Innate immune cells must be able to distinguish between direct binding to microbes and detection of components shed from the surface of microbes located at a distance. Dectin-1 (also known as CLEC7A) ...is a pattern-recognition receptor expressed by myeloid phagocytes (macrophages, dendritic cells and neutrophils) that detects β-glucans in fungal cell walls and triggers direct cellular antimicrobial activity, including phagocytosis and production of reactive oxygen species (ROS). In contrast to inflammatory responses stimulated upon detection of soluble ligands by other pattern-recognition receptors, such as Toll-like receptors (TLRs), these responses are only useful when a cell comes into direct contact with a microbe and must not be spuriously activated by soluble stimuli. In this study we show that, despite its ability to bind both soluble and particulate β-glucan polymers, Dectin-1 signalling is only activated by particulate β-glucans, which cluster the receptor in synapse-like structures from which regulatory tyrosine phosphatases CD45 and CD148 (also known as PTPRC and PTPRJ, respectively) are excluded (Supplementary Fig. 1). The 'phagocytic synapse' now provides a model mechanism by which innate immune receptors can distinguish direct microbial contact from detection of microbes at a distance, thereby initiating direct cellular antimicrobial responses only when they are required.
Celotno besedilo
Dostopno za:
DOBA, IJS, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Objective To study national prevalence of dizziness and balance problems in US children and explore associated risk factors and patterns of healthcare utilization. Study design A multistage, ...nationally representative, probability sample of children (n = 10 954; aged 3-17 years) was examined based on the 2012 National Health Interview Survey Child Balance Supplement. Parents were asked if during the past year their child was bothered by symptoms of dizziness and balance problems: vertigo (motion sensation), light-headedness/fainting, clumsiness/poor coordination, poor balance/unsteadiness when standing-up or walking, frequent falls, or other dizziness and balance problems. Logistic regression was used to examine associations with sociodemographic information, birth weight, developmental delays, and significant health conditions. Results Prevalence of dizziness and balance problems was 5.3% (3.3 million US children); females, 5.7%, males, 5.0%. Non-Hispanic white (6.1%) had increased prevalence compared with Hispanic (4.6%) and non-Hispanic black (4.3%) children, P = .01. Prevalence increased with age, from 4.1% for children aged 3-5 years to 7.5% for children aged 15-17 years, P < .001. Even though the majority had symptoms rated as “no problem” or “a small problem,” 18.6% (600 000 US children) had symptoms rated as “moderate,” “big,” or “very big” problems. Overall, 36.0% of children with dizziness and balance problems were seen by healthcare professionals during the past year and 29.9% received treatment. Among children with dizziness and balance problems rated as moderate/big/very big problems, 71.6% had seen healthcare professionals and 62.4% received treatment for dizziness and balance problems. Conclusions The risk factors identified provide useful epidemiologic information about dizziness and balance problems in children and will be used in tracking the Healthy People 2020 goal to increase utilization of healthcare services for these children.
Abstract Decentering is defined as the ability to observe one’s thoughts and feelings as temporary, objective events in the mind, as opposed to reflections of the self that are necessarily true. The ...Experiences Questionnaire (EQ) was designed to measure both decentering and rumination but has not been empirically validated. The current study investigated the factor structure of the EQ in both undergraduate and clinical populations. A single, unifactorial decentering construct emerged using 2 undergraduate samples. The convergent and discriminant validity of this decentering factor was demonstrated in negative relationships with measures of depression symptoms, depressive rumination, experiential avoidance, and emotion regulation. Finally, the factor structure of the EQ was replicated in a clinical sample of individuals in remission from depression, and the decentering factor evidenced a negative relationship to concurrent levels of depression symptoms. Findings from this series of studies offer initial support for the EQ as a measure of decentering.
Antidepressant medication (ADM) and psychotherapy are effective treatments for major depressive disorder (MDD). It is unclear, however, if treatments differ in their effectiveness at the symptom ...level and whether symptom information can be utilised to inform treatment allocation. The present study synthesises comparative effectiveness information from randomised controlled trials (RCTs) of ADM versus psychotherapy for MDD at the symptom level and develops and tests the Symptom-Oriented Therapy (SOrT) metric for precision treatment allocation.
First, we conducted systematic review and meta-analyses of RCTs comparing ADM and psychotherapy at the individual symptom level. We searched PubMed Medline, PsycINFO, and the Cochrane Central Register of Controlled Trials databases, a database specific for psychotherapy RCTs, and looked for unpublished RCTs. Random-effects meta-analyses were applied on sum-scores and for individual symptoms for the Hamilton Rating Scale for Depression (HAM-D) and Beck Depression Inventory (BDI) measures. Second, we computed the SOrT metric, which combines meta-analytic effect sizes with patients' symptom profiles. The SOrT metric was evaluated using data from the Munich Antidepressant Response Signature (MARS) study (n = 407) and the Emory Predictors of Remission in Depression to Individual and Combined Treatments (PReDICT) study (n = 234).
The systematic review identified 38 RCTs for qualitative inclusion, 27 and 19 for quantitative inclusion at the sum-score level, and 9 and 4 for quantitative inclusion on individual symptom level for the HAM-D and BDI, respectively. Neither meta-analytic strategy revealed significant differences in the effectiveness of ADM and psychotherapy across the two depression measures. The SOrT metric did not show meaningful associations with other clinical variables in the MARS sample, and there was no indication of utility of the metric for better treatment allocation from PReDICT data.
This registered report showed no differences of ADM and psychotherapy for the treatment of MDD at sum-score and symptom levels. Symptom-based metrics such as the proposed SOrT metric do not inform allocation to these treatments, but predictive value of symptom information requires further testing for other treatment comparisons.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
An array of phenotypically diverse myeloid cells and macrophages (MC&M) resides in the tumor microenvironment, requiring multiplexed detection systems for visualization. Here we report an automated, ...multiplexed staining approach, named PLEXODY, that consists of five MC&M-related fluorescently-tagged antibodies (anti - CD68, - CD163, - CD206, - CD11b, and - CD11c), and three chromogenic antibodies, reactive with high- and low-molecular weight cytokeratins and CD3, highlighting tumor regions, benign glands and T cells. The staining prototype and image analysis methods which include a pixel/area-based quantification were developed using tissues from inflamed colon and tonsil and revealed a unique tissue-specific composition of 14 MC&M-associated pixel classes. As a proof-of-principle, PLEXODY was applied to three cases of pancreatic, prostate and renal cancers. Across digital images from these cancer types we observed 10 MC&M-associated pixel classes at frequencies greater than 3%. Cases revealed higher frequencies of single positive compared to multi-color pixels and a high abundance of CD68+/CD163+ and CD68+/CD163+/CD206+ pixels. Significantly more CD68+ and CD163+ vs. CD11b+ and CD11c+ pixels were in direct contact with tumor cells and T cells. While the greatest percentage (~70%) of CD68+ and CD163+ pixels was 0-20 microns away from tumor and T cell borders, CD11b+ and CD11c+ pixels were detected up to 240 microns away from tumor/T cell masks. Together, these data demonstrate significant differences in densities and spatial organization of MC&M-associated pixel classes, but surprising similarities between the three cancer types.
The Black Lives Matter Movement, which gained unprecedented global momentum in mid‐2020, triggered critical reflection on systemic discrimination of disadvantaged groups across many domains of ...society.
It prompted us, as early‐career researchers (ECRs) in conservation science, to examine our own awareness of ongoing injustices within our field, the role we play in perpetuating or countering these injustices, and how to move forward.
Colonialist ideologies and power dynamics throughout the history of conservation practice and research have left a long‐lasting legacy of inequality and systemic racism. While improvements have been made, these legacies continue to influence teaching and practice today.
In this perspective piece, we reflect on the impacts of conservation’s colonial past and how the sector has developed. We then explore how current traditional routes into conservation, and the dominance of these approaches, can leave ECRs underprepared to address modern‐day conservation issues due to a limited understanding of conservation’s history and key theories from other fields. We end by offering a set of suggestions encouraging others to learn and practise fairer and more inclusive conservation practices.
Read the free Plain Language Summary for this article on the Journal blog.
摘要
人权运动 “黑人的命也是命” (Black Lives Matter) 在2020年中期在全球以前所未有的势头发展, 引发了社会许多领域中对于弱势群体的系统性歧视的批判性思考。
作为处于职业初期的保护科学研究者，这促使我们审视自身学科领域中尚存的不公正现象，我们在延续或对抗这些不公正时所扮演的角色，以及如何改进。
殖民统治所遗留的意识形态和权力动态在保护研究和实践的历史上产生了长久的影响。即便有逐步的改进，这种不平等及种族歧视观念仍然影响着当今保护科学的教学与实践。
在此篇观点论文中，我们反思了殖民时期对自然保护的影响及此学科的演变过程，并探讨其在保护科学学科中的主流化程度，以及当下进入保护行业的传统路径。我们认为这些传统思路会限制职业初期的保护科学研究者解决现代保护问题的能力，尤其在他们对保护历史和其他领域的关键理论缺乏理解时。进而，我们在本文中提出了一系列针对性的建议，以鼓励年轻学者以更平等、更有包容性的方法开展保护研究与实践。
Résumé
Le mouvement Black Lives Matter, qui a pris une ampleur mondiale sans précédent à la mi‐2020, a déclenché une réflexion critique sur la discrimination systémique des groupes défavorisés dans de nombreux domaines de la société.
Il nous a incitées, en tant que chercheuses en début de carrière dans le domaine de la conservation de la biodiversité, à examiner notre propre conscience des injustices qui persistent dans notre domaine de recherche, le rôle que nous jouons dans la perpétuation ou la lutte contre ces injustices, et comment aller de l'avant.
Les idéologies coloniales et les dynamiques de pouvoir à travers l’histoire de la pratique et la recherche dans le domaine de la conservation ont laissé un héritage durable d’inégalité. Ce racisme systémique continue à influencer l’enseignement et la pratique aujourd’hui.
Dans cet article d’opinion, nous réfléchissons à l’héritage colonial au sein de la conservation de la biodiversité. Il nous semble que la domination de certaines approches et le parcours professionnel classique dans les sciences de la conservation laissent les chercheurs au début de carrière sans préparation à cause d’une compréhension limitée de l’histoire de la conservation et des théories clés d’autres disciplines. Nous concluons avec une liste de suggestions visant à encourager nos lecteurs à apprendre et à appliquer une pratique de conservation plus équitable et inclusive.
Resumen
El movimiento “Black Lives Matter” (“Las vidas negras importan”, BLM por sus siglas en Inglés), ganó fuerza y representación en los medios a mediados del año 2020, impulsando una reflexión crítica sobre la discriminación de grupos minoritarios en muchos ámbitos de la sociedad.
También impulsó a nuestro grupo, formado por investigadores al inicio de nuestra carrera en la ciencias ambientales y de la conservación, a reflexionar sobre las prácticas que promueven la desigualdad en nuestro campo. Examinamos nuestra propia falta de conocimiento y nuestro papel en fomentar o evitar tales prácticas discriminatorias.
Las ideologías asociadas al colonialismo, y las dinámicas de poder que éstas crean, han formado parte del movimiento de conservación de la biodiversidad a través de su historia, dejando un legado de racismo sistémico y/o institucional. A pesar de haber avanzado, este legado sigue presente en muchos ámbitos de la investigación, la educación y las estrategias de conservación.
En este artículo de opinión reflexionamos sobre el impacto del pasado colonial del movimiento conservacionista, y los avances del sector. Exploramos cómo una formación ‘tradicional’, basada en ciencias naturales y occidentales, puede dejarnos poco preparados para enfrentarnos a las complejidades socio‐ecológicas del campo de la conservación hoy en día. Terminamos presentando nuestras ideas sobre cómo fomentar el aprendizaje y la auto‐reflexión para que otros investigadores al inicio de su carrera reconozcan y adopten prácticas más respetuosas e inclusivas.
Resumo
O Movimento “Vidas Negras Importam” (tradução livre do inglês “Black Lives Matter”, também conhecido pela sigla BLM), ganhou projeção global sem precedentes em meados de 2020 e desencadeou uma reflexão crítica sobre a discriminação sistêmica de grupos desfavorecidos em muitos campos da sociedade.
Como pesquisadoras em início de carreira na área de ciência da conservação, este movimento nos levou a examinar nossa própria experiência a respeito de injustiças dentro de nosso campo profissional, o papel que desempenhamos na perpetuação e combate às mesmas, e como prosseguir daqui em diante.
Ideologias e dinâmicas de poder colonialistas presentes ao longo da história da prática e pesquisa da conservação, deixaram um legado duradouro de desigualdade e racismo sistêmico. Embora melhorias tenham sido feitas, esse legado continua a influenciar o ensino e a prática da conservação até hoje.
Neste artigo de perspectiva, fazemos uma reflexão sobre os impactos do passado colonialista da conservação e como o setor se desenvolveu. Em seguida, exploramos como as vias tradicionais implementadas nesta área, assim como a dominância das mesmas, deixam pesquisadores em início de carreira despreparados para lidar com questões da conservação moderna, devido a uma compreensão limitada da história da conservação e de teorias‐chave oferecidas por outras áreas do conhecimento. Finalizamos o artigo apresentando um conjunto de sugestões que visam incentivar o aprendizado e a prática da conservação de maneira mais justa e inclusiva.
Read the free Plain Language Summary for this article on the Journal blog.
Theories of epidemiologic transition analyze the shift in causes of mortality due to changes in risk factors over time, and through processes of urbanization and development by comparing risk factors ...between countries or over time. These theories do not account for health inequities such as those resulting from environmental injustice, in which minority and lower income residents are more likely to be exposed to environmental hazards or have less access to environmental goods. Neighborhoods with histories of environmental injustice are also at risk for gentrification as they undergo environmental improvements and new greening projects. We aimed to understand how environmental injustice, urban renewal and green gentrification could inform the understanding of epidemiologic risk transitions. We examined 7 case neighborhoods in cities in the United States and Western Europe which were representative in terms of city region and type, which 1) had experienced a history of environmental injustice and 2) exhibited evidence of recent processes of urban renewal and/or gentrification. In each city, we conducted semi-structured qualitative interviews (n = 172) with city representatives, activists, non-profits, developers and residents. Respondents reported health implications of traditional (heavy pollutants, poor social conditions), transitional (decontamination, new amenities), new (gentrification, access to amenities), and emerging (displacement, climate-related risks, re-emergence of traditional exposures) exposures. Respondents reported renewed, complexified and overlapping exposures leading to poor mental and physical health and to new patterns of health inequity. Our findings point to the need for theories of environmental and epidemiologic risk transitions to incorporate analysis of trends 1) on a city-scale, acknowledging that segregation and patterns of environmental injustice have created unequal conditions within cities and 2) over a shorter and more recent time period, taking into account worsening patterns of social inequity in cities.
•Lasting risk factors due to historical environmental injustices are overlapping and complex.•At the neighborhood scale, gentrification complexifies environmental risk factors.•Redevelopment patterns influence patterns related to the environmental risk transition.
The ability to retrieve specific, single-incident autobiographical memories has been consistently posited as a predictor of recurrent depression. Elucidating the role of autobiographical memory ...specificity in patient-response to depressive treatments may improve treatment efficacy and facilitate use of science-driven interventions. We used recent methodological advances in individual patient data meta-analysis to determine a) whether memory specificity is improved following mindfulness-based cognitive therapy (MBCT), relative to control interventions, and b) whether pre-treatment memory specificity moderates treatment response. All bar one study evaluated MBCT for relapse prevention for depression. Our initial analysis therefore focussed on MBCT datasets only(n = 708), then were repeated including the additional dataset(n = 880). Memory specificity did not significantly differ from baseline to post-treatment for either MBCT and Control interventions. There was no evidence that baseline memory specificity predicted treatment response in terms of symptom-levels, or risk of relapse. Findings raise important questions regarding the role of memory specificity in depressive treatments.
•Individual participant data meta-analysis of memory specificity and treatment response.•All bar one study evaluated MBCT for relapse prevention.•Memory specificity did not change from baseline to post-treatment.•No evidence that memory specificity predicted treatment response or risk of relapse.
Vascular endothelial growth factor (VEGF), a key mediator of angiogenesis, plays a key role in physiological processes and is a major contributor to several diseases including cancer and psoriasis. ...Anti-VEGF therapies are widely used as cancer and ophthalmological treatments. There is some evidence that VEGF blockade may have utility in the management of psoriasis, although their potential has been largely unexplored. We hypothesized that a human skin organ culture could provide a stable ex vivo model in which the cutaneous microvascular network could be studied and experimentally manipulated.
Punch biopsies (3 mm) of skin, donated by healthy individuals (39-72 years old, n = 5), were incubated with monoclonal antibody (mAb) to human VEGF (bevacizumab) at doses based on data from animal and clinical studies. After 3-day culture, cell death and proliferation as well as vascular endothelial cell changes were assessed using quantitative immunohistomorphometry.
Anti-VEGF mAb at 0.8 mg/mL induced a significant increase in cleaved caspase-3 expression in CD31+ cells (p < 0.05). None of the doses tested increased TUNEL or decreased Ki-67 expression in the basal layer of the epidermis, confirming the model's viability. In addition, the lactate dehydrogenase (LDH) assay showed no increase in LDH activity in treated samples compared to untreated control. The highest anti-VEGF mAb dose (0.8 mg/mL) induced an increase in TUNEL expression in the upper epidermis, which did not correlate with caspase-3 immunoreactivity. Further investigation revealed that anti-VEGF mAb did not change the expression of markers of terminal differentiation such as keratin 10, filaggrin, and involucrin, suggesting that VEGF depletion does not affect keratinocyte terminal differentiation. In contrast to the control group, levels of VEGF protein were undetectable in the culture supernatant of samples treated with 0.8 mg/mL of anti-VEGF mAb, suggesting sufficient dose.
Our pilot study provides the first evidence that anti-VEGF therapy promotes endothelial cell apoptosis in human skin ex vivo. Our pragmatic human skin organ culture assay offers a valuable tool for future preclinical endothelial cell and translational microvascular network/anti-angiogenesis research in human skin.
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