Optimal phenology of life history events in Calanus finmarchicus: exit from diapause in relation to interannual variation in spring bloom timing and predation.

Respiration of lipids by copepods during diapause (overwintering dormancy) contributes to ocean carbon sequestration via the seasonal lipid pump (SLP). Parameterizing this flux in predictive models requires a mechanistic understanding of how life history adaptation in copepods shapes their timing of exit from diapause. We investigate the optimal phenology of Calanus finmarchicus in the Norwegian Sea using an individual-based model in which diapause exit is represented as a trait characterized by phenotypic mean and variance. Without interannual variability, optimal exit correlated with the onset of the spring phytoplankton bloom and phenotypic variance was of no benefit. In contrast, copepods endured reduced fitness and adopted bet-hedging strategies when exposed to interannual variability in bloom timing and predation: later exit from diapause and phenotypic variance maintained adult numbers in anomalous late-bloom years. Exit nevertheless remained well before the peak of the bloom which is a favorable strategy when low predation early in the year enhances survival of eggs and early developmental stages. Our work highlights the complex interactions between C. finmarchicus and its environment and the need for improved understanding of bet-hedging strategies and the cues of diapause exit to progress the representation of the SLP in global biogeochemical models.

A genus-specific nsp12 region impacts polymerase assembly in Alpha- and Gammacoronaviruses.

Coronavirus relevancy for human health has surged over the past 20 years as they have a propensity for spillover into humans from animal reservoirs resulting in pandemics such as COVID-19. The diversity within the Coronavirinae subfamily and high infection frequency in animal species worldwide creates a looming threat that calls for research across all genera within the Coronavirinae subfamily. We sought to contribute to the limited structural knowledge within the Gammacoronavirus genera and determined the structure of the viral core replication-transcription complex (RTC) from Infectious Bronchitis Virus (IBV) using single-particle cryo-EM. Comparison between our IBV structure with published RTC structures from other Coronavirinae genera reveals structural differences across genera. Using in vitro biochemical assays, we characterized these differences and revealed their differing involvement in core RTC formation across different genera. Our findings highlight the value of cross-genera Coronavirinae studies, as they show genera specific features in coronavirus genome replication. A broader knowledge of coronavirus replication will better prepare us for future coronavirus spillovers.

Environmental, economic, and social sustainability in aquaculture: the aquaculture performance indicators.

Aquaculture is a rapidly growing food production technology, but there are significant concerns related to its environmental impact and adverse social effects. We examine aquaculture outcomes in a three pillars of sustainability framework by analyzing data collected using the Aquaculture Performance Indicators. Using this approach, comparable data has been collected for 57 aquaculture systems worldwide on 88 metrics that measure social, economic, or environmental outcomes. We first examine the relationships among the three pillars of sustainability and then analyze performance in the three pillars by technology and species. The results show that economic, social, and environmental outcomes are, on average, mutually reinforced in global aquaculture systems. However, the analysis also shows significant variation in the degree of sustainability in different aquaculture systems, and weak performance of some production systems in some dimensions provides opportunity for innovative policy measures and investment to further align sustainability objectives.

A Case of Stress-Induced Cardiomyopathy After Ketamine Infusion.

We report the case of a 64-year-old female with a history of hypothyroidism and isolated parotid sarcoidosis who presented with acute-onset chest pain and dyspnea. Echocardiogram demonstrated transiently reduced ejection fraction with apical hypokinesis, without evidence of obstructive coronary lesions on angiography, compatible with stress-induced cardiomyopathy. She received a ketamine infusion as a mental health treatment shortly before the development of symptoms, suggesting that this medication may have precipitated her cardiomyopathy. In recent years, ketamine has become a popular option for treating mental health disorders, including major depressive disorder and substance use disorders. It should be used with caution in patients with known cardiovascular disease, and its cardiac effects warrant further study.

Molecular Imaging and Therapy of Differentiated Thyroid Carcinoma in Adults.

ABSTRACT: Differentiated thyroid carcinoma (DTC) has been increasing in incidence in the United States over the last several decades, although mortality rates have remained low. Radioactive iodine therapy (RAI-T) has been a mainstay of treatment for DTC since the 1940s. Imaging of DTC before and after RAI-T primarily focuses on molecular imaging of the sodium iodide symporter. The expanding understanding of the molecular profile of DTC has increased available treatment options. Incorporation of risk stratification to treatment approaches has led to deintensification of both surgical and nonsurgical treatments, leading to decreased morbidity without compromising disease control.

An alphacoronavirus polymerase structure reveals conserved replication factor functions.

Coronaviruses are a diverse subfamily of viruses containing pathogens of humans and animals. This subfamily of viruses replicates their RNA genomes using a core polymerase complex composed of viral non-structural proteins: nsp7, nsp8 and nsp12. Most of our understanding of coronavirus molecular biology comes from betacoronaviruses like SARS-CoV and SARS-CoV-2, the latter of which is the causative agent of COVID-19. In contrast, members of the alphacoronavirus genus are relatively understudied despite their importance in human and animal health. Here we have used cryo-electron microscopy to determine structures of the alphacoronavirus porcine epidemic diarrhea virus (PEDV) core polymerase complex bound to RNA. One structure shows an unexpected nsp8 stoichiometry despite remaining bound to RNA. Biochemical analysis shows that the N-terminal extension of one nsp8 is not required for in vitro RNA synthesis for alpha- and betacoronaviruses. Our work demonstrates the importance of studying diverse coronaviruses in revealing aspects of coronavirus replication and identifying areas of conservation to be targeted by antiviral drugs.

Keeping the promise: a critique of the current state of microdosing research.

Introduction: The practice of taking small, sub-hallucinogenic doses of psychedelics, known as microdosing, has exploded in popularity over the last decade. Users claim benefits ranging from improved mood and enhanced creativity to an increased sense of meaning and connectedness in life. While research on microdosing is still lagging behind the shift in public opinion, several papers have been published in the last five years which attempted to assess the effects of microdosing. Methods: This review paper aimed to critically analyze the research practices used in the recent wave of microdosing research: We reviewed 15 papers published before the closing date of this review in March 2022. Results: Our review concludes that it is premature to draw any conclusions about the efficacy or safety of microdosing since the research quality cannot be considered confirmatory. Discussion: We propose some potential causes for the current state of the literature and some suggestions for how these causes may be ameliorated.

FDG PET/CT Imaging 1 Week after a Single Dose of Pembrolizumab Predicts Treatment Response in Patients with Advanced Melanoma.

PURPOSE: Immunologic response to anti-programmed cell death protein 1 (PD-1) therapy can occur rapidly with T-cell responses detectable in as little as one week. Given that activated immune cells are FDG avid, we hypothesized that an early FDG PET/CT obtained approximately 1 week after starting pembrolizumab could be used to visualize a metabolic flare (MF), with increased tumor FDG activity due to infiltration by activated immune cells, or a metabolic response (MR), due to tumor cell death, that would predict response. PATIENTS AND METHODS: Nineteen patients with advanced melanoma scheduled to receive pembrolizumab were prospectively enrolled. FDG PET/CT imaging was performed at baseline and approximately 1 week after starting treatment. FDG PET/CT scans were evaluated for changes in maximum standardized uptake value (SUVmax) and thresholds were identified by ROC analysis; MF was defined as >70% increase in tumor SUVmax, and MR as >30% decrease in tumor SUVmax. RESULTS: An MF or MR was identified in 6 of 11 (55%) responders and 0 of 8 (0%) nonresponders, with an objective response rate (ORR) of 100% in the MF-MR group and an ORR of 38% in the stable metabolism (SM) group. An MF or MR was associated with T-cell reinvigoration in the peripheral blood and immune infiltration in the tumor. Overall survival at 3 years was 83% in the MF-MR group and 62% in the SM group. Median progression-free survival (PFS) was >38 months (median not reached) in the MF-MR group and 2.8 months (95% confidence interval, 0.3-5.2) in the SM group (P = 0.017). CONCLUSIONS: Early FDG PET/CT can identify metabolic changes in melanoma metastases that are potentially predictive of response to pembrolizumab and significantly correlated with PFS.

The association of intraoperative opioid dose with postanesthesia care unit outcomes in children: a retrospective study.

PURPOSE: In children, the relationship between the dose of intraoperative opioid and postoperative outcomes is unclear. We examined the relationship between intraoperative opioid dose and postanesthesia care unit (PACU) pain scores and opioid and antiemetic administrations. METHODS: We performed a single-institution retrospective cohort study. Patients who were aged < 19 yr, had an American Society of Anesthesiologists Physical Status of I-III, were undergoing one of 11 procedures under general anesthesia and without regional anesthesia, and who were admitted to the PACU were included. Patients were analyzed by quartiles of total intraoperative opioid dose using multivariable regression, adjusting for confounders including procedure. An exploratory analysis of opioid-free anesthetics was also performed. RESULTS: Three thousand, seven hundred and thirty-three cases were included, and the mean age of included patients was 8.3 yr. After adjustment, there were no significant differences between the lowest and higher quartiles for first conscious pain score, mean pain score, PACU opioid dose, or PACU length of stay; in addition, estimated differences were small. Patients in higher quartiles were estimated to be more likely to receive antiemetics, significantly so for those in the second quartile. Patients in the lowest quartile received significantly more intraoperative nonopioid analgesics. In the exploratory analysis, no significant difference in PACU pain scores was found in cases without intraoperative opioids. CONCLUSIONS: Children who received lower doses of intraoperative opioids did not have worse PACU pain outcomes but required fewer antiemetics and received greater numbers of nonopioid analgesics intraoperatively. These findings suggest that lower doses of intraoperative opioids may be administered to children as long as other analgesics are used.

RéSUMé: OBJECTIF: Chez les enfants, la relation entre la dose peropératoire d'opioïdes et les issues postopératoires n'est pas claire. Nous avons examiné la relation entre la dose peropératoire d'opioïdes, les scores de douleur en salle de réveil, et les administrations d'opioïdes et d'antiémétiques. MéTHODE: Nous avons réalisé une étude de cohorte rétrospective dans un seul établissement. Nous avons inclus les patient·es âgé·es < 19 ans ayant un statut physique ASA de I-III et bénéficiant de l'une de 11 interventions sous anesthésie générale et sans anesthésie régionale, et qui avaient été admis·es en salle de réveil. Les patient·es ont été analysé·es par quartiles de la dose totale d'opioïdes peropératoires en utilisant une régression multivariée, en ajustant les données pour tenir compte des facteurs de confusion, notamment de l'intervention. Une analyse exploratoire des anesthésiques sans opioïdes a également été réalisée. RéSULTATS: Au total 3733 cas ont été inclus, et l'âge moyen des enfants était de 8,3 ans. Après ajustement, il n'y avait pas de différences significatives entre les quartiles inférieur et supérieur pour le premier score de douleur chez l'enfant conscient·e, le score de douleur moyen, la dose d'opioïdes en salle de réveil ou la durée du séjour en salle de réveil; de plus, les différences estimées étaient faibles. On a estimé que les patient·es des quartiles supérieurs étaient plus susceptibles de recevoir des antiémétiques et ce, de manière significative pour ceux et celles du deuxième quartile. Les patient·es du quartile inférieur ont reçu significativement plus d'analgésiques non opioïdes peropératoires. Dans l'analyse exploratoire, aucune différence significative dans les scores de douleur en salle de réveil n'a été trouvée dans les cas sans opioïdes peropératoires. CONCLUSION: Les enfants qui ont reçu des doses plus faibles d'opioïdes peropératoires n'ont pas eu de pires issues de douleur en salle de réveil, mais ont eu besoin de moins d'antiémétiques et ont reçu un plus grand nombre d'analgésiques non opioïdes en peropératoire. Ces résultats suggèrent que des doses plus faibles d'opioïdes peropératoires peuvent être administrées aux enfants tant que d'autres analgésiques sont utilisés.

Understanding temporal variability across trophic levels and spatial scales in freshwater ecosystems.

A tenet of ecology is that temporal variability in ecological structure and processes tends to decrease with increasing spatial scales (from locales to regions) and levels of biological organization (from populations to communities). However, patterns in temporal variability across trophic levels and the mechanisms that produce them remain poorly understood. Here we analyzed the abundance time series of spatially structured communities (i.e., metacommunities) spanning basal resources to top predators from 355 freshwater sites across three continents. Specifically, we used a hierarchical partitioning method to disentangle the propagation of temporal variability in abundance across spatial scales and trophic levels. We then used structural equation modeling to determine if the strength and direction of relationships between temporal variability, synchrony, biodiversity, and environmental and spatial settings depended on trophic level and spatial scale. We found that temporal variability in abundance decreased from producers to tertiary consumers but did so mainly at the local scale. Species population synchrony within sites increased with trophic level, whereas synchrony among communities decreased. At the local scale, temporal variability in precipitation and species diversity were associated with population variability (linear partial coefficient, ß = 0.23) and population synchrony (ß = -0.39) similarly across trophic levels, respectively. At the regional scale, community synchrony was not related to climatic or spatial predictors, but the strength of relationships between metacommunity variability and community synchrony decreased systematically from top predators (ß = 0.73) to secondary consumers (ß = 0.54), to primary consumers (ß = 0.30) to producers (ß = 0). Our results suggest that mobile predators may often stabilize metacommunities by buffering variability that originates at the base of food webs. This finding illustrates that the trophic structure of metacommunities, which integrates variation in organismal body size and its correlates, should be considered when investigating ecological stability in natural systems. More broadly, our work advances the notion that temporal stability is an emergent property of ecosystems that may be threatened in complex ways by biodiversity loss and habitat fragmentation.

Five draft genome assemblies from Bacillaceae isolated from a degraded wetland environment.

We isolated five Bacillaceae from a degraded wetland environment and sequenced their genomes using Illumina NextSeq. Here, we report draft genome sequences of Bacillus velezensus-SC119, Priestia megaterium strain SC120, Bacillus zhangzhouensis strain SC123, Bacillus pumilis strain SC124, and Bacillus idriensis strain SC127. The genomes range between 3,657,353 and 5,772,725 bp with % GC between 37.62% and 46.38%.

An alphacoronavirus polymerase structure reveals conserved co-factor functions.

Coronaviruses are a diverse subfamily of viruses containing pathogens of humans and animals. This subfamily of viruses replicates their RNA genomes using a core polymerase complex composed of viral non-structural proteins: nsp7, nsp8 and nsp12. Most of our understanding of coronavirus molecular biology comes from the betacoronaviruses like SARS-CoV and SARS-CoV-2, the latter of which is the causative agent of COVID-19. In contrast, members of the alphacoronavirus genus are relatively understudied despite their importance in human and animal health. Here we have used cryo-electron microscopy to determine the structure of the alphacoronavirus porcine epidemic diarrhea virus (PEDV) core polymerase complex bound to RNA. Our structure shows an unexpected nsp8 stoichiometry in comparison to other published coronavirus polymerase structures. Biochemical analysis shows that the N-terminal extension of one nsp8 is not required for in vitro RNA synthesis for alpha and betacoronaviruses as previously hypothesized. Our work shows the importance of studying diverse coronaviruses to reveal aspects of coronavirus replication while also identifying areas of conservation to be targeted by antiviral drugs.

Focused ultrasound-induced inhibition of peripheral nerve fibers in an animal model of acute pain.

BACKGROUND: Moderate-to-severe acute pain is prevalent in many healthcare settings and associated with adverse outcomes. Peripheral nerve blockade using traditional needle-based and local anesthetic-based techniques improves pain outcomes for some patient populations but has shortcomings limiting use. These limitations include its invasiveness, potential for local anesthetic systemic toxicity, risk of infection with an indwelling catheter, and relatively short duration of blockade compared with the period of pain after major injuries. Focused ultrasound is capable of inhibiting the peripheral nervous system and has potential as a pain management tool. However, investigations of its effect on peripheral nerve nociceptive fibers in animal models of acute pain are lacking. In an in vivo acute pain model, we investigated focused ultrasound's effects on behavior and peripheral nerve structure. METHODS: Focused ultrasound was applied directly to the sciatic nerve of rats just prior to a hindpaw incision; three control groups (focused ultrasound sham only, hindpaw incision only, focused ultrasound sham+hindpaw incision) were also included. For all four groups (intervention and controls), behavioral testing (thermal and mechanical hyperalgesia, hindpaw extension and flexion) took place for 4 weeks. Structural changes to peripheral nerves of non-focused ultrasound controls and after focused ultrasound application were assessed on days 0 and 14 using light microscopy and transmission electron microscopy. RESULTS: Compared with controls, after focused ultrasound application, animals had (1) increased mechanical nociceptive thresholds for 2 weeks; (2) sustained increase in thermal nociceptive thresholds for ≥4 weeks; (3) a decrease in hindpaw motor response for 0.5 weeks; and (4) a decrease in hindpaw plantar sensation for 2 weeks. At 14 days after focused ultrasound application, alterations to myelin sheaths and nerve fiber ultrastructure were observed both by light and electron microscopy. DISCUSSION: Focused ultrasound, using a distinct parameter set, reversibly inhibits A-delta peripheral nerve nociceptive, motor, and non-nociceptive sensory fiber-mediated behaviors, has a prolonged effect on C nociceptive fiber-mediated behavior, and alters nerve structure. Focused ultrasound may have potential as a peripheral nerve blockade technique for acute pain management. However, further investigation is required to determine C fiber inhibition duration and the significance of nerve structural changes.

The process of replication target selection in psychology: what to consider?

Increased execution of replication studies contributes to the effort to restore credibility of empirical research. However, a second generation of problems arises: the number of potential replication targets is at a serious mismatch with available resources. Given limited resources, replication target selection should be well-justified, systematic and transparently communicated. At present the discussion on what to consider when selecting a replication target is limited to theoretical discussion, self-reported justifications and a few formalized suggestions. In this Registered Report, we proposed a study involving the scientific community to create a list of considerations for consultation when selecting a replication target in psychology. We employed a modified Delphi approach. First, we constructed a preliminary list of considerations. Second, we surveyed psychologists who previously selected a replication target with regards to their considerations. Third, we incorporated the results into the preliminary list of considerations and sent the updated list to a group of individuals knowledgeable about concerns regarding replication target selection. Over the course of several rounds, we established consensus regarding what to consider when selecting a replication target. The resulting checklist can be used for transparently communicating the rationale for selecting studies for replication.

Association of Common Pediatric Surgeries With New Onset Chronic Pain in Patients 0-21 Years of Age in the United States.

Chronic pain (CP) is a major public health issue. While new onset CP is known to occur frequently after some pediatric surgeries, its incidence after the most common pediatric surgeries is unknown. This retrospective cohort study used insurance claims data from 2002 to 2017 for patients 0 to 21 years of age. The primary outcome was CP 90 to 365 days after each of the 20 most frequent surgeries in 5 age categories (identified using CP ICD codes). Multivariable logistic regression identified surgeries and risk factors associated with CP after surgery. A total of 424,590 surgical patients aged 0 to 21 were included, 22,361 of whom developed CP in the 90 to 365 days after surgery. The incidences of CP after surgery were: 1.1% in age group 0 to 1 years; 3.0% in 2 to 5 years; 5.6% in 6 to 11 years; 10.1% in 12 to 18 years; 9.9% in 19 to 21 years. Some surgeries and patient variables were associated with CP. Approximately 1 in 10 adolescents who underwent the most common surgeries developed CP, as did a striking percentage of children in other age groups. Given the long-term consequences of CP, resources should be allocated toward identification of high-risk pediatric patients and strategies to prevent CP after surgery. PERSPECTIVE: This study identifies the incidences of and risk factors for chronic pain after common surgeries in patients 0 to 21 years of age. Our findings suggest that resources should be allocated toward the identification of high-risk pediatric patients and strategies to prevent CP after surgery.

Interfering with nucleotide excision by the coronavirus 3'-to-5' exoribonuclease.

Some of the most efficacious antiviral therapeutics are ribonucleos(t)ide analogs. The presence of a 3'-to-5' proofreading exoribonuclease (ExoN) in coronaviruses diminishes the potency of many ribonucleotide analogs. The ability to interfere with ExoN activity will create new possibilities for control of SARS-CoV-2 infection. ExoN is formed by a 1:1 complex of nsp14 and nsp10 proteins. We have purified and characterized ExoN using a robust, quantitative system that reveals determinants of specificity and efficiency of hydrolysis. Double-stranded RNA is preferred over single-stranded RNA. Nucleotide excision is distributive, with only one or two nucleotides hydrolyzed in a single binding event. The composition of the terminal basepair modulates excision. A stalled SARS-CoV-2 replicase in complex with either correctly or incorrectly terminated products prevents excision, suggesting that a mispaired end is insufficient to displace the replicase. Finally, we have discovered several modifications to the 3'-RNA terminus that interfere with or block ExoN-catalyzed excision. While a 3'-OH facilitates hydrolysis of a nucleotide with a normal ribose configuration, this substituent is not required for a nucleotide with a planar ribose configuration such as that present in the antiviral nucleotide produced by viperin. Design of ExoN-resistant, antiviral ribonucleotides should be feasible.

Nailing distal tibial fractures: does entry technique affect distal alignment?

PURPOSE: In treating distal third tibial fractures, restoration of the axial alignment and therefore accurate reduction of the distal fragment minimise the risk of tibiotalar joint malalignment. The aim of this study is to investigate whether there was a difference in accuracy of reduction and axial alignment, when nailing distal third tibial fractures using either the suprapatellar or the infrapatellar tibial nailing entry technique. METHODS: This retrospective cohort study compared alignment of intramedullary nails performed for distal third tibial fractures between 2015 and 2018 through the suprapatellar and infrapatellar approach at a UK Level 1 trauma centre. It compared a consecutive series of 74 suprapatellar nails and 51 infrapatellar nails, with radiographic assessment of tibial alignment in the antero-posterior and sagittal planes. It included inter- and intra-observer analyses of radiographic measurements. RESULTS: In the coronal plane, mean malalignment in the suprapatellar technique group was 2.8 ± 0.7° and 4.7 ± 0.9° in the infrapatellar technique group (P < 0.01). In the sagittal plane, mean malalignment in the suprapatellar technique group was 4.0 ± 0.8° and 3.5 ± 0.9° in the infrapatellar technique group (P = 0.42). Intra- and inter-observer analysis showed strongly positive correlations between observers. CONCLUSIONS: We suggest that the suprapatellar technique may improve coronal plane alignment when intramedullary nailing distal tibial fractures. There was no significant difference in alignment in the sagittal plane. We conclude that the suprapatellar technique may be superior in preventing malalignment when treating distal third tibial fractures, potentially improving clinical outcome.

Treatment of Open Traumatic Medial Malleolus Bone Loss With Osteochondral Allograft: A Case Report.

Osteochondral damage to the ankle joint can be a difficult problem to manage in a young active patient. There are several described surgical treatments ranging from cartilage repair techniques to arthrodesis and ankle replacement. In this case, we present a 28-year-old male who sustained a right type IIIA open medial malleolus fracture following an all-terrain vehicle crash. After sharp debridement, the clinical decision was made to treat the patient with an osteochondral allograft. At one- and two-year post-allograft reconstruction, radiographs demonstrated good incorporation of the graft. The patient was ambulating with no pain or assistive devices. Our case report specifically describes the successful treatment of a traumatic medial malleolus ankle fracture with bone loss using an osteochondral allograft in a young active patient.

Perfusion-only imaging in pregnant women: A comparative reader study with implications for practice patterns.

This study seeks to understand the value of ventilation imaging in pregnant patients imaged for suspected pulmonary embolism (PE). Ventilation-perfusion (VQ) scans in this high-risk population were compared to ventilation-only scans. We hypothesize that in this relatively healthy population, the exclusion of ventilation scans will not impact the rate of scans interpreted as positive. This retrospective blinded comparative reader study on collated VQ scans performed on pregnant patients in the course of routine clinical care in a > 5 year period (03/2012 to 07/2017). Each set of VQ and perfusion only (Q) studies were reviewed by 8 readers (4 nuclear radiology fellows and 4 nuclear medicine faculty) in random order; the Q scans simply omitted the ventilation images. Readers recorded each study as PE, no PE, or non-diagnostic (prospective investigative study of acute PE diagnosis classifications). Logistic mixed effects models were used to test the association between scan type (VQ vs Q). 203 pairs of studies in 197 patients were included (6 patients had 2 scans). Subjects ranged from 14 to 45 years of age, with a median 28 years. A significant association between scan type and positive/negative classification. Q-scans received more positive classifications than VQ-scans (median of 7.6% vs 6.7%). No association was seen between scan type and positive/indeterminate classification, nor between scan type and negative/indeterminate classification. The exclusion of ventilation images in VQ-scans was associated with a higher rate of positive studies, but this difference was small (<1%). Given the overwhelmingly normal percentage of Q-exams (>90% in our study), and the benefits of omitting ventilation imaging, perfusion-only imaging should be considered a reasonable option for imaging the pregnant patient to exclude PE.