[Thrombotic occlusion of the extracorporeal circulation during hepatic chemosaturation despite targeted anticoagulation : A case report]. / Thrombotischer Verschluss der extrakorporalen Zirkulation während hepatischer Chemosaturation trotz zielgerechter Antikoagulation : Ein Fallbericht.

Percutaneous hepatic chemosaturation is a treatment option for unresectable primary or secondary liver tumors. In this procedure the part of the inferior vena cava (VCI) that collects blood from the hepatic veins is isolated using a double balloon catheter. Like this, systemic distribution of the chemotherapeutic agent melphalan which is administered via the hepatic artery can be prevented. After passage through the liver and drainage from the retrohepatic VCI, the chemosaturated blood passes through two extracorporeal filters. Subsequently, the filtered blood is returned via the jugular vein. The procedure is often accompanied by severe hemodynamic instability, the cause of which is still not completely understood. In addition, coagulation management of extracorporeal circulation is often challenging. The authors report a case in which a thrombus formed in the returning leg of the extracorporeal circulation despite sufficient activated clotting time (ACT). Targeted problem search and resolution were necessary simultaneously to hemodynamic stabilization and interdisciplinary collaboration to successfully perform the intervention and provide the patient with safe treatment.

Modification Strategies of Kapok Fiber Composites and Its Application in the Adsorption of Heavy Metal Ions and Dyes from Aqueous Solutions: A Systematic Review.

Kapok fiber (Ceiba pentandra) belongs to a group of natural fibers that are mainly composed of cellulose, lignin, pectin, and small traces of inorganic compounds. These fibers are lightweight with hollow tubular structure that is easy to process and abundant in nature. Currently, kapok fibers are used in industry as filling material for beddings, upholstery, soft toys, and nonwoven materials. However, kapok fiber has also a potential application in the adsorptive removal of heavy metal ions and dyes from aqueous systems. This study aims to provide a comprehensive review about the recent developments on kapok fiber composites including its chemical properties, wettability, and surface morphology. Effective and innovative kapok fiber composites are analyzed with the help of characterization tools such as scanning electron microscopy, X-ray diffraction, X-ray photoelectron spectroscopy, thermogravimetric analysis, Fourier transform infrared spectroscopy, energy-dispersive X-ray spectroscopy, and Brunauer-Emmett-Teller analysis. Different pre-treatment methods such as alkali and acid pre-treatment, oxidation pre-treatment, and Fenton reaction are discussed. These techniques are applied to enhance the hydrophilicity and to generate rougher fiber surfaces. Moreover, surface modification and synthesis of kapok fiber-based composites and its environmental applications are examined. There are various methods in the fabrication of kapok fiber composites that include chemical modification and polymerization. These procedures allow the kapok fiber composites to have higher adsorption capacities for selective heavy metal and dye removal.

Testicular immune cell populations and macrophage polarisation in adult male mice and the influence of altered activin A levels.

Detailed morphological characterization of testicular leukocytes in the adult CX3CR1 gfp/+ transgenic mouse identified two distinct CX3CR1 + mononuclear phagocyte (macrophage and dendritic cell) populations: stellate/dendriform cells opposed to the seminiferous tubules (peritubular), and polygonal cells associated with Leydig cells (interstitial). Using confocal microscopy combined with stereological enumeration of CX3CR1gfp/+ cells established that there were twice as many interstitial cells (68%) as peritubular cells (32%). Flow cytometric analyses of interstitial cells from mechanically-dissociated testes identified multiple mononuclear phagocyte subsets based on surface marker expression (CX3CR1, F4/80, CD11c). These cells comprised 80% of total intratesticular leukocytes, as identified by CD45 expression. The remaining leukocytes were CD3+ (T lymphocytes) and NK1.1+ (natural killer cells). Functional phenotype assessment using CD206 (an anti-inflammatory/M2 marker) and MHC class II (an activation marker) identified a potentially tolerogenic CD206+MHCII+ sub-population (12% of total CD45+ cells). Rare testicular subsets of CX3CR1 +CD11c+F4/80+ (4.3%) mononuclear phagocytes and CD3+NK1.1+ (3.1%) lymphocytes were also identified for the first time. In order to examine the potential for the immunoregulatory cytokine, activin A to modulate testicular immune cell populations, testes from adult mice with reduced activin A (Inhba+/-) or elevated activin A (Inha+/-) were assessed using flow cytometry. Although the proportion of F4/80+CD11b+ leukocytes (macrophages) was not affected, the frequency of CD206+MHCII+cells was significantly lower and CD206+MHCII- correspondingly higher in Inha+/- testes. This shift in expression of MHCII in CD206+ macrophages indicates that changes in circulating and/or local activin A influence resident macrophage activation and phenotype and, therefore, the immunological environment of the testis.

Correction: Role of growth arrest-specific gene 6-mer axis in multiple myeloma.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

Impairments in episodic future thinking for positive events and anticipatory pleasure in major depression.

BACKGROUND: Characteristic of the cardinal symptom of anhedonia, people with clinical depression report lower levels of anticipatory pleasure. However, the psychological mechanisms underlying these deficits are poorly understood. This is the first study to assess whether, and to what extent, phenomenological characteristics of episodic future thinking for positive future events are associated with anticipatory pleasure among depressed individuals. METHODS: Individuals with a Major Depressive Episode (MDE; N = 117) and without (N = 47) completed ratings scales for depressive symptoms and trait anticipatory and consummatory pleasure. They then provided descriptions of personally-relevant positive future events and rated them for phenomenological characteristics and state anticipatory pleasure. RESULTS: Between-groups analysis showed that those with MDE reported lower trait anticipatory and consummatory pleasure. They also simulated future events with less specificity, less detail/vividness, less use of mental imagery, less use of first-person perspective, less plausibility/perceived likelihood of occurring, and reported less associated state anticipatory pleasure. In regression analyses in the depressed group, lower scores for detail/vividness, mental imagery, and personal significance all uniquely predicted lower state anticipatory pleasure. LIMITATIONS: Cognitive functioning was not assessed, which may help clarify deficits that underpin these findings. History of previous depressive episodes in the comparison group were not assessed, which may mean the observed between-group effects are underestimated. CONCLUSIONS: This study provides further evidence of deficits in episodic future thinking and anticipatory pleasure in depressed individuals. It also establishes links between particular characteristics of episodic future thinking and state anticipatory pleasure, and indicates cognitive targets that may be amenable to intervention in order to reduce anhedonia.

Vitamin D Status and Prevalent Early Age-Related Macular Degeneration in African Americans and Caucasians: The Atherosclerosis Risk in Communities (ARIC) Study.

OBJECTIVES: Vitamin D status has been hypothesized to protect against development of early age-related macular degeneration (AMD) via its anti-inflammatory properties and its possible beneficial influence on blood pressure control. We investigated the association between vitamin D status and prevalent early AMD in a community-based cohort. DESIGN: This was a cross-sectional study. SETTING: This was a secondary data analysis of already existing data from the Atherosclerosis Risk in Communities Study (ARIC) cohort collected from 1990 to 1995. PARTICIPANTS: There were 9,734 (7,779 Caucasians, 1,955 African American) ARIC participants (aged 46 to 70 at visit 2 [1990-1992]) with 25(OH)D data available at visit 2, AMD assessment at visit 3 (1993-1995), and complete covariate data. MEASUREMENTS: Vitamin D status was assessed with serum 25-hydroxyvitamin D (25(OH)D) concentrations from bloods drawn at visit 2. Prevalent, early AMD (n=511) was assessed at visit 3 (1993-95) with nonmydriatic retinal photographs of one randomly chosen eye. Logistic regression was used to estimate odds ratios (ORs) and 95% confidence intervals (CIs) for early AMD by categories of 25(OH)D in nmol/L (deficient <30, inadequate 30-<50, and two categories of adequate status: 50-<75 and ≥75). Linear trend was estimated using continuous 25(OH)D concentrations. ORs were adjusted for age, race, and smoking status. We further adjusted for hypertension status to examine if vitamin D status influenced early AMD via its effects on blood pressure. Exploratory analyses of effect modification by age, sex, race and high risk genotypes [Y402H complement factor H (CFH) rs1061170 and the A69S age-related maculopathy susceptibility 2 (ARMS2) rs10490924 polymorphisms] were conducted. RESULTS: The prevalence of early AMD was 5%, and 5% of participants were vitamin D deficient. The adjusted OR (95% CIs) for early AMD among those with adequate (≥75 nmol/L) compared to deficient (<30 nmol/L) vitamin D status was 0.94 (0.59-1.50), p-trend=0.86. Further adjustment for hypertension status did not influence results (OR [95% CI]=0.95 [0.59-1.52], p-trend=0.84). Results did not vary significantly by age, race, sex, early AMD subtype (soft drusen or retinal pigment epithelium depigmentation), or ARMS2 genotype. Results did not vary significantly by CFH genotype in African Americans. The p for multiplicative interaction between 25(OH)D and CFH genotype was 0.06 in Caucasians, but OR [95% CIs] for AMD by vitamin D status were similar in each CFH genotype and not statistically significant. CONCLUSIONS: Vitamin D status was not associated with early AMD in this cohort sample.

An in vitro model demonstrates the potential of neoplastic human germ cells to influence the tumour microenvironment.

Testicular germ cell tumours (TGCT) typically contain high numbers of infiltrating immune cells, yet the functional nature and consequences of interactions between GCNIS (germ cell neoplasia in situ) or seminoma cells and immune cells remain unknown. A co-culture model using the seminoma-derived TCam-2 cell line and peripheral blood mononuclear cells (PBMC, n = 7 healthy donors) was established to investigate how tumour and immune cells each contribute to the cytokine microenvironment associated with TGCT. Three different co-culture approaches were employed: direct contact during culture to simulate in situ cellular interactions occurring within seminomas (n = 9); indirect contact using well inserts to mimic GCNIS, in which a basement membrane separates the neoplastic germ cells and immune cells (n = 3); and PBMC stimulation prior to direct contact during culture to overcome the potential lack of immune cell activation (n = 3). Transcript levels for key cytokines in PBMC and TCam-2 cell fractions were determined using RT-qPCR. TCam-2 cell fractions showed an immediate increase (within 24 h) in several cytokine mRNAs after direct contact with PBMC, whereas immune cell fractions did not. The high levels of interleukin-6 (IL6) mRNA and protein associated with TCam-2 cells implicate this cytokine as important to seminoma physiology. Use of PBMCs from different donors revealed a robust, repeatable pattern of changes in TCam-2 and PBMC cytokine mRNAs, independent of potential inter-donor variation in immune cell responsiveness. This in vitro model recapitulated previous data from clinical TGCT biopsies, revealing similar cytokine expression profiles and indicating its suitability for exploring the in vivo circumstances of TGCT. Despite the limitations of using a cell line to mimic in vivo events, these results indicate how neoplastic germ cells can directly shape the surrounding tumour microenvironment, including by influencing local immune responses. IL6 production by seminoma cells may be a practical target for early diagnosis and/or treatment of TGCT.

e-TC: Development and pilot testing of a web-based intervention to reduce anxiety and depression in survivors of testicular cancer.

e-TC is an online intervention designed to address common psychosocial concerns of testicular cancer survivors. It aims to reduce anxiety, depression and fear of cancer recurrence by providing evidence-based information and psychological intervention. This paper details the development and pilot testing of e-TC. During pilot testing, 25 men (with varying psychological profiles) who had completed treatment for testicular cancer, 6 months to 5 years ago (which had not recurred), used e-TC over a 10-week period and provided quantitative and qualitative feedback on the feasibility and acceptability of the programme. Six men also completed a qualitative interview to provide detailed feedback on their experiences using e-TC. Fourteen men (56%) completed at least 80% of the programme. Participants reported a high level of satisfaction with the programme. Men's limited time was a barrier to programme use and completion, and participants suggested that men with a more recent diagnosis and a higher level of distress may be more likely to engage with the programme. e-TC appears to be a feasible and acceptable online intervention for survivors of testicular cancer. Findings from this study are currently being used to refine e-TC and guide the design of a larger efficacy study.

RECQ1 helicase is involved in replication stress survival and drug resistance in multiple myeloma.

Multiple myeloma (MM) is a plasma cell cancer with poor survival, characterized by the expansion of multiple myeloma cells (MMCs) in the bone marrow. Using a microarray-based genome-wide screen for genes responding to DNA methyltransferases (DNMT) inhibition in MM cells, we identified RECQ1 among the most downregulated genes. RecQ helicases are DNA unwinding enzymes involved in the maintenance of chromosome stability. Here we show that RECQ1 is significantly overexpressed in MMCs compared to normal plasma cells and that increased RECQ1 expression is associated with poor prognosis in three independent cohorts of patients. Interestingly, RECQ1 knockdown inhibits cells growth and induces apoptosis in MMCs. Moreover, RECQ1 depletion promotes the development of DNA double-strand breaks, as evidenced by the formation of 53BP1 foci and the phosphorylation of ataxia-telangiectasia mutated (ATM) and histone variant H2A.X (H2AX). In contrast, RECQ1 overexpression protects MMCs from melphalan and bortezomib cytotoxicity. RECQ1 interacts with PARP1 in MMCs exposed to treatment and RECQ1 depletion sensitizes MMCs to poly(ADP-ribose) polymerase (PARP) inhibitor. DNMT inhibitor treatment results in RECQ1 downregulation through miR-203 deregulation in MMC. Altogether, these data suggest that association of DNA damaging agents and/or PARP inhibitors with DNMT inhibitors may represent a therapeutic approach in patients with high RECQ1 expression associated with a poor prognosis.

Perception, culture, and science: A framework to identify in-home heating options to improve indoor air quality in the Navajo Nation.

A 2010 study identified higher than average incidence of respiratory disease in Shiprock, NM, the largest city in the Navajo Nation. That study suggested that the potential cause was the combustion of solid fuels in in-home heating stoves and that respiratory disease could be greatly reduced by changing indoor heating behaviors and improving heating stove quality. Since the Navajo people are deeply embedded in culture and traditions that strongly influence their daily lives, a new framework was needed to identify feasible heating alternatives that could reduce the negative environmental and health impacts related to solid fuel use while respecting the culture of the Navajo people. The resulting Navajo framework included perception, cultural, and technical assessments to evaluate seven heating alternatives perceived viable by Navajo stakeholders. Cultural experts at the Diné Policy Institute identified potential cultural limitations and motivating factors for each alternative. A limited technical assessment of the health benefits of these options was conducted and integrated into the process. A parallel convergent mixed-methods approach was employed to integrate qualitative and quantitative results. The results and framework developed and presented here may be useful for decision makers in communities heavily reliant on solid fuels for heat, especially Native Nations, where culture plays an important role in the success of any intervention.

Atrial arrhythmia after newborn eye exam, to caffeine or not to caffeine?

Mydriatic drops are routinely administered to premature neonates to screen for retinopathy of prematurity. Adverse anticholinergic side effects, particularly convulsions and tachycardia have been reported in the pediatric age group following instillation of mydriatics for diagnostic fundus examination [1, 2]. Caffeine is frequently used for apnea of prematurity. In the neonatal intensive care unit, the combined use of caffeine and mydriatic drops is a common practice. Here we report two cases of atrial arrhythmias after neonatal eye exam that improved with conservative management. Both patients were receiving caffeine at the time of events.

Sustained supplementation and monitored response with differing carotenoid formulations in early age-related macular degeneration.

PURPOSE: To compare the impact of sustained supplementation using different macular carotenoid formulations on macular pigment (MP) and visual function in early age-related macular degeneration (AMD). PATIENTS AND METHODS: Sixty-seven subjects with early AMD were randomly assigned to: Group 1 (20 mg per day lutein (L), 0.86 mg per day zeaxanthin (Z); Ultra Lutein), Group 2 (10 mg per day meso-zeaxanthin (MZ), 10 mg per day L, 2 mg per day Z; Macushield; Macuhealth), Group 3 (17 mg per day MZ, 3 mg per day L, 2 mg per day Z). MP was measured using customised heterochromatic flicker photometry and visual function was assessed by measuring contrast sensitivity (CS) and best-corrected visual acuity (BCVA). AMD was graded using the Wisconsin Age-Related Maculopathy Grading System (AREDS 11-step severity scale). RESULTS: At 3 years, a significant increase in MP from baseline was observed in all groups at each eccentricity (P<0.05), except at 1.75° in Group 1 (P=0.160). Between 24 and 36 months, significant increases in MP at each eccentricity were seen in Group 3 (P<0.05 for all), and at 0.50° in Group 2 (P<0.05), whereas no significant increases were seen in Group 1 (P>0.05 for all). At 36 months, compared with baseline, the following significant improvements (P<0.05) in CS were observed: Group 2-1.2, 6, and 9.6 cycles per degree (c.p.d.); Group 1-15.15 c.p.d.; and Group 3-6, 9.6, and 15.15 c.p.d. No significant changes in BCVA, or progression to advanced AMD, were observed. CONCLUSION: In early AMD, MP can be augmented with a variety of supplements, although the inclusion of MZ may confer benefits in terms of panprofile augmentation and in terms of CS enhancement.

Time-dependent retinal ganglion cell loss, microglial activation and blood-retina-barrier tightness in an acute model of ocular hypertension.

Glaucoma is a group of neurodegenerative diseases characterized by the progressive loss of retinal ganglion cells (RGCs) and their axons, and is the second leading cause of blindness worldwide. Elevated intraocular pressure is a well known risk factor for the development of glaucomatous optic neuropathy and pharmacological or surgical lowering of intraocular pressure represents a standard procedure in glaucoma treatment. However, the treatment options are limited and although lowering of intraocular pressure impedes disease progression, glaucoma cannot be cured by the currently available therapy concepts. In an acute short-term ocular hypertension model in rat, we characterize RGC loss, but also microglial cell activation and vascular alterations of the retina at certain time points. The combination of these three parameters might facilitate a better evaluation of the disease progression, and could further serve as a new model to test novel treatment strategies at certain time points. Acute ocular hypertension (OHT) was induced by the injection of magnetic microbeads into the rat anterior chamber angle (n = 22) with magnetic position control, leading to constant elevation of IOP. At certain time points post injection (4d, 7d, 10d, 14d and 21d), RGC loss, microglial activation, and microvascular pericyte (PC) coverage was analyzed using immunohistochemistry with corresponding specific markers (Brn3a, Iba1, NG2). Additionally, the tightness of the retinal vasculature was determined via injections of Texas Red labeled dextran (10 kDa) and subsequently analyzed for vascular leakage. For documentation, confocal laser-scanning microscopy was used, followed by cell counts, capillary length measurements and morphological and statistical analysis. The injection of magnetic microbeads led to a progressive loss of RGCs at the five time points investigated (20.07%, 29.52%, 41.80%, 61.40% and 76.57%). Microglial cells increased in number and displayed an activated morphology, as revealed by Iba1-positive cell number (150.23%, 175%, 429.25%,486.72% and 544.78%) and particle size analysis (205.49%, 203.37%, 412.84%, 333.37% and 299.77%) compared to contralateral control eyes. Pericyte coverage (NG2-positive PC/mm) displayed a significant reduction after 7d of OHT in central, and after 7d and 10d in peripheral retina. Despite these alterations, the tightness of the retinal vasculature remained unaltered at 14 and 21 days after OHT induction. While vascular tightness was unchanged in the course of OHT, a progressive loss of RGCs and activation of microglial cells was detected. Since a significant loss in RGCs was observed already at day 4 of experimental glaucoma, and since activated microglia peaked at day 10, we determined a time frame of 7-14 days after MB injection as potential optimum to study glaucoma mechanisms in this model.

Role of Growth arrest-specific gene 6-Mer axis in multiple myeloma.

Multiple myeloma is a mostly incurable malignancy characterized by the expansion of a malignant plasma cell (PC) clone in the human bone marrow (BM). Myeloma cells closely interact with the BM stroma, which secretes soluble factors that foster myeloma progression and therapy resistance. Growth arrest-specific gene 6 (Gas6) is produced by BM-derived stroma cells and can promote malignancy. However, the role of Gas6 and its receptors Axl, Tyro3 and Mer (TAM receptors) in myeloma is unknown. We therefore investigated their expression in myeloma cell lines and in the BM of myeloma patients and healthy donors. Gas6 showed increased expression in sorted BMPCs of myeloma patients compared with healthy controls. The fraction of Mer(+) BMPCs was increased in myeloma patients in comparison with healthy controls whereas Axl and Tyro3 were not expressed by BMPCs in the majority of patients. Downregulation of Gas6 and Mer inhibited the proliferation of different myeloma cell lines, whereas knocking down Axl or Tyro3 had no effect. Inhibition of the Gas6 receptor Mer or therapeutic targeting of Gas6 by warfarin reduced myeloma burden and improved survival in a systemic model of myeloma. Thus, the Gas6-Mer axis represents a novel candidate for therapeutic intervention in this incurable malignancy.

Nitrogen starvation for lipid accumulation in the microalga species Desmodesmus sp.

Recently, to obtain lipids from microalgae has been the object of extensive research, since it is viewed as a promising feedstock for biodiesel production, especially when compared with crops such as soybean and sunflower, in terms of theoretical performance. The reduction of nutrient availability in culture media, especially nitrogen, stresses the microorganisms and affects cell growth, thus inducing lipid accumulation. This is an interesting step in biodiesel feedstock obtention from microalgae and should be better understood. In this study, four levels of nitrogen concentration in the BG-11 culture medium were evaluated in the growth of the chlorophycean microalga Desmodesmus sp. Both cell growth and lipid content were monitored over 7 days of cultivation, which yielded a final cell density of 33 × 10(6) cells mL(-1) with an initial NaNO3 concentration of 750 mg L(-1) in the medium and a maximum lipid content of 23 % with total nitrogen starvation. It was observed that the microalgae presented high lipid accumulation in the fourth day of cultivation with nitrogen starvation, although with moderate cell growth.

Diagnosing attention-deficit hyperactivity disorder (ADHD) in children involved with child protection services: are current diagnostic guidelines acceptable for vulnerable populations?

Children involved with child protection services (CPS) are diagnosed and treated for attention-deficit hyperactivity disorder (ADHD) at higher rates than the general population. Children with maltreatment histories are much more likely to have other factors contributing to behavioural and attentional regulation difficulties that may overlap with or mimic ADHD-like symptoms, including language and learning problems, post-traumatic stress disorder, attachment difficulties, mood disorders and anxiety disorders. A higher number of children in the child welfare system are diagnosed with ADHD and provided with psychotropic medications under a group care setting compared with family-based, foster care and kinship care settings. However, children's behavioural trajectories change over time while in care. A reassessment in the approach to ADHD-like symptoms in children exposed to confirmed (or suspected) maltreatment (e.g. neglect, abuse) is required. Diagnosis should be conducted within a multidisciplinary team and practice guidelines regarding ADHD diagnostic and management practices for children in CPS care are warranted both in the USA and in Canada. Increased education for caregivers, teachers and child welfare staff on the effects of maltreatment and often perplexing relationship with ADHD-like symptoms and co-morbid disorders is also necessary. Increased partnerships are needed to ensure the mental well-being of children with child protection involvement.