Pre-existing H1N1 immunity reduces severe disease with bovine H5N1 influenza virus.

The emergence of highly pathogenic H5N1 avian influenza in dairy cattle herds across the United States has caused multiple mild human infections. There is an urgent need to understand the risk of spillover into humans. Here, we show that pre-existing immunity from the 2009 H1N1 pandemic influenza virus provided protection from mortality and severe clinical disease to ferrets intranasally infected with bovine H5N1. H1N1 immune ferrets exhibited a differential tissue tropism with little bovine H5N1 viral dissemination to organs outside the respiratory tract and significantly less H5N1 virus found in nasal secretions and the respiratory tract. Additionally, ferrets with H1N1 prior immunity produced antibodies that cross-reacted with H5N1 neuraminidase protein. Taken together, these results suggest that mild disease in humans may be linked to prior immunity to human seasonal influenza viruses.

The relative data hungriness of unpenalized and penalized logistic regression and ensemble-based machine learning methods: the case of calibration.

BACKGROUND: Machine learning methods are increasingly being used to predict clinical outcomes. Optimism is the difference in model performance between derivation and validation samples. The term "data hungriness" refers to the sample size needed for a modelling technique to generate a prediction model with minimal optimism. Our objective was to compare the relative data hungriness of different statistical and machine learning methods when assessed using calibration. METHODS: We used Monte Carlo simulations to assess the effect of number of events per variable (EPV) on the optimism of six learning methods when assessing model calibration: unpenalized logistic regression, ridge regression, lasso regression, bagged classification trees, random forests, and stochastic gradient boosting machines using trees as the base learners. We performed simulations in two large cardiovascular datasets each of which comprised an independent derivation and validation sample: patients hospitalized with acute myocardial infarction and patients hospitalized with heart failure. We used six data-generating processes, each based on one of the six learning methods. We allowed the sample sizes to be such that the number of EPV ranged from 10 to 200 in increments of 10. We applied six prediction methods in each of the simulated derivation samples and evaluated calibration in the simulated validation samples using the integrated calibration index, the calibration intercept, and the calibration slope. We also examined Nagelkerke's R2, the scaled Brier score, and the c-statistic. RESULTS: Across all 12 scenarios (2 diseases × 6 data-generating processes), penalized logistic regression displayed very low optimism even when the number of EPV was very low. Random forests and bagged trees tended to be the most data hungry and displayed the greatest optimism. CONCLUSIONS: When assessed using calibration, penalized logistic regression was substantially less data hungry than methods from the machine learning literature.

The filamentous γ-prefoldin chaperone is not essential for growth and thermal adaptation in Methanocaldococcus jannaschii.

Elucidating the role of molecular chaperones in extremely thermophilic archaea, including the gamma prefoldin (γPFD) in the deep-sea methanogen Methanocaldococcus jannaschii, is integral to understanding microbial adaptation to hot environments. This study focuses on genetically engineered knock-out and overexpression strains to evaluate the importance of γPFD in the growth and thermal tolerance of M. jannaschii. An in-depth analysis of cell growth, morphology and transcriptional responses to heat stress revealed that although the gene encoding γPFD is substantially upregulated in response to heat shock, the γPFD is not indispensable for high-temperature survival. Instead, its absence in the knock-out strain is compensated for by the upregulation of several proteolytic proteins in the absence of heat shock, nearly matching the corresponding transcription profile of selected transcripts for proteins involved in protein synthesis and folding in the wild-type strain following heat shock, using quantitative reverse-transcription PCR (RT-qPCR). These findings bridge environmental adaptation with molecular biology, underscoring the versatility of extremophiles and providing a deeper mechanistic understanding of how they cope with stress.

Self-Assessment and Coaching Techniques Utilized in an Intraoperative Resident Peer Coaching Program.

OBJECTIVES: To evaluate junior resident self-assessments and utilization of effective coaching principles by chief resident coaches in a resident peer surgical coaching program. DESIGN: All residents underwent the Surgical Coaching for Operative Performance Enhancement (SCOPE) coaching curriculum. Junior residents ("coachees") were paired with chief resident coaches. A case was selected for coaching. The coaching structure was: 1) junior resident preoperative goal setting, 2) unscrubbed, intraoperative case observation by the coach, 3) postoperative coaching debrief. Debriefs were recorded to determine frequency of junior resident self-assessment and use of the effective coaching principles (goal setting, collaborative analysis, constructive feedback, action planning). Deductive thematic analysis was conducted. SETTING: A general surgery residency at a single, large academic medical center. PARTICIPANTS: 16 junior resident (PGY1-3) coachees and 6 chief resident (PGY5) coaches. RESULTS: There were 18 recorded coaching debrief sessions that lasted an average of 12.65 minutes (range 4-31 minutes). All debrief sessions included self-assessments by the junior resident coachees. There were numerous examples of the 4 effective coaching principles with all debriefs including use of at least 3. The most commonly used were collaborative analysis and constructive feedback. For technical skills, these highlighted body positioning, needle angles, and dissection techniques, including instrument choice, laparoscopic instrument technique, and use of electrocautery. Collaborative analysis of nontechnical skills emphasized communication with the attending surgeon, specifically operative decision-making and advocating for resident autonomy. Nontechnical constructive feedback addressed strategies the coaches themselves used for managing stress, interacting with attendings, and excelling in the operating room. CONCLUSIONS: Self-assessments and use of effective coaching principles were frequent throughout peer coaching debriefs. Collaborative analysis and constructive feedback were employed to promote operative technical and nontechnical skill development. Within a peer coaching program, residents are able to employ high level teaching and coaching techniques to encourage operative performance enhancement.

Mortality After Multivessel Revascularization in Patients With Diabetes and Acute Coronary Syndromes.

Background: The optimal revascularization strategy in patients with diabetes and multivessel disease in the setting of a non-ST-segment elevation myocardial infarction (NSTEMI) is unknown. Objectives: The purpose of this study was to compare all-cause mortality between coronary artery bypass grafting (CABG) and multivessel percutaneous coronary intervention (PCI) among patients with diabetes and NSTEMI. Methods: All patients with diabetes and multivessel disease admitted for NSTEMI in Ontario, Canada, between April 2009 and March 2020 were included. Those with previous CABG, PCI in the previous 90 days, or shock were excluded. The primary outcome was all-cause mortality. Propensity score matching was used to account for confounding. Patients who had a cardiac surgeon consultation and then received PCI were classified as being potentially ineligible for CABG. Results: The cohort included 4,649 CABG and 6,760 PCI patients (mean age: 67.8 ± 11.5 years; 70.4% males), resulting in 2,385 matched pairs. CABG was associated with reduced all-cause mortality compared to PCI over a median follow-up of 5.5 years (5-year estimates: 23.4% vs 26.5%; HR: 0.89; 95% CI: 0.80-0.98; P = 0.021). However, no significant differences in mortality were observed between CABG and PCI patients without a surgical consultation (2,130 pairs; HR: 0.97; 95% CI: 0.86-1.08), while CABG was associated with reduced mortality when compared against PCI patients who had received a surgical consultation (388 pairs; HR: 0.72; 95% CI: 0.58-0.88; P = 0.002). Conclusions: While CABG was associated with reduced all-cause mortality compared to multivessel PCI in patients with diabetes and NSTEMI, CABG benefit was seen only against PCI patients potentially ineligible for CABG after receiving a preprocedure surgical consultation.

Acetaminophen production in the edible, filamentous cyanobacterium Arthrospira platensis.

Spirulina is the common name for the edible, nonheterocystous, filamentous cyanobacterium Arthrospira platensis that is grown industrially as a food supplement, animal feedstock, and pigment source. Although there are many applications for engineering this organism, until recently no genetic tools or reproducible transformation methods have been published. While recent work showed the production of a diversity of proteins in A. platensis, including single-domain antibodies for oral delivery, there remains a need for a modular, characterized genetic toolkit. Here, we independently establish a reproducible method for the transformation of A. platensis and engineer this bacterium to produce acetaminophen as proof-of-concept for small molecule production in an edible host. This work opens A. platensis to the wider scientific community for future engineering as a functional food for nutritional enhancement, modification of organoleptic traits, and production of pharmaceuticals for oral delivery.

Trauma and 'Whole' Body Computed Tomography: Role, Protocols, Appropriateness, and Evidence to Support its Use and When.

Imaging plays a crucial role in the immediate evaluation of the trauma patient, particularly using multi-detector computed tomography (CT), and especially in moderately to severely injured trauma patients. There are specific areas of relative consensus, while other aspects of whole-body computed tomography (WB-CT) use remain controversial and are subject to opinion/debate based on the current literature. Even a few hours of a delayed diagnosis may result in a detrimental outcome for the patient. One must utilize all the tools available to enhance the interpretation of images. It is also important to recognize imaging pitfalls and artifacts to avoid unnecessary intervention.

Potpourri of Contrast Controversies and Myths: Where Is the Actual Evidence?

There are many misconceptions related to the usage of intravenous contrast agents for medical imaging. These misconceptions can affect patient care, as they can lead to nonoptimal examination usage. Knowledge of the current contrast-related misconceptions can help radiologists provide higher quality care to their patients.

Automated analysis of operative video in surgical training: scoping review.

BACKGROUND: There is increasing availability of operative video for use in surgical training. Emerging technologies can now assess video footage and automatically generate metrics that could be harnessed to improve the assessment of operative performance. However, a comprehensive understanding of which technology features are most impactful in surgical training is lacking. The aim of this scoping review was to explore the current use of automated video analytics in surgical training. METHODS: PubMed, Scopus, the Web of Science, and the Cochrane database were searched, to 29 September 2023, following PRISMA extension for scoping reviews (PRISMA-ScR) guidelines. Search terms included 'trainee', 'video analytics', and 'education'. Articles were screened independently by two reviewers to identify studies that applied automated video analytics to trainee-performed operations. Data on the methods of analysis, metrics generated, and application to training were extracted. RESULTS: Of the 6736 articles screened, 13 studies were identified. Computer vision tracking was the common method of video analysis. Metrics were described for processes (for example movement of instruments), outcomes (for example intraoperative phase duration), and critical safety elements (for example critical view of safety in laparoscopic cholecystectomy). Automated metrics were able to differentiate between skill levels (for example consultant versus trainee) and correlated with traditional methods of assessment. There was a lack of longitudinal application to training and only one qualitative study reported the experience of trainees using automated video analytics. CONCLUSION: The performance metrics generated from automated video analysis are varied and encompass several domains. Validation of analysis techniques and the metrics generated are a priority for future research, after which evidence demonstrating the impact on training can be established.

They Will Come, You Must Build It: A Modified Delphi Process Applied to Preparing Acute Care Facilities Infrastructure for High-Consequence Infectious Diseases.

Patients with suspected or confirmed high-consequence infectious diseases (HCIDs) may present for care at any acute care facility. However, there are limited data to inform recommendations for the design, maintenance, and operation of isolation spaces for patients with suspected or confirmed HCIDs. To address this gap, we developed consensus statements by convening a group of 29 subject matter experts to participate in a modified Delphi process facilitated by a validated tool (the RAND-developed ExpertLens system). The subject matter experts participated in 3 consensus rounds, providing feedback and rating the appropriateness of 36 draft consensus statements. These draft statements were then revised based on their feedback. As a result, we developed 36 consensus statements addressing 5 domains: (1) patient room physical space, (2) doors and windows, (3) air handling, (4) electrical and plumbing, and (5) soiled utility rooms and waste management. These statements could inform the approaches of frontline acute care facilities when building new spaces or modifying existing spaces to enable appropriate HCID patient isolation and care.

Gastrointestinal germinal center B cell depletion and reduction in IgA+ plasma cells in HIV-1 infection.

Gastrointestinal (GI) B cells and plasma cells (PCs) are critical to mucosal homeostasis and the host response to HIV-1 infection. Here, high-resolution mapping of human B cells and PCs sampled from the colon and ileum during both viremic and suppressed HIV-1 infection identified a reduction in germinal center (GC) B cells and follicular dendritic cells (FDCs) during HIV-1 viremia. Immunoglobulin A-positive (IgA+) PCs are the major cellular output of intestinal GCs and were significantly reduced during viremic HIV-1 infection. PC-associated transcriptional perturbations, including type I interferon signaling, persisted in antiretroviral therapy (ART)-treated individuals, suggesting ongoing disruption of the intestinal immune milieu during ART. GI humoral immune perturbations were associated with changes in the intestinal microbiome composition and systemic inflammation. These findings highlight a key immune defect in the GI mucosa due to HIV-1 viremia.

Palbociclib in Solid Tumor Patients With Genomic Alterations in the cyclinD-cdk4/6-INK4a-Rb Pathway: Results From National Cancer Institute-Children's Oncology Group Pediatric Molecular Analysis for Therapy Choice Trial Arm I (APEC1621I).

PURPOSE: The National Cancer Institute-Children's Oncology Group Pediatric Molecular Analysis for Therapy Choice trial assigned patients age 1-21 years with relapsed or refractory solid tumors, lymphomas, and histiocytic disorders to phase II treatment arms of molecularly targeted therapies on the basis of genetic alterations detected in their tumor. Patients with tumors that harbored prespecified genomic alterations in the cyclinD-CDK4/6-INK4a-Rb pathway with intact Rb expression were assigned and treated with the cdk4/6 inhibitor palbociclib. METHODS: Patients received palbociclib orally once daily for 21 days of 28-day cycles until disease progression, intolerable toxicity, or up to 2 years. The primary end point was objective response rate; secondary end points included safety/tolerability and progression-free survival. RESULTS: Twenty-three patients (median age, 15 years; range, 8-21) were enrolled; 20 received protocol therapy and were evaluable for toxicity and response. Of the evaluable patients, the most common diagnoses were osteosarcoma (n = 9) and rhabdomyosarcoma (n = 6). A single actionable gene amplification was found in 19 tumors (CDK4, n = 11, CDK6, n = 2, CCND3, n = 6), with one tumor harboring two amplifications (CDK4 and CCND2). Hematologic toxicities were the most common treatment-related events. No objective responses were seen. Two patients with tumors harboring CDK4 amplifications (neuroblastoma and sarcoma) had best response of stable disease for six and three cycles. Six-month progression was 10% (95% CI, 1.7 to 27.2). CONCLUSION: The CDK4/6 inhibitor palbociclib at 75 mg/m2 orally daily was tolerable in this heavily pretreated cohort. No objective responses were observed in this histology-agnostic biomarker-selected population with treatment-refractory solid tumors, demonstrating that pathway alteration alone is insufficient in pediatric cancers to generate a response to palbociclib monotherapy.

Do nonfatal events during the first 5 years after coronary artery bypass surgery influence 10 year outcomes?

OBJECTIVE: Few have examined the influence of early adverse events after coronary artery bypass grafting (CABG) on long-term survival. We sought to determine if the occurrence of nonfatal major adverse cardiac and cerebrovascular events (MACCE) during the first 5 years after CABG influences survival and adverse events at 10 years. METHODS: All patients who underwent isolated CABG from 1990 to 2014 at a single center in Ontario, Canada, were included. Primary end point was all-cause mortality. The secondary end point of interest was MACCE, a composite of mortality, nonfatal myocardial infarction, stroke, and repeat revascularization. RESULTS: A total of 20,444 cases of elective primary isolated CABG were identified as being alive at 5 years, with 11% of patients developing nonfatal MACCE within the first 5 years after CABG (MACCE group) and the remaining 89% were alive without a MACCE event at 5 years (non-MACCE group). Following propensity score matching, 2167 patient-pairs were formed. Among the MACCE group, 972 out of 2167 (44.9%) developed a myocardial infarction, 519 out of 2167 (24.0%) had a stroke, and 946 out of 2167 (43.7%) required a repeat revascularization within the first 5 years after CABG. Non-MACCE was associated with better overall survival (hazard ratio, 1.42; 95% CI, 1.25-1.63; P < .01) and freedom from MACCE (hazard ratio, 1.61; 95% CI, 1.45-1.79; P < .01) up to 10 years after CABG compared with MACCE cases. CONCLUSIONS: Patients who experienced nonfatal MACCE during the first 5 years after CABG experienced worse survival and more MACCE at 10 years. Prevention of major adverse events during the first 5 years after surgical revascularization may be an important strategy to improve late outcomes.

Evaluating sampling techniques for quantifying Asiatic garden beetle (Maladera formosae) (Coleoptera: Scarabaeidae) infestations in commercial mint.

The Asiatic garden beetle, Maladera formosae Brenske (AGB), has become a significant pest of commercial mint fields in northern Indiana. Larval feeding on mint roots can cause stunted growth and plant death when densities are high. Sampling approaches that provide reliable estimates of larval densities in mint have not been established, leaving farmers without the knowledge necessary to implement integrated pest management (IPM) strategies. To address this knowledge gap, we evaluated strategies for estimating AGB larval densities and plant performance in commercial mint systems. We used 2 sampling methods to collect larval density and plant performance data from 3 mint fields and conducted simulations to optimize sampling intensity (accuracy and precision) and sampling scheme (random vs. systematic) using these data. Additionally, we examined the sensitivity and efficiency of each sampling method. Compared to the cup-cutter method, the quadrat method provided the most accurate and precise estimates of larval density and plant performance, with ≤ 7 samples required per 0.2 ha. Quadrat excavation was also more sensitive, increasing the probability of detecting AGB larvae within a 32 m2 plot by 76.7%, and requiring significantly less time to survey an equivalent volume of soil for AGB larvae. When the quadrat method was employed, random sampling schemes provided below-ground biomass estimates that were significantly closer to the true mean of the sampling area. The results of this research will facilitate the development of IPM decision-making tools for farmers and support future research for AGB and other soil insect pests affecting mint production.

Impact of Elevated Serum Triglycerides on Children with Acute Recurrent or Chronic Pancreatitis from INSPPIRE-2.

OBJECTIVE: To determine if mild-moderate hypertriglyceridemia (HTG) is associated with increased development of chronic pancreatitis (CP) or pancreatitis-associated complications in children with acute recurrent or CP. STUDY DESIGN: Longitudinal data from the INternational Study group of Pediatric Pancreatitis: In search for a cuRE-2 (INSPPIRE-2) cohort of children with acute recurrent or CP (n = 559) were analyzed. Subjects were divided into normal triglycerides (<150 mg/dL; 1.7 mmol/L), any HTG (≥150 mg/dL; ≥1.7 mmol/L), mild-moderate HTG (150-499 mg/dL; 1.7-5.6 mmol/L), moderate HTG (500-999 mg/dL; 5.6-11.3 mmol/L), and severe HTG groups (≥1000 mg/dL; ≥11.3 mmol/L), based on highest serum triglyceride value. Laboratory, imaging, pancreatitis and hospital events, complications, and quality of life data were analyzed. RESULTS: In children with acute recurrent or CP and HTG, there was no increase in the number of pancreatitis attacks per person-years, nor an increase in CP prevalence. However, HTG severity was associated with increased pancreatic inflammation, pancreatic cysts, pain, hospital days, number of hospitalizations, intensive care, and missed school days. CONCLUSIONS: Mild-moderate HTG in children with acute recurrent or CP was not associated with increased pancreatitis frequency, nor increased development of CP, but was associated with increased pancreatitis complications and disease burden. As a treatable condition, treatment of mild-moderate HTG may be considered to reduce pancreatitis-associated complications and medical burden in children with acute recurrent or CP.

Pioglitazone attenuates behavioral and electrophysiological dysfunctions induced by two-hit model of schizophrenia in adult rodent offspring.

Maternal infection and stress exposure, especially during childhood and adolescence, have been implicated as risk factors for schizophrenia. Both insults induce an exacerbated inflammatory response, which could mediate disturbance of neurodevelopmental processes and, ultimately, malfunctioning of neural systems observed in this disorder. Thus, anti-inflammatory drugs, such as PPARγ agonists, may potentially be used to prevent the development of schizophrenia. Microglia culture was prepared from the offspring of saline or poly(I:C)-injected mice. The cells were pretreated with pioglitazone and then, stimulated by LPS. Proinflammatory mediators and phagocytic activity were measured. Also, pregnant rats were injected with saline or poly(I:C) on GD17. The offspring were subjected to footshock during adolescence and subsequently injected with pioglitazone or vehicle. At adulthood, behavior and dopaminergic activity were evaluated. Pioglitazone reduced proinflammatory mediators induced by poly(I:C) microglia stimulated by LPS without affecting their decreased phagocytic activity. The PPARγ agonist also prevented the emergence of social and cognitive impairments, as well as attenuated the increased number of spontaneously active dopamine neurons in the VTA, observed in both males and females from poly(I:C) and stress group. Therefore, pioglitazone could potentially prevent the emergence of the schizophrenia-like alterations induced by the two-hit model via reduction of microglial activation.

Association of Pneumatosis Intestinalis With Surgical Outcomes and Mortality: A Matched, Retrospective Cohort Study and Literature Review.

Background: To determine the clinical importance of pneumatosis intestinalis (PI) on surgical decision-making and patient outcomes. Methods: A matched cohort observational study was conducted including all clinical encounters for both ambulatory and inpatient care at UCLA Health between February 15, 2006 and January 31, 2023. Patients were initially identified using encounter diagnostic codes for "other specified diseases of intestine." A radiologic diagnosis of PI was then assessed using natural language processing techniques followed by confirmation using manual chart review. Patients who did not have PI served as a control group. Patient comorbidity was assessed using Elixhauser comorbidity scores. Logistic regression and Cox hazard analyses were used to assess associations between PI and mortality. The main outcome was 90-day all-cause mortality. Secondary outcomes were the proportion of patients undergoing surgery and, of those, how many required bowel resections. Results: Of the 16,728 patients identified by diagnostic coding, 315 were confirmed to have a diagnosis of PI. The 90-day mortality rate for all patients with PI was 29%. Surgery was performed for 62 patients (20%), of whom 46 (72%) underwent bowel resection and 16 (28%) underwent abdominal exploration alone. Most patients underwent surgery for peritonitis (37%), bowel obstruction (31%), and/or pneumoperitoneum (23%) in association with PI; whereas only 8% of patients received surgery exclusively for PI. There was no statistically significant association between PI and mortality with logistic regression conditioned on other risk factors for mortality. In contrast, survival analysis of a matched cohort demonstrated a small effect of PI on mortality (hazard ratio = 1.24: 95% confidence interval = 1.16-1.32, P = 0.021). Conclusions: Most patients with a diagnosis of PI survive without requiring surgery. Of those who undergo surgery, nearly all have indications for laparotomy exclusive of PI. Mortality in patients who have pneumatosis is strongly associated with comorbid disease, with little to no independent association with PI. Our findings suggest that the presence of PI should not be a primary indication for surgical intervention.

Triatomines know no boundaries: Triatoma delpontei Romaña & Abalos, 1947 (Heteroptera: Reduviidae) discovered in Mato Grosso do Sul State, Brazil.

Triatominae are recognized as vectors of Trypanosoma cruzi, a protozoan which is the etiological agent of Chagas disease. A specimen of Triatoma delpontei was found at Porto Murtinho in Mato Grosso do Sul State, Brazil. This is the first report of the occurrence of T. delpontei to the state of Mato Grosso do Sul, Brazil. With the present finding, the total number of triatomines recorded in Mato do Grosso do Sul reaches 17 species, while T. delpontei, previously recorded only from Rio Grande do Sul, is now recorded to a second Brazilian state. Based on the information available in the literature, a meticulous and organized compilation has been crafted, highlighting the cytogenetics differentiations of the species occurring in this state. This work emphasizes the importance of continuous research and surveillance on Triatominae, recognized as vectors of T. cruzi.