Gene co-expression patterns in Atlantic salmon adipose tissue provide a molecular link among seasonal changes, energy balance and age at maturity.

Sexual maturation in many fishes requires a major physiological change that involves a rapid transition between energy storage and usage. In Atlantic salmon, this transition for the initiation of maturation is tightly controlled by seasonality and requires a high-energy status. Lipid metabolism is at the heart of this transition since lipids are the main energy storing molecules. The balance between lipogenesis (lipid accumulation) and lipolysis (lipid use) determines energy status transitions. A genomic region containing a transcription co-factor of the Hippo pathway, vgll3, is the main determinant of maturation timing in Atlantic salmon. Interestingly, vgll3 acts as an inhibitor of adipogenesis in mice and its genotypes are potentially associated with seasonal heterochrony in lipid storage and usage in juvenile Atlantic salmon. Here, we explored changes in expression of more than 300 genes directly involved in the processes of adipogenesis, lipogenesis and lipolysis, as well as the Hippo pathway in the adipose tissue of immature and mature Atlantic salmon with distinct vgll3 genotypes. We found molecular evidence consistent with a scenario in which immature males with different vgll3 genotypes exhibit contrasting seasonal dynamics in their lipid profiles. We also identified components of the Hippo signalling pathway as potential major drivers of vgll3 genotype-specific differences in adipose tissue gene expression. This study demonstrates the importance of adipose gene expression patterns for directly linking environmental changes with energy balance and age at maturity through genetic factors bridging lipid metabolism, seasonality and sexual maturation.

Sex-specific trait architecture in a spider with sexual size dimorphism.

Sexual dimorphism, or sex-specific trait expression, may evolve when selection favours different optima for the same trait between sexes, that is, under antagonistic selection. Intra-locus sexual conflict exists when the sexually dimorphic trait under antagonistic selection is based on genes shared between sexes. A common assumption is that the presence of sexual-size dimorphism (SSD) indicates that sexual conflict has been, at least partly, resolved via decoupling of the trait architecture between sexes. However, whether and how decoupling of the trait architecture between sexes has been realized often remains unknown. We tested for differences in architecture of adult body size between sexes in a species with extreme SSD, the African hermit spider (Nephilingis cruentata), where adult female body size greatly exceeds that of males. Specifically, we estimated the sex-specific importance of genetic and maternal effects on adult body size among individuals that we laboratory-reared for up to eight generations. Quantitative genetic model estimates indicated that size variation in females is to a larger extent explained by direct genetic effects than by maternal effects, but in males to a larger extent by maternal than by genetic effects. We conclude that this sex-specific body-size architecture enables body-size evolution to proceed much more independently than under a common architecture to both sexes.

Characteristics of inflammatory and infectious diseases of the pituitary gland in patients undergoing transsphenoidal surgery.

PURPOSE: Inflammatory and infectious diseases of the pituitary gland (IIPD) are rare lesions often misdiagnosed preoperatively. Immediate surgery is indicated especially in cases of neurological impairment. However, (chronic) inflammatory processes can mimic other pituitary tumors, such as adenomas, and data on the preoperative diagnostic criteria for IIPD are sparse. METHODS: We retrospectively reviewed medical records of 1317 patients who underwent transsphenoidal surgery at our institution between March 2003 and January 2023. A total of 26 cases of histologically confirmed IIPD were identified. Patient records, laboratory parameters, and postoperative course were analyzed and compared with an age, sex, and tumor volume-matched control group of nonfunctioning pituitary adenomas. RESULTS: Pathology confirmed septic infection in ten cases, most commonly caused by bacteria (3/10) and fungi (2/10). In the aseptic group, lymphocytic hypophysitis (8/26) and granulomatous inflammation (3/26) were most frequently observed. Patients with IIPD commonly presented with endocrine and/or neurological dysfunction. No surgical mortality occurred. Preoperative radiographic findings (cystic/solid tumor mass, contrast enhancement) did not significantly differ between IIPD and adenomas. At follow-up, 13 patients required permanent hormone substitution. CONCLUSION: In conclusion, correct preoperative diagnosis of IIPD remains challenging, as neither radiographic findings nor preoperative laboratory workup unequivocally identify these lesions. Surgical treatment facilitates decompression of supra- and parasellar structures. Furthermore, this low-morbidity procedure enables the identification of pathogens or inflammatory diseases requiring targeted medical treatment, which is crucial for these patients. Establishing a correct diagnosis through surgery and histopathological confirmation thus remains of utmost importance.

Cis-regulatory differences in isoform expression associate with life history strategy variation in Atlantic salmon.

A major goal in biology is to understand how evolution shapes variation in individual life histories. Genome-wide association studies have been successful in uncovering genome regions linked with traits underlying life history variation in a range of species. However, lack of functional studies of the discovered genotype-phenotype associations severely restrains our understanding how alternative life history traits evolved and are mediated at the molecular level. Here, we report a cis-regulatory mechanism whereby expression of alternative isoforms of the transcription co-factor vestigial-like 3 (vgll3) associate with variation in a key life history trait, age at maturity, in Atlantic salmon (Salmo salar). Using a common-garden experiment, we first show that vgll3 genotype associates with puberty timing in one-year-old salmon males. By way of temporal sampling of vgll3 expression in ten tissues across the first year of salmon development, we identify a pubertal transition in vgll3 expression where maturation coincided with a 66% reduction in testicular vgll3 expression. The late maturation allele was not only associated with a tendency to delay puberty, but also with expression of a rare transcript isoform of vgll3 pre-puberty. By comparing absolute vgll3 mRNA copies in heterozygotes we show that the expression difference between the early and late maturity alleles is largely cis-regulatory. We propose a model whereby expression of a rare isoform from the late allele shifts the liability of its carriers towards delaying puberty. These results exemplify the potential importance of regulatory differences as a mechanism for the evolution of life history traits.

Pathogenesis of non-infection related inflammatory root resorption in permanent teeth: A narrative review.

BACKGROUND: The mechanism of action of root resorption in a permanent tooth can be classified as infection-related (e.g., microbial infection) or non-infection-related (e.g., sterile damage). Infection induced root resorption occurs due to bacterial invasion. Non-infection-related root resorption stimulates the immune system through a different mechanism. OBJECTIVES: The aim of this narrative review is to describe the pathophysiologic process of non-infection-related inflammatory processes involved in root resorption of permanent teeth. METHODS: A literature search on root resorption was conducted using Scopus (PubMed and Medline) and Google Scholar databases to highlight the pathophysiology of bone and root resorption in non-infection-related situations. The search included key words covering the relevant category. It included in vitro and in vivo studies, systematic reviews, case series, reviews, and textbooks in English. Conference proceedings, lectures and letters to the editor were excluded. RESULTS: Three types of root resorption are related to the non-infection mechanism of action, which includes surface resorption due to either trauma or excessive orthodontic forces, external replacement resorption and external cervical resorption. The triggers are usually damage associated molecular patterns and hypoxia conditions. During this phase macrophages and clastic cells act to eliminate the damaged tissue and bone, eventually enabling root resorption and bone repair as part of wound healing. DISCUSSION: The resorption of the root occurs during the inflammatory phase of wound healing. In this phase, damaged tissues are recognized by macrophages and neutrophiles that secrete interlaukines such as TNF-α, IL-1, IL-6, IL-8. Together with the hypoxia condition that accelarates the secretion of growth factors, the repair of the damaged perioduntiom, including damaged bone, is initiated. If the precementum and cementoblast are injured, root resorption can occur. CONCLUSIONS: Wound healing exhibits different patterns of action that involves immune stimulation in a bio-physiological activity, that occurs in the proper sequence, with overlapping phases. Two pathologic conditions, DAMPs and hypoxia, can activate the immune cells including clastic cells, eliminating damaged tissue and bone. Under certain conditions, root resorption occurs as a side effect.

Accessory nerve schwannoma extending into the fourth ventricle: case report and review of literature.

Accessory nerve schwannoma is a rare entity in patients presenting with cranial nerve (CN) deficits. Most of these tumours arise from the cisternal segment of the eleventh CN and extend caudally. Herein, we report the third case of an accessory schwannoma extending cranially into the fourth ventricle. A 61-year-old female presented with a history of variable headaches. Cerebral magnetic resonance imaging (cMRI) revealed a large inhomogeneous contrast-enhancing lesion at the craniocervical junction extending through the foramen of Magendi and concomitant hydrocephalus due to obstruction of the foramina of Luschkae. Microsurgical tumour resection was performed in the half-sitting position. Intraoperatively, the tumour arose from a vestigial fascicle of the spinal accessory nerve. At three month follow-up, neither radiological tumour recurrence nor neurological deficits were observed.

Host Developmental Stage Effects on Parasite Resistance and Tolerance.

AbstractHosts can defend themselves against parasites either by preventing or limiting infections (resistance) or by limiting parasite-induced damage (tolerance). However, it remains underexplored how these defense types vary over host development with shifting patterns of resource allocation priorities. Here, we studied the role played by developmental stage in resistance and tolerance in Atlantic salmon (Salmo salar). This anadromous fish has distinct life stages related to living in freshwater and seawater. We experimentally exposed 1-year-old salmon, either at the freshwater stage or at the stage transitioning to the marine phase, to the trematode Diplostomum pseudospathaceum. Using 56 pedigreed families and multivariate animal models, we show that developmental transition is associated with reduced resistance but does not affect tolerance. Furthermore, by comparing tolerance slopes (host fitness against parasite load) based on additive genetic effects among infected and unexposed control relatives, we observed that the slopes can be largely independent of the infection, that is, they may not reflect tolerance. Together, our results suggest that the relative importance of different defense types may vary with host development and emphasize the importance of including control treatments for more confident interpretations of tolerance estimates.

Changes in R-wave amplitude at implantation are associated with gender and orientation of insertable cardiac monitor: observations from the confirm Rx™ body posture and physical activity study.

BACKGROUND: Insertable cardiac monitors (ICMs) are small subcutaneously implanted devices that detect changes in R-wave amplitudes (RWAs), effective in arrhythmia-monitoring. Although ICMs have proven to be immensely successful, electrical artefacts are frequent and can lead to misdiagnosis. Thus, there is a growing need to sustain and increase efficacy in detection rates by gaining insight into various patient-specific factors such as body postures and activities. METHODS: RWAs were measured in 15 separate postures, including supine, lying on the right-side (RS) or left-side (LS) and sitting, and two separate ICM orientations, immediately after implantation of Confirm Rx™ ICM in 99 patients. RESULTS: The patients (53 females and 46 males, mean ages 66.62 ± 14.7 and 66.40 ± 12.25 years, respectively) had attenuated RWAs in RS, LS and sitting by ~ 26.4%, ~ 27.8% and ~ 21.2% respectively, compared to supine. Gender-based analysis indicated RWAs in RS (0.32 mV (0.09-1.03 mV), p < 0.0001) and LS (0.37 mV (0.11-1.03 mV), p = 0.004) to be significantly attenuated compared to supine (0.52 mV (0.20-1.03 mV) for female participants. Similar attenuation was not evident for male participants. Further, parasternally oriented ICMs (n = 44), attenuated RWAs in RS (0.37 mV(0.09-1.03 mV), p = 0.05) and LS (0.34 mV (0.11-1.03 mV), p = 0.02) compared to supine (0.48 mV (0.09-1.03 mV). Similar differences were not observed in participants with ICMs in the 45°-relative-to-sternum (n = 46) orientation. When assessing the combined effect of gender and ICM orientation, female participants demonstrated plausible attenuation in RWAs for RS and LS postures compared to supine, an effect not observed in male participants. CONCLUSION: This is the first known study depicting the effects on RWA due to body postures and activities immediately post-implantation with an overt impact by gender and orientation of ICM. Future work assessing the cause of gender-based differences in RWAs may be critical. TRIAL REGISTRATION: Clinical Trials, NCT03803969. Registered 15 January 2019 - Retrospectively registered, https://clinicaltrials.gov/NCT03803969.

A novel hyperbaric swimming respirometer allows the simulation of varying swimming depths in fish respirometry studies.

The understanding of swimming physiology and knowledge on the metabolic costs of swimming are important for assessing effects of environmental factors on migratory behavior. Swim tunnels are the most common experimental setups for measuring swimming performance and oxygen uptake rates in fishes; however, few can realistically simulate depth and the changes in hydrostatic pressure that many fishes experience, e.g. during diel vertical migrations. Here, we present a new hyperbaric swimming respirometer (HSR) that can simulate depths of up to 80 m. The system consists of three separate, identical swimming tunnels, each with a volume of 205 L, a control board and a storage tank with water treatment. The swimming chamber of each tunnel has a length of 1.40 m and a diameter of 20 cm. The HSR uses the principle of intermittent-flow respirometry and has here been tested with female European eels (Anguilla anguilla). Various pressure, temperature and flow velocity profiles can be programmed, and the effect on metabolic activity and oxygen consumption can be assessed. Thus, the HSR provides opportunities to study the physiology of fish during swimming in a simulated depth range that corresponds to many inland, coastal and shelf waters.

Psychosocial Correlates of Insomnia Among College Students.

INTRODUCTION: Among college students, insomnia remains a topic of research focus, especially as it pertains to its correlates and the extent of its association with mental conditions. This study aimed to shed light on the chief predictors of insomnia among college students. METHODS: A cross-sectional survey on a convenience sample of college students (aged ≥18 years) at 2 large midwestern universities was conducted from March 18 through August 23, 2019. All participants were administered validated screening instruments used to screen for insomnia, depression, and attention deficit hyperactivity disorder (ADHD). Insomnia correlates were identified by using multivariate logistic regression. RESULTS: Overall, 26.4% of students experienced insomnia; 41.2% and 15.8% had depression and had ADHD symptoms, respectively. Students with depression (adjusted odds ratio, 9.54; 95% CI, 4.50-20.26) and students with ADHD (adjusted odds ratio, 3.48; 95% CI, 1.48-8.19) had significantly higher odds of insomnia. The odds of insomnia were also significantly higher among employed students (odds ratio, 2.10; 95% CI, 1.05-4.18). CONCLUSION: This study showed an association between insomnia and mental health conditions among college students. Policy efforts should be directed toward primary and secondary prevention programs that enforce sleep education interventions, particularly among employed college students and those with mental illnesses.

Comorbidities, substance abuse, weight and age are independent risk factors for postoperative complications following operation for proximal humerus fractures: a retrospective analysis of 1109 patients.

INTRODUCTION: This study aimed to investigate the influence of epidemiologic parameters on complications that needed operative revision of operatively treated proximal humerus fractures. METHODS: We performed a retrospective single-center study in a level 1 trauma center. We included all patients with operatively treated proximal humerus fractures from January 1 2005 to December 31 2015. We characterized our cohort and subgroup using descriptive statistics. The primary outcome was postoperative complications. For this purpose, postoperative complications were defined in advance, an operative revision was necessary on a general rule. The secondary outcome was a model of the risk factors for complications created with multiple logistic regression. RESULTS: We included 1109 patients. The average age was 67.2 years (± 16.4), and 71.4% of the fractures occurred in women. A total of 644 patients (58.1%) had between one to three comorbidities, and 27.8% had four or more. The fracture morphology was as follows: 3 part 41.8%, 4 part 26.9%, 2 part 24.3%, and dislocation fracture 6.7%. Complications occurred in 150 patients (13.5%). The number of comorbidities [odds ratio (OR) 2.85, p < 0.01], body weight (OR 1.15, p = 0.02), and substance abuse (OR 1.82, p = 0.04) significantly correlated with the risk of complications. We achieved a sensitivity of 48% and a specificity of 74% for the variables body weight, substance abuse, age, and comorbidities CONCLUSION: The epidemiologic parameters, comorbidities, substance abuse, weight, and age are independent risk factors for complications. If these factors are present, one can predict a postoperative complication requiring surgical revision with low sensitivity and moderate specificity. Therefore, concerning the high number of multi-morbid patients with proximal humerus fractures, an increased postoperative complication rate can be expected. LEVEL OF EVIDENCE: Level of evidence IV.

International students challenges during the COVID-19 pandemic in a university in the United States: A focus group study.

Research suggests that the COVID-19 pandemic has deeply impacted college students. However, very few studies have attended to the specific plight of  international students . The purpose of this study was to document challenges international students may have encountered while studying in the United States during the pandemic. Focus groups (N = 4; 13 students total) were conducted with students who were ≥ 18 years of age, enrolled at least part-time, on an F1 visa, and non-resident alien, who did not have parents/guardians living in the United States and were able to read and write in English. Focus groups lasted 1.5-2 h in duration and followed a standardized script. These sessions were audio-recorded and professionally transcribed. Two researchers performed qualitative content analysis. Six themes emerged from the analysis and included residency challenges, lifestyle changes, coping, negative affect, social support, and university structure. It appears that the challenges associated with residency and lifestyle directly impacted students' negative affect. However, the remaining themes moderated this relationship. These findings highlight the role universities can play in providing relief to international students during these challenging times and suggest areas for improving their experiences. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s12144-022-02776-x.

The alternative oxidase (AOX) increases sulphide tolerance in the highly invasive marine invertebrate Ciona intestinalis.

Ecological communities and biodiversity are shaped by both abiotic and biotic factors. This is well illustrated by extreme environments and invasive species. Besides naturally occurring sulphide-rich environments, global change can lead to an increase in hydrogen sulphide episodes that threaten many multicellular organisms. With the increase in the formation, size and abundance of oxygen minimum zones and hypoxic environments, bacterial-associated sulphide production is favoured and, as such, hydrogen-sulphide-rich environments are likely to also increase in size and abundance. Many species are challenged by the inhibiting effect of sulphide on aerobic energy production via cytochrome c oxidase, ultimately causing the death of the organism. Interestingly, many protist, yeast, plant and also animal species possess a sulphide-resistant alternative oxidase (AOX). In this study, we investigated whether AOX is functionally involved in the sulphide stress response of the highly invasive marine tunicate Ciona intestinalis. At the LC50, the sulphide-induced reduction of developmental success was three times stronger in AOX knock-down embryos than in control embryos. Further, AOX mRNA levels were higher under sulphide than under control conditions, and this effect increased during embryonic development. Together, we found that AOX is indeed functionally involved in the sulphide tolerance of C. intestinalis embryos, hence, very likely contributing to its invasive potential; and that the response of AOX to sulphide seems to be controlled at the transcriptional level. We suggest that AOX-possessing species play an important role in shaping marine ecological communities, and this importance may increase under ongoing global change.

Interventions to improve physical activity in colorectal cancer survivors: protocol for a systematic review and meta-analysis of randomized controlled trials.

AIM: To examine the effectiveness of physical activity (PA) interventions on changes in PA among colorectal cancer survivors, including an examination of theoretical versus atheoretical-driven approaches, with a special focus on their effectiveness across ethnic and racial minorities. DESIGN: Systematic review with aggregated data meta-analyses. DATA SOURCES: Using six databases (Cochrane Central Register of Controlled Trials, PubMed, PsycINFO, CINAHL with full text, Scopus and Web of Science), we will screen for randomized controlled trials written in English from May 1, 1993 up to December 31, 2020. REVIEW METHODS: Dual study-selection and data abstraction will be performed. The Behavior Change Technique Taxonomy (v1) will be used to examine behavior change techniques among selected studies, while the Theory Coding Scheme will be used to assess the extent of theory use. Risk of bias will be assessed using the revised Cochrane risk-of-bias tool for randomized trials, while the strength of the evidence will be assessed using the Grading of Recommendations Assessment, Development, and Evaluation instrument. In addition, intervention delivery will be appraised using the Template for Intervention Description and Replication. Changes in PA from each study will be calculated using the standardized mean difference effect size (Hedge's g). Results will be pooled using the inverse-variance heterogeneity model. Heterogeneity (Cochran's Q) and inconsistency (I2 ) will be examined, while small-study effects (publication bias) will be evaluated using the Doi plot and LFK Index. Meta-regression will also be conducted to examine for potential associations between changes in physical activity and selected covariates (theoretical versus atheoretical-driven approaches, race/ethnicity). DISCUSSION: This systematic review will identify specific racial/ethnic minorities for whom interventions are most effective and summarize the evidence of the effectiveness of theoretical vs. theoretical based intervention. IMPACT: This systematic review can direct policymakers and practitioners towards actions that are likely to bring about positive physical activity behaviour change.

SCAN! A pharmacy-based, sun safety feasibility study.

OBJECTIVES: Skin cancer is the most common form of cancer, and individuals from the medically underserved Appalachian region are at elevated risks for cancer morbidity and mortality. Skin cancer can be prevented by decreasing ultraviolet light exposure (sunscreen sun protection factor 30, shade, clothing, sunglasses, hats) and can be caught at an early treatable stage through a routine skin examination. The Skin Cancer Awareness Now! (SCAN!) pilot project promoted skin cancer prevention and screening in community pharmacies, using a dynamic communication model. The objectives of the study were to understand (1) the feasibility of the SCAN! and (2) the preliminary impact of the SCAN! METHODS: We conducted pre- and postintervention surveys of the SCAN!, a student pharmacist-led or pharmacy resident-led intervention in community pharmacies (n = 3). RESULTS: Participants (n = 90) had a mean age of 43.8 (SD= 18.4) years, were predominantly white (92.1%), without a college degree (65.6%), and had an average family income in the range of $25,000-$49,999, with approximately 16% falling below the poverty level. To begin, the SCAN! scored highly in attention (mean = 5.8), liking (mean = 6.1), comprehension (mean = 6.7), and intentions to be sun safe (mean = 6.0). Most improved in their knowledge of the amount of sunscreen needed per application for sun safety (66%, P < 0.01) and of melanoma features from pre- and postintervention (39%, P < 0.01). A multivariate analysis of variance indicated that knowledge and intentions improved (all P's < 0.01). Interaction effects indicated that improvements in knowledge were greater for those in the rural pharmacy (P = 0.03), and improvements in perceived importance were greater for those in urban pharmacies (P = 0.01). CONCLUSION: The SCAN! intervention was well received by the population. Our study provides evidence that community pharmacy is a novel venue for skin cancer prevention interventions, particularly for rural, medically underserved populations.

Hindfoot blast injuries caused by improvised explosive devices: long-term functional assessment in French military personnel.

PURPOSE: The chosen treatment and long-term evaluation of hindfoot blast injuries are not well-represented in the literature. The first objective of this retrospective study was to evaluate functional outcomes in French service personnel who had sustained such injuries caused by improvised explosive devices. The second objective was to compare the results for patients who had amputations with those who did not. The hypothesis was that amputee recovered better function. METHODS: Long-term functional evaluations were carried out using the American Orthopaedic Foot and Ankle Society scale (AOFAS), the Foot and Ankle Ability Measure (FAAM), and the Short Form 12 health survey (SF-12). RESULTS: Eight servicemen with ten hindfoot blast injuries were reviewed at a mean follow-up time of seven years. Primary management was always conservative although half of the patients required late amputation for chronic pain. The patients who underwent amputation reported significantly lower levels of pain than those who did not have an amputation, with higher FAAM and SF-12 scores. CONCLUSION: In this series, long-term functional results appear better in the amputated group.

Rationale and design of a global registry to evaluate real-world clinical outcomes in patients with atrial fibrillation and high risk of stroke treated with left atrial appendage occlusion using the AMPLATZER amulet device-Perspective of available/ongoing registries of catheter-based LAA occlusion.

OBJECTIVES: To describe the rationale and design of a global prospective registry on catheter-based left atrial appendage (LAA) occlusion using the second generation AMPLATZER Amulet LAA occlusion device and to provide a comprehensive perspective on available/ongoing registries for catheter-based LAA occlusion. BACKGROUND: Given the increasing clinical application of catheter-based LAA occlusion, there is an important need for prospective real-world clinical data regarding this cardiac intervention. METHODS: The Global Amplatzer Amulet LAA registry aims to provide prospective real-world data from an all-comer population of atrial fibrillation (AF) patients undergoing catheter-based LAA occlusion for stroke prevention. This observational, prospective, multicenter registry will provide peri-procedural and long-term clinical outcome data for catheter-based LAA occlusion using a second generation LAA occlusion device. The global registry will enroll 1,000 patients at up to 75 institutions. Patients will be followed for 2 years after implantation. Primary endpoints will report procedural and long-term data on ischemic stroke, systemic embolism, cardiovascular death and major bleeding. The study will involve independent event adjudication and echocardiographic core laboratory evaluation. Long-term follow-up data are expected in 2018. RESULTS: The Global Amplatzer Amulet LAA registry will collect safety and efficacy information on catheter-based LAA occlusion. Characteristics of available and ongoing catheter-based LAA occlusion registries are described. CONCLUSIONS: There is an important need for prospective real-world clinical data of catheter-based LAA occlusion given the increasing application of this intervention. The present global real-world registry will expand our knowledge on peri-procedural and long-term outcome of catheter-based LAA occlusion using a second generation occlusion device.

Effects of EphB4 receptor expression on colorectal cancer cells, tumor growth, vascularization and composition.

BACKGROUND: Colorectal cancer (CRC) is one of the most common causes of cancer-related deaths worldwide. Increased expression of the molecular target, EphB4 receptor, has been observed in several cancer types. However, studies on the role of EphB4 receptor in CRC have yielded contradictory results. The aim of this study was to investigate the influence of EphB4 expression levels on CRC cell behavior and its contribution to tumor growth and vascularization. METHODS: SW480, LIM2405 and CT26 CRC cell lines were transfected with EphB4 expression vector. High EphB4 expressing cells were compared to low EphB4 expressing empty vector controls. Proliferation and migration assays as well as EphrinB2-Fc cell stimulations were conducted in vitro and subcutaneous xenografts of CRC were analyzed in vivo. RESULTS: High EphB4 expression enhanced migratory ability of these CRC cell lines in vitro and contributed to a significant increase in tumor growth and vascularization in vivo. Tumours induced with high EphB4 expressing SW480 and LIM2405 cells yielded homogenous masses densely packed with cancer cells. EphrinB2-Fc cell stimulations induced cell clustering of high EphB4 expressing SW480 and LIM2405 in vitro. CONCLUSION: These results suggest that with enhanced vascularization and an increase in migratory abilities, the high EphB4 expressing cells may be able to metastasize more readily.

Bispectral Index Measurements Are Not Degraded During Aeromedical Evacuations.

For a decade, depth of anesthesia monitoring has become a reality in the operating room. It provides valuable help for managing anesthesia, especially for unstable patients. This might be particularly relevant during aeromedical evacuation. In this study, we aimed to assess the validity of the bispectral index (BIS) during long-range patient transportation aboard fixed-wing aircraft. BIS was recorded in 30 patients, 25 under anesthesia and 5 awake, during aeromedical evacuations performed by the French Air Force. BIS index was available and analyzable (signal quality index above 50%) more than 90% of time. Despite potential pitfalls related to mechanical or electrical interference, BIS monitor can be reliably used to monitor depth of anesthesia during individual strategic aeromedical evacuations.

Quantitative Genetic Variation in, and Environmental Effects on, Pathogen Resistance and Temperature-Dependent Disease Severity in a Wild Trout.

Health after pathogen contact varies among individuals because of differences in pathogen load (which is limited by resistance) and disease severity in response to pathogen load (which is limited by tolerance). To understand pathogen-induced host evolution, it is critical to know not only the relative contributions of nongenetic and genetic variation to resistance and tolerance but also how they change environmentally. We quantified nongenetic and genetic variation in parasite load and the associated temperature-dependent disease among trout siblings from two rivers. We detected a genetic variance for parasite load 6.6 times as large in the colder river. By contrast, genetic variance for disease traits tended to be larger in the warmer river, where the disease was manifested more severely. The relationships between disease severity and pathogen load (tolerance) exhibited plateaus at low pathogen load and stronger steepening slopes at high pathogen load in the warmer river. Our study demonstrates the environmental influence on disease severity, nongenetic and genetic variance for health-damage-limiting host abilities, and the shape of tolerance curves. Environmental variability is predicted to govern the presence and intensity of selection, change the relative contributions of nongenetic and genetic variance, and therefore hamper evolution toward more resistant and tolerant hosts.