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Dipeptidyl peptidase 4 (DPP4; CD26) is involved in the regulation of various metabolic, immunological, and neurobiological processes in healthy individuals. Observations based on epidemiological data indicate that DPP4 inhibition by gliptins, typically used in patients with diabetes, may reduce the risk for cerebral ischemia and may also improve related outcomes. However, as DPP4 inhibitor application is neither complete nor specific for suppression of DPP4 enzymatic activity and DPP4 has non-enzymatic functions as well, the variety of consequences is a matter of debate. Therefore, we here used DPP4 knock-out (KO) mice to analyze the specific contribution of DPP4 to cellular, immunological, and functional consequences of experimental focal cerebral ischemia.We observed a significantly higher survival rate of DPP4 KO mice after ischemia, which was accompanied by a lower abundance of the pro-inflammatory chemokine CCL2 and reduced activation of Iba1-positive microglia cells in brain tissue of DPP4 KO mice. In addition, after ischemia for 24 h to 72 h, decreased concentrations of CCL5 and CCL12 in plasma and of CCL17 in brain tissue of DPP4 KO mice were observed when compared to wild type mice. Other aspects analyzed, such as the functional Menzies score, astrocyte activation and chemokine levels in plasma and brain tissue were affected by ischemia but appeared to be unaffected by the DPP4 KO genotype.Taken together, experimental ablation of DPP4 functions in mice improves survival and ameliorates aspects of cellular and molecular inflammation after focal cerebral ischemia.

This Indigenous-led project aims to better understand historical and contemporary ways in which Alaska Native Peoples steward salmon and the values connected to salmon stewardship. Indigenous Peoples have stewarded Alaska lands and waters for thousands of years yet have been largely excluded from western science and management systems. In this project, we utilize a participatory approach that allows for the equitable valuing of ideas and knowledges to document the breadth and depth of Yup'ik and Athabascan knowledge and governance systems in southwestern Alaska. We reshape research methodologies by centering Indigenous frameworks and methodologies, including circle dialogues and multi-generational interviews led by Indigenous scholars and students in their home communities and regions. In this paper, we share the Yup'ik and Athabascan values, knowledge, management, and governance mechanisms that can improve the long-term sustainability and equity of Alaska salmon systems. This research elevates the voices of Alaska Native salmon stewards and experts from the Kuskokwim Bay and the Kuskokwim River. We elaborate on five key themes that emerged from this research, including traditional Indigenous ways of life, Indigenous stewardship, self-determination, food and livelihood sovereignty, and ecosystem changes, and identify a more equitable and sustainable path forward for salmon and people in Alaska.

This article provides perspectives on the graying of the fleet and research efforts to understand it in Alaska fisheries, discusses recent abrupt multifaceted challenges faced by Alaskan fishermen, and compares divergent public perceptions and support programs for farmers and fishermen in the United States. Equity concerns have seen a resurgence in academic and policy realms and the graying of the fleet is now a common example of distributional inequity, yet despite in-depth research attention on the issue, few substantive programmatic modifications have been made to address it in Alaska. Aging trends in United States fisheries have typically been framed as one of changing aspirational preferences. Research suggests coastal youth do desire and highly value fishing careers, but structural and financial barriers limit opportunities for new generations. The precarity of the fishing industry was highlighted in 2023 with sudden global seafood market instability, rising interest rates and operating costs, destabilized geopolitical tensions, and hastening climate change impacts. This recent industry turmoil disproportionately impacts those on the margins and adds an additional layer of complexity to addressing graying of the fleet trends. Unlike in fisheries, there are numerous federal programs to support young farmers and the agricultural industry. This paper calls for proactive and comprehensive measures to stabilize and support fishing communities and the viability of next generation pathways amidst recent fishing industry market turmoil and longer term inequities in fishery governance.

Glutaminyl cyclase (QC) and its isoenzyme (isoQC) catalyze the formation of N-terminal pyroglutamate (pGlu) from glutamine on a number of neuropeptides, peptide hormones and chemokines. Chemokines of the C-C ligand (CCL) motif family are known to contribute to inflammation in neurodegenerative conditions. Here, we used a model of transient focal cerebral ischemia to explore functional, cellular and molecular responses to ischemia in mice lacking genes for QC, isoQC and their substrate CCL2. Mice of the different genotypes were evaluated for functional consequences of stroke, infarct volume, activation of glia cells, and for QC, isoQC and CCL2 expression. The number of QC-immunoreactive, but not of isoQC-immunoreactive, neurons increased robustly in the infarct area at 24 and 72 h after ischemia. In parallel, immunohistochemical signals for the QC substrate CCL2 increased from 24 to 72 h after ischemia induction without differences between genotypes analyzed. The increase in CCL2 was accompanied by morphological activation of Iba1-immunoreactive microglia and recruitment of MHC-II-positive cells at 72 h after ischemia. Among other chemokines quantified in the brain tissue, CCL17 showed higher concentrations at 72 h compared to 24 h after ischemia. Collectively, these data suggest a critical role for QC in inflammatory processes in the stroke-affected brain.

Objective: We sought to better understand what defines a critical incident experience for the surgical trainee. Summary Background Data: Critical incidents are formative moments stamped indelibly on one's memory that shape professional identity. The critical incident technique—using participants' narratives to identify patterns and learn from their perceptions—has been explored in some healthcare settings, but there has been no inquiry within surgery. Methods: Surgical residents at 5 residency programs (1 community, 1 university-affiliated, 3 university) were surveyed using an online questionnaire from November to December 2020. Convenience sampling was used to identify the study population. Participants were invited to write about formative, impactful experiences in training. Interpretive description was the qualitative methodology used to locate information, analyze, and record patterns in the data. Individual responses were categorized and assessed for overlying themes. Results: Overall, 28 narratives were collected from surgery residents in 3 specialties (general surgery, plastic surgery, and urology), with postgraduate year representation of post-graduate years 1 to 6. Respondents were 40% female. Nineteen of the narratives reported a negative experience. Four themes were identified from responses: 1) growth through personal self-reflection, 2) difficult interpersonal interactions, 3) positive team dynamics as a psychological safety net, and 4) supportive program cultures that promote learning. Conclusions: Critical incident narratives among surgical residents indicate that unforgettable and formative experiences—both positive and negative— occur in 4 domains: within the individual, within a relationship, among a team, and within a program. Further exploring these domains in surgical training will inform optimal educational programming to support trainee development and wellbeing. [ABSTRACT FROM AUTHOR]

The rise in attention to equity as a goal in fisheries management has revealed a dearth of data related to how certain communities and groups participate in, rely on, and may be impacted by fishery management decisions. Lack of data on impacts to Tribal and Indigenous participants and other underserved communities have been identified as a primary barrier to assessing and improving equity considerations in fishery governance. Data on fishery participation trends, including who benefits from fisheries, is essential to determining if and how fishery management and decision-making are achieving desired management objectives such as providing for intergenerational access and preserving a way of life. Understanding changes in participation trends is also critical for developing effective conservation solutions. In Alaska salmon fisheries, shifts in permit holdings are generally categorized by the residency of permit holders. This means that little is known about how Alaska Native participation, as well as women's participation, in Alaska commercial fisheries has changed over time. This paper presents a case study on local salmon permit holdings in the Bristol Bay region of southwest Alaska. We discuss the consequences of conflating rural with Alaska Native in data-driven decision-making, and highlight the ways in which official fishery statistics can mask past and ongoing harms to Indigenous communities and peoples. We situate this study in the broader science-policy arena of state and federal fishery governance and data collection efforts that often render invisible impacts to Indigenous communities and livelihoods. • Keeping fishing rights in the hands of rural Alaskans dependent on fisheries is a key goal of Alaska's Limited Entry Act. • The loss of rural permit holdings in Bristol Bay occurs at the intersection of gender and race/ethnicity. • The conflation of rural/local with Alaska Native/Indigenous renders impacts to Indigenous participants largely invisible. • Data on participation trends is essential to determining if fishery decision-makers are achieving desired objectives. • Lack of data on Tribal/Indigenous participation is a barrier to assessing and improving equity in fisheries. [ABSTRACT FROM AUTHOR]

Dipeptidyl peptidase 4 (DPP4; CD26) is involved in the regulation of various metabolic, immunological, and neurobiological processes in healthy individuals. Observations based on epidemiological data indicate that DPP4 inhibition by gliptins, typically used in patients with diabetes, may reduce the risk for cerebral ischemia and may also improve related outcomes. However, as DPP4 inhibitor application is neither complete nor specific for suppression of DPP4 enzymatic activity and DPP4 has non-enzymatic functions as well, the variety of consequences is a matter of debate. Therefore, we here used DPP4 knock-out (KO) mice to analyze the specific contribution of DPP4 to cellular, immunological, and functional consequences of experimental focal cerebral ischemia. We observed a significantly higher survival rate of DPP4 KO mice after ischemia, which was accompanied by a lower abundance of the pro-inflammatory chemokine CCL2 and reduced activation of Iba1-positive microglia cells in brain tissue of DPP4 KO mice. In addition, after ischemia for 24 h to 72 h, decreased concentrations of CCL5 and CCL12 in plasma and of CCL17 in brain tissue of DPP4 KO mice were observed when compared to wild type mice. Other aspects analyzed, such as the functional Menzies score, astrocyte activation and chemokine levels in plasma and brain tissue were affected by ischemia but appeared to be unaffected by the DPP4 KO genotype. Taken together, experimental ablation of DPP4 functions in mice improves survival and ameliorates aspects of cellular and molecular inflammation after focal cerebral ischemia., Competing Interests: Declaration of competing interest The authors declare that they have no competing interests., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Glutaminyl cyclase (QC) and its isoenzyme (isoQC) catalyze the formation of N-terminal pyroglutamate (pGlu) from glutamine on a number of neuropeptides, peptide hormones and chemokines. Chemokines of the C-C ligand (CCL) motif family are known to contribute to inflammation in neurodegenerative conditions. Here, we used a model of transient focal cerebral ischemia to explore functional, cellular and molecular responses to ischemia in mice lacking genes for QC, isoQC and their substrate CCL2. Mice of the different genotypes were evaluated for functional consequences of stroke, infarct volume, activation of glia cells, and for QC, isoQC and CCL2 expression. The number of QC-immunoreactive, but not of isoQC-immunoreactive, neurons increased robustly in the infarct area at 24 and 72 h after ischemia. In parallel, immunohistochemical signals for the QC substrate CCL2 increased from 24 to 72 h after ischemia induction without differences between genotypes analyzed. The increase in CCL2 was accompanied by morphological activation of Iba1-immunoreactive microglia and recruitment of MHC-II-positive cells at 72 h after ischemia. Among other chemokines quantified in the brain tissue, CCL17 showed higher concentrations at 72 h compared to 24 h after ischemia. Collectively, these data suggest a critical role for QC in inflammatory processes in the stroke-affected brain.

Background: Schwannomatosis is a relatively rare disorder and is related to neurofibromatosis type 2. Although there is clinical overlap between schwannomatosis and neurofibromatosis type 2, these diseases have to be regarded as separate entities due to the genetic origin and course of the disease., Methods: A comprehensive review of the literature was conducted for relevant studies using Pubmed and Cochrane databases to discuss the epidemiology, clinical presentation, diagnostic criteria, pathological and imaging features, treatment and genetics of schwannomatosis., Results: Germline mutations SMARCB1 and LZTRI together with the NF2 gene play a role in the pathophysiology of schwannomatosis. The most common symptom is pain with affection of the spine and peripheral nerves in the majority of patients. High quality contrast enhanced MRI scan is the imaging modality of choice. Treatment is conservative if asymptomatic and surgical if symptomatic. The goal is symptom control with preservation of neurological function., Conclusion: Schwannomatosis is a relatively rare disorder in which the main goal is to preserve neurological function.