Toward Truly Water‐Soluble Rodlike Polyelectrolytes: Synthesis of Poly(para‐phenylenes) Wrapped in Ethylene Oxideand Amino Side Groups

Suzuki and Yamamoto cross‐coupling protocols are applied to synthesize water‐soluble poly(p‐phenylene) (PPP) derivatives decorated with oligoethylene oxide (OEO) and tertiary amino side groups. It is shown that constitutionally well‐defined PPPs can be obtained having degrees of polycondensation, P _n, of 30–60. In some cases, however the heteroatoms in the side chains affect the monomer synthesis and prevent proper chain growth through coordination of metal species present in the reaction medium. It is shown that essentially uncharged but still water‐soluble PPPs result if (i) the side groups bear their heteroatoms in the right position, and (ii) if the water‐soluble segments of the lateral substituents prevent intermolecular hydrophobic interactions of the apolar main chains reliably. In other words, the lateral substituents have to wrap the PPP core structure tightly in a closed outer shell of water‐soluble OEO moieties. These PPPs constitute a valuable new pool of model systems for future polyelectrolyte research, being highly complementary to what has been available so far.

     

Dispersities of Polyesters of Various Diphenols Prepared by Irreversible Polycondensations

Polyesters of bisphenol‐A, bisphenol‐P, catechol, and sebacic acid are prepared and different synthetic methods are compared. The diphenols are condensed with sebacoyl chloride either in dichloromethane/pyridine or in refluxing chlorobenzene without HCl‐acceptor. Furthermore, bisphenol‐A acetate is polycondensed with sebacic acid in bulk. All experiments are worked up so that fractionation is avoided. The extent of cyclization is estimated by matrix‐assisted laser desorption/ionization mass spectrometry (MALDI MS) and the molar mass distribution by size exclusion chromatography (SEC). Polycondensations in solution yield larger fractions of cyclics and higher dispersities (up to 11). Polycondensations in bulk give lower fractions of cycles and dispersities from 4.6 to 6.3 for high molar mass polyesters or 2.8 to 3.5 for low molar mass products. Characteristic curves describing the dependence of the dispersity on the initial monomer concentration are elaborated.

     

Ophthalmic epidemiology in Europe: the “European Eye Epidemiology” (E3) consortium

The European Eye Epidemiology (E3) consortium is a recently formed consortium of 29 groups from 12 European countries. It already comprises 21 population-based studies and 20 other studies (case–control, cases only, randomized trials), providing ophthalmological data on approximately 170,000 European participants. The aim of the consortium is to promote and sustain collaboration and sharing of data and knowledge in the field of ophthalmic epidemiology in Europe, with particular focus on the harmonization of methods for future research, estimation and projection of frequency and impact of visual outcomes in European populations (including temporal trends and European subregions), identification of risk factors and pathways for eye diseases (lifestyle, vascular and metabolic factors, genetics, epigenetics and biomarkers) and development and validation of prediction models for eye diseases. Coordinating these existing data will allow a detailed study of the risk factors and consequences of eye diseases and visual impairment, including study of international geographical variation which is not possible in individual studies. It is expected that collaborative work on these existing data will provide additional knowledge, despite the fact that the risk factors and the methods for collecting them differ somewhat among the participating studies. Most studies also include biobanks of various biological samples, which will enable identification of biomarkers to detect and predict occurrence and progression of eye diseases. This article outlines the rationale of the consortium, its design and presents a summary of the methodology.     

Effectiveness of metacognitive interventions for mental disorders in adults—A systematic review and meta‐analysis (METACOG)

We evaluated the effectiveness and acceptability of metacognitive interventions for mental disorders. We searched electronic databases and included randomized and nonrandomized controlled trials comparing metacognitive interventions with other treatments in adults with mental disorders. Primary effectiveness and acceptability outcomes were symptom severity and dropout, respectively. We performed random‐effects meta‐analyses. We identified Metacognitive Training (MCTrain), Metacognitive Therapy (MCTherap), and Metacognition Reflection and Insight Therapy (MERIT). We included 49 trials with 2,609 patients. In patients with schizophrenia, MCTrain was more effective than a psychological treatment (cognitive remediation, SMD = ?0.39). It bordered significance when compared with standard or other psychological treatments. In a post hoc analysis, across all studies, the pooled effect was significant (SMD = ?0.31). MCTrain was more effective than standard treatment in patients with obsessive–compulsive disorder (SMD = ?0.40). MCTherap was more effective than a waitlist in patients with depression (SMD = ?2.80), posttraumatic stress disorder (SMD = ?2.36), and psychological treatments (cognitive–behavioural) in patients with anxiety (SMD = ?0.46). In patients with depression, MCTherap was not superior to psychological treatment (cognitive–behavioural). For MERIT, the database was too small to allow solid conclusions. Acceptability of metacognitive interventions among patients was high on average. Methodological quality was mostly unclear or moderate. Metacognitive interventions are likely to be effective in alleviating symptom severity in mental disorders. Although their add‐on value against existing psychological interventions awaits to be established, potential advantages are their low threshold and economy.     

Obesity and dysregulated central and peripheral macrophage–neuron cross‐talk

The involvement of macrophages in the pathogenesis of obesity has been recognized since 2003. Early studies mostly focused on the role of macrophages in adipose tissue (AT) and in obesity‐associated chronic low‐grade inflammation. Lately, AT macrophages were shown to undergo intrinsic metabolic changes that affect their immune function (i.e., immunometabolism), corresponding to their unique properties along the range of pro‐ versus anti‐inflammatory activity. In parallel, recent studies in mice revealed critical neuronal–macrophage interactions, both in the CNS and in peripheral tissues, including in white and brown AT. These intercellular activities impinge on energy and metabolic homeostasis, partially by also engaging adipocytes in a neuronal–macrophage–adipocyte ménage à trois. Finally, neuropeptides (NP), such as NPY and appetite‐reducing NPFF, may prove as mediators in such intercellular network. In this concise review, we highlight some of these recent insights on adipose macrophage immunometabolism, as well as central and peripheral neuronal–macrophage interactions with emphasis on their impact on adipocyte biology and whole‐body metabolism. We also discuss the expanding view on the role of the NP, NPY and NPFF, in obesity.     

Electrospun Bacteria‐Gold Nanoparticle/Polymer Composite Mesofiber Nonwovens for Catalytic Application

Polymer composite nonwovens with living Micrococcus luteus (ML), a very common gram‐positive bacterium present on human skin, are prepared by electrospinning followed by coating via the chemical vapor deposition (CVD) of poly(p‐xylylene) (PPX). The encapsulated living ML convert Au(III) ions to gold nanoparticles (AuNPs) when the composite nonwovens are dipped in an aqueous chloroauric acid solution. As a result of this process, AuNPs are formed on the ML. The ML‐immobilized AuNPs can be used for catalytic reactions with acetone as the solvent at a very low gold concentration. Despite the presence of acetone, ML survive the catalytic reaction. Interestingly, the catalytic reactions are possible only when the ML in the nonwovens are alive. In contrast, nonwovens with dead ML do not show any significant catalytic activity.     

Chemonucleolysis. Development, experience, perspectives

Concerning the so-called minimal invasive procedures currently available for the treatment of lumbar disc prolapse (percutaneous endoscopic discectomy, APLD, laser decompression, chemonucleolysis), the intradiscal application of Chymopapain represents the method with the longest period of clinical use and experience. Long-term studies have shown good clinical results. When considering of the indication and the few contraindications--particularly allergic diathesis--chemonucleolysis provides a low-risk, efficient, minimally invasive therapy that closes the therapeutic window between conservative and open surgical treatment.     

Cumulative risk of developing polyps or malignancy at the ileal pouch-anal anastomosis in patients with familial adenomatous polyposis

Restorative proctocolectomy with an ileal pouch-anal anastomosis is performed in an increasing number of patients with familial adenomatous polyposis (FAP). Two techniques are currently used to construct an ileal pouch-anal anastomosis: (1) a double-stapled anastomosis between the pouch and the anal canal and (2) mucosectomy with a hand-sewn iteoanal anastomosis at the dentate line. Although this procedure is thought to abolish the risk of colorectal adenoma, an increasing number of case reports have been published concerning the development of adenoma at the anastomotic site. The purpose of this study was to evaluate the overall cumulative risk of developing adenomatous polyps after ileal pouch-anal anastomosis and to compare the cumulative risk after either anastomotic technique. A total of 126 consecutive FAP patients undergoing a restorative proctocolectomy were identified from polyposis registries in The Netherlands, Denmark, Italy, Germany, and New York. Life-table analysis was used to calculate the cumulative risk of developing polyps in 97 patients with at least 1 year of endoscopic follow-up (median 66 months, range 12 to 188 months). A double-stapled anastomosis was used in 35 patients, whereas in 62 patients a handsewn anastomosis with a mucosectomy was performed. In 13 patients polyps developed at the anastomotic site, four with severe and four with moderate dysplasia. None of the patients developed a carcinoma at the anastomotic site. The cumulative risk of developing a polyp at the anastomotic site was 8% (95% confidence interval 2% to 14%) at 3.5 years and 18% (95% confidence interval 8% to 28%) at 7 years, respectively. The risk of developing a polyp at the anastomotic site within 7 years was 31 % for patients with a double-stapled vs. 10% for patients with a hand-sewn anastomosis with mucosectomy (P = 0.03 [log-rank test]). Because FAP patients undergoing a restorative proctocolectomy with either a double-stapled or hand-sewn anastomosis have a substantial risk of developing adenomatous polyps at the anastomotic site, lifelong endoscopic surveillance is mandatory in both groups. Presented at the Thirty-Ninth Annual Meeting of The Society for Surgery of the Alimentary Tract, New Orleans, La., May 17–20, 1998.     

Three-dimensional acquisition and visualization of dental arch features from optically digitized models

A method for the acquisition and evaluation of 3D coordinates from anatomically oriented plaster casts is presented, which is based on optical phase shifting profilometry (a fringe projection technique). With the computer-controlled setup, measurements from different views can be combined to obtain a complete three dimensional reconstruction of the model surface. To allow faster evaluation, the result is converted into a range image. From this digital data set the characteristic features like cusp tips can be identified and located semi-automatically. Based on these marks, quantitative values for differences between situation models like local displacements, e.g. during orthodontic treatment, can be determined. The results are visualized as interactively controllable 3D computer graphics, which helps to make spatial relations clearer.     

Immunohistochemical detection of somatostatin sst2a receptors in the lymphatic, smooth muscular, and peripheral nervous systems of the human gastrointestinal tract: facts and artifacts.

The cellular distribution of the somatostatin sst2A receptor protein was investigated in the lymphatic, smooth muscular, and nervous components of the human gastrointestinal tract using subtype-specific antibody R2-88 for immunohistochemical staining of cryostat and formalin-fixed, paraffin-embedded tissue sections. Germinal centers of intestinal lymphatic follicles were immunostained, exhibiting a predominantly plasma membrane localization of the receptor. Similarly, nerve fibers and cells in the submucosal and myenteric plexus were stained for sst2A. Antibody preabsorption with 100 nmol/L antigen peptide abolished staining in all of these tissues, and immunohistochemical staining correlated with the labeling observed after receptor autoradiography using the sst2-preferring radioligand 125I-[Tyr3]octreotide. Cytoplasmic immunostaining was detected in gastrointestinal smooth muscle cells and was inhibited by antibody pre-absorption with antigen peptide. However, 125I-[Tyr3]octreotide autoradiography was negative, and Western blots showed no band at the usual 70-90 kDa location for sst2A. Instead, a band was observed at 205 kDa. This band comigrated with the rabbit myosin standard, which was also stained with R2-88, although antibody sensitivity for myosin was less than 0.002% of that for the sst2A receptor. Rigorous computer-based sequence analysis demonstrated the peptide sequence chosen for antibody production was unique. Moreover, standard sequence alignment protocols were unable to identify the sequences in myosin responsible for the observed reactivity with the R2-88 antiserum. The observed cross-reactivity emphasizes the need for extensive controls to prove the specificity of immunostaining for such low abundance proteins as receptors even when the peptide sequence chosen for antibody production is unique. This study demonstrates for the first time the presence of specific sst2A receptor protein by immunohistochemistry in the human gastrointestinal lymphatic and nervous components, but not in gastrointestinal circular and longitudinal smooth muscle.