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The utility of the lined shore crab Pachygrapsus crassipes as an indicator of small-scale variation in the condition of salt marshes was determined by conducting detailed mark-recapture studies of the spatial and temporal patterns of movement in 2 marshes in northern and southern California, and by conducting a stable isotope study along a nutrient gradient at one of the marshes. Crabs (1158) were captured from creek bank and vegetated marsh habitats, tagged, and released. Most crabs were recaptured in the same trap where they were originally tagged, and on average, they traveled less than 5 m from the site of first capture. The mean distance traveled did not increase significantly with the time between captures. A high percentage of crabs (62.1%) tagged near the creek bank remained there; fewer tagged crabs moved between the creek bank and the marsh plain (18.2%) or remained on the marsh plain (12.6%). Crabs moved least along creek banks and farthest when crossing creeks, although few of them did the latter (6.2%). During spring tides, crabs moved from tidal creeks onto the marsh plain. The nitrogen isotope data mirrored the gradient in nutrient input, supporting the conclusion that P. crassipes remained and fed within a localized area. Thus, the lined shore crab can serve as an indicator of small-scale differences in contaminant exposure. Furthermore, semiterrestrial species that are readily sampled and move little are abundant around the world, making them ideal indicators of habitat condition. © Inter-Research 2006.

Background Homeopaths report that individuals with heightened self-reported environmental chemical intolerance (CI) exhibit increased reactivity to homeopathic remedies. Persons high in CI sensitize their electroencephalographic (EEG) alpha responses to repeated intermittent chemical exposures. Primary Study Objective The present feasibility study explored interactions between CI and one of two specific homeopathic remedies over time (Sulphur or Pulsatilla nigricans [Pulsatilla]). Design This study used a two-arm, double-blind, placebo-controlled repeated measures design. Intervention Participants underwent a series of three once-weekly sessions during which they repeatedly sniffed one remedy (6c, 12c, 30c; one potency per week) matched to their Homeopathic Constitutional Type Questionnaire (CTQ) type and two solvent controls (distilled water and a waterethanol [95%] solution). Within sessions, remedies and control solvents were administered via 2-second sniffs (eight sniffs of each of four different succussion levels per potency, in randomized order). Participants Participants were college student volunteers (N = 96, ages 18-30, both sexes), screened for good health and relatively elevated Sulphur or Pulsatilla symptom pattern scores on the Homeopathic Constitutional Type Questionnaire (CTQ). Participants also completed a validated trait CI scale. Primary Outcome Measures Average 19-lead relative EEG alpha power (alpha 1 8-10 Hz; alpha 2 10-12 Hz). Results Trait CI interacted significantly with time factors for each remedy (both over visit weeks and over sniff cycles during sessions). The patterns were nonlinear and differed between the two remedies. Individuals high in CI showed greater variability over time in remedy EEG alpha effects than did those low in CI. Conclusion The data suggest that CI, with an underlying susceptibility to time-dependent sensitization and oscillatory responses, could contribute to nonlinear dose-response patterns and inconsistent reproducibility of homeopathic clinical care and research. (Altern Ther Health Med. 2013;19(1):46-57.). [ABSTRACT FROM AUTHOR]

Introduction: The value of synchronous liver resection and cryotherapy ablation remains controversial for colorectal metastases where complete resection is not possible by conventional liver surgery alone.Objective: To review the long-term survival of patients treated using this approach at our institution.Methods: A review was undertaken of data held in the prospectively collected liver surgery database of all patients who underwent synchronous liver resection and cryotherapy. Survival analysis was performed and data recorded on the total number of metastases at initial surgery and the number of lesions treated by cryoablation.Results: Ninety-three patients with colorectal metastases underwent synchronous liver resection and cryotherapy. Data were available on 86 patients with a median follow-up of 18 months (range 1-83). The median number of metastases at initial surgery was four (range 2-11) and the number of lesions treated by cryotherapy ablation was two (range 1-8). Eighty-four per cent had a hepatic artery catheter inserted at surgery and at least one cycle of post-operative hepatic artery chemotherapy. One-, three- and five-year survival was 85%, 43% and 19% respectively, with a median survival of 33 months (95% confidence interval 19.9-42.1). Site of recurrence was recorded and presented.Conclusions: Patients with liver metastases that are not amenable to resection alone can achieve worthwhile median survival with synchronous liver resection and cryotherapy ablation. [ABSTRACT FROM AUTHOR]

Purpose: To investigate whether the communities where employees reside are associated with employee perception of overall physical health after adjusting for individual factors.Design: Retrospective cross-sectional.Setting: Active employees from a large manufacturing company representing 157 zip code tabulation areas (ZCTAs) in Michigan.Participants: 22,012 active employees who completed at least one voluntary health risk appraisal (HRA) during 1999-2001.Method: Community deprivation and racial segregation at the ZCTA level were obtained using indices created from 2000 U.S. Census data. Demographics and HRA-related data (health-related behaviors, medical history, and quality of life indicators) at the individual level were used as independent variables. A two-level logistic regression model (employees nested in ZCTA) was used to model the probability of better self-rated health perception (SRH) (better health: 89.1% versus poor health: 10.9%).Results: Relative to those living in highly deprived communities, employees residing in less-deprived communities showed 2.06 (95% confidence interval [CI], 1.57-2.72) and those living in moderately deprived communities showed 1.83 (95% CI, 1.42-2.35) increased odds of better SRH. After adjusting for individual-level variables, employees living in less-deprived communities had increased odds (1.31 [95% CI, 1.07-1.60]) and those living in moderately deprived communities had increased odds (1.33 [95% CI, 1.11-1.59]) of better SRH compared with individuals from highly deprived communities. The association of racial segregation with employees' SRH was mediated after adjusting for other variables. Individual-level variables showed significant statistical associations with SRH.Conclusion: Communities do have a modest association with SRH of the employees living there. After adjusting for individual-level and demographic variables, employees living in less/moderately deprived communities are more likely to perceive better physical health relative to those who live in highly deprived communities. [ABSTRACT FROM AUTHOR]

Freshwater ecosystems are being degraded by a wide range of stressors resulting from human activities. Various structural and functional metrics or indices are used to assess the 'health' or condition of riverine ecosystems. It is uncertain if structural or functional metrics or indices respond to different stressors and whether some are more responsive to stressors in general. Here we conducted a multi-study synthesis, similar to a meta-analysis, across four independent outdoor mesocosm experiments involving the manipulation of various chemical stressors - two types of salinity (synthetic marine salts (SMS) and sodium bicarbonate), two insecticides (malathion and sulfoxaflor), increased nutrients (N and P), increased sedimentation and two combinations of stressors (1: malathion, nutrients and sedimentation, 2: sulfoxaflor, nutrients and sedimentation). We compare the effects of these singular or multiple stressors on stream macroinvertebrate community structure, and Eucalyptus camaldulensis leaf litter breakdown rates by microbes and total (microbes and invertebrates). Macroinvertebrate communities were adversely affected by the two sets of multiple stressors, SMS, and both insecticides yet, and in contrast to several published studies, both microbial and total leaf litter was unaffected. Nutrients and sodium bicarbonate, increased breakdown rates or had a unimodal 'Ո' shaped response, with maxima at intermediate levels. Sedimentation by fine sand, however, decreased total leaf litter breakdown, while not affecting microbial leaf litter breakdown. Divergent responses between the effects of stressors on leaf litter breakdown rates that we observed and those in the literature may be caused by multiple mechanisms, including differences between communities, functional redundancy and differences in stressor magnitude and interactions with other (unknown) variables., 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., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Objective: This study describes knowledge change, self-assessed confidence in providing integrative medicine approach, and respondents' perspective on value and feasibility for the Integrative Medicine in Residency-Psychiatry (IMR-Psychiatry) curriculum, a 100-h elective offered during psychiatry training., Methods: Residents/fellows completed pre-post Medical Knowledge tests and self-assessment instruments tracking self-rated confidence. Participants were also interviewed for feedback about their experience using a semi-structured design after completion of the program., Results: Thirty-five of 37 (94.6%) participants completed all elective requirements. Items on the self-assessment instrument with the greatest positive pre-post change (p < 0.001) included ability to identify authoritative sources about botanicals (Cohen d = 2.15), effectively respond to patients' questions regarding the use of herbs/supplements (Cohen d = 2.67), and interpret labels on nutraceuticals (Cohen d = 2.28). Mean score on the Medical Knowledge test (n = 30) increased from 64.7% correct at pretest to 81.6% at posttest. Responses tracking self-assessed confidence in providing an IM approach to address 18 common medical and psychiatric conditions all increased significantly pre to post (p < 0.001). Qualitative interviews provided important insights into challenges and recommendations for improvement, and all participants highly recommended the curriculum and found it feasible to complete during training., Conclusion: The IMR-Psychiatry curriculum provides trainees skills that promote comprehensive person-centered care; as a tool to optimize patient care and safety while enhancing physician well-being, wider-spread incorporation of the curriculum into psychiatry residency programs would be beneficial., Competing Interests: Declarations Ethics Approval On behalf of all authors, the corresponding author states that there is no ethical consideration. Disclosures Amelia Villagomez, MD, received consulting fees from the University of Arizona and honoraria for presentations from Integrative Psychiatry Institute, LLC, and Andrew Weil Center for Integrative Medicine. Noshene Ranjbar, MD, received honoraria at the following institutions: Integrative Psychiatry Institute LLC, The Center for Mind–Body Medicine, Andrew Weil Center for Integrative Medicine. She received support for travel/attending meetings from The Center for Mind–Body Medicine and Integrative Psychiatry Institute LLC. She also serves on an advisory board to Andrew Weil Center for Integrative Medicine. In addition, she serves as the Vice-Chair of the American Board of Integrative Medicine, a member of the Complementary and Integrative Medicine Committee of the American Academy of Child and Adolescent Psychiatry, and Integrative Mental Health Special Interest Group Chair of the Academic Consortium for Integrative Medicine and Health.Mari Ricker, MD, serves as a board member of the American Board of Integrative Medicine Board of Directors., (© 2024. The Author(s).)

Natural killer (NK) cells play a vital role in innate immunity and show great promise in cancer immunotherapy. Traditional sources of NK cells, such as the peripheral blood, are limited by availability and donor variability. In addition, in vitro expansion can lead to functional exhaustion and gene editing challenges. This study aimed to harness induced pluripotent stem cell (iPSC) technology to provide a consistent and scalable source of NK cells, overcoming the limitations of traditional sources and enhancing the potential for cancer immunotherapy applications. We developed human placental-derived iPSC lines using reprogramming techniques. Subsequently, an optimized two-step differentiation protocol was introduced to generate high-purity NK cells. Initially, iPSCs were differentiated into hematopoietic-like stem cells using spin-free embryoid bodies (EBs). Subsequently, the EBs were transferred to ultra-low attachment plates to induce NK cell differentiation. iPSC-derived NK (iNK) cells expressed common NK cell markers (NKp46, NKp30, NKp44, CD16 and eomesodermin) at both RNA and protein levels. iNK cells demonstrated significant resilience to cryopreservation and exhibited enhanced cytotoxicity. The incorporation of a chimeric antigen receptor (CAR) construct further augmented their cytotoxic potential. This study exemplifies the feasibility of generating iNK cells with high purity and enhanced functional capabilities, their improved resilience to cryopreservation and the potential to have augmented cytotoxicity through CAR expression. Our findings offer a promising pathway for the development of potential cellular immunotherapies, highlighting the critical role of iPSC technology in overcoming challenges associated with traditional NK cell sources., (© 2024 The Author(s). Immunology & Cell Biology published by John Wiley & Sons Australia, Ltd on behalf of the Australian and New Zealand Society for Immunology, Inc.)

In rodents, loss of growth hormone (GH) or its receptor is associated with extended lifespan. We aimed to determine the signaling process resulting in this longevity using GH receptor (GHR)-mutant mice with key signaling pathways deleted and correlate this with cancer incidence and expression of genes associated with longevity. GHR uses both canonical janus kinase (JAK)2-signal transducer and activator of transcription (STAT) signaling as well as signaling via the LYN-ERK1/2 pathway. We used C57BL/6 mice with loss of key receptor tyrosines and truncation resulting in 1) loss of most STAT5 response to GH; 2) total inability to generate STAT5 to GH; 3) loss of Box1 to prevent activation of JAK2 but not LYN kinase; or 4) total knockout of the receptor. For each mutant we analyzed lifespan, histopathology to determine likely cause of death, and hepatic gene and protein expression. The extended lifespan is evident in the Box1-mutant males (retains Lyn activation), which have a median lifespan of 1016 days compared to 890 days for the Ghr-/- males. In the females, GhrBox1-/- mice have a median lifespan of 970 days compared to 911 days for the knockout females. Sexually dimorphic GHR-STAT5 is repressive for longevity, since its removal results in a median lifespan of 1003 days in females compared to 734 days for wild-type females. Numerous transcripts related to insulin sensitivity, oxidative stress response, and mitochondrial function are regulated by GHR-STAT5; however, LYN-responsive genes involve DNA repair, cell cycle control, and anti-inflammatory response. There appears to be a yin-yang relationship between JAK2 and LYN that determines lifespan., (© The Author(s) 2024. Published by Oxford University Press on behalf of the Endocrine Society.)

Background: Well-being initiatives are essential components in fostering an engaged workforce and creating an effective health care ecosystem. Health care professional (HCP) burnout is widespread and has worsened since the COVID-19 pandemic. In 2014, with Health Resources and Services Administration funding support, the Andrew Weil Center for Integrative Medicine created an online course for HCP well-being. It was subsequently studied in medical residents and revised in 2020. In this study, we explore the impact of the course across larger systems, as well as the long-term impact on HCPs., Methods: The Health Care Professional Well-Being course is 4.5 hours of interactive online education that explores personal well-being, promoters and detractors of well-being, and systemic factors that influence the overall impact of well-being in health care systems. Participants were recruited through institutional members of the Academic Consortium for Integrative Medicine and Health and were randomized to either active or waitlist control groups. Assessments were taken pre-course, 1-month post-course, and 6-months post-course in the areas of burnout, compassion, resiliency, and lifestyle behaviors., Results: Burnout measures of depersonalization and emotional exhaustion showed a significant improvement amongst active participants, sustained for 6 months after the course. However, no significant improvement in either the resiliency or the compassion measurements was noted for the active group. Initially, the active group showed improvement in personal accomplishment; however, both groups showed a decline overall. Most noteworthy, a large number of active participants demonstrated adoption of new health-promoting behavior; 95% incorporated at least 1 new lifestyle behavior learned from the course., Conclusion: This study of a brief, asynchronous, online well-being course with interprofessional HCPs, demonstrates that the course is associated with improvement in individual burnout measures and can educate HCPs about healthy behaviors and a framework for professional engagement., Competing Interests: Conflicts of Interest: The authors declare they have no conflicts of interest., (© 2024 HCA Physician Services, Inc. d/b/a Emerald Medical Education.)

Serum ferritin concentrations increase during hepatic inflammation and correlate with the severity of chronic liver disease. Here, we report a molecular mechanism whereby the heavy subunit of ferritin (FTH) contributes to hepatic inflammation. We found that FTH induced activation of the NLRP3 inflammasome and secretion of the proinflammatory cytokine interleukin-1β (IL-1β) in primary rat hepatic stellate cells (HSCs) through intercellular adhesion molecule-1 (ICAM-1). FTH-ICAM-1 stimulated the expression of Il1b , NLRP3 inflammasome activation, and the processing and secretion of IL-1β in a manner that depended on plasma membrane remodeling, clathrin-mediated endocytosis, and lysosomal destabilization. FTH-ICAM-1 signaling at early endosomes stimulated Il1b expression, implying that this endosomal signaling primed inflammasome activation in HSCs. In contrast, lysosomal destabilization was required for FTH-induced IL-1β secretion, suggesting that lysosomal damage activated inflammasomes. FTH induced IL-1β production in liver slices from wild-type mice but not in those from Icam1 -/- or Nlrp3 -/- mice. Thus, FTH signals through its receptor ICAM-1 on HSCs to activate the NLRP3 inflammasome. We speculate that this pathway contributes to hepatic inflammation, a key process that stimulates hepatic fibrogenesis associated with chronic liver disease.

Background: The incidence of contralateral prophylactic mastectomy (CPM) for unilateral breast cancer (UBC) has continued to increase, despite an absent survival benefit except in populations at highest risk for developing contralateral breast cancer (CBC). CPM rates may be higher in rural populations but causes remain unclear. A study performed at our institution previously found that 21.8 % of patients with UBC underwent CPM from 2000 to 2009. This study aimed to evaluate the CPM trend at a single institution serving a rural population and identify the CPM rate in average-risk patients., Methods: Retrospective review of patients who underwent mastectomies for UBC at our institution from 2017 to 2021 was performed. Analysis utilized frequencies and percentages, descriptive statistics, chi-square, and independent sample t -tests., Results: A total of 438 patients were included, of whom 64.4 % underwent bilateral mastectomy for UBC (CPM). Patients who underwent CPM were significantly younger, underwent genetic testing, had germline pathogenic variants, had a family history of breast cancer, had smaller tumors, underwent reconstruction, and had more wound infections. Of CPM patients, 50.4 % had no identifiable factors for increased risk of developing CBC., Conclusions: The rate of CPM in a rural population at a single institution increased from 21.8 % to 64.4 % over two decades, with an average-risk CPM rate of 50.4 %. Those that undergo CPM are more likely to undergo reconstruction and have more wound infections. Identifying characteristics of patients undergoing CPM in a rural population and the increased associated risks allows for a better understanding of this trend to guide conversations with patients., Key Message: This study demonstrates that the rate of contralateral prophylactic mastectomy for unilateral breast cancers performed at a single institution serving a largely rural population has nearly tripled over the last two decades, with half of these patients having no factors that increase the risk for developing contralateral breast cancers. Contralateral prophylactic mastectomy was significantly associated with smaller tumors, younger age, genetic testing, germline pathogenic variants, family history of breast cancer, breast reconstruction, and increased wound infections., Competing Interests: The authors have no declarations of interest to disclose including direct or indirect financial or personal relationships, interests, or affiliations relevant to the subject matter of the manuscript that have occurred over the last two years, or that are expected in the foreseeable future. This disclosure includes, but is not limited to, grants or funding, employment, affiliations, patents (in preparation, filed, or granted), inventions, honoraria, consultancies, royalties, stock options/ownership, or expert testimony. All authors acknowledge that the conflict of interest disclosures are complete for themselves, and their co-authors as stated above., (© 2024 The Authors.)

Increasing salinity is a concern for biodiversity in many freshwater ecosystems globally. Single species laboratory toxicity tests show major differences in freshwater organism survival depending on the specific ions that comprise salinity types and/or their ion ratios. Toxicity has been shown to be reduced by altering ionic composition, despite increasing (total) salinity. For insistence, single species tests show the toxicity of sodium bicarbonate (NaHCO 3 , which commonly is a large proportion of the salts from coalbeds) to freshwater invertebrates is reduced by adding magnesium (Mg 2+ ) or chloride (Cl - ). However, it is uncertain whether reductions in mortality observed in single-species laboratory tests predict effects within populations, communities and to ecosystem processes in more complex multi-species systems both natural and semi-natural. Here we report the results of an outdoor multi-species mesocosm experiment to determine if the effects of NaHCO 3 are reduced by increasing the concentrations of Mg 2+ or Cl - on: a) stream macroinvertebrate populations and communities; b) benthic chlorophyll-a and; c) the ecosystem process of leaf litter decomposition. We found a large effect of a high NaHCO 3 concentration (≈4.45 mS/cm) with reduced abundances of multiple taxa, reduced emergence of adult insects and reduced species richness, altered community structure and increased leaf litter breakdown rates but no effect on benthic chlorophyll-a. However, despite predictions based on laboratory findings, we found no evidence that the addition of either Mg 2+ or Cl - altered the effect of NaHCO 3 . In semi-natural environments such as mesocosms, and natural environments, organisms are subject to varying temperature and habitat factors, while also interacting with other species and trophic levels (e.g. predation, competition, facilitation), which are absent in single species laboratory tests. Thus, it should not be assumed single-species tests are good predictors of the effects of changing ionic compositions on stream biota in more natural environments., Competing Interests: Declaration of competing interest We declare that we have no known conflict of interests., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Protein kinases (PKs) are proteins at the core of cellular signalling and are thereby responsible for most cellular physiological processes and their regulations. As for all intracellular proteins, PKs are subjected to Brownian thermal energy that tends to homogenise their distribution throughout the volume of the cell. To access their substrates and perform their critical functions, PK localisation is therefore tightly regulated in space and time, relying upon a range of clustering mechanisms. These include post-translational modifications, protein-protein and protein-lipid interactions, as well as liquid-liquid phase separation, allowing spatial restriction and ultimately regulating access to their substrates. In this review, we will focus on key mechanisms mediating PK nanoclustering in physiological and pathophysiological processes. We propose that PK nanoclusters act as a cellular quantal unit of signalling output capable of integration and regulation in space and time. We will specifically outline the various super-resolution microscopy approaches currently used to elucidate the composition and mechanisms driving PK nanoscale clustering and explore the pathological consequences of altered kinase clustering in the context of neurodegenerative disorders, inflammation, and cancer., Competing Interests: RG, RM, AB, FM No competing interests declared, (© 2024, Gormal et al.)