Identification and manipulation of tumor associated macrophages in human cancers

Evading immune destruction and tumor promoting inflammation are important hallmarks in the development of cancer. Macrophages are present in most human tumors and are often associated with bad prognosis. Tumor associated macrophages come in many functional flavors ranging from what is known as classically activated macrophages (M1) associated with acute inflammation and T-cell immunity to immune suppressive macrophages (M2) associated with the promotion of tumor growth. The role of these functionally different myeloid cells is extensively studied in mice tumor models but dissimilarities in markers and receptors make the direct translation to human cancer difficult. This review focuses on recent reports discriminating the type of infiltrating macrophages in human tumors and the environmental cues present that steer their differentiation. Finally, immunotherapeutic approaches to interfere in this process are discussed

Small RNA-based antimicrobial immunity

Protection against microbial infection in eukaryotes is provided by diverse cellular and molecular mechanisms. Here, we present a comparative view of the antiviral activity of virus-derived small interfering RNAs in fungi, plants, invertebrates and mammals, detailing the mechanisms for their production, amplification and activity. We also highlight the recent discovery of viral PIWI-interacting RNAs in animals and a new role for mobile host and pathogen small RNAs in plant defence against eukaryotic pathogens. In turn, viruses that infect plants, insects and mammals, as well as eukaryotic pathogens of plants, have evolved specific virulence proteins that suppress RNA interference (RNAi). Together, these advances suggest that an antimicrobial function of the RNAi pathway is conserved across eukaryotic kingdoms

Small RNA Profiling in Dengue Virus 2-Infected Aedes Mosquito Cells Reveals Viral piRNAs and Novel Host miRNAs

Contains fulltext : 171518.PDF (publisher's version ) (Open Access)In Aedes mosquitoes, infections with arthropod-borne viruses (arboviruses) trigger or modulate the expression of various classes of viral and host-derived small RNAs, including small interfering RNAs (siRNAs), PIWI interacting RNAs (piRNAs), and microRNAs (miRNAs). Viral siRNAs are at the core of the antiviral RNA interference machinery, one of the key pathways that limit virus replication in invertebrates. Besides siRNAs, Aedes mosquitoes and cells derived from these insects produce arbovirus-derived piRNAs, the best studied examples being viruses from the Togaviridae or Bunyaviridae families. Host miRNAs modulate the expression of a large number of genes and their levels may change in response to viral infections. In addition, some viruses, mostly with a DNA genome, express their own miRNAs to regulate host and viral gene expression. Here, we perform a comprehensive analysis of both viral and host-derived small RNAs in Aedes aegypti Aag2 cells infected with dengue virus 2 (DENV), a member of the Flaviviridae family. Aag2 cells are competent in producing all three types of small RNAs and provide a powerful tool to explore the crosstalk between arboviral infection and the distinct RNA silencing pathways. Interestingly, besides the well-characterized DENV-derived siRNAs, a specific population of viral piRNAs was identified in infected Aag2 cells. Knockdown of Piwi5, Ago3 and, to a lesser extent, Piwi6 results in reduction of vpiRNA levels, providing the first genetic evidence that Aedes PIWI proteins produce DENV-derived small RNAs. In contrast, we do not find convincing evidence for the production of virus-derived miRNAs. Neither do we find that host miRNA expression is strongly changed upon DENV2 infection. Finally, our deep-sequencing analyses detect 30 novel Aedes miRNAs, complementing the repertoire of regulatory small RNAs in this important vector species

Fiber-reinforced dental composites in beam testing

OBJECTIVES: The purpose of this study was to systematically review current literature on in vitro tests of fiber-reinforced composite (FRC) beams, with regard to studies that followed criteria described in an International Standard. The reported reinforcing effects of various fibers on the flexural strength and elastic modulus of composite resin beams were analyzed. SOURCES: Original, peer reviewed papers, selected using Medline from 1950 to 2007, on in vitro testing of FRC beams in comparison to non-reinforced composite beams. Also information from conference abstracts (IADR) was included. DATA: With the keywords (fiber or fibre) and (resin or composite) and (fixed partial denture or FPD), the literature search revealed 1427 titles. Using this strategy a broad view of the clinical and non-clinical literature on fiber-reinforced FPDs was obtained. Restricting to three-point bending tests, 7 articles and 1 abstract (out of 126) were included. Finally, the data of 363 composite beams were analyzed. The differences in mean flexural strength and/or modulus between reinforced and unreinforced beams were set out in a forest plot. Meta-regression analyses were performed (single and multiple regression models). CONCLUSIONS: Under specific conditions we have been able to show that fibers do reinforce resin composite beams. The flexural modulus not always seems to increase with polyethylene-reinforcement, even when fibers are located at the tensile side. Besides, fiber architecture (woven vs. unidirectional) seems to be more important than the type of fiber for flexural strength and flexural modulus

Effect of infant orthopedics on facial appearance of toddlers with complete unilateral cleft lip and palate (Dutchcleft)

Objective: To evaluate the effect of infant orthopedics (IO) on facial appearance of 54 patients with unilateral cleft lip and palate (UCLP), aged 4 and 6 years. Design: Prospective two-arm randomized controlled clinical trial in three Cleft Palate Centers in the Netherlands (Dutchcleft-trial). Interventions: Patients were divided randomly into two groups. Half of the patients (IO+) had a plate until surgical closure of the soft palate at the age of +/- 52 weeks; the other half (IO-) received no intervention. Main outcome measures: Facial appearance at 4 and 6 years of age assessed on full face photographs and photographs showing only nose and mouth. Ratings were performed on a VAS-scale by professionals and laymen. Results: At 4 years of age the full face pictures of IO+ children were scored to be more attractive than those of IO- children. However, this difference had disappeared at 6 years of age. At the age of 6, only professionals saw a significant difference on nasolabial photographs between IO+ and IO-. Regression analysis showed a minor effect of occlusion, lip revision, or type of nose reconstruction on the esthetic results. Conclusions: IO had a positive effect on full facial appearance of UCLP children at the age of 4 years, but at the age of 6, only professionals saw a positive effect of IO on the nasolabial photographs. This is irrelevant for UCLP patients since they deal with laymen in their daily life

Early salivary changes in multiple myeloma patients undergoing autologous HSCT

Objective 2 One explorative observational study in 2 parts was performed to examine early salivary changes in 3 relation to oral mucositis (OM) in multiple myeloma patients treated with high-dose melphalan and 4 autologous hematopoietic stem cell transplantation (HSCT). As cryotherapy was introduced after part 5 A as regular care, its effect on OM could be evaluated. 6Methods 7 Unstimulated (UWS) and stimulated (SWS) whole mouth saliva was collected and OM was scored 8 with the OMNI instrument at days -3, 0, 4, 7, 11 and 15 after HSCT. Salivary flow rate, total protein 9 (BCA assay), mucin 5B, albumin (western blot), total IgA, lactoferrin and myeloperoxidase levels 10 (ELISA) were determined. 11Results 12 Trends of decreasing UWS and SWS flow rates and total IgA levels were observed. At days 7 and 11, 13 increases in lactoferrin and albumin levels were found in UWS and SWS. A positive correlation was 14 found between OMNI scores and albumin and lactoferrin levels in SWS (R2= 0.56, p= 0.029 and R2= 15 0.49, p= 0.043, respectively). In part B, cryotherapy significantly lowered peak OMNI scores. 16Conclusion 17 Compositional changes in saliva reflecting inflammation were found in the first days after HSCT and 18 the use of cryotherapy in the second part was associated with decreased OM severity

Caries trends 1996-2002 among 6- and 12-year-old children and erosive wear prevalence among 12-year-old children in The Hague.

Item does not contain fulltextIn 2002 a dental survey amongst 6- and 12-year-old schoolchildren (n = 832) in The Hague was carried out. The caries findings were compared with findings from earlier studies in The Hague. Caries prevalence (% of caries-free children) and caries experience (mean dmfs scores) among 6-year-old children had not changed significantly in the period 1996-2002. However, a significant increase of caries-free 12-year-old children of low socio-economic status was found in the period 1996-2002. The proportions of caries-free 12-year-old Dutch, Turkish and Moroccan children of low socio-economic status were 88, 69 and 78%, respectively, in 2002. The average DMFT score of 12-year-olds reached a minimum of 0.2. In 2002, 24% of the 12-year-olds exhibited signs of erosion, indicating that the presence of erosive wear was high among youngsters in The Hague

Development of the ProPal-COPD tool to identify patients with COPD for proactive palliative care

RG Duenk,1 C Verhagen,1 EM Bronkhorst,2 RS Djamin,3 GJ Bosman,4 E Lammers,5 PNR Dekhuijzen,6 KCP Vissers,1 Y Engels,1,* Y Heijdra6,* 1Department of Anesthesiology, Pain and Palliative Medicine, 2Department of Health Evidence, Radboud University Medical Center, Nijmegen, 3Department of Respiratory Medicine, Amphia Hospital, Breda, 4Department of Respiratory Medicine, Slingeland Hospital, Doetinchem, 5Department of Respiratory Medicine, Gelre Hospitals, Zutphen, 6Department of Pulmonary Diseases, Radboud University Medical Center, Nijmegen, the Netherlands *These authors contributed equally to this work Background: Our objective was to develop a tool to identify patients with COPD for proactive palliative care. Since palliative care needs increase during the disease course of COPD, the prediction of mortality within 1 year, measured during hospitalizations for acute exacerbation COPD (AECOPD), was used as a proxy for the need of proactive palliative care.Patients and methods: Patients were recruited from three general hospitals in the Netherlands in 2014. Data of 11 potential predictors, a priori selected based on literature, were collected during hospitalization for AECOPD. After 1 year, the medical files were explored for the date of death. An optimal prediction model was assessed by Lasso logistic regression, with 20-fold cross-validation for optimal shrinkage. Missing data were handled using complete case analysis.Results: Of 174 patients, 155 patients were included; of those 30 (19.4%) died within 1 year. The optimal prediction model was internally validated and had good discriminating power (AUC =0.82, 95% CI 0.81–0.82). This model relied on the following seven predictors: the surprise question, Medical Research Council dyspnea questionnaire (MRC dyspnea), Clinical COPD Questionnaire (CCQ), FEV1% of predicted value, body mass index, previous hospitalizations for AECOPD and specific comorbidities. To ensure minimal miss out of patients in need of proactive palliative care, we proposed a cutoff in the model that prioritized sensitivity over specificity (0.90 over 0.73, respectively). Our model (ProPal-COPD tool) was a stronger predictor of mortality within 1 year than the CODEX (comorbidity, age, obstruction, dyspnea, and previous severe exacerbations) index.Conclusion: The ProPal-COPD tool is a promising multivariable prediction tool to identify patients with COPD for proactive palliative care. Keywords: COPD, exacerbation, proactive palliative care, prognosis, mortalit