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The rote of environmental factors on the hatching response of O. albifasciatus (Macquart) eggs is studied by simulating winter conditions in the laboratory. The hypothesis tested was that hatching response is affected by: (1) time that eggs remain at low temperature, (2) storage conditions, and (3) acclimatization time. Eggs were stored at 5°C in drought and immersion conditions during 7, 21, 35, 90 and 146 days, immediately after, they were acclimatized at 22°C during 24, 72, and 168 hours, and then eggs were flooded to induce hatching. Percent of hatched eggs was analyzed with a Generalized Lineal Model with a binomial distribution. Results show that: (1) a long storage period at cold temperature and long acclimatization periods improve the hatching response; (2) storage conditions have a moderate effect on hatching, being more evident in eggs stored dry; (3) a long time of acclimatization favors the hatching response in submerged eggs more than in eggs stored dry; (4) long time at cold favors the hatching response in eggs stored dry more than in submerged eggs; (5) the hatching response of eggs that remain for a long time at low temperature is higher when the time of acclimatization is long. [ABSTRACT FROM AUTHOR]

Subtelomeric regions reveal a relatively high degree of polymorphism due to the increased frequency of recombination events in these chromosome loci. In a search for molecular markers applicable to genotyping of potato varieties, we focused on two possible sources of polymorphism occurring in this region: (i) arrangement of blocks of subtelomeric chromatin; (ii) structure of telomere-subtelomere boundary. Analysis of the internal arrangement of subtelomeric sequences showed several types of cultivar-specific spectra of PCR products arising from the variant orientation of sequence units of the ST3-subtelomeric sequence, or from different lengths of regions linking the individual sequence units. Further, the telomere-subtelomere boundary sequences were amplified using telomeric and ST3-specific primers and the obtained products were cloned. Sequence analysis of the clones resulted in characterisation of a novel telomere-associated sequence (FIN2). Primers derived from this sequence were then used alone or in combination with telomeric or ST3-specific primers to generate cultivar-specific spectra of PCR products. The described combinations of sequence-specific primers may be used for the fast, cheap and reproducible PCR-genotyping of selected potato varieties.

Recent investigations have revealed that the genetic deletion of P2X7 receptors (P2rx7) results in an antidepressant phenotype in mice. However, the link between the deficiency of P2rx7 and changes in behavior has not yet been explored. In the present study, we studied the effect of genetic deletion of P2rx7 on neurochemical changes in the hippocampus that might underlie the antidepressant phenotype. P2X7 receptor deficient mice (P2rx7-/-) displayed decreased immobility in the tail suspension test (TST) and an attenuated anhedonia response in the sucrose preference test (SPT) following bacterial endotoxin (LPS) challenge. The attenuated anhedonia was reproduced through systemic treatments with P2rx7 antagonists. The activation of P2rx7 resulted in the concentration-dependent release of [(3)H]glutamate in P2rx7+/+ but not P2rx7-/- mice, and the NR2B subunit mRNA and protein was upregulated in the hippocampus of P2rx7-/- mice. The brain-derived neurotrophic factor (BDNF) expression was higher in saline but not LPS-treated P2rx7-/- mice; the P2rx7 antagonist Brilliant blue G elevated and the P2rx7 agonist benzoylbenzoyl ATP (BzATP) reduced BDNF level. This effect was dependent on the activation of NMDA and non-NMDA receptors but not on Group I metabotropic glutamate receptors (mGluR1,5). An increased 5-bromo-2-deoxyuridine (BrdU) incorporation was also observed in the dentate gyrus derived from P2rx7-/- mice. Basal level of 5-HT was increased, whereas the 5HIAA/5-HT ratio was lower in the hippocampus of P2rx7-/- mice, which accompanied the increased uptake of [(3)H]5-HT and an elevated number of [(3)H]citalopram binding sites. The LPS-induced elevation of 5-HT level was absent in P2rx7-/- mice. In conclusion there are several potential mechanisms for the antidepressant phenotype of P2rx7-/- mice, such as the absence of P2rx7-mediated glutamate release, elevated basal BDNF production, enhanced neurogenesis and increased 5-HT bioavailability in the hippocampus.

Extreme-ultraviolet to x-ray free-electron lasers (FELs) in operation for scientific applications are up to now single-user facilities. While most FELs generate around 100 photon pulses per second, FLASH at DESY can deliver almost two orders of magnitude more pulses in this time span due to its superconducting accelerator technology. This makes the facility a prime candidate to realize the next step in FELs—dividing the electron pulse trains into several FEL lines and delivering photon pulses to several users at the same time. Hence, FLASH has been extended with a second undulator line and self-amplified spontaneous emission (SASE) is demonstrated in both FELs simultaneously. FLASH can now deliver MHz pulse trains to two user experiments in parallel with individually selected photon beam characteristics. First results of the capabilities of this extension are shown with emphasis on independent variation of wavelength, repetition rate, and photon pulse length.

Sodium channels are one of the most intensively studied drug targets. Sodium channel inhibitors (e.g., local anesthetics, anticonvulsants, antiarrhythmics and analgesics) exert their effect by stabilizing an inactivated conformation of the channels. Besides the fast-inactivated conformation, sodium channels have several distinct slow-inactivated conformational states. Stabilization of a slow-inactivated state has been proposed to be advantageous for certain therapeutic applications. Special voltage protocols are used to evoke slow inactivation of sodium channels. It is assumed that efficacy of a drug in these protocols indicates slow-inactivated state preference. We tested this assumption in simulations using four prototypical drug inhibitory mechanisms (fast or slow-inactivated state preference, with either fast or slow binding kinetics) and a kinetic model for sodium channels. Unexpectedly, we found that efficacy in these protocols (e.g., a shift of the "steady-state slow inactivation curve"), was not a reliable indicator of slow-inactivated state preference. Slowly associating fast-inactivated state-preferring drugs were indistinguishable from slow-inactivated state-preferring drugs. On the other hand, fast- and slow-inactivated state-preferring drugs tended to preferentially affect onset and recovery, respectively. The robustness of these observations was verified: i) by performing a Monte Carlo study on the effects of randomly modifying model parameters, ii) by testing the same drugs in a fundamentally different model and iii) by an analysis of the effect of systematically changing drug-specific parameters. In patch clamp electrophysiology experiments we tested five sodium channel inhibitor drugs on native sodium channels of cultured hippocampal neurons. For lidocaine, phenytoin and carbamazepine our data indicate a preference for the fast-inactivated state, while the results for fluoxetine and desipramine are inconclusive. We suggest that conclusions based on voltage protocols that are used to detect slow-inactivated state preference are unreliable and should be re-evaluated.

BACKGROUND: There is only one established drug binding site on sodium channels. However, drug binding of sodium channels shows extreme promiscuity: ∼25% of investigated drugs have been found to potently inhibit sodium channels. The structural diversity of these molecules suggests that they may not share the binding site, and/or the mode of action. Our goal was to attempt classification of sodium channel inhibitors by measuring multiple properties of inhibition in electrophysiology experiments. We also aimed to investigate if different properties of inhibition correlate with specific chemical properties of the compounds. METHODOLOGY/PRINCIPAL FINDINGS: A comparative electrophysiological study of 35 compounds, including classic sodium channel inhibitors (anticonvulsants, antiarrhythmics and local anesthetics), as well as antidepressants, antipsychotics and neuroprotective agents, was carried out using rNav1.2 expressing HEK-293 cells and the QPatch automatic patch-clamp instrument. In the multi-dimensional space defined by the eight properties of inhibition (resting and inactivated affinity, potency, reversibility, time constants of onset and offset, use-dependence and state-dependence), at least three distinct types of inhibition could be identified; these probably reflect distinct modes of action. The compounds were clustered similarly in the multi-dimensional space defined by relevant chemical properties, including measures of lipophilicity, aromaticity, molecular size, polarity and electric charge. Drugs of the same therapeutic indication typically belonged to the same type. We identified chemical properties, which were important in determining specific properties of inhibition. State-dependence correlated with lipophilicity, the ratio of the neutral form of molecules, and aromaticity: We noticed that the highly state dependent inhibitors had at least two aromatic rings, logP>4.0, and pKa

A task force of scientists is searching for effective whitefly controls.

May lead to a rapid method for detecting the disease in commercial strawberries

Aphid control on potatoes by the use of some of the newer organic chemical compounds as aphicides was studied in the spring of 1948 in two series of small replicated plots in Kern County.

Background: The effect of a liberal transfusion strategy as compared with a restrictive strategy on outcomes in critically ill patients with traumatic brain injury is unclear., Methods: We randomly assigned adults with moderate or severe traumatic brain injury and anemia to receive transfusion of red cells according to a liberal strategy (transfusions initiated at a hemoglobin level of ≤10 g per deciliter) or a restrictive strategy (transfusions initiated at ≤7 g per deciliter). The primary outcome was an unfavorable outcome as assessed by the score on the Glasgow Outcome Scale-Extended at 6 months, which we categorized with the use of a sliding dichotomy that was based on the prognosis of each patient at baseline. Secondary outcomes included mortality, functional independence, quality of life, and depression at 6 months., Results: A total of 742 patients underwent randomization, with 371 assigned to each group. The analysis of the primary outcome included 722 patients. The median hemoglobin level in the intensive care unit was 10.8 g per deciliter in the group assigned to the liberal strategy and 8.8 g per deciliter in the group assigned to the restrictive strategy. An unfavorable outcome occurred in 249 of 364 patients (68.4%) in the liberal-strategy group and in 263 of 358 (73.5%) in the restrictive-strategy group (adjusted absolute difference, restrictive strategy vs. liberal strategy, 5.4 percentage points; 95% confidence interval, -2.9 to 13.7). Among survivors, a liberal strategy was associated with higher scores on some but not all the scales assessing functional independence and quality of life. No association was observed between the transfusion strategy and mortality or depression. Venous thromboembolic events occurred in 8.4% of the patients in each group, and acute respiratory distress syndrome occurred in 3.3% and 0.8% of patients in the liberal-strategy and restrictive-strategy groups, respectively., Conclusions: In critically ill patients with traumatic brain injury and anemia, a liberal transfusion strategy did not reduce the risk of an unfavorable neurologic outcome at 6 months. (Funded by the Canadian Institutes of Health Research and others; HEMOTION ClinicalTrials.gov number, NCT03260478.)., (Copyright © 2024 Massachusetts Medical Society.)

Objectives: To evaluate the effectiveness of ICU rounding checklists on outcomes., Data Sources: Five electronic databases (MEDLINE, Embase, CINAHL, Cochrane Library, and Google Scholar) were searched from inception to May 10, 2024., Study Selection: Cohort studies, case-control studies, and randomized controlled trials comparing the use of rounding checklists to no checklists were included. Other article types were excluded., Data Extraction: The primary outcome was in-hospital mortality. Secondary outcomes included ICU and 30-day mortality; hospital and ICU length of stay (LOS); duration of mechanical ventilation; and frequency of catheter-associated urinary tract infections, central line-associated bloodstream infections (CLABSI), and ventilator-associated pneumonia. Additional outcomes included healthcare provider perceptions of checklists., Data Synthesis: Pooled estimates were obtained using an inverse-variance random-effects meta-analysis model. Certainty of evidence was evaluated using Grading of Recommendations Assessment, Development, and Evaluation. There were 30 included studies (including > 32,000 patients) in the review. Using an ICU rounding checklist was associated with reduced in-hospital mortality (risk ratio [RR] 0.80; 95% CI, 0.70-0.92; 12 observational studies; 17,269 patients; I2 = 48%; very low certainty of evidence). The use of an ICU rounding checklist was also associated with reduced ICU mortality (8 observational studies, p = 0.006), 30-day mortality (2 observational studies, p < 0.001), hospital LOS (11 observational studies, p = 0.02), catheter-associated urinary tract infections (CAUTI) (6 observational studies, p = 0.01), and CLABSI (6 observational studies, p = 0.02). Otherwise, there were no significant differences with using ICU rounding checklists on other patient-related outcomes. Healthcare providers' perceptions of checklists were generally positive., Conclusions: The use of an ICU rounding checklist may improve in-hospital mortality, as well as other important patient-related outcomes. However, well-designed randomized studies are necessary to increase the certainty of evidence and determine which elements should be included in an ICU rounding checklist., (Copyright © 2024 The Authors. Published by Wolters Kluwer Health, Inc. on behalf of the Society of Critical Care Medicine.)

Background: Whether proton-pump inhibitors are beneficial or harmful for stress ulcer prophylaxis in critically ill patients undergoing invasive ventilation is unclear., Methods: In this international, randomized trial, we assigned critically ill adults who were undergoing invasive ventilation to receive intravenous pantoprazole (at a dose of 40 mg daily) or matching placebo. The primary efficacy outcome was clinically important upper gastrointestinal bleeding in the intensive care unit (ICU) at 90 days, and the primary safety outcome was death from any cause at 90 days. Multiplicity-adjusted secondary outcomes included ventilator-associated pneumonia, Clostridioides difficile infection, and patient-important bleeding., Results: A total of 4821 patients underwent randomization in 68 ICUs. Clinically important upper gastrointestinal bleeding occurred in 25 of 2385 patients (1.0%) receiving pantoprazole and in 84 of 2377 patients (3.5%) receiving placebo (hazard ratio, 0.30; 95% confidence interval [CI], 0.19 to 0.47; P<0.001). At 90 days, death was reported in 696 of 2390 patients (29.1%) in the pantoprazole group and in 734 of 2379 patients (30.9%) in the placebo group (hazard ratio, 0.94; 95% CI, 0.85 to 1.04; P = 0.25). Patient-important bleeding was reduced with pantoprazole; all other secondary outcomes were similar in the two groups., Conclusions: Among patients undergoing invasive ventilation, pantoprazole resulted in a significantly lower risk of clinically important upper gastrointestinal bleeding than placebo, with no significant effect on mortality. (Funded by the Canadian Institutes of Health Research and others; REVISE ClinicalTrials.gov number, NCT03374800.)., (Copyright © 2024 Massachusetts Medical Society.)

To determine the number of patients with acute respiratory distress syndrome (ARDS) who would be eligible to receive veno-venous extracorporeal membrane oxygenation (VV-ECMO). We conducted a retrospective observational study of ARDS patients admitted to Regina General Hospital Intensive Care Unit (ICU). VV-ECMO eligibility was assessed using selection criteria from the Extracorporeal Membrane Oxygenation for Severe Acute Respiratory Syndrome trial (EOLIA), the Extracorporeal Life Support Organization (ELSO), New South Wales (NSW), Critical Care Services Ontario (CCSO) and a Regina-restrictive criteria. Of 415 patients admitted between October 16, 2018, and January 21, 2021, 103 (25%) had mild, 175 (42%) had moderate, and 64 (15%) had severe ARDS. Of the cohort, 144 (35%) had bacterial pneumonia, 86 (21%) had viral pneumonia (including COVID-19), and 72 (17%) had aspiration pneumonia. Using the EOLIA, ELSO, NSW, CCSO and Regina-restrictive criteria, 7/415 (1.7%), 6/415 (1.5%), 19/415 (4.6%), 26/415 (6.3%) and 12/415 (2.9%) were eligible for VV-ECMO, respectively. Of all ECMO-eligible patients, only one (2.4%) actually received VV-ECMO, 20/42 (48%) received prone positioning and 21/42 (50%) received neuromuscular blockade. There is potential for service expansion of VV-ECMO in Regina; however, there is still a need to improve the delivery of evidence-based ARDS therapies., (© 2023. Springer Nature Limited.)

Triple arthrodesis is a time-tested procedure toward primary salvage in the context of posterior tibial tendon dysfunction, symptomatic rigid and severe hindfoot malalignment, end-stage degenerative and posttraumatic arthritis, and sequelae of paralytic diseases. Today, the indication for hindfoot arthrodesis is applied to correct painful deformities and arthritic joints, such as advanced cases of adult-acquired flatfoot secondary to ligament collapse and insufficiency of the posterior tibial tendon. Although the triple arthrodesis is an effective and reliable outcome procedure, the popularity of a medial double arthrodesis has increased., (Published by Elsevier Inc.)

Background: Among critically ill patients receiving mechanical ventilation, Candida spp. are commonly detected in the lower respiratory tract (LRT). This is generally considered to represent colonization., Objective: To evaluate the use of antifungal treatments and the clinical outcomes of patients with Candida colonization of the LRT., Methods: This retrospective analysis involved consecutive patients admitted to the intensive care unit between April 2016 and May 2021with positive results on Candida spp. testing of LRT samples. Data related to antifungal treatment and clinical outcomes were analyzed descriptively, and multivariable logistic regression was performed., Results: Of 200 patients initially identified, 160 (80%) died in hospital. Antifungal therapy was given to 103 (51.5%) of the patients, with treatment being more likely among those with shock and those who received parenteral nutrition. Mortality was high among patients with positive Candida results on LRT culture, regardless of treatment. Multivariable logistic regression, with adjustment for age, sex, comorbidities, and sequential organ failure assessment (SOFA) score, showed that antifungal treatment was associated with lower odds of death (odds ratio 0.39, 95% confidence interval 0.17-0.87) compared with no treatment (p = 0.021)., Conclusions: This study showed higher mortality rates than have been reported previously. Further investigation into the role of antifungal therapy among critically ill patients with Candida spp. colonization is required., Competing Interests: Competing interests: None declared., (2023 Canadian Society of Hospital Pharmacists. All content in the Canadian Journal of Hospital Pharmacy is copyrighted by the Canadian Society of Hospital Pharmacy. In submitting their manuscripts, the authors transfer, assign, and otherwise convey all copyright ownership to CSHP.)

Exploitation of wildlife represents one of the greatest threats to species survival according to the Intergovernmental Science-Policy Platform on Biodiversity and Ecosystem Services. Whilst detrimental impacts of illegal trade are well recognised, legal trade is often equated to being sustainable despite the lack of evidence or data in the majority of cases. We review the sustainability of wildlife trade, the adequacy of tools, safeguards, and frameworks to understand and regulate trade, and identify gaps in data that undermine our ability to truly understand the sustainability of trade. We provide 183 examples showing unsustainable trade in a broad range of taxonomic groups. In most cases, neither illegal nor legal trade are supported by rigorous evidence of sustainability, with the lack of data on export levels and population monitoring data precluding true assessments of species or population-level impacts. We propose a more precautionary approach to wildlife trade and monitoring that requires those who profit from trade to provide proof of sustainability. We then identify four core areas that must be strengthened to achieve this goal: (1) rigorous data collection and analyses of populations; (2) linking trade quotas to IUCN and international accords; (3) improved databases and compliance of trade; and (4) enhanced understanding of trade bans, market forces, and species substitutions. Enacting these core areas in regulatory frameworks, including CITES, is essential to the continued survival of many threatened species. There are no winners from unsustainable collection and trade: without sustainable management not only will species or populations become extinct, but communities dependent upon these species will lose livelihoods., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper. However, the authors are members of the following IUCN/SSC specialist groups: Asian Songbird Trade (VN, CSR), pigeon and dove (CSR), hornbill (CSR), primates (VN), bears (VN, CSR), pangolin (CRS), small carnivores (CRS), otter (CRS), tortoise and freshwater turtles (CRS, MA, SA), skinks (JJ), monitor lizards (MA, JJ, ES), molluscs (VN). Their views may or may not represent those of some members of the IUCN/SSC. Some of the authors are previous (VN) or current members (JJ) of national CITES Scientific Authorities. This manuscript represents the views of the authors and does not necessarily reflect that of the respective CITES Scientific Authorities., (Copyright © 2023 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Monitoring of residual host cell proteins (HCPs) in therapeutic protein is essential to ensure product quality, safety and efficacy. Despite the development of advanced mass spectrometry techniques and optimized workflows, identifying and quantifying all problematic HCPs present at low levels remain challenging. Here, we developed a practical, effective strategy for the identification and quantification of low abundance HCPs, which facilitates the improvement of downstream purification process to eliminate potentially problematic HCPs. A case study of using this strategy to investigate a problematic HCP is presented. Initially, a commonly used native digestion approach coupled with UPLC-MS/MS was applied for HCP profiling, wherein several lipases and proteases were identified in a monoclonal antibody named mAb1 in early stages of purification process development. A highly active lipase, liver carboxylesterase (CES), was found to be responsible for polysorbate 80 degradation. To facilitate process improvement, after the identification of CES, we developed a highly sensitive LC-MS/MS-MRM assay with a lower limit of quantification of 0.05 ppm for routine monitoring of the CES in mAb1 produced through the different processes. This workflow was applied in low-level lipase identification and absolute quantification, which facilitated the investigation of polysorbate degradation and downstream purification improvement to further remove the problematic HCP. The current MRM method increased the sensitivity of HCP quantification by over 10-fold that in previously published studies, thus meeting the needs for quantification of problematic HCPs at sub-ppm to ppb levels during drug development. This workflow could be readily adapted to the detection and quantification of other problematic HCPs present at extremely low levels in therapeutic protein drug candidates., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 The Authors. Published by Elsevier Inc. All rights reserved.)

Hepatocellular carcinoma (HCC) is the most common primary malignant tumor of the liver worldwide. Noninvasive diagnosis of HCC is possible based on imaging features, without the need for tissue diagnosis. Liver Imaging Reporting and Data System (LI-RADS) CT/MRI diagnostic algorithm allows for standardized radiological interpretation and reporting of imaging studies for patients at high risk for HCC. Diagnostic categories of LR-1 to LR-5 designate each liver observation to reflect the probability of overall malignancy, HCC, or benignity based on imaging features, where LR-5 category has > 95% probability of HCC. Optimal imaging protocol and scanning technique as described by the technical recommendations for LI-RADS are essential for the depiction of features to accurately characterize liver observations. The LI-RADS MRI technical guidelines recommend the minimum required sequences of T1-weighted out-of-phase and in-phase Imaging, T2-weighted Imaging, and multiphase T1-weighted Imaging. Additional sequences, including diffusion-weighted imaging, subtraction imaging, and the hepatobiliary phase when using gadobenate dimeglumine as contrast, improve diagnostic confidence, but are not required by the guidelines. These optional sequences can help differentiate true lesions from pseudolesions, detect additional observations, identify parenchymal observations when other sequences are suboptimal, and improve observations conspicuity. This manuscript reviews the optional sequences, the advantages they offer, and discusses technical optimization of these sequences to obtain the highest image quality and to avoid common artifacts., (© 2022. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Objectives: Critically ill patients are increasingly being discharged directly home from PICU as opposed to discharged home, via the ward. The objective was to assess the prevalence, safety, and satisfaction of discharge directly home from PICUs., Data Sources: We searched PubMed, Medline, EMBASE, PsycINFO, and CINAHL for studies published between January 1991 and June 2021., Study Selection: We included observational or randomized studies, of children up to 18 years old, that reported on the prevalence, safety, or satisfaction of discharge directly home from the PICU, compared with the ward. Safety outcomes included readmission, unplanned visits to hospital, and any adverse events. We excluded case series, reviews, and studies discharging patients to other facilities., Data Extraction: Two independent reviewers evaluated 88 full-text articles; five studies met eligibility (362,868 patients). Only one study had discharge directly home as a primary outcome., Data Synthesis: Prevalence of discharge directly to home from the PICU ranged from less than 1% to 23% (random effects proportion 7.7 [95% CI, 1.3-18.6]). Readmissions to the PICU (only safety outcome) were significantly lower in the discharge directly home group compared with the ward group, in two of three studies (p < 0.0001). No studies reported on patient or family satisfaction., Conclusions: The prevalence of discharge directly home from the PICU ranges from 1% to 23%. PICU readmission rates do not appear to increase after discharge directly home. Caution is needed in the interpretation of the results, given the significant heterogeneity of the included studies. Further high-quality studies are needed to evaluate the safety of discharge directly home from the PICU and support families in this transition., Competing Interests: Dr. Daoust received a student bursary from Dr. Roumeliotis for her research work on this project over the summer of 2021. Dr. Sy’s institution received funding from the Saskatchewan Health Research Foundation; he disclosed that he is currently funded by a Saskatchewan Health Research Foundation Grant. Dr. Lau’s institution received funding from the University of Alberta Hospital Foundation and the EuroQoL Foundation. The remaining authors have disclosed that they do not have any potential conflicts of interest., (Copyright © 2023 by the Society of Critical Care Medicine and the World Federation of Pediatric Intensive and Critical Care Societies.)

Objectives: Few surveys have focused on physician moral distress, burnout, and professional fulfilment. We assessed physician wellness and coping during the COVID-19 pandemic., Design: Cross-sectional survey using four validated instruments., Setting: Sixty-two sites in Canada and the United States., Subjects: Attending physicians (adult, pediatric; intensivist, nonintensivist) who worked in North American ICUs., Intervention: None., Measurements and Main Results: We analysed 431 questionnaires (43.3% response rate) from 25 states and eight provinces. Respondents were predominantly male (229 [55.6%]) and in practice for 11.8 ± 9.8 years. Compared with prepandemic, respondents reported significant intrapandemic increases in days worked/mo, ICU bed occupancy, and self-reported moral distress (240 [56.9%]) and burnout (259 [63.8%]). Of the 10 top-ranked items that incited moral distress, most pertained to regulatory/organizational ( n = 6) or local/institutional ( n = 2) issues or both ( n = 2). Average moral distress (95.6 ± 66.9), professional fulfilment (6.5 ± 2.1), and burnout scores (3.6 ± 2.0) were moderate with 227 physicians (54.6%) meeting burnout criteria. A significant dose-response existed between COVID-19 patient volume and moral distress scores. Physicians who worked more days/mo and more scheduled in-house nightshifts, especially combined with more unscheduled in-house nightshifts, experienced significantly more moral distress. One in five physicians used at least one maladaptive coping strategy. We identified four coping profiles (active/social, avoidant, mixed/ambivalent, infrequent) that were associated with significant differences across all wellness measures., Conclusions: Despite moderate intrapandemic moral distress and burnout, physicians experienced moderate professional fulfilment. However, one in five physicians used at least one maladaptive coping strategy. We highlight potentially modifiable factors at individual, institutional, and regulatory levels to enhance physician wellness., Competing Interests: Dr. Burns disclosed that the Canadian Critical Care Society (CCSS) paid for the statistical analyses. Dr. Lorens received funding from the CCCS. Drs. Lorens and Kerlin disclosed work for hire. Drs. Viglianti, Kohn, Peltan, and Schnapp received support for article research from the National Institutes of Health (NIH). Dr. Fox-Robichaud’s institution received funding from the Canadian Institutes of Health Research and Hamilton Academic Hospitals. Dr. Mathews’ institution received funding from the National Heart, Lung, and Blood Institute (NHLBI); he received funding from Roivant/Kinevant Sciences. Dr. Jain is supported by the National Institute on Aging (NIA) T32AG019134, the Pepper Scholar Award from Yale Claude D. Pepper Older American Independence Center (P30AG021342), NIA of the NIH GEMSSTAR Award (R03AG078942), Parker B. Francis Fellowship Award, and Yale Physician-Scientist Development Award. Drs. Akgun and Crothers disclosed government work. Dr. Gershengorn received funding from the American Thoracic Society (ATS), Gilead Sciences, and Southeastern Critical Care Summit. Dr. Martin’s institution received funding from BARDA; he received funding from Genetech. Dr. Stapleton disclosed that she is chair of DSMB for Altimmune and a member of the ATS Board of Directors 2019–2021 (elected to Chair the Critical Care Assembly which includes a position on the Board). Dr. Attia’s institution received funding from the NHBLI (NHLBI K23 HL129888 and R03 [pending]), the Centers for Aids Research, and Pediatric HIV/AIDS Cohort Study. Dr. Maddux’s institution received funding from the National Institute of Child Health and Human Development (K23HD096018) and the Francis Family Foundation. Dr. Bagshaw received funding from Baxter and Bioporto. Dr. Crothers’ institution received funding from the NIH and Veteran’s Affairs. Dr. Peltan’s institution received funding from Regeneron and Asahi Kasei Pharma; he received funding from the NIH (K23GM129661) and Janssen. Dr. Schnapp received funding from UptoDate and Elsevier. Dr. Kraft’s institution received funding from the NIH, the American Lung Association, Sanofi, and AstraZeneca Consulting; she received funding from Sanofi, Astra-Zeneca, Chiesi Speaking, and UptoDate; she disclosed she is a cofounder and Chief Medical Officer of RaeSedo LLC. The remaining authors have disclosed that they do not have any potential conflicts of interest., (Copyright © 2022 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the Society of Critical Care Medicine and Wolters Kluwer Health, Inc.)