Corrigendum: Impaired antigen-specific B-cell responses after Influenza vaccination in kidney transplant recipients receiving co-stimulation blockade with Belatacept.

[This corrects the article DOI: 10.3389/fimmu.2022.918887.].

Reimagining general surgery resident selection: Collaborative innovation through design thinking.

Introduction: The process by which surgery residency programs select applicants is complex, opaque, and susceptible to bias. Despite attempts by program directors and educational researchers to address these issues, residents have limited ability to affect change within the process at present. Here, we present the results of a design thinking brainstorm to improve resident selection and propose this technique as a framework for surgical residents to creatively solve problems and generate actionable changes. Methods: Members of the Collaboration of Surgical Education Fellows (CoSEF) used the design thinking framework to brainstorm ways to improve the resident selection process. Members participated in one virtual focus group focused on identifying pain points and developing divergent solutions to those pain points. Pain points and solutions were subsequently organized into themes. Finally, members participated in a second virtual focus group to design prototypes to test the proposed solutions. Results: Sixteen CoSEF members participated in one or both focus groups. Participants identified twelve pain points and 57 potential solutions. Pain points and solutions were grouped into the three themes of transparency, fairness, and applicant experience. Members subsequently developed five prototype ideas that could be rapidly developed and tested to improve resident selection. Conclusions: The design thinking framework can help surgical residents come up with creative ideas to improve pain points within surgical training. Furthermore, this framework can supplement existing quantitative and qualitative methods within surgical education research. Future work will be needed to implement the prototypes devised during our sessions and turn them into complete interventions. Key message: In this paper, we demonstrate the results of a resident-led design thinking brainstorm on improving resident selection in which our team identified twelve pain points in resident selection, ideated 57 solutions, and developed five prototypes for further testing. In addition to sharing our results, we believe design thinking can be a useful framework for creative problem solving within surgical education.

Serum mass spectrometry for treatment monitoring in patients with multiple myeloma receiving ARI0002h CAR T-cells.

Chimeric antigen receptor (CAR) T-cell therapies have increased the patients with relapsed/refractory multiple myeloma (RRMM) in whom standard electrophoretic techniques fail to detect the M-protein. Quantitative immunoprecipitation mass spectrometry (QIP-MS) can accurately measure serum M-protein with high sensitivity, and identify interferences caused by therapeutic monoclonal antibodies. Here, we investigate the outcome of QIP-MS in 33 patients treated with the academic BCMA-directed CAR T-cell ARI0002h (Cesnicabtagene Autoleucel). QIP-MS offered more detailed insights than serum immunofixation (sIFE), identifying glycosylated M-proteins and minor additional peaks. Moreover, the potential interferences owing to daratumumab or tocilizumab treatments were successfully detected. When analysing different assay platforms during patient's monitoring after ARI0002h administration, we observed that QIP-MS showed a high global concordance (78.8%) with sIFE, whereas it was only moderate (55.6%) with bone marrow (BM)-based next-generation flow cytometry (NGF). Furthermore, QIP-MS consistently demonstrated the lowest negativity rate across the different timepoints (27.3% vs. 60.0% in months 1 and 12, respectively). Patients with QIP-MS(+)/BM-based NGF(-) showed a non-significant shorter median progression free survival than those with QIP-MS(-)/BM-based NGF(-). In summary, we show the first experience to our knowledge demonstrating that QIP-MS could be particularly useful as a non-invasive technique when evaluating response after CAR T-cell treatment in MM.

Nontraumatic Pseudoaneurysm of the Deep Palmar Arch in a 10-Month-Old Infant: A Case Report.

CASE: Pseudoaneurysms of the hand are rare among the adult population and even more rare in pediatric patients. We report a case of a 10-month-old boy who presented with a nontraumatic pseudoaneurysm of the deep palmar arch, likely of congenital etiology. Magnetic resonance imaging and angiography identified the growing left hand palmar mass. Surgical excision without the need for vascular reconstruction was performed successfully with no recurrence or complications at 1-year follow-up. CONCLUSION: Surgical excision is an effective treatment for large or symptomatic palmar pseudoaneurysms of likely congenital origin. Vascular reconstruction after excision must be considered on a case-by-case basis to ensure adequate hand perfusion.

Incidence of adult rib fracture injuries and changing hospitalization practice patterns: a 10-year analysis.

PURPOSE: Rib fractures are common after blunt thoracic trauma and can be associated with significant morbidity and mortality. We investigated trends of rib fracture injuries among adults presenting to United States (US) emergency departments, factors related to increased likelihood of hospitalization, and hospitalization practice patterns. METHODS: We queried the National Electronic Injury Surveillance System database between 2012 and 2021 for all patients 18 years of age and older with rib fractures. These data were extrapolated to provide national estimates. Regression analysis was performed to identify trends for injury and risk factors for hospitalization. RESULTS: We identified 32,233 adult patients with rib fractures; this extrapolated to a national estimate of 1,430,270 patients with rib fractures during the 10-year period. Between 2012 and 2021, there was a 52% increase in the incidence rate per 100,000 persons (R2 = 0.94, p < 0.001). Males accounted for 58% of patients with rib fractures, and 50% of patients were 65 years or older. Hospitalization was required in 38% of patients, and the hospitalization rate increased by 96% during the study period (R2 = 0.96, p < 0.001). When comparing hospitals of different sizes, a 20% greater increase in the odds of hospitalization over time was identified among patients presenting to "larger" hospitals compared to "smaller" hospitals. CONCLUSION: The incidence of rib fractures and the associated hospitalization rates are both increasing nationally, with half of cases occurring in patients aged 65 years or older. Our findings emphasize the urgent need to implement evidence-based preventive measures and current management guidelines when managing the increasing caseload of rib fracture injuries.

How I GPT It: Development of Custom Artificial Intelligence (AI) Chatbots for Surgical Education.

Artificial Intelligence (AI) chatbots provide a novel format for individuals to interact with large language models (LLMs). Recently released tools allow nontechnical users to develop chatbots using natural language. Surgical education is an exciting area in which chatbots developed in this manner may be rapidly deployed, though additional work will be required to ensure their accuracy and safety. In this paper, we outline our initial experience with AI chatbot creation in surgical education and offer considerations for future use of this technology.

Expanded Access to Video-Based Laparoscopic Skills Assessments: Ease, Reliability, and Accuracy.

OBJECTIVE: Video-based performance assessments provide essential feedback to surgical residents, but in-person and remote video-based assessment by trained proctors incurs significant cost. We aimed to determine the reliability, accuracy, and difficulty of untrained attending staff surgeon raters completing video-based assessments of a basic laparoscopic skill. Secondarily, we aimed to compare reliability and accuracy between 2 different types of assessment tools. DESIGN: An anonymous survey was distributed electronically to surgical attendings via a national organizational listserv. Survey items included demographics, rating of video-based assessment experience (1 = have never completed video-based assessments, 5 = often complete video-based assessments), and rating of favorability toward video-based and in-person assessments (0 = not favorable, 100 = favorable). Participants watched 2 laparoscopic peg transfer performances, then rated each performance using an Objective Structured Assessment of Technical Skill (OSATS) form and the McGill Inanimate System for Training and Evaluation of Laparoscopic Skills (MISTELS). Participants then rated assessment completion ease (1 = Very Easy, 5 = Very Difficult). SETTING: National survey of practicing surgeons. PARTICIPANTS: Sixty-one surgery attendings with experience in laparoscopic surgery from 10 institutions participated as untrained raters. Six experienced laparoscopic skills proctors participated as expert raters. RESULTS: Inter-rater reliability was substantial for both OSATS (k = 0.75) and MISTELS (k = 0.85). MISTELS accuracy was significantly higher than that of OSATS (κ: MISTELS = 0.18, 95%CI = [0.06,0.29]; OSATS = 0.02, 95%CI = [-0.01,0.04]). While participants were inexperienced with completing video-based assessments (median = 1/5), they perceived video-based assessments favorably (mean = 73.4) and felt assessment completion was "Easy" on average. CONCLUSIONS: We demonstrate that faculty raters untrained in simulation-based assessments can successfully complete video-based assessments of basic laparoscopic skills with substantial inter-rater reliability without marked difficulty. These findings suggest an opportunity to increase access to feedback for trainees using video-based assessment of fundamental skills in laparoscopic surgery.

INHIBITORS OF INORGANIC POLYPHOSPHATE AND NUCLEIC ACIDS ATTENUATE IN VITRO THROMBIN GENERATION IN PLASMA FROM TRAUMA PATIENTS.

ABSTRACT: Background: Inorganic polyphosphate (polyP) is a procoagulant polyanion. We assessed the impact of polyP inhibition on thrombin generation after trauma using the novel polyP antagonists, macromolecular polyanion inhibitor 8 (MPI 8), and universal heparin reversal agent 8 (UHRA-8). Methods: Plasma thrombin generation (calibrated automated thrombogram, CAT), in 56 trauma patients and 39 controls +/- MPI 8 and UHRA-8 (50 µg/mL), was expressed as lag time (LT, minutes), peak height (PH, nM), and time to peak (ttPeak, minutes), with change in LT (ΔLT) and change in ttPeak (ΔttPeak) quantified. Results expressed in median and quartiles [Q1, Q3], Wilcoxon matched-pairs testing, P < 0.05 significant. Results: Trauma patients had greater baseline PH than controls (182.9 [121.0, 255.2]; 120.5 [62.1, 174.8], P < 0.001). MPI 8 treatment prolonged LT and ttPeak in trauma (7.20 [5.88, 8.75]; 6.46 [5.45, 8.93], P = 0.020; 11.28 [8.96, 13.14]; 11.00 [8.95, 12.94], P = 0.029) and controls (7.67 [6.67, 10.50]; 6.33 [5.33, 8.00], P < 0.001; 13.33 [11.67, 15.33]; 11.67 [10.33, 13.33], P < 0.001). UHRA-8 treatment prolonged LT and ttPeak and decreased PH in trauma (9.09 [7.45, 11.33]; 6.46 [5.45, 8.93]; 14.02 [11.78, 17.08]; 11.00 [8.95, 12.94]; 117.4 [74.5, 178.6]; 182.9 [121.0, 255.2]) and controls (9.83 [8.00, 12.33]; 6.33 [5.33, 8.00]; 16.67 [14.33, 20.00]; 11.67 [10.33, 13.33]; 55.3 [30.2, 95.9]; 120.5 [62.1, 174.8]), all P < 0.001. Inhibitor effects were greater for controls (greater ΔLT and ΔttPeak for both inhibitors, P < 0.001). Conclusion: PolyP inhibition attenuates thrombin generation, though to a lesser degree in trauma than in controls, suggesting that polyP contributes to accelerated thrombin generation after trauma.

Segmentation and fragmentation of health systems and the quest for universal health coverage: conceptual clarifications from the Mexican case.

Health systems are complex entities. The Mexican health system includes the private and public sectors, and subsystems that target different populations based on corporatist criteria. Lack of unity and its consequences can be better understood using two concepts, segmentation and fragmentation. These reveal mechanisms and strategies that impede progress toward universality and equity in Mexico and other low- and middle-income countries. Segmentation refers to separation of the population by position in the labour market. Fragmentation refers to institutions, and to financial aspects, health care levels, states' systems of care, and organizational models. These elements explain inequitable allocation of resources and packages of health services offered by each institution to its population. Overcoming segmentation will require a shift from employment to citizenship as the basis for eligibility for public health care. Shortcomings of fragmentation can be avoided by establishing a common package of guaranteed benefits. Mexico illustrates how these two concepts characterize a common reality in low- and middle-income countries.

Barriers and facilitators for breast cancer early diagnosis in an indigenous community in Mexico: voices of otomí women.

BACKGROUND: Literature on barriers and facilitators for early detection of Breast Cancer (BC) among indigenous women is very scarce. This study aimed to identify barriers and facilitators for BC early diagnosis as perceived by women of the otomí ethnic group in Mexico. METHODS: We performed an exploratory qualitative study. Data was collected in 2021 through three focus group interviews with 19 otomí women. The interview transcripts were analyzed using the constant comparison method and guided by a conceptual framework that integrates the Social Ecological Model (SEM), the Health Belief Model and the Institute of Medicine's Healthcare Quality Framework. RESULTS: Barriers and facilitators were identified at several levels of the SEM. Among the main barriers reported by the study participants were: beliefs about illness, cancer stigma, cultural gender norms, access barriers to medical care, and mistreatment and discrimination by health care personnel. Our participants perceived as facilitators: information provided by doctors, social support, perceived severity of the disease and perceived benefits of seeking care for breast symptoms. CONCLUSIONS: Healthcare policies need to be responsive to the particular barriers faced by indigenous women in order to improve their participation in early detection and early help-seeking of care for breast symptoms. Measures to prevent and eradicate all forms of discrimination in healthcare are required to improve the quality of healthcare provided and the trust of the indigenous population in healthcare practitioners.

A murine multiple-injury model for the study of thromboinflammation.

INTRODUCTION: Neutrophil extracellular traps (NETs) contribute to trauma-induced coagulopathy. We aimed to develop a murine multiple-injury model that induces thrombo-inflammatory response, that is, NETosis and accelerated thrombin generation. METHODS: Wild-type male mice (n = 10, aged 8-12 weeks) underwent multiple injuries (gastrocnemius crush, femur fracture, and laparotomy) and were compared with an uninjured control group (n = 10). Mice were euthanized by cardiac puncture performed 3 hours after injury. Whole blood samples were immediately processed to platelet poor plasma for thrombin generation kinetics (calibrated automated thrombogram), myeloperoxidase (MPO), and von Willebrand factor quantification. Immunohistochemistry of lung tissue was performed to assess for citrullinated histone 3 (CitH3) and MPO. A NETosis cluster was defined as 3+ neutrophils staining for CitH3 at 400× magnification (CitH3 cluster). Data were presented either as mean (SD) or median (interquartile range) with p < 0.05 significant. Sham and trauma treated animals were compared by the two-sample Wilcoxon rank-sum test. RESULTS: Animals subjected to multiple injuries had accelerated thrombin generation compared with controls with greater peak height (61.3 [41.2-73.2] vs. 28.4 [19.5-37.5] nM, p = 0.035) and shorter time to peak (3.37 [2.81-3.81] vs. 4.5 [4.08-4.75] minutes, p = 0.046). Markers of neutrophil activation were greater following multiple injuries than in controls (MPO, 961.1 [858.1-1116.8] vs. 481.3 [438.0-648.9] ng/mL; p = 0.004). NETosis, as evidenced by the aforementioned defined number of CitH3 clusters in the lung, was greater in multiple-injury animals than in controls (mean [SD], 3 [2.9] vs. 0.2 [0.7]; p = 0.009). CONCLUSION: This is the first study to demonstrate that NETosis and accelerated thrombin generation can be induced using a murine multiple-injury model, as early as 3 hours following injury.

The academic point-of-care anti-CD19 chimeric antigen receptor T-cell product varnimcabtagene autoleucel (ARI-0001 cells) shows efficacy and safety in the treatment of relapsed/refractory B-cell non-Hodgkin lymphoma.

Varnimcabtagene autoleucel (var-cel) is an academic anti-CD19 chimeric antigen receptor (CAR) product used for the treatment of non-Hodgkin lymphoma (NHL) in the CART19-BE-01 trial. Here we report updated outcomes of patients with NHL treated with var-cel. B-cell recovery was compared with patients with acute lymphoblastic leukaemia (ALL). Forty-five patients with NHL were treated. Cytokine release syndrome (any grade) occurred in 84% of patients (4% grade ≥3) and neurotoxicity in 7% (2% grade ≥3). The objective response rate was 73% at Day +100, and the 3-year duration of response was 56%. The 3-year progression-free and overall survival were 40% and 52% respectively. High lactate dehydrogenase was the only covariate with an impact on progression-free survival. The 3-year incidence of B-cell recovery was lower in patients with NHL compared to ALL (25% vs. 60%). In conclusion, in patients with NHL, the toxicity of var-cel was manageable, while B-cell recovery was significantly prolonged compared to ALL. This trial was registered as NCT03144583.

Medical Students' Perceptions of Clinical and Research Training: An International Needs Assessment of 26 Countries.

Objective: Despite calls to incorporate research training into medical school curriculum, minimal research has been conducted to elucidate trends in research knowledge, opportunities, and involvement globally. This study aims to: (1) assess medical students' perceptions of the level of training they received on research based on their medical school training, and (2) evaluate the obstacles related to conducting research as part of medical students' training. Methods: A 94-question, bilingual survey designed by a small focus group of individuals from medical schools across the globe and administered to medical students from different parts of the world, distributed via social media networks (Twitter, Now X, Facebook) and email distributions via international partnerships from November 1 to December 31, 2020. The survey collected demographic information including age, gender, medical institution and country, degree, year in training, clinical rotations completed, plans for specialization, and additional graduate degrees completed. Statistical analysis included a summary of survey participant characteristics, and a comparison between regions, with a variety of comparison and logistic regression models used. Results: A total of 318 medical students from 26 countries successfully completed the survey. Respondents were majority female (60.1%), from Latin America (LA) (53.1%), North America (NA) (28.6%), and Other world regions (Other) (18.2%). Students felt research was an important component of medical training (87.7%), although many reported lacking research support from their institution (47.5%). There were several reported barriers to research, including lack of research opportunities (69.4%), lack of mentors (56.6%), lack of formal training (54.6%), and barriers due to the coronavirus disease 2019 (COVID-19) pandemic (49.3%). Less frequent were barriers related to financial resources (41.6%), physical resources (computer or internet access) (18%), and English language ability (6.9%). Students from Latin America and Other were more likely to report a desire to pursue research later in their medical careers compared with students from North America. Conclusions and Implications for Translation: Despite significant interest in research, medical students globally report a lack of formal research training, opportunities, and several barriers to conducting research, including the COVID-19 pandemic. The study highlights the need for student research training internationally and the role of further regional-specific and institutional-specific evaluation of research training needs.

Inequitable Financial Protection in Health for Indigenous Populations: the Mexican Case.

BACKGROUND: There is an important gap in the literature concerning the level, inequality, and evolution of financial protection for indigenous (IH) and non-indigenous (NIH) households in low- and middle-income countries. This paper offers an assessment of the level, socioeconomic inequality and middle-term trends of catastrophic (CHE), impoverishing (IHE), and excessive (EHE) health expenditures in Mexican IHs and NIHs during the period 2008-2020. METHODS: We conducted a pooled cross-sectional analysis using the last seven waves of the National Household Income and Expenditure Survey (n = 315,829 households). We assessed socioeconomic inequality in CHE, IHE, and EHE by estimating their Wagstaff concentration indices according to indigenous status. We adjusted the CHE, IHE, and EHE by estimating a maximum-likelihood two-stage probit model with robust standard errors. RESULTS: We observed that, during the period analyzed, CHE, IHE, and EHE were concentrated in the poorest IHs. CHE decreased from 5.4% vs. 4.7% in 2008 to 3.4% vs. 2.9% in 2014 in IHs and NIHs, respectively, and converged at 2008 levels towards 2020. IHE remained unchanged from 2008 to 2014 (1.6% for IHs vs. 1.0% for NIHs) and increased by 40% in IHs and NIHs during 2016-2020. EHE plunged in 2014 (4.6% in IHs vs. 3.8% in NIHs), then rose, and remained unchanged during 2016-2020 (6.7% in IHs and 5.6% in NIHs). CONCLUSION: In pursuit of universal health coverage, health authorities should formulate and implement effective financial protection mechanisms to address structural inequalities, especially forms of discrimination including racialization, that vulnerable social groups such as indigenous peoples have systematically faced. Doing so would contribute to closing the persistent ethnic gaps in health.

Degradation of Penicillinic Antibiotics and ß-Lactamase Enzymatic Catalysis in a Biomimetic Zn-Based Metal-Organic Framework.

Invited for the cover of this issue are Jesús Ferrando-Soria, Donatella Armentano, Antonio Leyva-Pérez, Emilio Pardo and co-workers at University of Valencia, Technical University of Valencia and University of Calabria. The image depicts the crystal structure of a novel ZnII biological metal-organic framework that mimics ß-lactamase enzymes. Read the full text of the article at 10.1002/chem.202301325.

Spontaneous splenic rupture due to Peliosis and the association with malignancy: A case series and literature review.

INTRODUCTION AND IMPORTANCE: Isolated splenic peliosis is an extremely rare condition. The associations of splenic peliosis with various infections, medications, and conditions have unclear significance. We present three patients from the past twenty years with spontaneous splenic rupture due to peliosis, two of whom had hematologic malignancy, to draw attention to a possible correlation. CASE PRESENTATION: A 31-year-old male with essential thrombocytopenia and antiphospholipid-antibody syndrome presented with worsening abdominal pain and hypotension. The patient denied any trauma. Computed-tomography demonstrated hemoperitoneum and splenic rupture with innumerable blood-filled splenic cysts. An uncomplicated emergency open splenectomy was performed with shed-blood reinfusion. The patient was discharged on postoperative day five. The patient developed acute myelogenous leukemia and died six years later. A 44-year-old otherwise healthy male presented with left upper-quadrant and shoulder pain without reported trauma. Computed-tomography (CT) imaging revealed splenomegaly, multiple splenic cystic lesions, and free intraperitoneal blood. A laparoscopic splenectomy, complicated by a pancreatic leak that was managed with a drain, was performed. The patient was discharged on postoperative day three and was well at 37 months follow-up. A 78-year-old male with splenomegaly and chronic anemia on warfarin for atrial fibrillation presented in shock with a distended abdomen after falling from a standing height. The patient was resuscitated with two units of packed red blood cells and underwent emergent abdominal exploration. The spleen was ruptured. An open splenectomy was performed and four liters of intraperitoneal blood were evacuated. Pathology confirmed splenic peliosis and historic diffuse large B-cell lymphoma. The patient had an excellent response to chemotherapy but died 12 years later. CLINICAL DISCUSSION: Splenic peliosis is a rare vascular phenomenon of unclear etiology. Several toxic and pharmaceutical agents have been associated with spontaneous splenic rupture in patients with peliosis. There are also a number of reported patients who were noted to have hematologic disorders, suggestive of a potential association to the pathophysiology of peliosis. CONCLUSION: Based on our clinical experience and focused literature review, it appears likely that there is a relationship between splenic peliosis and hematologic malignancy.

Calves severely affected by bovine respiratory disease have reduced protection against histone toxicity and exhibit lower complement activity.

Bovine respiratory disease (BRD) remains the greatest challenge facing the beef industry. Calves affected by BRD can manifest illness ranging from subclinical infection to acute death. In pathologies similar to BRD, extracellular histones have been implicated as major contributors to lung tissue damage. Histones are basic proteins responsible for DNA organization in cell nuclei, however when released extracellularly during cell injury or via neutrophil activation they become cytotoxic. Cattle suffering severe cases of BRD demonstrate reduced capacity to protect against the cytotoxic effects of histones, however, the protective mechanism(s) of serum remain(s) unknown. Therefore, the objective was to identify components within serum that contribute to protection against histone toxicity. Serum proteins from animals considered protective (P; N = 4) and nonprotective (NP; N = 4) against the toxic effects of histones were precipitated by the addition and incubation of exogenous histones. Proteins that interact with histones from both groups were isolated by sodium dodecyl sulfate-polyacrylamide gel electrophoresis and identified via label free "shotgun" proteomics. Sixteen candidate proteins increased by ≥2-fold change in P vs. NP animals were identified, with several associated with the complement system. A subsequent study was conducted to evaluate complement system activity and serum protective capacity against exogenous histones in feedlot heifers. Serum samples were collected from 118 heifer calves (BW at arrival = 229 ±â€…2.4 kg) at feedlot arrival. Animals were retrospectively assigned to groups consisting of: calves not requiring treatment with antibiotics for BRD (CONT; N = 80), calves treated once (1TRT; N = 21), calves treated twice (2TRT; N = 5), calves treated thrice (3TRT; N = 3), or calves that died from BRD within 1 wk of entering the feedlot (DA; N = 9). Serum from DA animals was less protective than CONT (P = 0.0005) animals against histone toxicity. Complement activity of DA animals was reduced compared to CONT (P = 0.0044) animals. Additionally, the use of both assays as a ratio resulted in increased ability to detect DA animals. Results suggest that cattle predisposed to severe cases of respiratory disease may have impaired complement activity presumably contributing to reduced protective capacity against histone toxicity.

Bovine respiratory disease (BRD) remains the leading cause of feedlot calf sickness and death. In respiratory disease affecting humans and mice, major tissue damage is caused by release of histones. Histones are proteins found in the nucleus of cells that condense DNA, however, cells that become damaged release histones extracellularly. Research has shown that calves with severe cases of BRD are less able to protect against the toxic effects of histones residing outside of the cell. It is speculated that components within the blood may interact with histones and confer protection from histone toxicity. This study evaluated serum from protective and nonprotective cattle against histone toxicity and identified 16 proteins that were elevated in protective animals. Several proteins were associated with the complement system of the innate immune system. To evaluate immune complement activity and protective capacity against histone toxicity, serum was collected from heifers at feedlot arrival. Calves suffering from a severe case of BRD demonstrated reduced capacity to protect against histone toxicity. Complement activity of calves severely affected with BRD was reduced as well. Results suggest that cattle susceptible to severe cases of BRD may have impaired complement activity likely contributing to reduced protective capacity against histone toxicity.

Evidence for Ruthenium(II) Peralkene Complexes as Catalytic Species during the Isomerization of Terminal Alkenes in Solution.

The isomerization (chain-walking) reaction of terminal to internal alkenes is catalyzed by part-per-million amounts of practically any Ru source when the reaction is carried out with a neat terminal alkene. Here, we provide evidence that the soluble starting Ru sources evolve to catalytically active peralkene Ru(II) species under reaction conditions. These species may also explain the isomerization products found during other Ru-catalyzed alkene processes, i.e., alkene metathesis reactions. A Finke-Watzky mechanism for catalyst formation is consistent with the evidence obtained.

Degradation of Penicillinic Antibiotics and ß-Lactamase Enzymatic Catalysis in a Biomimetic Zn-Based Metal-Organic Framework.

ß-Lactam antibiotics are one of the most commonly prescribed drugs to treat bacterial infections. However, their use has been somehow limited given the emergence of bacteria with resistance mechanisms, such as ß-lactamases, which inactivate them by degrading their four-membered ß-lactam rings. So, a total knowledge of the mechanisms governing the catalytic activity of ß-lactamases is required. Here, we report a novel Zn-based metal-organic framework (MOF, 1), possessing functional channels capable to accommodate and interact with antibiotics, which catalyze the selective hydrolysis of the penicillinic antibiotics amoxicillin and ceftriaxone. In particular, MOF 1 degrades, very efficiently, the four-membered ß-lactam ring of amoxicillin, acting as a ß-lactamase mimic, and expands the very limited number of MOFs capable to mimic catalytic enzymatic processes. Combined single-crystal X-ray diffraction (SCXRD) studies and density functional (DFT) calculations offer unique snapshots on the host-guest interactions established between amoxicillin and the functional channels of 1. This allows to propose a degradation mechanism based on the activation of a water molecule, promoted by a Zn-bridging hydroxyl group, concertedly to the nucleophilic attack to the carbonyl moiety and the cleaving of C-N bond of the lactam ring.

Rising incidence of stair-related upper extremity fractures among older adults in the United States: a 10-year nationwide analysis.

Upper extremity (UE) fractures are prevalent age-related fractures, and stair-associated falls are a common mechanism for these injuries. Our study has identified an increasing incidence of stair-related UE fractures and associated hospitalization rates among the older United States population between 2012-2021. Targeted prevention efforts should be implemented by health systems. INTRODUCTION: To analyze United States (US) emergency department trends in upper extremity stair-related fractures among older adults and investigate risk factors associated with hospitalization. METHODS: We queried the National Electronic Injury Surveillance System (NEISS) for all stair-related fracture injuries between 2012 and 2021 among adults 65 years or older. The US Census Bureau International Database (IDB) was analyzed to calculate incidence rates. Descriptive analysis, linear regression analysis, and multivariate regression analysis were used to interpret the collected data. RESULTS: Our analysis estimated 251,041 (95% CI: 211,678-290,404) upper extremity stair-related fractures among older adults occurred between 2012 and 2021. The primary anatomical locations were the humeral shaft (27%), wrist (26%), and proximal humerus (18%). We found a 56% increase in injuries (R2 = 0.77, p < 0.001), 7% increase in incidence per 100,000 persons (R2 = 0.42, p < 0.05), and an 38% increase in hospitalization rate (R2 = 0.61, p < 0.01) during the 10-year study period. Women sustained the majority of fractures (76%) and most injuries occurred in homes (89%). Advanced age (p < 0.0001), males (p < 0.0001), proximal humerus fractures (p < 0.0001), humeral shaft fractures (p < 0.0001), and elbow fractures (p < 0.0001) were associated with increased odds of hospitalization after injury. CONCLUSION: Stair-related UE fracture injuries, incidence, and hospitalization rates among older adults are increasing significantly, particularly among older females. Improving bone health, optimizing functional muscle mass, and "fall-proofing" homes of older age groups may help mitigate the rising incidence of these injuries.