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• A high-fat diet impairs learning and memory in male mice and increases anxiety-like behavior across sexes and ages. • A high-fat diet exacerbates systemic inflammation across age and sex in mice and induces microglia in aged male mice. • Hypothalamic proteome reveals metabolic stress induced by a high-fat diet in aged male mice. Aging and age-related diseases are associated with cellular stress, metabolic imbalance, oxidative stress, and neuroinflammation, accompanied by cognitive impairment. Lifestyle factors such as diet, sleep fragmentation, and stress can potentiate damaging cellular cascades and lead to an acceleration of brain aging and cognitive impairment. High-fat diet (HFD) has been associated with obesity, metabolic disorders like diabetes, and cardiovascular disease. HFD also induces neuroinflammation, impairs learning and memory, and may increase anxiety-like behavior. Effects of a HFD may also vary between sexes. The interaction between Age- and Sex- and Diet-related changes in neuroinflammation and cognitive function is an important and poorly understood area of research. This study was designed to examine the effects of HFD on neuroinflammation, behavior, and neurodegeneration in mice in the context of aging or sex differences. In a series of studies, young (2–3 months) or old (12–13 months) C57BL/6J male mice or young male and female C57Bl/6J mice were fed either a standard diet (SD) or a HFD for 5–6 months. Behavior was assessed in Activity Chamber, Y-maze, Novel Place Recognition, Novel Object Recognition, Elevated Plus Maze, Open Field, Morris Water Maze, and Fear Conditioning. Post-mortem analyses assessed a panel of inflammatory markers in the plasma and hippocampus. Additionally, proteomic analysis of the hypothalamus, neurodegeneration, neuroinflammation in the locus coeruleus, and neuroinflammation in the hippocampus were assessed in a subset of young and aged male mice. We show that HFD increased body weight and decreased locomotor activity across groups compared to control mice fed a SD. HFD altered anxiety-related exploratory behavior. HFD impaired spatial learning and recall in young male mice and impaired recall in cued fear conditioning in young and aged male mice, with no effects on spatial learning or fear conditioning in young female mice. Effects of Age and Sex were observed on neuroinflammatory cytokines, with only limited effects of HFD. HFD had a more significant impact on systemic inflammation in plasma across age and sex. Aged male mice had induction of microglial immunoreactivity in both the locus coeruleus (LC) and hippocampus an effect that HFD exacerbated in the hippocampal CA1 region. Proteomic analysis of the hypothalamus revealed changes in pathways related to metabolism and neurodegeneration with both aging and HFD in male mice. Our findings suggest that HFD induces widespread systemic inflammation and limited neuroinflammation. In addition, HFD alters exploratory behavior in male and female mice, and impairs learning and memory in male mice. These results provide valuable insight into the impact of diet on cognition and aging pathophysiology. [ABSTRACT FROM AUTHOR]

This article analyses the political and scientific controversy surrounding a race science project undertaken by the anthropologist Egon Freiherr von Eickstedt under National Socialism. Beginning in 1934, Eickstedt and his team of assistants conducted a series of racial studies on the population of Upper Silesia, a contested borderland in East Prussia. Motivated by a nationalist desire to counter the work of Polish anthropologists in the region, Eickstedt argued that the population of Upper Silesia belonged predominantly to the so-called 'Nordic race' and that the territory was thus fundamentally German. Nazi officials, however, viewed the Silesian studies with alarm, since the results also appeared to show that people in the area were a racial mixture and that the 'Nordic race' made up less than 40 per cent of the population in some locales. They worried that Eickstedt's studies could undermine Germany's territorial claims in the region and threaten national unity. The ensuing controversy presents a case in which the anthropological concept of 'race', rather than serving its usual role in Nazi thinking as the biological underpinning of the Volk (or people), threatened to undermine its coherence. The reaction to Eickstedt's Silesian studies demonstrates a lack of consensus on race within the Nazi system, suggesting that understandings of race in Nazi Germany were neither as coherent nor as uniform as the paradigm of the 'racial state' has assumed. [ABSTRACT FROM AUTHOR]

* Context.--Unicentric Castleman disease (UCD) is a dynamic entity with a wide spectrum of morphologic findings. UCD can be further subdivided into hyaline-vascular and mixed/plasmacytic variants. Hyaline-vascular UCD has both follicular and interfollicular (stromal) changes, and occasionally these lesions show a skewed representation of either the follicular or stromal compartments. Plasmacytosis is usually minimal in the hyalinevascular variant. The mixed/plasmacytic variant of UCD is composed of sheets of plasma cells often associated with a variable number of follicles with regressive changes. Objective.--To illustrate the differential diagnosis of UCD, as it is quite broad and includes lymphomas, plasma cell neoplasms, stromal neoplasms such as follicular dendritic cell sarcoma and vascular neoplasms, immunoglobulin G4-related disease, infections, and other rare lesions. An additional objective is to enhance awareness of the morphologic features of UCD in excisional and in small core-needle biopsy specimens, the latter of which may inadvertently target follicle- or stroma-rich areas, causing diagnostic challenges. Data Sources.--In this review, we provide readers a concise illustration of the morphologic spectrum of UCD that we have encountered in our practice and a brief discussion of entities in the differential diagnosis. Conclusions.--UCD exhibits a broad spectrum of morphologic changes, and awareness of these morphologic variations is key to avoid misdiagnosis. [ABSTRACT FROM AUTHOR]

Introduction Mixed reality has been used in trauma and emergency medicine simulation for more than a decade. As mixed reality potential in trauma simulation continues to expand, so too does the need to validate it as a surrogate for real-life emergency scenarios. Validation of these simulations can occur by measuring fidelity, or the degree to which a computing system can reproduce real-world experiences. After performing a literature review, we determined that most fidelity assessments of trauma and emergency simulations focus on how the user subjectively experiences the simulation. Although subjective user assessment is an important component of determining fidelity, we pose an introductory three-part framework that may assess mixed reality trauma simulation more adequately. Materials and Methods A literature review was conducted using Google Scholar, PubMed, and the Uniformed Services University PowerER search database. Relevant articles were assessed to identify how studies measured fidelity in trauma simulation. We then designed the three-part framework to aid researchers in assessing the fidelity of mixed reality trauma simulations. Results The domains we determined to best assess mixed reality emergency simulation are as follows: 1. Continue assessing fidelity via subjective user assessments. This allows the researcher to know how real the simulation looked and felt to the user based on their individual report. 2. Determine whether the trauma simulation changes the medical decision-making capacity of the user. If the user's decision-making capacity changes with a stress-inducing trauma simulation versus a non–stress-inducing simulation, then the stress-inducing trauma environment would be approaching greater fidelity. 3. Study the domain of our newly proposed concept: physiologic fidelity. We define physiologic fidelity as the degree to which the simulation elicits a measurable, autonomic response independent of observed emotion or perceived affect. Recreating objective autonomic arousal may be the best way to ensure a trauma simulation reaches fidelity. Conclusion We propose a methodology to assess mixed reality trauma simulation fidelity. Once fidelity is more fully known to the researcher and the simulation user, adjustments can be made to approach reality more closely. Improved simulators may enrich the preparedness of both junior and senior learners for real-life emergencies. We believe assessing the three domains using the Wide Area Virtual Experience at the Val G. Hemming simulation center in Bethesda, MD, will validate mixed reality-trauma simulators as invaluable surrogates for real-life emergency scenarios and ultimately contribute to improved clinical outcomes for clinicians and their patients. [ABSTRACT FROM AUTHOR]

Questions: Livestock grazing is an expanding land management tool for habitat and fuel management in California grassland ecosystems, despite mixed conclusions about its effects. Our study investigated the following questions: Does a targeted grazing regime promote grassland functioning by clearing bare ground and reducing dead litter cover?Does targeted grazing reduce grassland fuels?Does targeted grazing promote native species cover and diversity?Does targeted grazing reduce non‐native, invasive species cover and diversity? Location: The Santa Lucia Preserve, Carmel, California, USA. Methods: Monitoring grazed and ungrazed treatment plots within 17 study sites, we surveyed the effects of a targeted grazing regime on bare ground cover, litter cover and depth, herb height, and diversity and cover of different native and non‐native species groups over an eight‐year period. Results: On average, grazing successfully increased bare ground (by 2.8% cover), decreased litter depth (by 3.5 cm) and cover (by 12%), and decreased herb height (by 3.9 cm). Grazed plots had greater cover of native annual forbs (+1.2% cover), while decreasing invasive Bromus diandrus (by 6.0% cover). There was no difference in either native or non‐native species diversity. Conclusions: Targeted grazing can be an appropriate tool to accomplish conservation goals, including biomass management and canopy clearing, while improving native annual forbs without risk to native species as a whole. Further steps in adaptive management must examine how the application of grazing may be altered to further promote native species and to inhibit invasive species. [ABSTRACT FROM AUTHOR]

The article focuses on the clinical assessment of tremor for diagnosing and treating patients. It discusses the revised guidelines for tremor classification and provides recommendations for history-taking and examination. The article also highlights different causes of tremor and management options, emphasizing the importance of accurate diagnosis and individualized treatment.

Background: Using Personal‐Disclosure Mutual‐Sharing (PDMS) with students transitioning to Higher Education (HE) has yet to be researched in education. Aims: In two studies, we aimed to explore the immediate effects of a Coping Oriented Personal‐Disclosure Mutual‐Sharing (COPDMS) intervention on first‐year undergraduate students' relational and organizational identification, perceived social support availability, and self‐efficacy for learning and performance. In our second study, we also aimed to examine student‐perceptions of participating in a COPDMS intervention. Sample and Methods: At the beginning of induction week in both studies, first‐year undergraduate students on the same degree programme at a HE provider in England received an education session where COPDMS was introduced. Students participated in a COPDMS session a few days later. During COPDMS sessions, students mutually‐shared and disclosed personal information and/or stories relating to transitional experiences. Results: Across both studies, students' relational identification with staff and perceived emotional, esteemed, and informational support availability from others on the degree programme significantly increased from pre‐ to post‐COPDMS phases. Findings relating to relational identification with other Year 1 students and perceived availability of tangible support were mixed. No significant changes occurred for organizational identification with the university and self‐efficacy for learning and performance. In Study 2, five higher‐order themes relating to students' perceptions of COPDMS were found: (1) emotionality; (2) personal development; (3) storytelling; (4) enhanced group processes; and (5) task appropriateness and value. Conclusions: Study findings provide evidence that COPDMS is a useful psychological intervention to deliver to students transitioning to HE. Practical considerations, limitations, and future research suggestions are provided. [ABSTRACT FROM AUTHOR]

This paper provides athlete and practitioner insights regarding a novel coping-oriented personal-disclosure mutual-sharing (COPDMS) intervention developed and administered in a youth soccer context. Participants were 18 male soccer athletes (mean age 17.29 ± 0.73 years) who belonged to the same professional academy in England. The COPDMS intervention comprised an initial sport psychology education session (Week 1), a session introducing COPDMS (Week 2), a COPDMS session (Week 4), and a follow-up session (Week 9). During the COPDMS session, athletes mutually shared personal stories and/or information about transitions as they approached a time when they would gain a professional contract or would be released from their soccer academy. Athletes communicated a range of contextually relevant demand and resource appraisals during the COPDMS session. Several athlete and practitioner insights about the COPDMS process and outcomes were provided that can guide future researchers and practitioners seeking to develop and deliver bespoke PDMS interventions in sport. [ABSTRACT FROM AUTHOR]

Context.--The original guideline, ''Validating Whole Slide Imaging for Diagnostic Purposes in Pathology,'' was published in 2013 and included 12 guideline statements. The College of American Pathologists convened an expert panel to update the guideline following standards established by the National Academies of Medicine for developing trustworthy clinical practice guidelines. Objective.--To assess evidence published since the release of the original guideline and provide updated recommendations for validating whole slide imaging (WSI) systems used for diagnostic purposes. Design.--An expert panel performed a systematic review of the literature. Frozen sections, anatomic pathology specimens (biopsies, curettings, and resections), and hematopathology cases were included. Cytology cases were excluded. Using the Grading of Recommendations Assessment, Development, and Evaluation approach, the panel reassessed and updated the original guideline recommendations. Results.--Three strong recommendations and 9 good practice statements are offered to assist laboratories with validating WSI digital pathology systems. Conclusions.--Systematic review of literature following release of the 2013 guideline reaffirms the use of a validation set of at least 60 cases, establishing intraobserver diagnostic concordance between WSI and glass slides and the use of a 2-week washout period between modalities. Although all discordances between WSI and glass slide diagnoses discovered during validation need to be reconciled, laboratories should be particularly concerned if their overall WSI--glass slide concordance is less than 95%. [ABSTRACT FROM AUTHOR]

Sustained motivation for Daily Mile participation at higher physical activity intensities may contribute to the attainment of children's daily moderate-to-vigorous physical activity (MVPA) targets and long-term health benefits. However, individual variability exists in the amount of MVPA accumulated by children during the Daily Mile. The current study explored children's motivation for participating in the Daily Mile at MVPA intensity, using a theory of planned behaviour framework. Twenty-five children (mean age = 10.07 ± 0.60 years) from the Northwest of England were recruited to the study; 52% were female and 88% were White. Participants completed a questionnaire, with an open-ended response format, probing behavioural, control, and normative beliefs for participation in the Daily Mile at MVPA intensity. Template analysis was conducted independently by two researchers to identify main themes and subthemes. Findings showed that children possessed a range of behavioural, control, and normative beliefs about MVPA participation during the Daily Mile. Prominent behavioural beliefs included fitness enhancement, implications for concentration and learning, positive affective states, and pain and discomfort. Key control beliefs included weather, space and health restrictions, and distractions from peers. Finally, peers and parents were salient normative beliefs. Children possessed a range of modal beliefs in relation to MVPA participation during the Daily Mile. Implications of the findings, and methods for practitioners seeking to maximise the contribution of the Daily Mile to children's daily MVPA targets are discussed. [ABSTRACT FROM AUTHOR]

• Aged mice have inflammation in the locus coeruleus and hippocampus. • Aged mice proteome reveals metabolic stress in the locus coeruleus and hippocampus. • Beta-blockers impair learning and memory in aged mice. The locus coeruleus (LC) provides the primary noradrenergic input to the forebrain and hippocampus, and may be vulnerable to degeneration and contribute to age-related cognitive decline and neuroinflammation. Additionally, inhibition of noradrenergic transmission by brain-permeable beta-blockers could exacerbate cognitive impairment. This study examined effects of age and acute beta-blocker administration on LC and hippocampus pathology, neuroinflammation and learning and memory behavior in mice. Male mice, 3 and 18 months old, were administered propranolol (beta-blocker) or mabuterol (beta-adrenergic agonist) acutely around behavioral assessment. Terminal inflammatory markers in plasma, hippocampus and LC were assessed alongside histopathology. An increase in hippocampal and LC microgliosis and inflammatory proteins in the hippocampus was detected in aged mice. We report pathological hyperphosphorylation of the postsynaptic NMDA receptor subunit 2B (NR2B) in the hippocampus, suggesting neuronal hyperexcitability. Furthermore, the aged proteome revealed an induction in proteins related to energy metabolism, and mitochondria dysfunction in the LC and hippocampus. In a series of hippocampal dependent behavioral assessment tasks acute beta-adrenergic agonist or beta blocker administration altered learning and memory behavior in both aged and young mice. In Y-maze, propranolol and mabuterol differentially altered time spent in novel versus familiar arms in young and aged mice. Propranolol impaired Novel Object Recognition in both young and aged mice. Mabuterol enhanced trace learning in fear conditioning. Aged mice froze more to context and less to cue. Propranolol impaired contextual recall in aged mice. Concluding, aged mice show LC and hippocampus pathology and heightened effects of beta-adrenergic pharmacology on learning and memory. [ABSTRACT FROM AUTHOR]

A patient with a 6‐year‐old left upper arm brachial cephalic AVF presented with symptoms of hemodialysis access‐induced distal ischemia (HAIDI). Physical exam findings showed a well‐developed AVF, but compression of the AVF aggravated arm pain and induced diffuse erythema of the left upper extremity. Angiographic evaluation disclosed the presence of a large axillary artery vascular malformation (AVM) as well as distal forearm hypo‐perfusion. We elected to publish this case report to describe the interesting physical exam findings related to the AVM, and discuss HAIDI treatment options that are peculiar to this case. We also highlight the importance of thorough vascular evaluation prior to AV access creation as well as during the investigation of the cause of HAIDI. [ABSTRACT FROM AUTHOR]

Background Fibromuscular dysplasia (FMD) is a non-atherosclerotic systemic arterial disease that is not infrequently discovered during kidney donor evaluation. Current guidelines do not provide recommendations regarding the use of kidneys from donors with FMD and there is a paucity of data on the outcomes of these donors. Methods The Renal and Lung Living Donor Evaluation (RELIVE) study addressed long-term outcomes of 8922 kidney donors who donated between 1963 and 2007. We compared the development of hypertension, cardiovascular disease (CVD), proteinuria and reduced estimated glomerular filtration rate (eGFR) in 113 kidney donors with FMD discovered during donor evaluation versus 452 propensity score matched donors without FMD. Outcomes modeling with logistic and Cox regression analysis and Kaplan–Meier statistics were performed. Results Donors with FMD were older (51 versus 39 years), were more likely to be women (80% versus 56%) and had a higher systolic blood pressure at donation (124.7 versus 121.3 mmHg) (P < 0.05 for all). After a mean ± standard deviation follow-up of 15.5 ± 8.9 years, a similar proportion of donors with and without FMD were alive, and developed hypertension (22.2% versus 19.8%), proteinuria (20.6% versus 13.7%) and CVD (13.3% versus 13.5%). No donor with FMD developed an eGFR <30 mL/min/1.73 m2 or end-stage kidney disease. The multivariable risk of mortality, CVD and renal outcomes in donors with FMD was not elevated. Conclusions Kidney donors with FMD appear to do well, do not appear to incur increased risks of hypertension, proteinuria, CVD or reduced eGFR, and perhaps carefully selected candidates with FMD can safely donate as long as involvement of other vascular beds is ruled out. [ABSTRACT FROM AUTHOR]

Anion exchange between ubiquitous low‐molecular‐weight organic acids (LMWOA), such as oxalate, and surface‐retained inorganic anions, such as F−, SO42− and OH−, can play a critical role in Al bioavailability and transport in acidic alpine tundra soil. A series of batch equilibration and composite soil column leaching studies were conducted to examine anion exchange reactions between F−, oxalate and OH−, and the impact of increased soil solution F− concentration on Al transport. The addition of either F− or oxalate to soil suspensions resulted in significantly higher solution pH, suggesting F− and oxalate exchange with surface –OH groups. Distinct stages of OH− release were observed for all soil horizons leached with 1.32 × 10−3 mol l−1 F−, with OH− release decreasing in the order O/A1 ~ A2> > Bw. A similar OH− release pattern was observed in the O/A1 horizon for the 7.81 × 10−4 mol l−1 oxalate treatment, suggesting that both F− and oxalate may be competing for common exchange sites in the O/A1 horizon. Fluoride displacement by oxalate, in batch equilibration experiments, was observed for both the 2.84 × 10−4 mol l−1 and 7.81 × 10−4 mol l−1 oxalate treatment. Individual soil horizons leached with 7.81 × 10−4 mol l−1 oxalate exhibited increased F− leaching in the order O/A1 > A2 ~ Bw, with pulsed F− movement being observed in the O/A1 horizon. Soil columns eluted with 1.32 × 10−3 mol l−1 F− exhibited increased Al solubilization and transport, with Al leaching increasing in the order Bw > A2 > O/A1. Sequential leaching of soil columns in the order D. I. H2O → 1.32 × 10−3 mol l−1 F− → D.I. H2O → 7.81 × 10−4 mol l−1 oxalate indicated that previously adsorbed F− was displaced by oxalate. Displacement of F− by oxalate increased in the order O/A1 > A2 > Bw. Hydroxyl displacement by both F− and oxalate may be an important source of acid neutralization in a soil wetting front, affecting Al speciation and transport. Highlights: Oxalate and F− compete for similar OH− exchange sites, increasing soil pH.Adsorbed F− can be displaced by oxalate anions.Al solubilization increases with F− adsorption in alpine tundra soil.Aluminium fluoride speciation changes rapidly within the soil wetting front.Anion exchange reactions should be considered in assessing soil ANC. [ABSTRACT FROM AUTHOR]

When social animals forage together, they may engage in frequency-dependent strategies either as producers, those who acquire food with their own energy, or as scroungers, those who feed on what the producers discover. An individual's choice of strategy may depend on the frequency of strategies within the group, or it may depend on the individual's own traits. Most of our understanding of producer–scrounger relationships comes from highly social species, but we may gain different insights by studying less social species. We used novel puzzle box experiments to study social foraging relationships and identify the traits associated with strategy choice in facultatively social yellow-bellied marmots, Marmota flaviventer. We found that marmots had consistent strategies as either producers or scroungers. Furthermore, several individuals specialized as scroungers, following the producers to the puzzle box before other scroungers. However, their roles were only associated with sex (males were more likely to produce), and not with age, boldness or dominance rank. Marmots' lack of trait-regulated foraging roles may be associated with their relatively abundant and not-entirely defensible food, or may emerge from their lack of obligate social structure. We discuss how multiple factors may explain variation in social foraging behaviour. • Producer–scrounger relationships are often studied in highly social species. • We used novel puzzle box experiments to study them in a facultatively social marmot. • Marmots had consistent strategies as either producers or scroungers. • Sex, but not age, boldness or dominance rank, explained production. • Producer–scrounger relationships may be meaningfully studied in less social species. [ABSTRACT FROM AUTHOR]

CCUS, recognized by both WHO5 and ICC systems, needs to be differentiated from ICUS (idiopathic cytopenia of undetermined significance), due to a higher risk of development of MDS/AML, therapy-related myeloid neoplasms, and cardiovascular mortality. Standard-of-care work-up for CCUS includes morphological assessment, traditional karyotyping, and NGS-based mutation analysis. Although sub-microscopic copy number abnormalities (CNA) and copy-neutral loss-of-heterozygosity (CNLOH) are well-established drivers detectable only by chromosomal microarray (CMA), few studies have explored this. Our goal was to perform a comprehensive genomic assessment (81-gene targeted NGS + aCGH/SNP CMA platform) to accurately diagnose CCUS in 94 patients with idiopathic cytopenia and normal karyotype without MDS/CMML. By NGS, 32 (42%) patients had at least 1 mutation (≥2% VAF), defining CCUS [recurrent genes: ASXL1, DNMT3A, GATA2, SF3B1, SRSF2, TET2 ; median VAF:16%]. By CMA, 33 (39%) patients showed ≥1 clonal aberration diagnosing CCUS [17 (18%) with CNA(s), 20 (21%) with CN-LOH, and 4 had both]. By combined NGS+CMA, 43 (56%) had CCUS. Based on genomic results, morphological diagnoses were revisited. Reclassification per WHO5 and ICC showed: CCUS [n=40 (WHO5), n=42 (ICC, due to SF3B1 mutations at >10% VAF)], CMML (n=3; SRSF2, TET2, ASXL1), MDS/MPN (n=2), and MDS (n=4; SF3B1, TP53). Two CCUS patients showed variants of suspected germline origin, involving GATA2 and DDX41 respectively. Both CMA and NGS abnormalities were seen in 7 patients. CMA upgraded the diagnosis to CCUS in 17 patients, while NGS upgraded in 6 patients, emphasizing the complementarity of these techniques. A comprehensive genomic work-up is essential for accurate CCUS diagnosis. [ABSTRACT FROM AUTHOR]

In a one group pretest-posttest design, 15 elite academy cricketers were exposed to two personal-disclosure mutual-sharing (PDMS) sessions during a preseason tour. Within PDMS1, athletes disclosed (via prepared speeches) relationship-oriented information and within PDMS2, mastery oriented information. Social identity, social identity content, and collective efficacy were measured at baseline (1 week before the tour), post-PDMS1, midpoint, and post-PDMS2, while social validation was also obtained after each intervention session. Quantitative data revealed significant increases in social identity and friendships identity content at post-PDMS1, and results identity content and collective efficacy at post-PDMS2. Qualitative social validation data highlighted the thoughts and feelings of the athletes before their speeches and supported the effectiveness of the PDMS sessions. In sum, the data suggest practitioners can develop team outcomes (e.g., a focus on results) through developing specific aspects of teams' identities. Study limitations, practitioner guidelines, and areas for future research are discussed. [ABSTRACT FROM AUTHOR]

The present study examined the effects of personal-disclosure mutual-sharing (PDMS) on a diverse set of group factors in a previously unexplored context. During a single bout of PDMS, 14 soccer-academy athletes voluntarily disclosed unknown personal stories to fellow teammates. Social identity, friendships identity content, results identity content, and collective efficacy were measured at baseline, post-PDMS, follow-up, and maintenance phases. In addition, team performance over the competitive season was assessed via goal difference and goal discrepancy. Data indicated that a short-term significant increase in friendships identity content and a sustained improvement in team performance occurred after the PDMS session, and social identity, results identity content, and collective efficacy remained elevated across all intervention phases. Data suggest that PDMS fosters immediate increases in aspects of team functioning that may exert a positive influence upon team performance. Future research would benefit from ascertaining the exact mechanisms in which PDMS encourages changes in team outcomes observed within the current study. [ABSTRACT FROM AUTHOR]

Emotion regulation through cognitive reappraisal is well-studied, but less so are the predispositional and superordinate beliefs that influence reappraisal. Recently, researchers developed the cognitive mediation beliefs questionnaire (CMBQ), which measures two emotion beliefs, namely stimulus-response (S-R) generation beliefs and cognitive mediation (C-M) change beliefs. In working populations S-R generation beliefs are inversely related to cognitive reappraisal tendencies and positive mental health, and positively related to emotion reactivity. C-M change beliefs are positively related to cognitive reappraisal tendencies, and inversely related to emotion reactivity and positive mental health. As yet, there is no evidence for the validity of the CMBQ within student samples, or for the associations between its subscales and cognitive reappraisal, emotion reactivity, and positive mental health. Therefore, in the present study the CMBQ is tested for factorial, convergent (associations with cognitive reappraisal), and concurrent (associations with emotion reactivity and positive mental health) validity in a cohort of 621 undergraduate students in the United Kingdom (U.K.). Results indicate support for the factorial and convergent validity of the CMBQ, with mixed evidence for the concurrent validity of the CMBQ. A CM-SR discrepancy score appeared to provide a promising variable when associated with emotion reactivity and positive mental health. The findings are discussed in terms of practical and research implications of the findings. [ABSTRACT FROM AUTHOR]

Background Community pharmacies in Wales delivered an NHS-funded sore throat test and treat (STTT) service during the period of increased invasive Group A Streptococcus (iGAS) incidents in winter 2022–23. Service users were screened using FeverPAIN/CENTOR scores, offered GAS rapid antigen detection tests (RADT) if appropriate, and antibiotics if indicated. Objectives To evaluate the service's response to a substantial rise in sore throat presentations during a period of heightened public anxiety. Methods Cross-sectional study with anonymized individual-level data from electronic pharmacy records of all eligible STTT service users, between January 2022 and March 2023. Results Antibiotics were supplied to 24% (95% CI: 23–24) of people who used the STTT service and 31% (95% CI: 31–32) of those who met the threshold for an RADT. Of 27 441 STTT consultations, 9308 (33.9%) occurred during December 2022. In the week commencing 2 December 2022, following the announcements of increased iGAS incidents, we observed a statistically significant increase of 1700 consultations (95% CI: 924–2476) and a statistically significant decrease in supply rate of 13.9 antibiotics per 100 RADT (95% CI: −18.40 to −9.40). Antibiotic supply rates increased thereafter to those observed before the announcements of iGAS incidents. Referral rates to other primary care or emergency settings remained below 10% throughout the study period. Conclusions Our findings suggest that, despite a dramatic increase in sore throat consultation rates in response to media reports, the pre-specified pathway followed by pharmacists ensured appropriate use of antibiotics, and absorbed a substantial workload that would otherwise end up in other healthcare settings. [ABSTRACT FROM AUTHOR]

In the late 1920s and early 1930s, professional anthropologists and prominent race scientists in Germany served as judges in a series of mail-in photographic competitions designed to identify the most representative examples of the so-called Nordic race. This essay examines the interactions between judges and audience in three of these contests. Race scientists and entrants collaborated to construct a vision of the Nordic race as primarily male and middle and upper class. More important, the contests served to configure the very categories of "science" and "lay public" for the new discipline of race science (Rassenkunde), setting them in an unequal relationship to each other. Race scientists portrayed their audience as the entire German people, or Volk , which they represented as desperately in need of racial knowledge that only experts in Rassenkunde could provide. Rather than breaking down divisions between race scientists and the public, the collaborative process of the contests served to construct those very categories. [ABSTRACT FROM AUTHOR]

Aims: Little has been written on the frequency and nature of incidental splenic lesions diagnosed on histopathological examination of pancreatosplenectomy specimens. Methods and results: For 191 such specimens, incidental histological findings after haematopathologist re‐review were tabulated. Cases suspicious for lymphoid malignancy underwent molecular analysis for immunoglobulin heavy and kappa light chain rearrangement. Follow‐up was obtained on selected cases. In five cases (3%), the spleen was sampled but not mentioned in the original microscopic report; all were normal on re‐review. Otherwise, most (171 of 186, 92%) were initially diagnosed as normal, with 160 (94%) remaining so on re‐review. Findings on re‐review not initially described (n = 11, 6%) included four cases with splenic morphology suspicious for possible leukaemia/lymphoma involvement. Additional findings included abscess formation, foamy macrophages, necrotising granulomas and simple cysts. Fifteen spleens were initially diagnosed as abnormal; the histopathological process was confirmed in all, including non‐necrotising granulomas, cysts, Gamna–Gandy bodies, foamy macrophages, involvement by pancreatic neoplasm and involvement by known chronic lymphocytic leukaemia (CLL). Molecular analysis was performed on the five cases of known/suspected lymphoma and two were positive for monoclonal gene rearrangement, including the known CLL and a previously undiagnosed case with similar immunophenotype. Conclusions: Incidental splenic findings are not uncommon in pancreatosplenectomy specimens. While most are of limited clinical significance, low‐grade lymphoproliferative disorders may go undetected if the spleen is overlooked. We recommend careful observation of splenic findings in these specimens, with a low threshold for haematopathological consultation when in doubt. [ABSTRACT FROM AUTHOR]

• A "traverse" is the passage over a level crossing by a road user. • New data on traverses in Britain are used to give fatality rates per traverse. • Fatality rates for pedestrians are ten times higher than for road vehicle users. • Fatality rates at passive crossings are 100 times higher than at controlled crossings. • The valuation of delays and of fatalities at active crossings are compared. This paper investigates relationships between traverses, delays and fatalities to road users at railway level crossings in Great Britain. A 'traverse' means a passage across a level crossing by a road user, who may be a pedestrian, cyclist, or occupant of a road vehicle. The paper finds that the road users with the highest fatality rate per traverse are pedestrians at passive crossings. Their rate is about three orders of magnitude higher than that of users with the lowest risk, who are road vehicle occupants at railway-controlled crossings. The paper considers the choice between automatic and railway-controlled crossings on public roads. Railway-controlled crossings are widely used in Britain. They are about one order of magnitude safer than automatic crossings, but they impose greater delays on users. A formula is developed to give the overall delay to road users at either type of crossing in terms of the numbers of road users and trains per day, and in terms of the length of time that the crossing must be closed to the road to allow the passage of one train. It is found that automatic level crossings cause substantially less delay than railway-controlled level crossings. The official monetary values of road user delay and of preventing a fatality were used to estimate the valuations of delays and fatalities at hypothetical but representative automatic and railway-controlled crossings. These valuations were then used to explore the effect of replacing representative railway-controlled with automatic crossings or vice-versa. It is found that the valuation of the reduced delays from adopting automatic crossings typically outweighs the valuation of the losses from the increased casualties. However, in practice Britain has chosen to retain a large number of railway-controlled crossings, which implies accepting the delays in return for a good level crossing safety record. Finally, an analysis is carried out to determine the additional risk of typical car and walk journeys that involve traversing a level crossing compared with similar journeys that do not. It is found that the additional risk is small for motor vehicle journeys, but substantial for walk journeys. [ABSTRACT FROM AUTHOR]

Impulse control disorders (ICDs) and related impulsive and compulsive behaviors (together called ICBs) have been increasingly recognized in the context of Parkinson's disease (PD) and treatment. The International Parkinson's and Movement Disorder Society commissioned a task force to assess available clinical screening instruments and rating scales, including their clinimetric properties, make recommendations regarding their utility, and suggest future directions in scale development and validation. The literature was systematically searched for scales measuring a range of reported ICBs in PD. A scale was designated "recommended" if the scale had been employed in PD studies, been used beyond the group that developed it, and had adequate clinimetric data published for PD. Numerous diagnostic screening tools and severity rating scales were identified for a range of ICBs, including compulsive medication use, punding/hobbyism, walkabout, pathological gambling, hypersexuality, compulsive or binge eating, compulsive buying, reckless driving, compulsive exercise, pyromania, trichotillomania, hoarding, kleptomania, intermittent explosive disorder, and internet addiction. For screening across the range of ICBs (except compulsive medication use), the Questionnaire for Impulsive-Compulsive Disorders in Parkinson's disease (QUIP) and QUIP-Rating Scale (QUIP-RS) are recommended, and for severity rating across the range of ICBs the QUIP-RS and the Ardouin Scale of Behavior in Parkinson's Disease are recommended. The Scale for Outcomes in Parkinson's Disease-Psychiatric Complications is recommended for rating of hypersexuality and the compulsive behaviors gambling/shopping. Further testing of established scales against gold standard diagnostic criteria is urgently required for all other individual ICBs in PD. © 2019 International Parkinson and Movement Disorder Society © 2019 International Parkinson and Movement Disorder Society. [ABSTRACT FROM AUTHOR]

* April 12, 2017 marked a significant day in the evolution of digital pathology in the United States, when the US Food and Drug Administration announced its approval of the Philips IntelliSite Pathology Solution for primary diagnosis in surgical pathology. Although this event is expected to facilitate more widespread adoption of whole slide imaging for clinical applications in the United States, it also raises a number of questions as to the means by which pathologists might choose to incorporate this technology into their clinical practice. This article from the College of American Pathologists Digital Pathology Committee reviews frequently asked questions on this topic and provides answers based on currently available information. [ABSTRACT FROM AUTHOR]

Key Clinical Message: We present the case of a 30‐year‐old woman with a history of perinatal complications as well as bladder and urinary disease through her childhood and adult life. Microarray comparative genomic hybridization (aCGH) analysis revealed a 1.3 megabase duplication at chromosome 8q21.11 encompassing the CASC9 and HNF4G genes. We present the case of a 30‐year‐old woman with a history of perinatal complications as well as bladder and urinary disease through her childhood and adult life. Microarray comparative genomic hybridization (aCGH) analysis revealed a 1.3 megabase duplication at chromosome 8q21.11 encompassing the CASC9 and HNF4G genes. [ABSTRACT FROM AUTHOR]

Abstract: This article summarises the information that should be provided to women and referring physicians about breast ultrasound (US). After explaining the physical principles, technical procedure and safety of US, information is given about its ability to make a correct diagnosis, depending on the setting in which it is applied. The following definite indications for breast US in female subjects are proposed: palpable lump; axillary adenopathy; first diagnostic approach for clinical abnormalities under 40 and in pregnant or lactating women; suspicious abnormalities at mammography or magnetic resonance imaging (MRI); suspicious nipple discharge; recent nipple inversion; skin retraction; breast inflammation; abnormalities in the area of the surgical scar after breast conserving surgery or mastectomy; abnormalities in the presence of breast implants; screening high-risk women, especially when MRI is not performed; loco-regional staging of a known breast cancer, when MRI is not performed; guidance for percutaneous interventions (needle biopsy, pre-surgical localisation, fluid collection drainage); monitoring patients with breast cancer receiving neo-adjuvant therapy, when MRI is not performed. Possible indications such as supplemental screening after mammography for women aged 40-74 with dense breasts are also listed. Moreover, inappropriate indications include screening for breast cancer as a stand-alone alternative to mammography. The structure and organisation of the breast US report and of classification systems such as the BI-RADS and consequent management recommendations are illustrated. Information about additional or new US technologies (colour-Doppler, elastography, and automated whole breast US) is also provided. Finally, five frequently asked questions are answered.Teaching Points: • US is an established tool for suspected cancers at all ages and also the method of choice under 40.• For US-visible suspicious lesions, US-guided biopsy is preferred, even for palpable findings.• High-risk women can be screened with US, especially when MRI cannot be performed.• Supplemental US increases cancer detection but also false positives, biopsy rate and follow-up exams.• Breast US is inappropriate as a stand-alone screening method. [ABSTRACT FROM AUTHOR]

Objective: Deep brain stimulation can be of benefit in carefully selected patients with severe intractable obsessive-compulsive disorder. The aim of this paper is to describe the outcomes of the first seven deep brain stimulation procedures for obsessive-compulsive disorder undertaken at the Neuropsychiatry Unit, Royal Melbourne Hospital. The primary objective was to assess the response to deep brain stimulation treatment utilising the Yale-Brown Obsessive Compulsive Scale as a measure of symptom severity. Secondary objectives include assessment of depression and anxiety, as well as socio-occupational functioning. Methods: Patients with severe obsessive-compulsive disorder were referred by their treating psychiatrist for assessment of their suitability for deep brain stimulation. Following successful application to the Psychosurgery Review Board, patients proceeded to have deep brain stimulation electrodes implanted in either bilateral nucleus accumbens or bed nucleus of stria terminalis. Clinical assessment and symptom rating scales were undertaken pre- and post-operatively at 6- to 8-week intervals. Rating scales used included the Yale-Brown Obsessive Compulsive Scale, Obsessive Compulsive Inventory, Depression Anxiety Stress Scale and Social and Occupational Functioning Assessment Scale. Results: Seven patients referred from four states across Australia underwent deep brain stimulation surgery and were followed for a mean of 31 months (range, 8–54 months). The sample included four females and three males, with a mean age of 46 years (range, 37–59 years) and mean duration of obsessive-compulsive disorder of 25 years (range, 15–38 years) at the time of surgery. The time from first assessment to surgery was on average 18 months. All patients showed improvement on symptom severity rating scales. Three patients showed a full response, defined as greater than 35% improvement in Yale-Brown Obsessive Compulsive Scale score, with the remaining showing responses between 7% and 20%. Conclusion: Deep brain stimulation was an effective treatment for obsessive-compulsive disorder in these highly selected patients. The extent of the response to deep brain stimulation varied between patients, as well as during the course of treatment for each patient. The results of this series are comparable with the literature, as well as having similar efficacy to ablative psychosurgery techniques such as capsulotomy and cingulotomy. Deep brain stimulation provides advantages over lesional psychosurgery but is more expensive and requires significant multidisciplinary input at all stages, pre- and post-operatively, ideally within a specialised tertiary clinical and/or academic centre. Ongoing research is required to better understand the neurobiological basis for obsessive-compulsive disorder and how this can be manipulated with deep brain stimulation to further improve the efficacy of this emerging treatment. [ABSTRACT FROM AUTHOR]

In Australia 1% of individuals aged over 50 years have Parkinson disease ( PD). Guidance for commencing device-assisted therapies ( DAT) for PD in Australia was developed based on a review of European recommendations and their relevance to the local clinical setting. An online survey and teleconference discussions were held by a group of eight local movement disorder experts to develop consensus. Referral to a movement disorder specialist and consideration of DAT is appropriate when motor fluctuations cause disability or reduced quality of life, response to treatment is inconsistent or motor fluctuations and dyskinesias require frequent treatment adjustment without apparent benefit and levodopa is required four or more times daily. Three types of DAT are available in Australia for patients with PD: continuous subcutaneous apomorphine; continuous levodopa-carbidopa intestinal gel infusion; and deep brain stimulation. All improve consistency of motor response. The most important aspects when considering which DAT to use are the preferences of the patient and their carers, patient comorbidities, age, cognitive function and neuropsychiatric status. Patients and their families need to be provided with treatment options that are suitable to them, with adequate explanations regarding the recommendations and comparison of potential device-related complications. DAT are best managed, where possible, in a specialist centre with experience in all three types of therapy. Proactive and early management of symptoms during disease progression is essential to maintain optimally motor responses and quality of life in patients with PD. [ABSTRACT FROM AUTHOR]

Introduction: The phenomenon of sleep benefit (SB) in Parkinson's disease (PD), whereby waking motor function is improved despite no dopaminergic treatment overnight, is controversial. Previous studies suggested a significant discrepancy between subjective functional and objective motor improvement. The aim of this study was to determine how well subjective reporting of SB correlates with objective measures and if true motor improvement can be predicted by a standardized questionnaire.Methods: Ninety-two patients with PD participated. A structured questionnaire was developed to assess subjective SB. Quantitative motor assessment was performed using a validated smartphone application. Objective motor SB was considered to be present when the waking motor function was similar or superior to the daytime on-state.Results: Twenty (22%) patients showed objective motor improvement on waking compared to end-of-dose. Most patients (77%) reported subjective SB without corresponding objective motor benefit. Our structured questionnaire could not predict Motor SB. The ability to delay morning medications and a perception of indifference or paradoxical worsening following the morning levodopa dose may suggest Motor SB.Conclusions: Most patients experience subjective SB with no measureable motor improvement. This perceived benefit could be related to non-motor improvement that is distinctly different to objective motor benefit. [ABSTRACT FROM AUTHOR]

Fibroadenomas and phyllodes tumours are fibroepithelial lesions of the breast. Fibroadenomas are common benign breast masses encountered both symptomatically and incidentally. Phyllodes tumours are uncommon and usually present symptomatically. Management of fibroadenomas focuses on reducing biopsies without missing cancers while radiological management of phyllodes tumours should focus on predicting the need for surgical excision with or without margins. [ABSTRACT FROM AUTHOR]

Background Sleep benefit ( SB) in Parkinson's disease refers to improved motor symptoms upon waking despite an entire night without medications. Although it was first proposed 30 years ago, this phenomenon proved difficult to investigate, and its true prevalence and underlying mechanisms remain unclear. Objective This study aimed to identify and quantify SB through measurement of motor function using a validated smartphone application and to identify disease characteristics that predicted SB. Methods Ninety-two patients recruited from 2 Movement Disorder Services were clinically assessed at home using a validated smartphone application. Each patient was tested in the on-state, at the end of dose, and on waking (before medications) 3 times. Differences between the 3 states were used to determine the impact of sleep and levodopa on motor function. SB was considered to be a 'measurable improvement in parkinsonism from the end of dose.' Results The morning waking motor function of 20 patients (22%) improved compared with the end-of-dose function, with 9 patients demonstrating superior function compared with their on-state. No clinical features predicted SB. Although all participants subjectively reported motor fluctuations, only 35 patients (38%) demonstrated an objective improvement with levodopa. Patients who had SB more often demonstrated objective motor fluctuations compared with those who did not (65% vs. 31%; P = 0.008). Conclusions SB is a genuine motor phenomenon: 1 in 5 patients have a measurable improvement in motor function on waking. It remains questionable whether this improvement is a direct effect of sleep. Until its underlying mechanism is better understood, it is more appropriate to refer to this phenomenon as simply morning improvement or diurnal fluctuation of motor symptoms. [ABSTRACT FROM AUTHOR]

Context.--There is growing interest in the use of digital pathology, especially whole slide imaging, for diagnostic purposes. Many issues need to be considered when incorporating this technology into a clinical laboratory. The College of American Pathologists (CAP) established a Digital Pathology Committee to support the development of CAP programs related to digital pathology. One of its many initiatives was a panel discussion entitled "Implementing Whole-Slide Imaging for Clinical Use: What to Do and What to Avoid," given for 3 years at the CAP annual meetings starting in 2014. Objectives.--To review major issues to consider when implementing whole slide imaging for clinical purposes as covered during the panel discussion. Design.--The views expressed and recommendations given are based primarily on the personal experience of the authors as early adopters of this technology. It is not intended to be an exhaustive review of digital pathology. Results.--Implementation is best approached in phases. Early efforts are directed toward identifying initial clinical applications and assembling an implementation team. Scanner selection should be based on intended use and budget. Recognizing pathologist concerns over the use of digital pathology for diagnostic purposes, ensuring adequate training, and performing appropriate validation studies will enhance adoption. Once implemented, the transition period from glass slide to image-based diagnostics will be associated with challenges, especially those related to a hybrid glass slide-digital slide workflow. Conclusions.--With appropriate preparation, planning, and stepwise implementation, whole slide imaging can be used safely and reliably for frozen sections, consultation, quality assurance, and primary diagnosis. [ABSTRACT FROM AUTHOR]

Degeneration of noradrenergic neurons occurs at an early stage of Alzheimer's Disease (AD). The noradrenergic system regulates arousal and learning and memory, and has been implicated in regulating neuroinflammation. Loss of noradrenergic tone may underlie AD progression at many levels. We have previously shown that acute administration of a partial agonist of the beta-1 adrenergic receptor (ADRB1), xamoterol, restores behavioral deficits in a mouse model of AD. The current studies examined the effects of chronic low dose xamoterol on neuroinflammation, pathology, and behavior in the pathologically aggressive 5XFAD transgenic mouse model of AD. In vitro experiments in cells expressing human beta adrenergic receptors demonstrate that xamoterol is highly selective for ADRB1 and functionally biased for the cAMP over the β-arrestin pathway. Data demonstrate ADRB1-mediated attenuation of TNF-α production with xamoterol in primary rat microglia culture following LPS challenge. Finally, two independent cohorts of 5XFAD and control mice were administered xamoterol from approximately 4.0–6.5 or 7.0–9.5 months, were tested in an array of behavioral tasks, and brains were examined for evidence of neuroinflammation, and amyloid beta and tau pathology. Xamoterol reduced mRNA expression of neuroinflammatory markers (Iba1, CD74, CD14 and TGFβ) and immunohistochemical evidence for microgliosis and astrogliosis. Xamoterol reduced amyloid beta and tau pathology as measured by regional immunohistochemistry. Behavioral deficits were not observed for 5XFAD mice. In conclusion, chronic administration of a selective, functionally biased, partial agonist of ADRB1 is effective in reducing neuroinflammation and amyloid beta and tau pathology in the 5XFAD model of AD. [ABSTRACT FROM AUTHOR]

Objective: This clinical update review focuses on treatment approaches of neuropsychiatric manifestations in Parkinson's disease.Methods: We conducted a systematic search of the literature using Pubmed and selected recent and relevant papers for this review.Results: Neuropsychiatric symptoms in Parkinson's disease usually require optimization of levodopa therapy as a first step. Most psychotropic drugs can be used in Parkinson's disease, however there is still lack of an evidence base due to limited studies and difficulties in diagnosis of neuropsychiatric disorders. Non-pharmacological treatments have also proved effective in Parkinson's disease. Cognitive impairment requires special consideration.Conclusions: Management of neuropsychiatric manifestations in Parkinson's disease is complicated by the lack of evidence. Treatment should be individualized and benefits and risks must be balanced. [ABSTRACT FROM AUTHOR]

Objective: This clinical update review focuses on the classification and description of common neuropsychiatric manifestations in Parkinson's disease (PD).Method: We conducted a systematic search of the literature using Pubmed and selected the most recent and relevant papers for this review.Results: Neuropsychiatric manifestations in PD are are very frequent and may arise from an abnormal psychopathological response to the disease, neurobiological changes related to the disease itself, complications of treatments or a combination of all of these.Conclusions: Neuropsychiatric symptoms may precede the motor clinical presentation of PD. Early recognition is essential. [ABSTRACT FROM AUTHOR]

A review is offered for the article "Intergenerational Ambivalence in Adolescence and Early Adulthood: Implications for Depressive Symptoms over Time" by Lauren A. Tighe and colleagues published in a 2016 issue of the periodical "Developmental Psychology."

Elasmobranchs are considered to be top marine predators, and in general play important roles in the transfer of energy within marine ecosystems. Despite this, little is known regarding the physiological processes of digestion and nutrient absorption in these fishes. One topic that is particularly understudied is the process of nutrient uptake across the elasmobranch gastrointestinal tract. Given their carnivorous diet, the present study sought to expand knowledge on dietary nutrient uptake in elasmobranchs by focusing on the uptake of products of protein digestion. To accomplish this, a full-length cDNA encoding peptide transporter 1 (PepT1), a protein previously identified within the brush border membrane of vertebrates that is responsible for the translocation of peptides released during digestion by luminal and membrane-bound proteases, was isolated from the bonnethead shark ( Sphyrna tiburo). A cDNA encoding the related peptide transporter PepT2 was also isolated from S. tiburo using the same methodology. The presence of PepT1 was then localized in multiple components of the bonnethead digestive tract (esophagus, stomach, duodenum, intestine, rectum, and pancreas) using immunohistochemistry. Vesicle studies were used to identify the apparent affinity of PepT1 and to quantify the rate of dipeptide uptake by its H-dependent cotransporter properties. The results of this study provide insight into the properties of peptide uptake within the bonnethead gut, and can facilitate future work on physiological regulation of protein metabolism and absorption including how these processes may vary in elasmobranchs that exhibit different feeding strategies. [ABSTRACT FROM AUTHOR]

Glucose deprivation, hypoxia and acidosis are characteristic features of the central core of most solid tumours. Myofibroblasts are stromal cells present in many such solid tumours, including those of the colon, and are known to be involved in all stages of tumour progression. HMGB1 is a nuclear protein with an important role in nucleosome stabilisation and gene transcription; it is also released from immune cells and is involved in the inflammatory process. We report that the microenvironmental condition of glucose deprivation is responsible for the active release of HMGB1 from various types of cancer cell lines (HT-29, MCF-7 and A549) under normoxic conditions. Recombinant HMGB1 (10 ng/ml) triggered proliferation in myofibroblast cells via activation of PI3K and MEK1/2. Conditioned medium collected from glucose-deprived HT-29 colon cancer cells stimulated the migration and invasion of colonic myofibroblasts, and these processes were significantly inhibited by immunoneutralising antibodies to HMGB1, RAGE and TLR4, together with specific inhibitors of PI3K and MEK1/2. Our data suggest that HMGB1 released from cancer cells under glucose deprivation is involved in stimulating colonic myofibroblast migration and invasion and that this occurs through the activation of RAGE and TLR4, resulting in the activation of the MAPK and PI3K signalling pathways. Thus, HMGB1 might be released by cancer cells in areas of low glucose in solid tumours with the resulting activation of myofibroblasts and is a potential therapeutic target to inhibit solid tumour growth. [ABSTRACT FROM AUTHOR]

Background. Nonmotor symptoms particularly olfactory dysfunction, RBD, depression, hallucinations, and constipation are currently not included in the typical clinical criteria for diagnosing Lewy body Parkinsonian disorders (LBPD). The aim of this study is to determine the diagnostic value of nonmotor symptoms in patients presenting with Parkinsonism and tremor. Methods. All new patients seen between January 2007 and May 2013 in the Movement Disorders Specialist Clinics of the Royal Melbourne Hospital (RMH), who were referred with a possible neurodegenerative syndrome or concerns of Parkinsonism and/or tremor, were included. Patients underwent routine evaluation with the four-minute “Sniffin Sticks” test, RBD, depression, and constipation. Results. 291 patients were included in the analysis. Conclusion. We found that lower olfaction scores based on “Sniffin Sticks” testing combined with reports of depression and constipation are independent predictors for the diagnosis of the spectrum of Lewy body Parkinsonian disorders (LBPD). Parkinson’s disease (PD) cannot be reliably clinically differentiated from other causes of Parkinsonism that share symptomatology and structural abnormalities. [ABSTRACT FROM AUTHOR]

Despite their potential impact on phytoplankton dynamics and biogeochemical cycles, biological associations between algae and bacteria are still poorly understood. The aim of the present work was to characterize the influence of bacteria on the growth and function of the dinoflagellate Alexandrium tamarense . Axenic microalgal cultures were inoculated with a microbial community and the resulting cultures were monitored over a 15-month period, in order to allow for the establishment of specific algal–bacterial associations. Algal cells maintained in these new mixed cultures first experienced a period of growth inhibition. After several months, algal growth and cell volume increased, and indicators of photosynthetic function also improved. Our results suggest that community assembly processes facilitated the development of mutualistic relationships between A. tamarense cells and bacteria. These interactions had beneficial effects on the alga that may be only partly explained by mixotrophy of A. tamarense cells. The potential role of organic exudates in the establishment of these algal–bacterial associations is discussed. The present results do not support a role for algal–bacterial interactions in dinoflagellate toxin synthesis. However, variations observed in the toxin profile of A. tamarense cells during culture experiments give new clues for the understanding of biosynthetic pathways of saxitoxin, a potent phycotoxin. [ABSTRACT FROM AUTHOR]

This paper presents an agent-based ‘monocentric’ model: assuming only a fixed location for firms, outcomes closely parallel those found in classical urban economic models, but emerge through ‘bottom-up’ interaction in an agent-based model. Agents make buying and movement decisions based on a set of simple costs they face from their current location. These spatial costs are reduced to two types: the costs of moving people and goods across geographical distances and the costs (and benefits) of ‘being here’ (the effects of being at a particular location such as land costs, amenities or disamenities). Two approaches to land cost are compared: landlords and a ‘density cost’ proxy. Emergent equilibrium outcomes are found to depend on the interaction of externalities and time. These findings are produced by looking at how agents react to changing four types of cost, two spatial and two non-spatial: commuting, wage, good cost and good delivery. The models explore equilibrium outcomes, the effect of changing costs and the impact of heterogeneous agents, before focusing in on one example to find the source of emergence in the externalities of agent choice. The paper finishes by emphasising the importance of thinking about emergence as a tool, not an end in itself. [ABSTRACT FROM AUTHOR]

A patient with relapsed and refractory chronic lymphocytic leukaemia with Richter transformation was treated with chimeric antigen receptor ( CAR)-modified T cells targeted for CD19 but later relapsed with a clonally related plasmablastic lymphoma. The loss of most routine markers of pre-plasma cell or B lymphoid differentiation (including CD19) highlights the ability of such mature lymphomas to evade lineage-specific targeted immunotherapy by differentiating along pathways comparable to their normal cellular counterparts. Molecular genetic evaluation demonstrated multiple independent lines of CD19-negative disease that eventually evolved in this single patient. Such plasticity represents potential challenges for antigen-directed CAR-T cell therapy, while serving as a testament to the selective pressure exerted by these engineered T cells over time. [ABSTRACT FROM AUTHOR]

It is thought that the elasmobranch corticosteroid hormone 1α-hydroxycorticosterone (1α-B) functions as both a glucocorticoid (GC) and mineralocorticoid (MC). Classical antinatriuretic MC activities would run counter to the osmoregulatory strategy of euryhaline elasmobranchs acclimating to fresh water (FW). Therefore we hypothesize that FW acclimation will be accompanied by a decrease in plasma corticosteroids in these animals. However, events that activate the “fight-or-flight” response could mask changes associated with acclimation to lower salinities. To better define the MC role of corticosteroids in elasmobranchs, we designed a transfer system that allows the acclimation of Atlantic stingrays ( Dasyatis sabina ) from seawater (SW) to FW over 12 h while minimizing other extraneous stressors. Blood and interrenal glands were sampled from one group of stingrays 24 h after FW transfer, while another group was sampled two weeks after FW transfer. Two other groups served as mock-transfer controls in that they were treated and sampled in the same way, but remained in SW for the entire period. Plasma corticosteroids, osmolality, chloride, and urea were significantly lower in FW-acclimated stingrays (compared to mock-transfer stingrays) 24 h after FW transfer. This pattern remained after two weeks in FW, with the exception that plasma corticosteroids returned to pre-acclimation levels. There were no significant differences between experimental groups in interrenal levels of mRNAs encoding key steroidogenic proteins (steroidogenic acute regulatory protein and cholesterol side chain cleavage enzyme). Temporally decreased corticosteroid levels during FW acclimation are consistent with the unique strategy of euryhaline elasmobranchs, whereby lower plasma osmolality is maintained in FW vs. SW environments to reduce hydromineral gradients. [ABSTRACT FROM AUTHOR]