Integrated organismal responses induced by projected levels of CO2 and temperature exposures in the early life stages of lake sturgeon.

Atmospheric CO2 and temperature are rising concurrently, and may have profound impacts on the transcriptional, physiological and behavioural responses of aquatic organisms. Further, spring snowmelt may cause transient increases of pCO2 in many freshwater systems. We examined the behavioural, physiological and transcriptomic responses of an ancient fish, the lake sturgeon (Acipenser fulvescens) to projected levels of warming and pCO2 during its most vulnerable period of life, the first year. Specifically, larval fish were raised in either low (16°C) or high (22°C) temperature, and/or low (1000 µatm) or high (2500 µatm) pCO2 in a crossed experimental design over approximately 8 months. Following overwintering, lake sturgeon were exposed to a transient increase in pCO2 of 10,000 µatm, simulating a spring melt based on data in freshwater systems. Transcriptional analyses revealed potential connections to otolith formation and reduced growth in fish exposed to high pCO2 and temperature in combination. Network analyses of differential gene expression revealed different biological processes among the different treatments on the edges of transcriptional networks. Na+/K+-ATPase activity increased in fish not exposed to elevated pCO2 during development, and mRNA abundance of the ß subunit was most strongly predictive of enzyme activity. Behavioural assays revealed a decrease in total activity following an acute CO2 exposure. These results demonstrate compensatory and compounding mechanisms of pCO2 and warming dependent on developmental conditions in lake sturgeon. Conserved elements of the cellular stress response across all organisms provide key information for how other freshwater organisms may respond to future climate change.

l-2-Hydroxyglutarate remodeling of the epigenome and epitranscriptome creates a metabolic vulnerability in kidney cancer models.

Tumor cells are known to undergo considerable metabolic reprogramming to meet their unique demands and drive tumor growth. At the same time, this reprogramming may come at a cost with resultant metabolic vulnerabilities. The small molecule l-2-hydroxyglutarate (l-2HG) is elevated in the most common histology of renal cancer. Similarly to other oncometabolites, l-2HG has the potential to profoundly impact gene expression. Here, we demonstrate that l-2HG remodels amino acid metabolism in renal cancer cells through combined effects on histone methylation and RNA N6-methyladenosine. The combined effects of l-2HG result in a metabolic liability that renders tumors cells reliant on exogenous serine to support proliferation, redox homeostasis, and tumor growth. In concert with these data, high-l-2HG kidney cancers demonstrate reduced expression of multiple serine biosynthetic enzymes. Collectively, our data indicate that high-l-2HG renal tumors could be specifically targeted by strategies that limit serine availability to tumors.

Novel 4th-generation phytase improves broiler growth performance and reduces woody breast severity through modulation of muscle glucose uptake and metabolism.

The objective of the present study was to determine the effect of a novel (4th generation) phytase supplementation as well as its mode of action on growth, meat quality, and incidence of muscle myopathies. One-day old male broilers (n = 720) were weighed and randomly allocated to 30 floor pens (24 birds/pen) with 10 replicate pens per treatment. Three diets were fed from hatch to 56- days-old: a 3-phase corn-soy based diet as a positive control (PC); a negative control (NC) formulated to be isocaloric and isonitrogenous to the PC and with a reduction in Ca and available P, respectively; and the NC supplemented with 2,000 phytase units per kg of diet (NC + P). At the conclusion of the experiment, birds fed with NC + P diet were significantly heavier and had 2.1- and 4.2-points better feed conversion ratio (FCR) compared to birds offered NC and PC diets, respectively. Processing data showed that phytase supplementation increased live weight, hot carcass without giblets, wings, tender, and skin-on drum and thigh compared to both NC and PC diets. Macroscopic scoring showed that birds fed the NC + P diet had lower woody breast (WB) severity compared to those fed the PC and NC diets, however there was no effect on white striping (WS) incidence and meat quality parameters (pH, drip loss, meat color). To delineate its mode of action, iSTAT showed that blood glucose concentrations were significantly lower in birds fed NC + P diet compared to those offered PC and NC diets, suggesting a better glucose uptake. In support, molecular analyses demonstrated that the breast muscle expression (mRNA and protein) of glucose transporter 1 (GLUT1) and glucokinase (GK) was significantly upregulated in birds fed NC + P diet compared to those fed the NC and PC diets. The expression of mitochondrial ATP synthase F0 subunit 8 (MT-ATP8) was significantly upregulated in NC + P compared to other groups, indicating intracellular ATP abundance for anabolic pathways. This was confirmed by the reduced level of phosphorylated-AMP-activated protein kinase (AMPKα1/2) at Thr172 site, upregulation of glycogen synthase (GYS1) gene and activation of mechanistic target of rapamycin and ribosomal protein S6 kinase (mTOR-P70S6K) pathway. In conclusion, this is the first report showing that in-feed supplementation of the novel phytase improves growth performance and reduces WB severity in broilers potentially through enhancement of glucose uptake, glycolysis, and intracellular ATP production, which used for muscle glycogenesis and protein synthesis.

Effect of a microencapsulated phyto/phycogenic blend supplementation on growth performance, processing parameters, meat quality, and sensory profile in male broilers.

Powered by consumer taste, value, and preferences, natural products including phytogenics and algae are increasingly and separately used in the food systems where they have been reported to improve growth performance in poultry and livestock. The present study aimed to determine the effects of a new feed additive, microencapsulated NUQO© NEX, which contains a combination of phytogenic and phycogenic, on broiler growth performance, blood chemistry, bone health, meat quality and sensory profile. Male Cobb500 chicks (n = 1,197) were fed a 3-phase feeding intervals; 1-14d starter, 15-28d grower, and 29-40d finisher. The dietary treatments included a corn-soy basal Control (CON), basal diet supplemented with NUQO© NEX at 100 g/ton from 1 to 28d then 75 g/ton from d 28 to 40 (NEX75), and basal diet supplemented with NUQO© NEX at 100 g/ton from 1 to 40d (NEX100). The NEX100 supplemented birds had 62 g more BWG increase and 2.1-point improvement in FCR compared with CON in the finisher and overall growth phase (p < 0.05), respectively. Day 40 processing body weights and carcass weights were heavier for the NEX100 supplemented birds (p < 0.05). The incidences of muscle myopathies were also higher in NEX treatments, which could be associated with the heavier weights, but the differences were not detected to be significant. The NEX75 breast filets had more yellowness than other dietary treatments (p = 0.003) and the NEX 100 treatment reduced the levels of breast filet TBARS at 7 days-post harvest (p = 0.053). Finally, both NEX treatments reduced the incidence of severe bone (tibia and femur) lesions. In conclusion, the supplementation of the phytogenic NUQO© NEX improved finisher performance parameters, whole phase FCR, processing carcass weights, and breast filet yellowness, at varying inclusion levels.

All-optical frequency division on-chip using a single laser.

The generation of spectrally pure microwave signals is a critical functionality in fundamental and applied sciences, including metrology and communications. Optical frequency combs enable the powerful technique of optical frequency division (OFD) to produce microwave oscillations of the highest quality1,2. Current implementations of OFD require multiple lasers, with space- and energy-consuming optical stabilization and electronic feedback components, resulting in device footprints incompatible with integration into a compact and robust photonic platform3-5. Here we demonstrate all-optical OFD on a photonic chip by synchronizing two distinct dynamical states of Kerr microresonators pumped by a single continuous-wave laser. The inherent stability of the terahertz beat frequency between the signal and idler fields of an optical parametric oscillator is transferred to a microwave frequency of a Kerr soliton comb, and synchronization is achieved via a coupling waveguide without the need for electronic locking. OFD factors of N = 34 and 468 are achieved for 227 GHz and 16 GHz soliton combs, respectively. In particular, OFD enables a 46 dB phase-noise reduction for the 16 GHz soliton comb, resulting in the lowest microwave noise observed in an integrated photonics platform. Our work represents a simple, effective approach for performing OFD and provides a pathway towards chip-scale devices that can generate microwave frequencies comparable to the purest tones produced in metrological laboratories.

Annual mpMRI surveillance: PI-RADS upgrading and increasing trend correlated with patients who harbor clinically significant disease.

INTRODUCTION: Prostate cancer screening has routinely identified men with very low- or low-risk disease, per the National Comprehensive Cancer Network guidelines. Current literature has demonstrated that the most appropriate management strategy for these patients is active surveillance (AS). The mainstay of AS includes periodic biopsies and biannual prostate-specific antigen tests. However, multiparametric magnetic resonance imaging (mpMRI) is uniquely posed to improve patient surveillance. This study aimed to evaluate the utility of an annual mpMRI in patients on AS, focusing on radiologic upgrading and Prostate Imaging-Reporting and Data System (PI-RADS) trends as indicators of clinically significant disease. METHODS: This prospective, single intuition, study enrolled 208 patients on AS who had at least two biopsies and 1 mpMRI with a median follow-up of 5.03 years. The main outcome variable was time to Gleason grade (GG) reclassification. RESULTS: After delineating patients on their initial PI-RADS score, men with score 3 and 5 lesions at first MRI had comparable GG reclassification-free survival to their counterparts. Conversely, men with initial PI-RADS 4 lesions showed a lower 5-year GG reclassification-free survival compared to those with PI-RADS score 1-2. The cohort was then subset to 70 patients who obtained ≥2 mpMRIs on protocol. Men experiencing uptrending mpMRI scores had an increased risk of GG reclassification, with a 35.4% difference in 5 year GG reclassification-free survival probability on the Kaplan-Meier curve analysis. CONCLUSION: In conclusion, this study demonstrates that for men on AS with stable recapitulated disease, an annual MRI may replace repeat biopsies after confirmatory sampling has been obtained. On the other hand, men who initiate AS with PI-RADS 4 and/or who display uptrending mpMRI scores require periodic biopsies along with repeat imaging. This study highlights the utility of integrating an annual MRI into AS protocols, thus promising a more effective approach to management.

Altered metabolism and DAM-signatures in female brains and microglia with aging.

Despite Alzheimer's disease (AD) disproportionately affecting women, the mechanisms remain elusive. In AD, microglia undergo 'metabolic reprogramming', which contributes to microglial dysfunction and AD pathology. However, how sex and age contribute to metabolic reprogramming in microglia is understudied. Here, we use metabolic imaging, transcriptomics, and metabolic assays to probe age- and sex-associated changes in brain and microglial metabolism. Glycolytic and oxidative metabolism in the whole brain was determined using Fluorescence Lifetime Imaging Microscopy (FLIM). Young female brains appeared less glycolytic than male brains, but with aging, the female brain became 'male-like.' Transcriptomic analysis revealed increased expression of disease-associated microglia (DAM) genes (e.g., ApoE, Trem2, LPL), and genes involved in glycolysis and oxidative metabolism in microglia from aged females compared to males. To determine whether estrogen can alter the expression of these genes, BV-2 microglia-like cell lines, which abundantly express DAM genes, were supplemented with 17ß-estradiol (E2). E2 supplementation resulted in reduced expression of DAM genes, reduced lipid and cholesterol transport, and substrate-dependent changes in glycolysis and oxidative metabolism. Consistent with the notion that E2 may suppress DAM-associated factors, LPL activity was elevated in the brains of aged female mice. Similarly, DAM gene and protein expression was higher in monocyte-derived microglia-like (MDMi) cells derived from middle-aged females compared to age-matched males and was responsive to E2 supplementation. FLIM analysis of MDMi from young and middle-aged females revealed reduced oxidative metabolism and FAD+ with age. Overall, our findings show that altered metabolism defines age-associated changes in female microglia and suggest that estrogen may inhibit the expression and activity of DAM-associated factors, which may contribute to increased AD risk, especially in post-menopausal women.

Prior experience with behavioral control over stress facilitates social dominance.

Dominance status has extensive effects on physical and mental health, and an individual's relative position can be shaped by experiential factors. A variety of considerations suggest that the experience of behavioral control over stressors should produce winning in dominance tests and that winning should blunt the impact of later stressors, as does prior control. To investigate the interplay between competitive success and stressor control, we first examined the impact of stressor controllability on subsequent performance in a warm spot competition test modified for rats. Prior experience of controllable, but not physically identical uncontrollable, stress increased later effortful behavior and occupation of the warm spot. Controllable stress subjects consistently ranked higher than did uncontrollable stress subjects. Pharmacological inactivation of the prelimbic (PL) cortex during behavioral control prevented later facilitation of dominance. Next, we explored whether repeated winning experiences produced later resistance against the typical sequelae of uncontrollable stress. To establish dominance status, triads of rats were given five sessions of warm spot competition. The development of stable dominance was prevented by reversible inactivation of the PL or NMDA receptor blockade in the dorsomedial striatum. Stable winning blunted the later stress-induced increase in dorsal raphe nucleus serotonergic activity, as well as prevented uncontrollable stress-induced social avoidance. In contrast, endocrine and neuroimmune responses to uncontrollable stress were unaffected, indicating a selective impact of prior dominance. Together, these data demonstrate that instrumental control over stress promotes later dominance, but also reveal that winning experiences buffer against the neural and behavioral outcomes of future adversity.

Suture Augmentation of a Four-Strand Semitendinosus Graft Improves Time-Zero Biomechanical Properties.

PURPOSE: To compare the time-zero biomechanical properties of hamstring graft preparations with or without suture augmentation for anterior cruciate ligament reconstruction (ACLR) in a full-construct cadaveric model. METHODS: Hamstring grafts were harvested from 24 fresh frozen human cadavers and prepared in 1 of 3 ways: quadrupled SemiTendinosus (SemiT), and quadrupled SemiT with suture augmentation (SemiT+2.0-mm tape or SemiT+1.3-mm tape; n = 8 per group). Adjustable loop suspensory implants and cortical buttons were used for fixation on a porcine tibia and acrylic block. Testing included force-controlled cyclic loading at 250 N and 400 N followed by load to failure. RESULTS: The 2 suture augmentation groups had less total elongation and increased stiffness compared to the nonsuture-augmented group (P = .025). The SemiT+2.0-mm tape group had 36% less total elongation and 34% increased stiffness compared to SemiT+1.3mm tape (P < .001). CONCLUSIONS: Suture augmentation improves construct biomechanics at time zero following hamstring tendon ACLR. Augmentation with 2.0-mm tape suture improves construct biomechanics compared to 1.3-mm tape suture. CLINICAL RELEVANCE: Independent suture augmentation of a quadrupled SemiT graft improves ACLR construct biomechanics. Outcomes were improved with augmentation using 2.0-mm tape suture compared to 1.3-mm tape suture.

The Engaged Learners Program: Effects on Student Engagement During Small Group Reading Instruction.

In this study we tested the usability, feasibility, social validity, and effectiveness of Engaged Learners, a behavior support program designed to be integrated into small group reading interventions. Participants included eight Grade 3 to 5 students with co-occurring reading difficulties and inattention. A concurrent multiple-baseline design was utilized to test the effects of Engaged Learners on engagement outcomes. Visual analysis and effect sizes indicated an improvement in engagement for seven students. Interventionists and students viewed the Engaged Learners program to be effective and socially valid. Limitations included lower than expected levels of fidelity for one interventionist and high student absenteeism. More research is needed to identify the extent to which Engaged Learners can support reading outcomes. Educators seeking an effective behavior support program that requires minimal training and coaching may consider integrating Engaged Learners into their small group reading instruction.

Altered Metabolism and DAM-signatures in Female Brains and Microglia with Aging.

Despite Alzheimer's disease (AD) disproportionately affecting women, the mechanisms remain elusive. In AD, microglia undergo 'metabolic reprogramming', which contributes to microglial dysfunction and AD pathology. However, how sex and age contribute to metabolic reprogramming in microglia is understudied. Here, we use metabolic imaging, transcriptomics, and metabolic assays to probe age-and sex-associated changes in brain and microglial metabolism. Glycolytic and oxidative metabolism in the whole brain was determined using Fluorescence Lifetime Imaging Microscopy (FLIM). Young female brains appeared less glycolytic than male brains, but with aging, the female brain became 'male-like.' Transcriptomic analysis revealed increased expression of disease-associated microglia (DAM) genes (e.g., ApoE, Trem2, LPL), and genes involved in glycolysis and oxidative metabolism in microglia from aged females compared to males. To determine whether estrogen can alter the expression of these genes, BV-2 microglia-like cell lines, which abundantly express DAM genes, were supplemented with 17ß-estradiol (E2). E2 supplementation resulted in reduced expression of DAM genes, reduced lipid and cholesterol transport, and substrate-dependent changes in glycolysis and oxidative metabolism. Consistent with the notion that E2 may suppress DAM-associated factors, LPL activity was elevated in the brains of aged female mice. Similarly, DAM gene and protein expression was higher in monocyte-derived microglia-like (MDMi) cells derived from middle-aged females compared to age-matched males and was responsive to E2 supplementation. FLIM analysis of MDMi from young and middle-aged females revealed reduced oxidative metabolism and FAD+ with age. Overall, our findings show that altered metabolism defines age-associated changes in female microglia and suggest that estrogen may inhibit the expression and activity of DAM-associated factors, which may contribute to increased AD risk, especially in post-menopausal women.

Location and Progression of Chondral Injuries at the Time of Revision ACL Surgery Varies by Sex.

PURPOSE: To quantify progression of chondral and meniscal injuries between primary and revision anterior cruciate ligament (ACL) surgery. METHODS: Patients who underwent both index and revision ACL reconstruction between 2000 and 2020 at our institution were identified, and dates of injury and surgery, demographics, and clinical data were obtained from operative reports. Outerbridge grade was recorded in each compartment, along with presence and location of meniscal injury. The frequency of each injury between first and second cases was calculated. Differences in injury and progression were compared over time as well as between patient sex and age. RESULTS: The study included 189 patients (96 female, 93 male). Age at first surgery was 31.7 ± 13.2 years. Mean time to second injury was 3.3 ± 3.0 years. In total, 116 patients had a new or previous chondral injury (odds ratio, 1.6; 95% CI, 1.2-2.1). The medial femoral condyle (31%) and the patella (21%) accounted for the highest proportion of new injury to articular surfaces, whereas new injury to menisci was comparable between the medial (25%) and lateral (23%) meniscus. At the time of revision ACL reconstruction, females had a high prevalence of chondral injuries to the lateral compartment, whereas males had a high prevalence of chondral injury to the medial femoral condyle. The prevalence of new chondral injuries was comparable between sexes, with males having a slightly higher proportion. While time between surgeries, sex, and age had graphical evidence of moderating risk, the effects were small and imprecise. CONCLUSIONS: Revision ACL reconstruction carried a 1.6 increase in the odds for new or progressive chondral lesions in our cohort. At the time of revision, females had a relatively higher proportion of lateral-sided chondral injuries, whereas males had a relatively higher proportion of medial femoral condyle injuries. The greatest increase in the prevalence of new and progressive lesions was observed in the medial femoral condyle and trochlea. This progression appeared to be moderated by time between surgeries, patient sex, and age; however, the differences were small and imprecise. STUDY DESIGN: Level IV, therapeutic case series.

Infrared thermography as a diagnostic tool to detect cranial cruciate ligament deficiency in dogs.

Cranial cruciate ligament (CCL) disease is the leading cause of canine lameness. Diagnosis is based on physical examination and diagnostic imaging findings. Limitations of diagnostic modalities, including patient temperament, cost, availability, and need for general anesthesia, preclude their use for many patients. Infrared thermography is an easy, non-invasive diagnostic screening technique with use in both human and veterinary musculoskeletal conditions. The objective of this study was to investigate the utility of infrared thermography to diagnose CCL disease in a large population of client-owned dogs and investigate for correlations between ability of thermography to diagnose CCL deficiency and recorded explanatory factors. A commercial grade thermal imaging camera was used to collect preoperative images of both stifles in 50 dogs with surgically confirmed CCL rupture in one stifle and a normal opposite stifle. The average maximum temperatures of the affected and unaffected stifles were collected from these images and used for statistical analysis. Infrared thermography was not successful in differentiating between CCL-deficient and unaffected stifles in this cohort. No significant differences in average maximal temperature were observed between stifles when comparing to explanatory factors or variables. Use of infrared thermography should not be relied upon to diagnose canine CCL disease.

La pathologie du ligament croisé crânien (CCL) est la principale cause de boiterie canine. Le diagnostic repose sur l'examen physique et les résultats de l'imagerie diagnostique. Les limites des modalités de diagnostic, y compris le tempérament du patient, le coût, la disponibilité et la nécessité d'une anesthésie générale, empêchent leur utilisation pour de nombreux patients. La thermographie infrarouge est une technique de dépistage diagnostique simple et non invasive, utilisable dans les conditions musculosquelettiques humaines et vétérinaires. L'objectif de cette étude était d'étudier l'utilité de la thermographie infrarouge pour diagnostiquer les problèmes de CCL dans une grande population de chiens appartenant à des clients et d'étudier les corrélations entre la capacité de la thermographie à diagnostiquer une déficience du CCL et les facteurs explicatifs enregistrés. Une caméra d'imagerie thermique de qualité commerciale a été utilisée pour collecter des images préopératoires des deux grassets chez 50 chiens avec une rupture du CCL confirmée chirurgicalement dans un grasset et un grasset opposé normal. Les températures maximales moyennes des grassets affectés et non affectés ont été recueillies à partir de ces images et utilisées pour l'analyse statistique. La thermographie infrarouge n'a pas réussi à différencier les grassets avec atteintes du CCL des grassets non affectés dans cette cohorte. Aucune différence significative dans la température maximale moyenne n'a été observée entre les grassets lors de la comparaison avec des facteurs ou variables explicatifs. L'utilisation de la thermographie infrarouge ne doit pas être utilisée pour diagnostiquer les pathologie du CCL canin.(Traduit par Docteur Serge Messier).

Wilms Tumor: An Unexpected Diagnosis in Adult Patients.

CONTEXT.­: Wilms tumor (WT) in adult patients is rare and has historically been a diagnostic and therapeutic conundrum, with limited data available in the literature. OBJECTIVE.­: To provide detailed diagnostic features, molecular profiling, and patient outcomes in a multi-institutional cohort of adult WT patients. DESIGN.­: We identified and retrospectively examined 4 adult WT cases. RESULTS.­: Two patients presented with metastatic disease, and diagnoses were made on fine-needle aspiration of their renal masses. The aspirates included malignant primitive-appearing epithelioid cells forming tubular rosettes and necrosis, and cell blocks demonstrated triphasic histology. In the remaining 2 cases, patients presented with localized disease and received a diagnosis on resection, with both patients demonstrating an epithelial-predominant morphology. Tumor cells in all cases were patchy variable positive for PAX8 and WT1 immunohistochemistry. Next-generation sequencing identified alterations previously reported in pediatric WT in 3 of 4 cases, including mutations in ASXL1 (2 of 4), WT1 (1 of 4), and the TERT promoter (1 of 4), as well as 1q gains (1 of 4); 1 case showed no alterations. Three patients were treated with pediatric chemotherapy protocols; during follow up (range, 26-60 months), 1 patient died of disease. CONCLUSIONS.­: WT is an unexpected and difficult entity to diagnose in adults and should be considered when faced with a primitive-appearing renal or metastatic tumor. Molecular testing may help exclude other possibilities but may not be sensitive or specific because of the relatively large number of driver mutations reported in WT.

Ultrasound evaluation of intraluminal magnets in an ex vivo model.

PURPOSE: The management of foreign body ingestion proves to be a challenge. Magnets pose a unique set of risks when ingested due to their attractive forces and subsequent risk of adherence, pressure necrosis, and perforation complications. Radiographs only provide a limited snapshot in the setting of multiple magnet ingestion when the risk of complication is highest. We hypothesize that abdominal ultrasound (US) has the potential to supplement radiographs in assessing ingested magnets by determining the presence of bowel loop entrapment and of any extraluminal fluid. METHODS: We recreated various scenarios of magnet configurations using animal cadaveric bowel models. X-ray and US images were obtained in various bowel-magnet orientations. RESULTS: We identified several key US features to suggest bowel wall tethering. These include direct visualization of bowel wall entrapment between magnets (what we term the "dangerous V sign"), anti-dependent positions of the magnets, and inability to separate loops of bowel with compression. CONCLUSION: These findings could potentially provide valuable information when directing the urgency of intervention in foreign body ingestion. Ultrasound may supplement and improve the current guidelines in management of magnet ingestion.

Hippocampal place cell remapping occurs with memory storage of aversive experiences.

Aversive stimuli can cause hippocampal place cells to remap their firing fields, but it is not known whether remapping plays a role in storing memories of aversive experiences. Here, we addressed this question by performing in vivo calcium imaging of CA1 place cells in freely behaving rats (n = 14). Rats were first trained to prefer a short path over a long path for obtaining food reward, then trained to avoid the short path by delivering a mild footshock. Remapping was assessed by comparing place cell population vector similarity before acquisition versus after extinction of avoidance. Some rats received shock after systemic injections of the amnestic drug scopolamine at a dose (1 mg/kg) that impaired avoidance learning but spared spatial tuning and shock-evoked responses of CA1 neurons. Place cells remapped significantly more following remembered than forgotten shocks (drug-free versus scopolamine conditions); shock-induced remapping did not cause place fields to migrate toward or away from the shocked location and was similarly prevalent in cells that were responsive versus non-responsive to shocks. When rats were exposed to a neutral barrier rather than aversive shock, place cells remapped significantly less in response to the barrier. We conclude that place cell remapping occurs in response to events that are remembered rather than merely perceived and forgotten, suggesting that reorganization of hippocampal population codes may play a role in storing memories for aversive events.

The human brain is able to remember experiences that occurred at specific places and times, such as a birthday party held at a particular restaurant. A part of the brain known as the hippocampus helps to store these episodic memories, but how exactly is not fully understood. Within the hippocampus are specialized neurons known as place cells which 'label' locations with unique patterns of brain activity. When we revisit a place, such as the restaurant, place cells recall the stored pattern of brain activity allowing us to recognize the familiar location. It has been shown that a new negative experience at a familiar place ­ for example, if we went back to the restaurant and had a terrible meal ­ triggers place cells to update the brain activity label associated with the location. However, it remains uncertain whether this re-labelling assists in storing the memory of the unpleasant experience. To investigate, Blair et al. used a technique known as calcium imaging to monitor place cells in the hippocampus of freely moving rats. The rats were given a new experience ­ a mild foot shock ­ at a previously explored location. Tiny cameras attached to their heads were then used to record the activity of hundreds of place cells before and after the shock. Initially, the rats remembered the aversive experience and avoided the location where they had been shocked. Over time, the rats began to return to the location; however, their place cells displayed different patterns of activity compared to their previous visits before the shock. To test whether this change in place cell activity corresponded with new memories, another group of rats were administered a mild amnesia-inducing drug before the shock, causing them to forget the experience. These rats did not avoid the shock site or show any changes in place cell activity when they revisited it. These findings imply that new events cause place cells to alter their 'label' for a location only if the event is remembered, not if it is forgotten. This indicates that alterations in place cell activity patterns may play a role in storing memories of unpleasant experiences. Having a better understanding of how episodic memories are stored could lead to better treatments for diseases that impair memory, such as Alzheimer's disease and age-related dementia.

Implementing strategies to prevent infections in acute-care settings.

This document introduces and explains common implementation concepts and frameworks relevant to healthcare epidemiology and infection prevention and control and can serve as a stand-alone guide or be paired with the "SHEA/IDSA/APIC Compendium of Strategies to Prevent Healthcare-Associated Infections in Acute Care Hospitals: 2022 Updates," which contain technical implementation guidance for specific healthcare-associated infections. This Compendium article focuses on broad behavioral and socio-adaptive concepts and suggests ways that infection prevention and control teams, healthcare epidemiologists, infection preventionists, and specialty groups may utilize them to deliver high-quality care. Implementation concepts, frameworks, and models can help bridge the "knowing-doing" gap, a term used to describe why practices in healthcare may diverge from those recommended according to evidence. It aims to guide the reader to think about implementation and to find resources suited for a specific setting and circumstances by describing strategies for implementation, including determinants and measurement, as well as the conceptual models and frameworks: 4Es, Behavior Change Wheel, CUSP, European and Mixed Methods, Getting to Outcomes, Model for Improvement, RE-AIM, REP, and Theoretical Domains.

Prior experience with behavioral control over stress facilitates social dominance.

Dominance status has extensive effects on physical and mental health, and an individual's relative position can be shaped by experiential factors. A variety of considerations suggest that the experience of behavioral control over stressors should produce winning in dominance tests and that winning should blunt the impact of later stressors, as does prior control. To investigate the interplay between competitive success and stressor control, we first examined the impact of stressor controllability on subsequent performance in a warm spot competition test modified for rats. Prior experience of controllable, but not physically identical uncontrollable, stress increased later effortful behavior and occupation of the warm spot. Controllable stress subjects consistently ranked higher than did uncontrollable stress subjects. Pharmacological inactivation of the prelimbic (PL) cortex during behavioral control prevented later facilitation of dominance. Next, we explored whether repeated winning experiences produced later resistance against the typical sequelae of uncontrollable stress. To establish dominance status, triads of rats were given five sessions of warm spot competition. Reversible inactivation of the PL or NMDA receptor blockade in the dorsomedial striatum led to a long-term reduction in social rank. Stable dominance blunted the later stress-induced increase in dorsal raphe nucleus serotonergic activity, as well as prevented stress-induced social avoidance. In contrast, endocrine and neuroimmune responses to uncontrollable stress were unaffected, indicating a selective impact of prior dominance. Together, these data demonstrate that instrumental control over stress promotes later dominance, but also reveal that winning experiences buffer against the neural and behavioral outcomes of future adversity.

Impact of Phytase Supplementation on Meat Quality of Heat-Stressed Broilers.

Heat stress (HS) is one of the most challenging stressors to poultry production sustainability. The adverse effects of HS range from feed intake and growth depression to alteration of meat quality and safety. As phytase supplementation is known to improve nutrient utilization and consequently growth, we undertook the present study to evaluate the effects of dietary phytase on growth and meat quality in heat-stressed broilers. A total of 720 day-old hatch Cobb 500 chicks were assigned to 24 pens within controlled environmental chambers and fed three diets: Negative Control (NC), Positive Control (PC), and NC diet supplemented with 2000 phytase units (FTU)/kg) of quantum blue (QB). On day 29, birds were exposed to two environmental conditions: thermoneutral (TN, 25 °C) or cyclic heat stress (HS, 35 °C, 8 h/d from 9 a.m. to 5 p.m.) in a 3 × 2 factorial design. Feed intake (FI), water consumption (WI), body weight (BW), and mortality were recorded. On day 42, birds were processed, carcass parts were weighed, and meat quality was assessed. Breast tissues were collected for determining the expression of target genes by real-time quantitative PCR using the 2-ΔΔCt method. HS significantly increased core body temperature, reduced feed intake and BW, increased water intake (WI), elevated blood parameters (pH, SO2, and iCa), and decreased blood pCO2. HS reduced the incidence of woody breast (WB) and white striping (WS), significantly decreased drip loss, and increased both 4- and 24-h postmortem pH. Instrumental L* and b* values were reduced (p < 0.05) by the environmental temperature at both 4- and 24-h postmortem. QB supplementation reduced birds' core body temperature induced by HS and improved the FCR and water conversion ratio (WCR) by 1- and 0.5-point, respectively, compared to PC under HS. QB increased blood SO2 and reduced the severity of WB and WS under TN conditions, but it increased it under an HS environment. The abovementioned effects were probably mediated through the modulation of monocarboxylate transporter 1, heat shock protein 70, mitogen-activated protein kinase, and/or glutathione peroxidase 1 gene expression, however, further mechanistic studies are warranted. In summary, QB supplementation improved growth performance and reduced muscle myopathy incidence under TN conditions. Under HS conditions, however, QB improved growth performance but increased the incidence of muscle myopathies. Therefore, further QB titration studies are needed.