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Objective: This study examined the role of central sensitization in the experience of pain among adolescents and young adults with the most severe genotypes of sickle cell disease (SCD). We hypothesized that adolescents and young adults with chronic SCD pain would demonstrate a higher perceptual response to repeated stimulation of identical intensity (i.e., temporal summation of pain, TSP) compared to counterparts with infrequent pain. We also examined psychological risk factors that can impact pain sensitivity., Methods: Patients ages 12-21 years, diagnosed with SCD type Hb SS or Hb S Beta0Thalasemia, who reported infrequent pain (≤2 pain days/month; n = 25) or met AAPT criteria for chronic SCD pain (n = 25) were enrolled. Patients were age- and sex-matched, with similar proportions receiving chronic blood transfusion and hydroxyurea. Patients completed static quantitative sensory testing (QST) and dynamic TSP testing to assess pain sensitivity. Patients and a caregiver completed demographic and psychological measures (depression, anxiety, pain interference, pain catastrophizing)., Results: Simple slope analysis revealed differentially elevated heat TSP among adolescents and young adults with chronic SCD pain (b = 3.14, p = .002) but not those with infrequent pain (b = 0.45, p = .61). Faster habituation was further observed for those with chronic compared to infrequent pain. Adolescents and young adults with chronic pain reported more frequent depression, anxiety, and pain interference symptoms; however, psychological symptoms and pain catastrophizing were not associated with QST or TSP (ps >.17)., Conclusion: Current results demonstrate that a well-established, prognostic, QST risk marker (i.e., TSP) may distinguish chronic from infrequent pain subgroups of adolescents and young adults with SCD., (© The Author(s) 2024. Published by Oxford University Press on behalf of the Society of Pediatric Psychology. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

IL17 is required for the initiation and progression of pancreatic cancer, particularly in the context of inflammation, as previously shown by genetic and pharmacological approaches. However, the cellular compartment and downstream molecular mediators of IL17-mediated pancreatic tumorigenesis have not been fully identified. This study examined the cellular compartment required by generating transgenic animals with IL17 receptor A (IL17RA), which was genetically deleted from either the pancreatic epithelial compartment or the hematopoietic compartment via generation of IL17RA-deficient (IL17-RA-/-) bone marrow chimeras, in the context of embryonically activated or inducible Kras. Deletion of IL17RA from the pancreatic epithelial compartment, but not from hematopoietic compartment, resulted in delayed initiation and progression of premalignant lesions and increased infiltration of CD8+ cytotoxic T cells to the tumor microenvironment. Absence of IL17RA in the pancreatic compartment affected transcriptional profiles of epithelial cells, modulating stemness, and immunological pathways. B7-H4, a known inhibitor of T-cell activation encoded by the gene Vtcn1, was the checkpoint molecule most upregulated via IL17 early during pancreatic tumorigenesis, and its genetic deletion delayed the development of pancreatic premalignant lesions and reduced immunosuppression. Thus, our data reveal that pancreatic epithelial IL17RA promotes pancreatic tumorigenesis by reprogramming the immune pancreatic landscape, which is partially orchestrated by regulation of B7-H4. Our findings provide the foundation of the mechanisms triggered by IL17 to mediate pancreatic tumorigenesis and reveal the avenues for early pancreatic cancer immune interception. See related Spotlight by Lee and Pasca di Magliano, p. 1130., (©2024 The Authors; Published by the American Association for Cancer Research.)

Purpose: The American Dental Association advocates for dentists' education on therapeutic and legal issues related to medical cannabis. It is important to understand current knowledge of cannabis and cannabinoids and to have a practical knowledge assessment instrument. This exploratory study is the first of its kind to assess dental students' knowledge of cannabis and aims to determine if there is a need for more instruction regarding cannabis in a dental school's curriculum., Methods: Predoctoral dental students at the University at Buffalo School of Dental Medicine were recruited to participate. A validated, anonymous 22-item online survey was adapted and administered to students in all 4 years of the dental program. There was a total of 56 knowledge points., Results: The average knowledge score was 21.6 points (SD = 5.2, range: 7-34), corresponding to 38.5% (SD = 9.2) of the answers correct. There were no overall differences in knowledge by gender, years in dental school, or by any reported source of formal education on cannabis. Those who reported doing their own research had higher knowledge scores. Most participants knew that there is an endogenous cannabinoid system (72.3%) and that Tetrahydrocannabinol (THC) is responsible for the "high" experienced with cannabis (76.6%). Most participants reported that they did not know the effective doses of THC (58.2%) and Cannabidiol (CBD) (66.7%); few provided an answer for THC (34%) or CBD (17%) in the acceptable range of 2-10 mg., Conclusion: Dental students did not have adequate knowledge on cannabis and cannabinoids. Given the rapid expansion of cannabis legalization, additional efforts are needed to integrate cannabis topics into coursework and learning experiences., (© 2024 American Dental Education Association.)

Anchialine systems are coastal groundwater habitats around the world which host a unique community of cave adapted species (stygobionts). Such communities are expected to be separated by haloclines into either fresh or saline groundwater communities, hence climate changes (e.g., eustatic sea level shifts) and anthropic driven changes (e.g., salinization) may have a great impact on these stygobiont communities. Here we used cave-restricted species of Typhlatya from the Yucatan Peninsula as models to identify physiological capacities that enable the different species to thrive in marine groundwater (T. dzilamensis) or fresh groundwater (T. mitchelli and T. pearsei), and test if their distribution is limited by their salinity tolerance capacity. We used behavior, metabolic rates, indicators of the antioxidant system and cellular damage, and lactate content to evaluate the response of individuals to acute changes in salinity, as a recreation of crossing a halocline in the anchialine systems of the Yucatan Peninsula. Our results show that despite being sister species, some are restricted to the freshwater portion of the groundwater, while others appear to be euryhaline., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Chávez Solís et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

The reproductive process in Octopus maya was analyzed to establish the amount of reactive oxygen species that the embryos inherit from females, during yolk synthesis. At the same time, respiratory metabolism, ROS production, and the expression of some genes of the antioxidant system were monitored to understand the ability of embryos to neutralize maternal ROS and those produced during development. The results indicate that carbonylated proteins and peroxidized lipids (LPO) were transferred from females to the embryos, presumably derived from the metabolic processes carried out during yolk synthesis in the ovary. Along with ROS, females also transferred to embryos glutathione (GSH), a key element of the antioxidant defense system, thus facilitating the neutralization of inherited ROS and those produced during development. Embryos are capable of neutralizing ROS thanks to the early expression of genes such as catalase (CAT) and superoxide dismutase (SOD), which give rise to the synthesis of enzymes when the circulatory system is activated. Also, it was observed that the levels of the routine metabolic rate of embryos are almost as high as those of the maximum activity metabolism, which leads, on the one hand, to the elevated production of ROS and suggests that, at this stage of the life cycle in octopuses, energy production is maximum and is physically limited by the biological properties inherent to the structure of embryonic life (oxygen transfer through the chorion, gill surface, pumping capacity, etc.). Due to its role in regulating vascularization, a high expression of HIf-1A during organogenesis suggests that circulatory system development has begun in this phase of embryo development. The results indicate that the routine metabolic rate and the ability of O. maya embryos to neutralize the ROS are probably the maximum possible. Under such circumstances, embryos cannot generate more energy to combat the free radicals produced by their metabolism, even when environmental factors such as high temperatures or contaminants could demand excess energy., (© 2024. The Author(s).)

The effects of two prepared feeds were tested on growth, survival, enzymatic activity, nutritive reserves in the digestive gland and oxygen consumption of Octopus maya juveniles. For the first time, a semihumid paste (HD, control) and a dry diet, in pelleted form (PD, experimental) with the same formulation were used for this species. The experiment lasted for 42 days. Results indicate that growth rates were similar for both diets (p > 0.05); however, survival (70%) was higher with the PD compared to the HD (48%) (p < 0.05). The performance index was higher for octopuses fed the PD (p < 0.05). No differences in acid proteases activity were observed. However, a higher activity of alkaline proteases in the octopuses fed the PD was observed (p < 0.05). Ingestion rate was higher for octopuses fed the PD. Routine energy inversion was similar in both treatments (p > 0.05). A greater energy inversion was observed in octopuses fed the PD, whose active metabolism was double compared to the octopuses fed the HD. Results showed that the PD promoted similar growth compared to the HD diet but favored survival, and a greater investment in the active metabolism, reflected in the apparent heat increase., (© 2024 The Authors. Journal of Animal Physiology and Animal Nutrition published by Wiley‐VCH GmbH.)

Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.