Skeletal muscle BMAL1 is necessary for transcriptional adaptation of local and peripheral tissues in response to endurance exercise training.

OBJECTIVE: In this investigation, we addressed the contribution of the core circadian clock factor, BMAL1, in skeletal muscle to both acute transcriptional responses to exercise and transcriptional remodeling in response to exercise training. Additionally, we adopted a systems biology approach to investigate how loss of skeletal muscle BMAL1 altered peripheral tissue homeostasis as well as exercise training adaptations in iWAT, liver, heart, and lung of male mice. METHODS: Combining inducible skeletal muscle specific BMAL1 knockout mice, physiological testing and standardized exercise protocols, we performed a multi-omic analysis (transcriptomics, chromatin accessibility and metabolomics) to explore loss of muscle BMAL1 on muscle and peripheral tissue responses to exercise. RESULTS: Muscle-specific BMAL1 knockout mice demonstrated a blunted transcriptional response to acute exercise, characterized by the lack of upregulation of well-established exercise responsive transcription factors including Nr4a3 and Ppargc1a. Six weeks of exercise training in muscle-specific BMAL1 knockout mice induced significantly greater and divergent transcriptomic and metabolomic changes in muscle. Surprisingly, liver, lung, inguinal white adipose and heart showed divergent exercise training transcriptomes with less than 5% of 'exercise-training' responsive genes shared for each tissue between genotypes. CONCLUSIONS: Our investigation has uncovered the critical role that BMAL1 plays in skeletal muscle as a key regulator of gene expression programs for both acute exercise and training adaptations. In addition, our work has uncovered the significant impact that altered exercise response in muscle and its likely impact on the system plays in the peripheral tissue adaptations to exercise training. Our work also demonstrates that if the muscle adaptations diverge to a more maladaptive state this is linked to increased gene expression signatures of inflammation across many tissues. Understanding the molecular targets and pathways contributing to health vs. maladaptive exercise adaptations will be critical for the next stage of therapeutic design for exercise mimetics.

Physiology evolves convergently but lags behind warming in cities.

Cities, through the generation of urban heat islands, provide a venue for exploring contemporary convergent evolution to climatic warming. We quantified how repeatable the evolution of heat tolerance, cold tolerance, and body size were among diverse lineages in response to urban heat islands. Our study revealed significant shifts towards higher heat tolerance and diminished cold tolerance among urban populations. We further found that the magnitude of trait divergence was significantly and positively associated with the magnitude of the urban heat island, suggesting that temperature played a major role in the observed divergence in thermal tolerance. Despite these trends, the magnitude of trait responses lagged behind environmental warming. Heat tolerance responses exhibited a deficit of 0.84°C for every 1°C increase in warming, suggesting limits on adaptive evolution and consequent adaptational lags. Other moderators were predictive of greater divergence in heat tolerance, including lower baseline tolerance and greater divergence in body size. Although terrestrial species did not exhibit systematic shifts towards larger or smaller body size, aquatic species exhibited significant shifts towards smaller body size in urban habitats. Our study demonstrates how cities can be used to address long-standing questions in evolutionary biology regarding the repeatability of evolution. Importantly, this work also shows how cities can be used as forecasting tools by quantifying adaptational lags and by developing trait-based associations with responses to contemporary warming.

Exploring a targeted approach for public health capacity restrictions during COVID-19 using a new computational model.

This work introduces the Queen's University Agent-Based Outbreak Outcome Model (QUABOOM). This tool is an agent-based Monte Carlo simulation for modelling epidemics and informing public health policy. We illustrate the use of the model by examining capacity restrictions during a lockdown. We find that public health measures should focus on the few locations where many people interact, such as grocery stores, rather than the many locations where few people interact, such as small businesses. We also discuss a case where the results of the simulation can be scaled to larger population sizes, thereby improving computational efficiency.

Tourniquet does not affect intraoperative kinematics during total knee arthroplasty: Results of a prospective study using a robotic assistance system.

PURPOSE: Tourniquet use during total knee arthroplasty (TKA) remains controversial. There are limited data demonstrating the effect of tourniquet use on flexion and extension gaps. The use of a tourniquet can theoretically affect the kinematics of the knee joint, specifically the extension and flexion gaps and the laxity, by mechanically compressing the soft tissues including the muscles above the knee joint. Therefore, this study was designed to prospectively evaluate changes in flexion and extension gaps with and without the use of a tourniquet. METHODS: The following prospective study included 50 consecutive patients who underwent TKA using a surgical robot. The inclusion criteria were advanced osteoarthritis (OA) and varus-alignment or valgus-alignment <3° (hip-knee-ankle angle, standing long-leg X-ray), and the exclusion criteria were BMI >35 kg/m2 and mechanical axis in >3° valgus. A CR-TKA was performed, and the medial and lateral gaps (in mm) throughout the full range of motion in 10° increments were recorded. The procedure was conducted both with and without an applied tourniquet (350 mmHg). RESULTS: No significant differences were observed in the medial joint space. By contrast, the lateral gap showed significant differences in 10-20° of flexion (with a tourniquet 1.9 mm vs. without a tourniquet 2.1 mm, p = 0.018), 20-30° (1.6 vs. 1.8 mm, p = 0.02), 100-110° (0.9 vs. 1.1 mm, p = 0.021), and 110-120° (0.8 vs. 1 mm, p = 0.038). Thus, at the above degrees of flexion on the lateral side, there was a decrease in the mean of 0.2 mm with the use of a tourniquet. CONCLUSION: Although the use of a tourniquet showed a detectable change in the lateral gap in four 10° segments of flexion, clinical relevance with an average difference of 0.2 mm is not achieved. Thus, the use of a tourniquet in TKA can still be advocated based on the presented data. LEVEL OF EVIDENCE: Level I.

Oxidative stress mediates associations between preoperative psychosocial phenotype and pain-related outcomes at 6 months following total knee arthroplasty: a longitudinal cohort study.

OBJECTIVE: Greater preoperative depression, anxiety, and pain catastrophizing are associated with more severe long-term pain following total knee arthroplasty (TKA). In a secondary analysis of previously reported data, we tested the hypothesis that these associations are mediated by oxidative stress (OS). DESIGN: A mixed between/within-subjects longitudinal cohort design. SETTING: A single academic medical center. SUBJECTS: Osteoarthritis patients (n = 91; 62.6% female) undergoing unilateral TKA. METHODS: We assessed depression, anxiety, and catastrophizing, as well as markers of central sensitization (widespread pain, temporal summation of pain) preoperatively. Blood samples were then obtained immediately prior to intraoperative tourniquet placement for quantification of in vivo biomarkers of systemic OS, F2-isoprostanes and isofurans. Post-TKA pain intensity (numeric rating scale worst pain [NRS], McGill Pain Questionnaire-2 [MPQ-2]) and function (PROMIS Pain Interference) were assessed at 6 months following TKA. RESULTS: Greater preoperative depression, catastrophizing, and widespread pain were associated with higher intraoperative combined OS (F2-isoprostanes+isofurans/2), which was in turn associated with higher post-TKA pain intensity and worse function (P < .05). All preoperative phenotype predictors except anxiety were correlated positively with post-TKA pain and/or function (P < .05). Bootstrapped mediation analyses revealed significant (P < .05) indirect (mediated) effects of depression (NRS Worst Pain, MPQ-2, PROMIS Pain Interference), anxiety (MPQ-2, PROMIS Pain Interference), and catastrophizing (PROMIS Pain Interference) on adverse long-term post-TKA outcomes via elevated OS. Central sensitization-related predictors demonstrated only direct effects (P < .05) on post-TKA outcomes that were independent of OS mechanisms. CONCLUSIONS: Results suggest that the adverse impact of depression, anxiety, and pain catastrophizing on post-TKA pain and functional outcomes are mediated in part by elevated OS.

Arthroscopy Association of Canada Position Statement on Opioid Prescription After Arthroscopic Surgery.

Background: Despite the ongoing opioid epidemic, most patients are still prescribed a significant number of opioid medications for pain management after arthroscopic surgery. There is a need for consensus among orthopaedic surgeons and solutions to aid providers in analgesic strategies that reduce the use of opioid pain medications. Purpose: This position statement was developed with a comprehensive systematic review and meta-analysis of exclusively randomized controlled trials (RCTs) to synthesize the best available evidence for managing acute postoperative pain after arthroscopic surgery. Study Design: Position statement. Methods: The Embase, MEDLINE, PubMed, Scopus, and Web of Science databases were searched from inception until August 10, 2022. Keywords included arthroscopy, opioids, analgesia, and pain, and associated variations. We included exclusively RCTs on adult patients to gather the best available evidence for managing acute postoperative pain after arthroscopic surgery. Patient characteristics, pain, and opioid data were extracted, data were analyzed, and trial bias was evaluated. Results: A total of 21 RCTs were identified related to the prescription of opioid-sparing pain medication after arthroscopic surgery. The following recommendations regarding noninvasive, postoperative pain management strategies were made: (1) multimodal oral nonopioid analgesic regimens-including at least 1 of acetaminophen-a nonsteroidal anti-inflammatory drug-can significantly reduce opioid consumption with no change in pain scores; (2) cryotherapy is likely to help with pain management, although the evidence on the optimal method of application (continuous-flow vs ice pack application) is unclear; (3) and (4) limited RCT evidence supports the efficacy of transcutaneous electrical nerve stimulation and relaxation exercises in reducing opioid consumption after arthroscopy; and (5) limited RCT evidence exists against the efficacy of transdermal lidocaine patches in reducing opioid consumption. Conclusion: A range of nonopioid strategies exist that can reduce postarthroscopic procedural opioid consumption with equivalent vocal pain outcomes. Optimal strategies include multimodal analgesia with education and restricted/reduced opioid prescription.

Spt5 C-terminal repeat domain phosphorylation and length negatively regulate heterochromatin through distinct mechanisms.

Heterochromatin is a condensed chromatin structure that represses transcription of repetitive DNA elements and developmental genes, and is required for genome stability. Paradoxically, transcription of heterochromatic sequences is required for establishment of heterochromatin in diverse eukaryotic species. As such, components of the transcriptional machinery can play important roles in establishing heterochromatin. How these factors coordinate with heterochromatin proteins at nascent heterochromatic transcripts remains poorly understood. In the model eukaryote Schizosaccharomyces pombe (S. pombe), heterochromatin nucleation can be coupled to processing of nascent transcripts by the RNA interference (RNAi) pathway, or to other post-transcriptional mechanisms that are RNAi-independent. Here we show that the RNA polymerase II processivity factor Spt5 negatively regulates heterochromatin in S. pombe through its C-terminal domain (CTD). The Spt5 CTD is analogous to the CTD of the RNA polymerase II large subunit, and is comprised of multiple repeats of an amino acid motif that is phosphorylated by Cdk9. We provide evidence that genetic ablation of Spt5 CTD phosphorylation results in aberrant RNAi-dependent nucleation of heterochromatin at an ectopic location, as well as inappropriate spread of heterochromatin proximal to centromeres. In contrast, truncation of Spt5 CTD repeat number enhanced RNAi-independent heterochromatin formation and bypassed the requirement for RNAi. We relate these phenotypes to the known Spt5 CTD-binding factor Prf1/Rtf1. This separation of function argues that Spt5 CTD phosphorylation and CTD length restrict heterochromatin through unique mechanisms. More broadly, our findings argue that length and phosphorylation of the Spt5 CTD repeat array have distinct regulatory effects on transcription.

Single-fly assemblies fill major phylogenomic gaps across the Drosophilidae Tree of Life.

Long-read sequencing is driving rapid progress in genome assembly across all major groups of life, including species of the family Drosophilidae, a longtime model system for genetics, genomics, and evolution. We previously developed a cost-effective hybrid Oxford Nanopore (ONT) long-read and Illumina short-read sequencing approach and used it to assemble 101 drosophilid genomes from laboratory cultures, greatly increasing the number of genome assemblies for this taxonomic group. The next major challenge is to address the laboratory culture bias in taxon sampling by sequencing genomes of species that cannot easily be reared in the lab. Here, we build upon our previous methods to perform amplification-free ONT sequencing of single wild flies obtained either directly from the field or from ethanol-preserved specimens in museum collections, greatly improving the representation of lesser studied drosophilid taxa in whole-genome data. Using Illumina Novaseq X Plus and ONT P2 sequencers with R10.4.1 chemistry, we set a new benchmark for inexpensive hybrid genome assembly at US $150 per genome while assembling genomes from as little as 35 ng of genomic DNA from a single fly. We present 183 new genome assemblies for 179 species as a resource for drosophilid systematics, phylogenetics, and comparative genomics. Of these genomes, 62 are from pooled lab strains and 121 from single adult flies. Despite the sample limitations of working with small insects, most single-fly diploid assemblies are comparable in contiguity (>1Mb contig N50), completeness (>98% complete dipteran BUSCOs), and accuracy (>QV40 genome-wide with ONT R10.4.1) to assemblies from inbred lines. We present a well-resolved multi-locus phylogeny for 360 drosophilid and 4 outgroup species encompassing all publicly available (as of August 2023) genomes for this group. Finally, we present a Progressive Cactus whole-genome, reference-free alignment built from a subset of 298 suitably high-quality drosophilid genomes. The new assemblies and alignment, along with updated laboratory protocols and computational pipelines, are released as an open resource and as a tool for studying evolution at the scale of an entire insect family.

Reproductive biology of Gazella arabica: Predictors of offspring weight and short- and long-term offspring survival.

Reproductive traits are central to organismal fitness, and so the factors influencing patterns of reproduction and offspring survival are at the heart of biology. Making use of breeding data collected over 16 years at the King Khalid Wildlife Research Centre in Saudi Arabia, we investigated the reproductive biology of Arabian gazelles Gazella arabica. Offspring survival was mainly a function of birth weight, with heavier offspring having higher survival rates than lighter offspring. However, while sons were heavier than daughters, daughters had higher survival rates. We could not find evidence that giving birth to sons negatively impacts offspring weight in the following year. We uncovered large narrow-sense heritability (h2) in offspring weight at birth, while maternal effects (m2) on birth weight were of lesser importance. However, maternal effects on offspring survival were strong until weaning age, while paternal effects dominated survival to sexual maturity and first reproduction. We propose that variation in maternal postnatal care might overshadow the effects of maternal inheritance of birth weights, while the overall strong heritability of weight at birth and the paternal effects on survival illustrates strong variance in sire fitness based on genetic quality, suggesting a role for sexual selection by female mate choice in wild populations.

Muscle Bmal1 is necessary for normal transcriptomic and metabolomic adaptation to endurance exercise training.

Objective: The skeletal muscle circadian clock plays a pivotal role in muscle homeostasis and metabolic flexibility. Recently, this clock mechanism has been linked to both transcriptional and metabolic responses to acute exercise. However, the contribution of the circadian clock mechanism to the molecular and phenotypic adaptations to exercise training have not been defined. Methods: Inducible skeletal muscle-specific Bmal1-floxed mice were treated with tamoxifen to induce skeletal muscle specific deletion of Bmal1 (iMSBmal1KO) or given a vehicle. Mice were assigned to normal cage conditions, or 6-weeks of progressive treadmill training. Exercise performance, body composition, and tissue/serum indices of metabolic health were assessed over the timecourse of training. Gastrocnemius muscles were collected 48-hours after their last exercise bout for histological, biochemical, and molecular analyses including RNA-sequencing and untargeted metabolomics. Results: Improvements in exercise workload and maximal performance were comparable between iMSBmal1KO mice and vehicle treated controls after 6-weeks of exercise training. However, exercise training in the absence of Bmal1 was not able to rescue the metabolic phenotype and hyperinsulinemia of the iMSBmal1KO mice, attributed to the continued dysregulation of core clock components and gene expression relating to glucose metabolism. Importantly, a much larger and divergent transcriptional reprogramming occurred in the muscle of iMSBmal1KO mice in comparison to their vehicle treated counterparts. This response included a large compensatory upregulation of genes associated with fatty acid ß-oxidation, pyruvate metabolism, citric acid cycle components and oxidative phosphorylation components, including mitochondrial subunits and mitoribosome units. Conclusions: Collectively, we propose that endurance training requires muscle Bmal1, and the core clock network, to elicit well recognized molecular adaptations. In the absence of Bmal1, exercise training results in a much larger and divergent re-networking of the basal skeletal muscle transcriptome and metabolome. We also demonstrate that skeletal muscle Bmal1 is indispensable for the transcriptional regulation of glucose homeostasis, even after a 6-weeks exercise training programme.

Sternal stress fracture presenting as acute chest pain.

Sternal fractures are rare and are typically caused by major trauma such as motor vehicle collisions. However, sternal insufficiency fractures can occur with minimal to no trauma in patients with exaggerated thoracic kyphosis from multiple thoracic compression fractures, especially in the setting of osteoporosis. We describe a case of a sternal insufficiency fracture that presented as chest pain resembling a myocardial infarction. As sternal insufficiency fractures may vary in clinical presentation, this case demonstrates that radiologists should carefully evaluate the sternum, especially when risk factors are present. Furthermore, awareness and identification of these fractures can prevent unnecessary cardiac workups.

Female lizards (Eremias argus) reverse Bergmann's rule across altitude.

The evolution of body size within and among species is predicted to be influenced by multifarious environmental factors. However, the specific drivers of body size variation have remained difficult to understand because of the wide range of proximate factors that covary with ectotherm body sizes across populations with varying local environmental conditions. Here, we used female Eremias argus lizards collected from different populations across their wide range in China, and constructed linear mixed models to assess how climatic conditions and/or available resources at different altitudes shape the geographical patterns of lizard body size across altitude. Lizard populations showed significant differences in body size across altitudes. Furthermore, we found that climatic and seasonal changes along the altitudinal gradient also explained variations in body size among populations. Specifically, body size decreased with colder and drier environmental conditions at high altitudes, reversing Bergmann's rule. Limited resources at high altitudes, measured by the low vegetative index, may also constrain body size. Therefore, our study demonstrates that multifarious environmental factors could strongly influence the intraspecific variation in organisms' body size.

Comparing the signaling and transcriptome profiling landscapes of human iPSC-derived and primary rat neonatal cardiomyocytes.

The inaccessibility of human cardiomyocytes significantly hindered years of cardiovascular research efforts. To overcome these limitations, non-human cell sources were used as proxies to study heart function and associated diseases. Rodent models became increasingly acceptable surrogates to model the human heart either in vivo or through in vitro cultures. More recently, due to concerns regarding animal to human translation, including cross-species differences, the use of human iPSC-derived cardiomyocytes presented a renewed opportunity. Here, we conducted a comparative study, assessing cellular signaling through cardiac G protein-coupled receptors (GPCRs) in rat neonatal cardiomyocytes (RNCMs) and human induced pluripotent stem cell-derived cardiomyocytes. Genetically encoded biosensors were used to explore GPCR-mediated nuclear protein kinase A (PKA) and extracellular signal-regulated kinase 1/ 2 (ERK1/2) activities in both cardiomyocyte populations. To increase data granularity, a single-cell analytical approach was conducted. Using automated high content microscopy, our analyses of nuclear PKA and ERK1/2 signaling revealed distinct response clusters in rat and human cardiomyocytes. In line with this, bulk RNA-seq revealed key differences in the expression patterns of GPCRs, G proteins and downstream effector expression levels. Our study demonstrates that human stem cell-derived models of the cardiomyocyte offer distinct advantages for understanding cellular signaling in the heart.

Keep your cool: Overwintering physiology in response to urbanization in the acorn ant, Temnothorax curvispinosus.

Winter presents a challenge for survival, yet temperate ectotherms have remarkable physiological adaptations to cope with low-temperature conditions. Under recent climate change, rather than strictly relaxing pressure on overwintering survival, warmer winters can instead disrupt these low-temperature trait-environment associations, with negative consequences for populations. While there is increasing evidence of physiological adaptation to contemporary warming during the growing season, the effects of winter warming on physiological traits are less clear. To address this knowledge gap, we performed a common garden experiment using relatively warm-adapted versus cold-adapted populations of the acorn ant, Temnothorax curvispinosus, sampled across an urban heat island gradient, to explore the effects of winter conditions on plasticity and evolution of physiological traits. We found no evidence of evolutionary divergence in chill coma recovery nor in metabolic rate at either of two test temperatures (4 and 10 °C). Although we found the expected plastic response of increased metabolic rate under the 10 °C acute test temperature as compared with the 4 °C test temperature, this plastic response, (i.e., the acute thermal sensitivity of metabolic rate), was not different across populations. Surprisingly, we found that winter-acclimated urban ant populations exhibited higher heat tolerance compared with rural ant populations, and that the magnitude of divergence was comparable to that observed among growing-season acclimated ants. Finally, we found no evidence of differences between populations with respect to changes in colony size from the beginning to the end of the overwintering experiment. Together, these findings indicate that despite the evolution of higher heat tolerance that is often accompanied by losses in low-temperature tolerance, urban acorn ants have retained several components of low-temperature physiological performance when assessed under ecologically relevant overwintering conditions. Our study suggests the importance of measuring physiological traits under seasonally-relevant conditions to understand the causes and consequences of evolutionary responses to contemporary warming.

Behavioral Parent Training via Telehealth for Autistic Children: Further Exploration of Feasibility During the COVID-19 Pandemic.

Objectives: Many autistic children exhibit challenging and disruptive behaviors that can present challenges for both children and their families by interfering with acquisition of adaptive skills and affecting family and peer relationships. Behavioral parent training (BPT) is an evidence-based approach to reducing autistic children's disruptive behavior, but many families face a number of barriers to accessing BPT, such as availability of BPT in their community, and transportation and scheduling challenges. Therefore, we sought to explore the feasibility and promise of effectiveness of adapting an established BPT program to a telehealth format during the COVID-19 pandemic. Methods: A feasibility trial of BPT via telehealth was conducted with fourteen parents of autistic children. Results: Parents and clinicians were able to implement BPT via telehealth with a high degree of fidelity, and parents rated both BPT and the telehealth format favorably. The program also showed promise of effectiveness in reducing autistic children's disruptive behavior, improving their adaptive skills, as well as reducing parents' stress, and improving parents' sense of parenting competence. Conclusions: The findings replicate and extend findings from previous studies, further demonstrating the promise of telehealth as a viable alternative format for delivering BPT. We also explore implications for future research, including the opportunity for more thorough evaluation of the effectiveness of BPT via telehealth.

An alternative mechanism for skeletal muscle dysfunction in long-term post-viral lung disease.

Chronic lung disease is often accompanied by disabling extrapulmonary symptoms, notably skeletal muscle dysfunction and atrophy. Moreover, the severity of respiratory symptoms correlates with decreased muscle mass and in turn lowered physical activity and survival rates. Previous models of muscle atrophy in chronic lung disease often modeled chronic obstructive pulmonary disease (COPD) and relied on cigarette smoke exposure and LPS stimulation, but these conditions independently affect skeletal muscle even without accompanying lung disease. Moreover, there is an emerging and pressing need to understand the extrapulmonary manifestations of long-term post-viral lung disease (PVLD) as found in COVID-19. Here, we examine the development of skeletal muscle dysfunction in the setting of chronic pulmonary disease caused by infection due to the natural pathogen Sendai virus using a mouse model of PVLD. We identify a significant decrease in myofiber size when PVLD is maximal at 49 days after infection. We find no change in the relative types of myofibers, but the greatest decrease in fiber size is localized to fast-twitch-type IIB myofibers based on myosin heavy chain immunostaining. Remarkably, all biomarkers of myocyte protein synthesis and degradation (total RNA, ribosomal abundance, and ubiquitin-proteasome expression) were stable throughout the acute infectious illness and chronic post-viral disease process. Together, the results demonstrate a distinct pattern of skeletal muscle dysfunction in a mouse model of long-term PVLD. The findings thereby provide new insights into prolonged limitations in exercise capacity in patients with chronic lung disease after viral infections and perhaps other types of lung injury.NEW & NOTEWORTHY Our study used a mouse model of post-viral lung disease to study the impact of chronic lung disease on skeletal muscle. The model reveals a decrease in myofiber size that is selective for specific types of myofibers and an alternative mechanism for muscle atrophy that might be independent of the usual markers of protein synthesis and degradation. The findings provide a basis for new therapeutic strategies to correct skeletal muscle dysfunction in chronic respiratory disease.

Recognizing Ethyl Chloride Neurotoxicity: Inhalant Abuse Hidden in Plain Sight.

Ethyl chloride is a common topical anesthetic. However, when abused as an inhalant, effects can range from headaches and dizziness to debilitating neurotoxicity requiring intubation. While previous case reports describe the short-term reversible neurotoxicity of ethyl chloride, ours show chronic morbidity and mortality outcome. During the initial evaluation, it is essential to consider the rising trend of commercially available inhalants being used as recreational drugs. We present a case of a middle-aged man presenting with subacute neurotoxicity due to repeated abuse of ethyl chloride.

Hypernatremia in Diabetic Ketoacidosis: A Rare Metabolic Derangement Requiring a Cautionary Approach in Fluid Resuscitation.

Diabetic ketoacidosis (DKA) with hypernatremia is an atypical metabolic derangement that warrants additional consideration in choosing IV fluids. Our patient, a middle-aged male with a history of insulin-dependent diabetes mellitus type 2 and hypertension, presented with DKA and hypernatremia in the setting of poor intake, community-acquired pneumonia (CAP), and COVID-19. DKA and hypernatremia led to a meticulous approach to fluid resuscitation, where a crystalloid solution was the choice in treating and preventing exacerbation of either condition. Successful treatment of these conditions requires understanding the unique pathophysiology, which demands further research on management.

Factor in Fear: Interference Competition in Polymorphic Spadefoot Toad Tadpoles and Its Potential Role in Disruptive Selection.

Disruptive selection arises when extreme phenotypes have a fitness advantage compared to more-intermediate phenotypes. Theory and evidence suggest that intraspecific resource competition is a key driver of disruptive selection. However, while competition can be indirect (exploitative) or direct (interference), the role of interference competition in disruptive selection has not been tested, and most models of disruptive selection assume exploitative competition. We experimentally investigated whether the type of competition affects the outcome of competitive interactions using a system where disruptive selection is common: Mexican spadefoot toads (Spea multiplicata). Spea tadpoles develop into alternative resource-use phenotypes: carnivores, which consume fairy shrimp and other tadpoles, and omnivores, which feed on algae and detritus. Tadpoles intermediate in phenotype have low fitness when competition is intense, as they are outcompeted by the specialized tadpoles. Our experiments revealed that the presence of carnivores significantly decreased foraging behavior in intermediate tadpoles, and that intermediate tadpoles had significantly lower growth rates in interference competition treatments with carnivores but not with omnivores. Interference competition may therefore be important in driving disruptive selection. As carnivore tadpoles are also cannibalistic, the 'fear' effect may have a greater impact on intermediate tadpoles than exploitative competition alone, similarly to non-consumptive effects in predator-prey or intraguild relationships.

Perceived health interests of college students.

Objective: Investigate how college students perceive positive aspects of health as compared to neutral and/or negative aspects of health. Participants: 20 college students (55% female, 50% Black, M age = 23 years, SD = 4.1 years) completed a card-sorting activity as part of a focus group. Methods: Each participant ranked 57 cards by perceived importance. The cards included positive (n = 19), neutral (n = 19), and negative (n = 19) health topics. Results: Positive and neutral health attributes were significantly more important than negative aspects of health, with student rankings indicating declining importance from positive to neutral to negative aspects of health. Conclusions: Findings suggest that campus health professionals should consider salutogenic approaches to health promotion that enable college students to achieve short-term health gains and health maintenance in addition to disease prevention and harm reduction.