Transcriptomic analysis of glucosidase II beta subunit (GluIIß) knockout A549 cells reveals its roles in regulation of cell adhesion molecules (CAMs) and anti-tumor immunity.

Glucosidase II beta subunit (GluIIß), encoded from PRKCSH, is a subunit of the glucosidase II enzyme responsible for quality control of N-linked glycoprotein folding and suppression of GluIIß led to inhibitory effect of the receptor tyrosine kinase (RTKs) activities known to be critical for survival and development of cancer. In this study, we investigated the effect of GluIIß knockout on the global gene expression of cancer cells and its impact on functions of immune cells. GluIIß knockout lung adenocarcinoma A549 cell line was generated using CRISPR/Cas9-based genome editing system and subjected to transcriptomic analysis. Among 23,502 expressed transcripts, 1068 genes were significantly up-regulated and 807 genes greatly down-regulated. The KEGG enrichment analysis showed significant down-regulation of genes related extracellular matrix (ECM), ECM-receptor interaction, cytokine-cytokine receptor interaction and cell adhesion molecules (CAMs) in GluIIß knockout cells. Of 9 CAMs encoded DEG identified by KEGG enrichment analysis, real time RT-PCR confirmed 8 genes to be significantly down-regulated in all 3 different GluIIß knockout clones, which includes cadherin 4 (CDH4), cadherin 2 (CDH2), versican (VCAN), integrin subunit alpha 4 (ITGA4), endothelial cell-selective adhesion molecule (ESAM), CD274 (program death ligand-1 (PD-L1)), Cell Adhesion Molecule 1 (CADM1), and Nectin Cell Adhesion Molecule 3 (NECTIN3). Whereas PTPRF (Protein Tyrosine Phosphatase Receptor Type F) was significantly decreased only in 1 out of 3 knockout clones. Microscopic analysis revealed distinctively different cell morphology of GluIIß knockout cells with lesser cytoplasmic and cell surface area compared to parental A549 cells and non-targeted transfected cells.Further investigations revealed that Jurkat E6.1 T cells or human peripheral blood mononuclear cells (PBMCs) co-cultured with GluIIß knockout A549 exhibited significantly increased viability and tumor cell killing activity compared to those co-cultured with non-target transfected cells. Analysis of cytokine released from Jurkat E6.1 T cells co-cultured with GluIIß knockout A549 cells showed significant increased level of angiogenin and significant decreased level of ENA-78. In conclusion, knockout of GluIIß from cancer cells induced altered gene expression profile that improved anti-tumor activities of co-cultured T lymphocytes and PBMCs thus suppression of GluIIß may represent a novel approach of boosting anti-tumor immunity.

Physicochemical Principles of Adhesion Mechanisms in the Brain.

The brain functions through neuronal circuits and networks that are synaptically connected. This type of connection can exist due to physical forces that interact to stabilize local contacts in the brain. Adhesion is a fundamental physical phenomenon that allows different layers, phases, and tissues to connect. Similarly, synaptic connections are stabilized by specialized adhesion proteins. This review discusses the basic physical and chemical properties of adhesion. Cell adhesion molecules (CAMs) such as cadherins, integrins, selectins, and immunoglobulin family of cell adhesion molecules (IgSF) will be discussed, and their role in physiological and pathological brain function. Finally, the role of CAMs at the synapse will be described. In addition, methods for studying adhesion in the brain will be presented.

Influence of Polydatin on the Tumor Microenvironment In Vitro: Studies with a Colon Cancer Cell Model.

The tumor microenvironment of colon carcinoma, the site at which tumor cells and the host immune system interact, is influenced by signals from tumor cells, immunocompetent cells, and bacterial components, including LPS. A large amount of LPS is available in the colon, and this could promote inflammation and metastasis by enhancing tumor cell adhesion to the endothelium. Polydatin (PD), the 3-ß-D-glucoside of trans-resveratrol, is a polyphenol with anti-cancer, anti-inflammatory, and immunoregulatory effects. This study was designed to explore whether PD is able to produce antiproliferative effects on three colon cancer lines, to reduce the expression of adhesion molecules that are upregulated by LPS on endothelial cells, and to decrease the proinflammatory cytokines released in culture supernatants. Actually, we investigated the effects of PD on tumor growth in a coculture model with human mononuclear cells (MNCs) that mimics, at least in part, an in vitro tumor microenvironment. The results showed that PD alone or in combination with MNC exerts antiproliferative and proapoptotic effects on cancer cells, inhibits the production of the immunosuppressive cytokine IL-10 and of the proinflammatory cytokines upregulated by LPS, and reduces E-selectin and VCAM-1 on endothelial cells. These data provide preclinical support to the hypothesis that PD could be of potential benefit as a therapeutic adjuvant in colon cancer treatment and prevention.

Spatiotemporal changes in aerosols over Bangladesh using 18 years of MODIS and reanalysis data.

In this study, combined Dark Target and Deep Blue (DTB) aerosol optical depth at 550 nm (AOD550 nm) data the Moderate Resolution Imaging Spectroradiometer (MODIS) flying on the Terra and Aqua satellites during the years 2003-2020 are used as a reference to assess the performance of the Copernicus Atmosphere Monitoring Services (CAMS) and the second version of Modern-Era Retrospective analysis for Research and Applications (MERRA-2) AOD over Bangladesh. The study also investigates long-term spatiotemporal variations and trends in AOD, and determines the relative contributions from different aerosol species (black carbon: BC, dust, organic carbon: OC, sea salt: SS, and sulfate) and anthropogenic emissions to the total AOD. As the evaluations suggest higher accuracy for CAMS than for MERRA-2, CAMS is used for further analysis of AOD over Bangladesh. The annual mean AOD from both CAMS and MODIS DTB is high (>0.60) over most parts of Bangladesh except for the eastern areas of Chattogram and Sylhet. Higher AOD is observed in spring and winter than in summer and autumn, which is mainly due to higher local anthropogenic emissions during the winter to spring season. Annual trends from 2003-2020 show a significant increase in AOD (by 0.006-0.014 year-1) over Bangladesh, and this increase in AOD was more evident in winter and spring than in summer and autumn. The increasing total AOD is caused by rising anthropogenic emissions and accompanied by changes in aerosol species (with increased OC, sulfate, and BC). Overall, this study improves understanding of aerosol pollution in Bangladesh and can be considered as a supportive document for Bangladesh to improve air quality by reducing anthropogenic emissions.

[Evidence-based psychotherapeutic methods of prevention and intervention in suicidal behaviour]. / A szuicid prevenció és intervenció bizonyítékokon alapuló pszichoterápiás lehetoségei.

There are several approached to suicide prevention based on various psychotherapeutic interventions, which are effective, especially when these are matched to the given psychiatric patient population, environment and context. In this paper the possibilities of psychotherapeutic methods of suicide prevention and intervention are described along with their indications. The following interventions are discussed: Cognitive Behavioral Therapy for Suicide Prevention (CBT-SP), Cognitive Therapy for Suicide Prevention (CT-SP), Brief Cognitive-Behavioral Therapy for Suicide Prevention (BCBT), Problem Solving Therapy (PST), Problem Adaptation Therapy (PATH), Dialectial Behavior Therapy (DBT), SchemaFocused Therapy (SFT), Mindfulness-Based Cognitive Therapy (MBCT), Mindfulness-Based Stress Reduction (MBSR), Acceptance and Commitment Therapy (ACT), Mentalization-Based Treatment (MBT), Interpersonal Psychotherapy (IPT), Transference-Focused Psychotherapy (TFP), Collaborative Assessment and Management of Suicidality (CAMS), Teachable Moment Brief Intervention (TMBI), Motivational Interviewing (MI), Attempted Suicide Short Intervention Program (ASSIP) and other Interned-Based Interventions (IBI). The effectiveness of the above methods may vary, however, they focus on the psychological processes playing a role in the emergence of suicidal behaviours including cognitive processes, as well as difficulties of problem solving and emotion regulation. As the efficacy of these interventions are supported by clinical trials, their use is recommended in case of this vulnerable patient population. The importance of using such methods in the clinical work with suicidal patients should be prioritized in our effort to provide a complex treatment for suicidal behaviour based on the most optimal and appropriate intervention considering the given patient.

An intercomparison of ozone taken from the Copernicus atmosphere monitoring service and the second Modern-Era retrospective analysis for research and applications over China during 2018 and 2019.

Spatiotemporal variations of ozone (O3) taken from the Copernicus Atmosphere Monitoring Service (CAMS) and the second Modern-Era Retrospective Analysis for Research and Applications (MERRA-2) were intercompared and evaluated with ground and ozone-sonde observations over China in 2018 and 2019. Intercomparison of the surface ozone from CAMS and MERRA-2 reanalysis showed significant negative bias (CAMS minus MERRA-2, same below) at Tibetan Plateau of up to 80 µg/m3, and the average R2 was about 0.6 across China. Evaluated with the ground observations from China National Environmental Monitoring Center (CNEMC), we found that CAMS and MERRA-2 reanalysis were capable of capturing the key patterns of monthly and diurnal variations of surface ozone over China except for the western region, and MERRA-2 overestimated the observations compared to CAMS. Vertically, the CAMS profiles overestimated the ozone-sonde from the World Ozone and Ultraviolet Radiation Data Center (WOUDC) above 200 hPa with the magnitude reaching up to 150 µg/m3, while little bias was found between the reanalysis and observations below 200 hPa. Intercomparison drawn from the vertical distribution between CAMS and MERRA-2 reanalysis showed that the negative bias appeared throughout the troposphere over China, while the positive bias emerged in the upper troposphere and lower stratosphere (UTLS) with high order of magnitude exceeding 100 µg/m3, indicating large uncertainties at higher altitudes. In summary, we concluded that CAMS reanalysis showed better agreement with the observations in contrast to MERRA-2, and the large discrepancy especially at higher altitudes between these two reanalysis datasets could not be ignored.

Delineating Calcium Signaling Machinery in Plants: Tapping the Potential through Functional Genomics.

Plants have developed calcium (Ca2+) signaling as an important mechanism of  regulation of  stress perception,  developmental cues, and  responsive gene  expression. The  post-genomic era has witnessed the successful unravelling of the functional characterization of genes and the creation of large datasets of molecular information. The major elements of Ca2+ signaling machinery include Ca2+ sensors and responders such as Calmodulins (CaMs), Calmodulin-like proteins (CMLs), Ca2+/CaM-dependent protein kinases (CCaMKs), Ca2+-dependent protein kinases (CDPKs), Calcineurin B-like proteins (CBLs) as well as transporters, such as Cyclic nucleotide-gated channels (CNGCs), Glutamate-like receptors (GLRs), Ca2+-ATPases, Ca2+/H+ exchangers (CAXs) and mechanosensitive channels. These elements play an important role in the regulation of physiological processes and plant responses to various stresses. Detailed genomic analysis can help us in the identification of potential molecular targets that can be exploited towards the development of stress-tolerant crops. The information sourced from model systems through omics approaches helps in the prediction and simulation of regulatory networks involved in responses to different stimuli at the molecular and cellular levels. The molecular delineation of Ca2+ signaling pathways could be a stepping stone for engineering climate-resilient crop plants. Here, we review the recent developments in Ca2+ signaling in the context of transport, responses, and adaptations significant for crop improvement through functional genomics approaches.

Light-weighted ensemble network with multilevel activation visualization for robust diagnosis of COVID19 pneumonia from large-scale chest radiographic database.

Currently, the coronavirus disease 2019 (COVID19) pandemic has killed more than one million people worldwide. In the present outbreak, radiological imaging modalities such as computed tomography (CT) and X-rays are being used to diagnose this disease, particularly in the early stage. However, the assessment of radiographic images includes a subjective evaluation that is time-consuming and requires substantial clinical skills. Nevertheless, the recent evolution in artificial intelligence (AI) has further strengthened the ability of computer-aided diagnosis tools and supported medical professionals in making effective diagnostic decisions. Therefore, in this study, the strength of various AI algorithms was analyzed to diagnose COVID19 infection from large-scale radiographic datasets. Based on this analysis, a light-weighted deep network is proposed, which is the first ensemble design (based on MobileNet, ShuffleNet, and FCNet) in medical domain (particularly for COVID19 diagnosis) that encompasses the reduced number of trainable parameters (a total of 3.16 million parameters) and outperforms the various existing models. Moreover, the addition of a multilevel activation visualization layer in the proposed network further visualizes the lesion patterns as multilevel class activation maps (ML-CAMs) along with the diagnostic result (either COVID19 positive or negative). Such additional output as ML-CAMs provides a visual insight of the computer decision and may assist radiologists in validating it, particularly in uncertain situations Additionally, a novel hierarchical training procedure was adopted to perform the training of the proposed network. It proceeds the network training by the adaptive number of epochs based on the validation dataset rather than using the fixed number of epochs. The quantitative results show the better performance of the proposed training method over the conventional end-to-end training procedure. A large collection of CT-scan and X-ray datasets (based on six publicly available datasets) was used to evaluate the performance of the proposed model and other baseline methods. The experimental results of the proposed network exhibit a promising performance in terms of diagnostic decision. An average F1 score (F1) of 94.60% and 95.94% and area under the curve (AUC) of 97.50% and 97.99% are achieved for the CT-scan and X-ray datasets, respectively. Finally, the detailed comparative analysis reveals that the proposed model outperforms the various state-of-the-art methods in terms of both quantitative and computational performance.

Axonal Growth of Midbrain Dopamine Neurons is Modulated by the Cell Adhesion Molecule ALCAM Through Trans-Heterophilic Interactions with L1cam, Chl1, and Semaphorins.

The growth of axons corresponding to different neuronal subtypes is governed by unique expression profiles of molecules on the growth cone. These molecules respond to extracellular cues either locally though cell adhesion interactions or over long distances through diffusible gradients. Here, we report that that the cell adhesion molecule ALCAM (CD166) can act as an extracellular substrate to selectively promote the growth of murine midbrain dopamine (mDA) neuron axons through a trans-heterophilic interaction with mDA-bound adhesion molecules. In mixed-sex primary midbrain cultures, the growth-promoting effect of ALCAM was abolished by neutralizing antibodies for components of the Semaphorin receptor complex Nrp1, Chl1, or L1cam. The ALCAM substrate was also found to modulate the response of mDA neurites to soluble semaphorins in a context-specific manner by abolishing the growth-promoting effect of Sema3A but inducing a branching response in the presence of Sema3C. These findings identify a previously unrecognized guidance mechanism whereby cell adhesion molecules act in trans to modulate the response of axonal growth cones to soluble gradients to selectively orchestrate the growth and guidance of mDA neurons.SIGNIFICANCE STATEMENT The mechanisms governing the axonal connectivity of midbrain dopamine (mDA) neurons during neural development have remained rather poorly understood relative to other model systems for axonal growth and guidance. Here, we report a series of novel interactions between proteins previously not identified in the context of mDA neuronal growth. Significantly, the results suggest a previously unrecognized mechanism involving the convergence in signaling between local, adhesion and long-distance, soluble cues. A better understanding of the molecules and mechanisms involved in establishment of the mDA system is important as a part of ongoing efforts to understand the consequence of conditions that may result from aberrant connectivity and also for cell replacement strategies for Parkinson's disease.

Collaborative Assessment and Management of Suicidality (CAMS) compared to enhanced treatment as usual (E-TAU) for suicidal patients in an inpatient setting: study protocol for a randomized controlled trial.

BACKGROUND: The Collaborative Assessment and Management of Suicidality (CAMS) is a therapeutic framework that has been shown to reduce suicidal ideation and overall symptom distress. CAMS has not been previously evaluated in a standard acute inpatient mental health care setting with only short treatment times for suicidal patients. In this randomized controlled trial (RCT) we are investigating whether CAMS is more effective than Enhanced-Treatment as Usual (E-TAU) in reducing suicidal thoughts as primary outcome variable. We are also investigating depressive symptoms, general symptom relief, and the quality of the therapeutic alliance as secondary outcomes. METHODS/DESIGN: This RCT is designed as a single-center, two-armed, parallel group observer-blinded clinical effectiveness investigation. We are recruiting and randomizing 60 participants with different diagnoses, who are admitted as inpatients because of acute suicidal thoughts or behaviors into the Clinic for Psychiatry and Psychotherapy, Ev. Hospital Bethel in Bielefeld, Germany. The duration of treatment will vary depending on patients' needs and clinical assessments ranging between 10 and 40 days. Patients are assessed four times, at admission, discharge, 1 month, and 5 months post-discharge. The primary outcome measure is the Beck Scale for Suicide Ideation. Other outcome measures are administered as assessment timepoints including severity of psychiatric symptoms, depression, reasons for living, and therapeutic relationship. DISCUSSION: This effectiveness study is being conducted on an acute ward in a psychiatric clinic where patients have multiple problems and diagnoses. Treatment is somewhat limited, and therapists have a large caseloads. The results of this study can thus be generalizable to a typical inpatient psychiatric hospital settings. TRIAL REGISTRATION: This clinical trial has been retrospectively registered with the German Clinical Trials Register; registration code/ DRKS-ID: DRKS00013727 (on January 12, 2018). In addition, the study was also registered with the International Clinical Trials Registry Platform of the World Health Organization (identical registration code). Registry Name: "Evaluation von CAMS versus TAU bei suizidalen Patienten - Ein stationärer RCT".

The Effects of Youth Anxiety Treatment on School Impairment: Differential Outcomes Across CBT, Sertraline, and their Combination.

Youth anxiety disorders are highly prevalent and are associated with considerable school impairment. Despite the identification of well-supported strategies for treating youth anxiety, research has yet to evaluate the differential effects of these treatments on anxiety-related school impairment. The present study leveraged data from the Child/Adolescent Anxiety Multimodal Study to examine differential treatment effects of CBT, sertraline, and their combination (COMB), relative to placebo (PBO), on anxiety-related school impairment among youth (N = 488). Latent growth modeling revealed that all three active treatments demonstrated superiority over PBO in reducing anxiety-related school impairment over time, with COMB showing the most robust effects. According to parent report, medication strategies may have stronger effects on anxiety-related school impairment among males than among females. Results were discrepant across parents and youth. Findings are discussed in terms of clinical implications for anxious youth and the need for continued research to examine treatment effects on anxiety-related school impairment.

The psychometric properties of the Collaborative Assessment and Management of Suicidality rating scale.

OBJECTIVE: The CAMS Rating Scale (CRS) is an adherence measure for the Collaborative Assessment and Management of Suicidality (CAMS), a suicide-specific clinical intervention. This study examined the ability of the CRS to assess adherence to CAMS. METHODS: Video-recorded therapy sessions of clinicians delivering either CAMS or Enhanced Care-As-Usual (E-CAU) were rated with the CRS. These ratings (N = 98) were used to evaluate criterion validity, internal consistency, and factor structure. RESULTS: Criterion validity and factor analyses did not support the organization of the CRS into its current subscales. Furthermore, the identified factor model and item-level statistics revealed weak CRS items. Finally, internal consistency was higher among CAMS clinicians than among clinicians delivering E-CAU. CONCLUSION: These results establish the CRS as a measure that can effectively assess the adherence to CAMS in its current form. Potential revisions to future iterations of the CRS are discussed.

A systematic review of efficacy of Collaborative Assessment and Management of Suicidality (CAMS) in managing suicide risk and deliberate self-harm in adult populations.

OBJECTIVE: Evaluate the efficacy of Collaborative Assessment and Management of Suicidality (CAMS) in managing suicide risk and deliberate self-harm in adults. METHODS: Ten databases were searched for publications referring to CAMS or the Suicide Status Form. Results were evaluated by two reviewers. RESULTS: Limited evidence that CAMS is effective in reducing suicide risk and deliberate self-harm in adult populations. CONCLUSIONS: Although CAMS appears to show promise in managing suicidal patients across a range of measures, further evidence is needed to clarify its efficacy in managing suicide risk and deliberate self-harm.

Xenopus laevis neuronal cell adhesion molecule (nrcam): plasticity of a CAM in the developing nervous system.

Neuron-glial-related cell adhesion molecule (NRCAM) is a neuronal cell adhesion molecule of the L1 immunoglobulin superfamily, which plays diverse roles during nervous system development including axon growth and guidance, synapse formation, and formation of the myelinated nerve. Perturbations in NRCAM function cause a wide variety of disorders, which can affect wiring and targeting of neurons, or cause psychiatric disorders as well as cancers through abnormal modulation of signaling events. In the present study, we characterize the Xenopus laevis homolog of nrcam. Expression of Xenopus nrcam is most abundant along the dorsal midline throughout the developing brain and in the outer nuclear layer of the retina.

Treating Suicidality in College Counseling Centers: A Response to Polychronis.

This is a commentary on the article by Paul D. Polychronis, "Changes Across Three Editions of The Suicidal Patient: Clinical and Legal Standards of Care: Relevance to Counseling Centers," published in this issue of the Journal of College Student Psychotherapy.

A comparison of patterns of spontaneous adverse drug reaction reporting with St. John's Wort and fluoxetine during the period 2000-2013.

Herbal medicines are perceived to be safe by the general public and medical practitioners, despite abundant evidence from clinical trials and case reports that show herbal preparations can have significant adverse effects. The overall impact of adverse events to herbal medicines in Australia is currently unknown. Post marketing surveillance of medications through spontaneous adverse drug reaction (ADR) reports to the Therapeutic Goods Administration (TGA) is one way to estimate this risk. The patterns of spontaneously reported ADRs provide insight to herbal dangers, especially when compared with patterns of a mechanistically similar conventional drug. The study compared the pattern of spontaneously reported ADRs to St. John's Wort (Hypericum perforatum), a common herbal treatment for depression which contains selective serotonin reuptake inhibitors (SSRI), to fluoxetine, a commonly prescribed synthetic SSRI antidepressant. Spontaneous ADR reports sent to the TGA between 2000-2013 for St. John's Wort (n = 84) and fluoxetine (n = 447) were obtained and analysed. The demographic information, types of interaction, severity of the ADR, and the body systems affected (using the Anatomical Therapeutic Chemical classification system) were recorded for individual ADR cases. The majority of spontaneously reported ADRs for St. John's Wort and fluoxetine were concerning females aged 26-50 years (28.6%, 22.8%). The organ systems affected by ADRs to St John's Wort and fluoxetine have a similar profile, with the majority of cases affecting the central nervous system (45.2%, 61.7%). This result demonstrates that herbal preparations can result in ADRs similar to those of prescription medications.

Thiram activates NF-kappaB and enhances ICAM-1 expression in human microvascular endothelial HMEC-1 cells.

Thiram (TMTD) is a fungicidal and bactericidal agent used as antiseptic, seed disinfectant and animal repellent. In the light of known properties, thiram is considered to be used as an inhibitor of angiogenesis and/or inflammation. Since angiogenesis requires the growth of vascular endothelial cells we have used microvascular endothelial cell line HMEC-1 to elucidate the effect of thiram on normal and stimulated cells. We cultured HMEC-1 cells in the presence of thiram at low concentration (0.5 µg/mL or 2 µg/mL) (0.2 µM or 0.8 µM) or TNF-α (10 ng/mL) alone, and thiram together with TNF-α. TNF-α was used as a cytokine that triggers changes characteristic for inflammatory state of the cell. We carried out an in vitro study aimed at assessing generation of reactive oxygen species (ROS), activation of NF-κB, and expression of cell adhesion molecules ICAM-1, VCAM-1, PECAM-1. It was found that TMTD produced ROS and activated NF-κB. Activation of NF-κB was concurrent with an increase in ICAM-1 expression on the surface of HMEC-1 cells. ICAM-1 reflects intensity of inflammation in endothelial cell milieu. The expression of VCAM-1 and PECAM-1 on these cells was not changed by thiram. It was also found that stimulation of the HMEC-1 cells with the pro-inflammatory cytokine TNF-α caused activation of ICAM-1 and VCAM-1 expression with concomitant decrease of PECAM-1 cell surface expression above the control levels. Treatment with thiram and TNF-α changed cellular response compared with effects observed after treatment with TNF-α alone, i.e. further increase of ICAM-1 expression and impairment of the TNF-α effect on PECAM-1 and VCAM-1 expression. This study demonstrated that thiram acts as a pro-oxidant, and elicits in endothelial cell environment effects characteristic for inflammation. However, when it is present concurrently with pro-inflammatory cytokine TNF-α interferes with its action.

My Horse Is My Therapist: The Medicalization of Pleasure among Women Equestrians.

Pink t-shirts that proclaim "My horse is my therapist" are for sale in a wide variety of horse-sport catalogues. Literature on the healing power of human-nonhuman animal encounters and the practice of a variety of animal-assisted therapy programs, such as hippotherapy and equine-facilitated therapy, show dramatic growth over the last 30 years. Less attention is paid to the role that horse-human interactions may play in more popular accountings of well-being and impairment among a sample of everyday riders. Analysis of 50 lifecycle narratives, collected from accomplished but nonprofessional equestriennes, demonstrates the complex and ambiguous ways in which women draw from their experience of human-horse relationships as they challenge and transgress the borderlands between pleasure and impairment. Combining the perspectives of multispecies ethnography and medical anthropology that engages the complexities of well-being, analysis is informed by and contributes to recent controversies concerning the medicalization of normality and pleasure in DSM 5.

Tumor and its microenvironment: a synergistic interplay.

The mutual and interdependent interaction between tumor and its microenvironment is a crucial topic in cancer research. Recently, it was reported that targeting stromal events could improve efficacies of current therapeutics and prevent metastatic spreading. Tumor microenvironment is a "complex network" of different cell types, soluble factors, signaling molecules and extracellular matrix components, which orchestrate the fate of tumor progression. As by definition, cancer stem cells (CSCs) are proposed to be the unique cell type able to maintain tumor mass and survive outside the primary tumor at metastatic sites. Being exposed to environmental stressors, including reactive oxygen species (ROS), CSCs have developed a GSH-dependent antioxidant system to improve ROS defense capability and acquire a malignant phenotype. Nevertheless, tumor progression is dependent on extracellular matrix remodeling, fibroblasts and macrophages activation in response to oxidative stress, as well as epithelial mesenchymal transition (EMT)-inducing signals and endothelial and perivascular cells recruitment. Besides providing a survival advantage by inducing de novo angiogenesis, tumor-associated vessels contribute to successful dissemination by facilitating tumor cells entry into the circulatory system and driving the formation of pre-metastatic niche. In this review, we focus on the synergistic effect of hypoxia inducible factors (HIFs) and vascular endothelial growth factors (VEGFs) in the successful outgrowth of metastasis, integrating therefore many of the emerging models and theories in the field.

Diet quality and markers of endothelial function: the CARDIA study.

BACKGROUND AND AIM: Dietary patterns are associated cross-sectionally with cellular adhesion molecules (CAMs). We studied prospective associations of three dietary patterns with CAMs. METHODS AND RESULTS: In the Coronary Artery Risk Development in Young Adults (CARDIA) study, diet was assessed at years 0 (1985-86) and 7 (1992-93) examinations. Four circulating CAMs (E-selectin, P-selectin, soluble intercellular adhesion molecule 1 (sICAM-1), and vascular cellular adhesion molecule (VCAM)) were assayed at years 7 and 15 (2000-01). We created one index score "A Priori Diet Quality Score" and derived dietary patterns using principal components analysis (PCA). Multivariable linear regression models predicted year 15 CAMs from averaged (year 0/7) dietary patterns. The A Priori Diet Quality Score rated 46 food groups beneficial, neutral or adverse based on hypothesized health effects. We derived two PCA dietary patterns: "fruit and vegetables (FV)" (high intakes of fruit, vegetables, and whole grains) and "meat" (high intakes of red meat, refined grain, and butter). All dietary patterns were related to E-selectin and sICAM-1. P-selectin was not related to the FV dietary pattern. VCAM was only related to the A Priori Diet Quality Score. Strongest associations were for the meat dietary pattern with E-selectin (effect size 28% of an SD (+3.9/13.7 ng/mL)) and P-selectin (effect size 37% of an SD (+4.1/11.2 ng/mL)) and the A Priori Diet Quality Score with sICAM-1 (effect size 34% of an SD (-15.1/44.7 ng/mL)) and VCAM (effect size of 26% of an SD (-45.1/170.3 ng/mL)). CONCLUSION: This prospective analysis suggests that dietary patterns are associated with CAMs.