pathophysiological mechanisms are poorly understood, largely due to the lack of suitable animal models that recapitulate key clinical and pathological symptoms. Here, we fully characterized AC70 line of human ACE2 transgenic (AC70 hACE2 Tg) mice for SARS-CoV-2 infection. We noted that this model is highly permissive to SARS-CoV-2 with values of 50% lethal dose and infectious dose as ~ 3 and ~ 0.5 TCID50 of SARS-CoV-2, respectively. Mice infected with 105 TCID50 of SARS-CoV-2 rapidly succumbed to infection with 100% mortality within 5 days. Lung and brain were the prime tissues harboring high viral titers, accompanied by histopathology. However, viral RNA and inflammatory mediators could be detectable in other organs, suggesting the nature of a systemic infection. Lethal challenge of AC70 hACE2 Tg mice caused acute onset of leukopenia, lymphopenia, along with an increased neutrophil-to-lymphocyte ratio (NLR). Importantly, infected animals recapitulated key features of COVID-19-associated coagulopathy. SARS-CoV-2 could induce the release of circulating neutrophil extracellular traps (NETs), along with activated platelet/endothelium marker. Immunohistochemical staining with anti-platelet factor-4 (PF4) antibody revealed profound platelet aggregates especially within blocked veins of the lungs. We showed that acute SARS-CoV-2 infection triggered a hypercoagulable state coexisting with ill-regulated fibrinolysis. Finally, we highlighted the potential role of Annexin A2 (ANXA2) in fibrinolytic failure. ANXA2 is a calcium-dependent phospholipid-binding protein that forms a heterotertrameric complexes localized at the extracellular membranes with two S100A10 small molecules acting as a co-receptor for tissue-plasminogen activator (t-PA), tightly involved in cell surface fibrinolysis. Thus, our results revealing elevated IgG type anti-ANXA2 antibody production, downregulated de novo ANXA2/S100A10 synthesis, and reduced ANXA2/S100A10 association in infected mice, this protein might serve as druggable targets for development of antithrombotic and/or anti-fibrinolytic agents to attenuate pathogenesis of COVID-19.

Association of Cigarette Smoking History With Drug Abuse History and Arterial Carboxyhemoglobin in Trauma Activation Patients: A Retrospective Study.

Introduction The relationship between cigarette smoking and arterial carboxyhemoglobin (CoHb) in trauma activation patients has not been investigated. The aim was to determine if cigarette smoking is associated with drug abuse history and arterial CoHb levels. Methodology This is a retrospective review of level I trauma center activations aged 18-60 during 2018-2020. A medical record audit was performed to assess each patient's cigarette smoking and drug abuse history and admission arterial CoHb level. The CoHb levels and smoking history for each patient were used to construct a receiver operating characteristic curve. Results Of the 742 trauma activations aged 18-60, 737 (99.3%) had a documented cigarette smoking history. Smoking history was positive in 49.7% (366) and negative in 50.3% (371). The positive smoking proportion was greater in patients with a drug abuse history (63.9% (234/366)) than those with a negative history (31.0% (115/371); p<0.0001; odds ratio=4.0). In 717 patients with a CoHb value, the CoHb was higher in smokers (3.9±2.2%) than in non-smokers (0.5±0.4%; p<0.0001; Cohen d=2.2). A CoHb >1.5% was higher in smokers (93.3% (333/357)) than non-smokers (1.7% (6/360); p<0.0001; odds ratio=818.6). The receiver operating characteristic curve for the relationship between CoHb and cigarette smoking history showed an area under the curve of 0.980 (p<0.0001). Using an arterial CoHb level >1.5% to predict a positive smoking history and a CoHb level ≤1.5% to predict a non-smoking history, sensitivity was 93.3% (333/357), specificity was 98.3% (354/360), and accuracy was 95.8% (687/717). Conclusion Cigarette smoking in trauma activations aged 18-60 is associated with drug abuse history and increased arterial CoHb levels on trauma center arrival.

Correction: Psychosocial and lifestyle impacts of spontaneous coronary artery dissection: A quantitative study.

[This corrects the article DOI: 10.1371/journal.pone.0296224.].

Investigation of the pathogen-specific antibody response in periprosthetic joint infection.

PURPOSE: Periprosthetic joint infections (PJIs) are a very demanding complication of arthroplasty. Diagnosis of PJI and pathogen identification pose considerable challenges in clinical practice. We hypothesized that the pathogen-specific immune response to PJI reflects the infection process, provides clinically relevant information on disease course, and has the potential to further optimize antimicrobial therapy. METHODS: We conducted a prospective matched cohort pilot study with 13 patients undergoing two-stage septic revision arthroplasty (PJI patients) between 06/2020 and 06/2021, as well as 11 control patients undergoing one-stage aseptic revision arthroplasty (Non-PJI patients). Pre-, intra- and postoperative serum samples were collected at standardized time points. We developed a custom Luminex®-based quantitative bead-based suspension array (Infection Array; IA), and used it for simultaneous measurement of antibody specificities against 32 pathogens commonly associated with PJI in 267 serum samples. RESULTS: The IA was able to trace the dynamics of the pathogen-specific humoral immune response in all patients against PJI-related pathogens, prominently coagulase-negative staphylococci and streptococci. Pathogen-specific serum antibody titers declined in 62% of PJI patients over the course of treatment, while no changes in antibody titers were observed in 82% of Non-PJI patients during this study. Our serological data strongly suggested that antibody signatures reflect an immune response to microbial invasion. CONCLUSION: Our results provide insights into the pathophysiology of PJI and information on the individual disease courses. The IA is therefore a promising and novel serological tool of high resolution for monitoring the immunoproteomic footprints of infectious pathogens in the course of PJI.

Non-cross-reactive epitopes dominate the humoral immune response to COVID-19 vaccination - kinetics of plasma antibodies, plasmablasts and memory B cells.

Introduction: COVID-19 vaccines are highly effective in inducing protective immunity. While the serum antibody response to COVID-19 vaccination has been studied in depth, our knowledge of the underlying plasmablast and memory B cell (Bmem) responses is still incomplete. Here, we determined the antibody and B cell response to COVID-19 vaccination in a naïve population and contrasted it with the response to a single influenza vaccination in a primed cohort. In addition, we analyzed the antibody and B cell responses against the four endemic human coronaviruses (HCoVs). Methods: Measurement of specific plasma IgG antibodies was combined with functional analyses of antibody-secreting plasmablasts and Bmems. SARS-CoV-2- and HCoV-specific IgG antibodies were quantified with an in-house bead-based multiplexed immunoassay. Results: The antibody and B cell responses to COVID-19 vaccination reflected the kinetics of a prime-boost immunization, characterized by a slow and moderate primary response and a faster and stronger secondary response. In contrast, the influenza vaccinees possessed robust immune memory for the vaccine antigens prior to vaccination, and the recall vaccination moderately boosted antibody production and Bmem responses. Antibody levels and Bmem responses waned several months after the 2nd COVID-19 vaccination, but were restored upon the 3rd vaccination. The COVID-19 vaccine-induced antibodies mainly targeted novel, non-cross-reactive S1 epitopes of the viral spike protein, while cross-reactive S2 epitopes were less immunogenic. Booster vaccination not only strongly enhanced neutralizing antibodies against an original SARS-CoV-2 strain, but also induced neutralizing antibodies against the Omicron BA.2 variant. We observed a 100% plasma antibody prevalence against the S1 subunits of HCoVs, which was not affected by vaccination. Discussion: Overall, by complementing classical serology with a functional evaluation of plasmablasts and memory B cells we provide new insights into the specificity of COVID-19 vaccine-induced antibody and B cell responses.