Poly(ethylene oxide)-b-poly(3-sulfopropyl methacrylate) block copolymers for calcium phosphate mineralization and biofilm inhibition.

Poly(ethylene oxide) (PEO) has long been used as an additive in toothpaste, partly because it reduces biofilm formation on teeth. It does not, however, reduce the formation of dental calculus or support the remineralization of dental enamel or dentine. The present article describes the synthesis of new block copolymers on the basis of PEO and poly(3-sulfopropyl methacrylate) blocks using atom transfer radical polymerization. The polymers have very large molecular weights (over 10(6) g/mol) and are highly water-soluble. They delay the precipitation of calcium phosphate from aqueous solution but, upon precipitation, lead to relatively monodisperse hydroxyapatite (HAP) spheres. Moreover, the polymers inhibit the bacterial colonization of human enamel by Streptococcus gordonii, a pioneer bacterium in oral biofilm formation, in vitro. The formation of well-defined HAP spheres suggests that a polymer-induced liquid precursor phase could be involved in the precipitation process. Moreover, the inhibition of bacterial adhesion suggests that the polymers could be utilized in caries prevention.

Survival of bonded lingual retainers with chemical or photo polymerization over a 2-year period: a single-center, randomized controlled clinical trial

INTRODUCTION The objective of this trial was to compare the survival rates of mandibular lingual retainers bonded with either chemically cured or light-cured adhesive after orthodontic treatment. METHODS Patients having undergone orthodontic treatment at a private orthodontic office were randomly allocated to fixed retainers placed with chemically cured composite or light-cured composite. Eligibility criteria included no active caries, restorations, or fractures on the mandibular anterior teeth, and adequate oral hygiene. The main outcome was any type of first-time lingual retainer breakage; pattern of failure (adapted adhesive remnant index scores) was a secondary outcome. Randomization was accomplished with random permuted blocks of 20 patients with allocation concealed in sequentially numbered, opaque, sealed envelopes. Blinding was applicable for outcome assessment only. Patients were reviewed at 1, 3, and 6 months and then every 6 months after placement of the retainer until completion of the study. Data were analyzed using survival analysis including Cox regression; sensitivity analysis was carried out after data imputation for subjects lost to follow-up. RESULTS Two hundred twenty patients (median age, 16 years; interquartile range, 2; range, 12-47 years) were randomized in a 1:1 ratio to either chemical or light curing. Baseline characteristics were similar between groups, the median follow-up period was 2.19 years (range, 0.003-3.64 years), and 16 patients were lost to follow-up. At a minimum follow-up of 2 years, 47 of 110 (42.7%) and 55 of 110 (50.0%) retainers had some type of failure with chemically cured and light-cured adhesive, respectively (log-rank test, P = 0.35). Data were analyzed on an intention-to-treat basis, and the hazard ratio (HR) was 1.15 (95% confidence interval [CI], 0.88-1.70; P = 0.47). There was weak evidence that age is a significant predictor for lingual retainer failures (HR, 0.96; 95% CI, 0.93-1.00; P = 0.08). Adhesive remnant index scoring was possible for only 66 of the 102 (64.7%) failures and did not differ between composites (Fisher exact test, P = 0.16). No serious harm was observed other than gingivitis associated with plaque accumulation. CONCLUSIONS The results of this study indicated no evidence that survival of mandibular lingual retainers differs between chemically and light-cured adhesives. The overall failure rate was 46.4%; however, this included any type of failure, which may have exaggerated the overall failure rate.

Perioperative use of crystalloids in patients undergoing open radical cystectomy: balanced Ringer's maleate versus a glucose 5%/potassium-based balanced solution: study protocol for a randomized controlled trial

BACKGROUND The optimal crystalloid solution to use perioperatively in patients undergoing open radical cystectomy remains unclear. Many of the fluids used for intravenous hydration contain supraphysiologic concentrations of chloride, which can induce hyperchloremia and metabolic acidosis, resulting in renal vasoconstriction and decreased renal function. In addition, patients receiving less fluid and less sodium show faster recovery of gastrointestinal (GI) function after colonic surgery. METHODS AND DESIGN This is an investigator-initiated, single-center, randomized, controlled, parallel group trial with assessor-blinded outcome assessment, in the Department of Urology, University Hospital Bern, Switzerland. The study will involve 44 patients with bladder cancer scheduled for radical cystectomy and urinary diversion. The primary outcome is the duration between the end of surgery and the return of the GI function (first defecation). Secondary outcomes are fluid balance (body weight difference postoperatively versus preoperatively) and the incidence of kidney function disorders according to the Risk-Injury-Failure-Loss-End Stage Renal Disease (RIFLE classification). An equal number of patients are allocated to receive Ringerfundin® solution or a glucose/potassium-based balanced crystalloid solution as baseline infusion during the entire time that intravenous administration of fluid is necessary during the perioperative period. The randomized crystalloid solution is infused at a rate of 1 ml/kg/h until the bladder has been removed, followed by 3 ml/kg/h until the end of surgery. Postoperative hydration is identical in both groups and consists of 1,500 ml of the randomized crystalloid solution per 24 hours. Postoperative patient care is identical in both groups; patients are allowed to drink clear fluids immediately after surgery, and liquid diet is started on postoperative day 1, as well as active mobilization and the use of chewing gum. Body weight is measured daily in the morning. Time of first flatus and first defecation are recorded. DISCUSSION This trial assesses the benefits and harms of two different balanced crystalloid solutions for perioperative fluid management in patients undergoing open radical cystectomy with urinary diversion, with regard to return of GI function and effects on postoperative renal function. TRIAL REGISTRATION Current Controlled Trials ISRCTN32976792 (registered on November 21 2013).

Conformationally Controlled Electron Delocalization in n-Type Rods: Synthesis, Structure, and Optical, Electrochemical, and Spectroelectrochemical Properties of Dicyanocyclophanes

A series of dicyanobiphenyl-cyclophanes 1-6 with various pi-backbone conformations and characteristic n-type semiconductor properties is presented. Their synthesis, optical, structural, electrochemical, spectroelectrochemical, and packing properties are investigated. The X-ray crystal structures of all n-type rods allow the systematic correlation of structural features with physical properties. In addition, the results are supported by quantum mechanical calculations based on density functional theory. A two-step reduction process is observed for all n-type rods, in which the first step is reversible. The potential gap between the reduction processes depends linearly on the cos(2) value of the torsion angle phi between the pi-systems. Similarly, optical absorption spectroscopy shows that the vertical excitation energy of the conjugation band correlates with the cos(2) value of the torsion angle phi. These correlations demonstrate that the fixed intramolecular torsion angle phi is the dominant factor determining the extent of electron delocalization in these model compounds, and that the angle phi measured in the solid-state structure is a good proxy for the molecular conformation in solution. Spectroelectrochemical investigations demonstrate that conformational rigidity is maintained even in the radical anion form. In particular, the absorption bands corresponding to the SOMO-LUMO+i transitions are shifted bathochromically, whereas the absorption bands corresponding to the HOMO-SOMO transition are shifted hypsochromically with increasing torsion angle phi.

A Radical Procedure for the Anti-Markovnikov Hydroazidation of Alkenes

A one-pot procedure for the efficient hydroazidation of alkenes involving hydroboration with catecholborane followed by reaction with benzenesulfonyl azide in the presence of a radical initiator is described. The regioselectivity is controlled by the hydroboration step and corresponds in most cases to an anti-Markovnikov regioselectivity. This procedure is applicable to a wide range of alkenes and gives excellent results with 1,2-disubstituted and trisubstituted alkenes.

Theta burst stimulation reduces disability during the activities of daily living in spatial neglect

Left-sided spatial neglect is a common neurological syndrome following right-hemispheric stroke. The presence of spatial neglect is a powerful predictor of poor rehabilitation outcome. In one influential account of spatial neglect, interhemispheric inhibition is impaired and leads to a pathological hyperactivity in the contralesional hemisphere, resulting in a biased attentional allocation towards the right hemifield. Inhibitory transcranial magnetic stimulation can reduce the hyperactivity of the contralesional, intact hemisphere and thereby improve spatial neglect symptoms. However, it is not known whether this improvement is also relevant to the activities of daily living during spontaneous behaviour. The primary aim of the present study was to investigate whether the repeated application of continuous theta burst stimulation trains could ameliorate spatial neglect on a quantitative measure of the activities of daily living during spontaneous behaviour. We applied the Catherine Bergego Scale, a standardized observation questionnaire that can validly and reliably detect the presence and severity of spatial neglect during the activities of daily living. Eight trains of continuous theta burst stimulation were applied over two consecutive days on the contralesional, left posterior parietal cortex in patients suffering from subacute left spatial neglect, in a randomized, double-blind, sham-controlled design, which also included a control group of neglect patients without stimulation. The results showed a 37% improvement in the spontaneous everyday behaviour of the neglect patients after the repeated application of continuous theta burst stimulation. Remarkably, the improvement persisted for at least 3 weeks after stimulation. The amelioration of spatial neglect symptoms in the activities of daily living was also generally accompanied by significantly better performance in the neuropsychological tests. No significant amelioration in symptoms was observed after sham stimulation or in the control group without stimulation. These results provide Class I evidence that continuous theta burst stimulation is a viable add-on therapy in neglect rehabilitation that facilitates recovery of normal everyday behaviour.

Postoperative radiotherapy after radical prostatectomy: indications and open questions

Biochemical relapse after radical prostatectomy occurs in approximately 15-40% of patients within 5 years. Postoperative radiotherapy is the only curative treatment for these patients. After radical prostatectomy, two different strategies can be offered, adjuvant or salvage radiotherapy. Adjuvant radiotherapy is defined as treatment given directly after surgery in the presence of risk factors (R1 resection, pT3) before biochemical relapse occurs. It consists of 60-64 Gy and was shown to increase biochemical relapse-free survival in three randomized controlled trials and to increase overall survival after a median followup of 12.7 years in one of these trials. Salvage radiotherapy, on the other hand, is given upon biochemical relapse and is the preferred option, by many centers as it does not include patients who might be cured by surgery alone. As described in only retrospective studies the dose for salvage radiotherapy ranges from 64 to 72 Gy and is usually dependent on the absence or presence of macroscopic recurrence. Randomized trials are currently investigating the role of adjuvant and salvage radiotherapy. Patients with biochemical relapse after prostatectomy should at the earliest sign of relapse be referred to salvage radiotherapy and should preferably be treated within a clinical trial.

Role and extent of lymphadenectomy during radical cystectomy for invasive bladder cancer

There is substantial variability in the extent of the node dissection performed during radical cystectomy for bladder cancer. Here, we review the diagnostic assessment of lymph node metastasis and the prognostic and therapeutic benefit for pelvic node dissection for bladder cancer. A review of the applicable urologic literature regarding the topics of lymphadenectomy for bladder cancer was conducted. Nodal metastasis above a limited or standard template is not uncommon, with up to 16% of all nodal metastasis detected proximal to the aortic bifurcation. However, skip metastasis is extremely rare. Proteins associated purely with epithelial tissue such as cytokeratin (CK)-19, CK-20, and uroplakin II have been observed in reportedly negative nodal specimens, which indicates that routine microscopic analysis of nodal tissue may miss small foci of metastatic cancer. In addition to the surgical technique, the total number of lymph nodes removed is influenced by patient anatomy and pathologic processing and therefore may be unsuitable as a procedural quality statement. Consecutively, meticulous removal of tissue within a defined and uniformly applied template may be more relevant than absolute nodal count. Observational cohort series indicate an improved oncologic outcome for patients undergoing extensive nodal dissection. The results of two randomized controlled trials addressing the extent of nodal dissection for bladder cancer are forthcoming.

Health risk appraisal in older people 1: are older people living alone an "at-risk" group?

BACKGROUND: In the UK, population screening for unmet need has failed to improve the health of older people. Attention is turning to interventions targeted at 'at-risk' groups. Living alone in later life is seen as a potential health risk, and older people living alone are thought to be an at-risk group worthy of further intervention. AIM: To explore the clinical significance of living alone and the epidemiology of lone status as an at-risk category, by investigating associations between lone status and health behaviours, health status, and service use, in non-disabled older people. Design of study: Secondary analysis of baseline data from a randomised controlled trial of health risk appraisal in older people. SETTING: Four group practices in suburban London. METHOD: Sixty per cent of 2641 community-dwelling non-disabled people aged 65 years and over registered at a practice agreed to participate in the study; 84% of these returned completed questionnaires. A third of this group, (n = 860, 33.1%) lived alone and two-thirds (n = 1741, 66.9%) lived with someone else. RESULTS: Those living alone were more likely to report fair or poor health, poor vision, difficulties in instrumental and basic activities of daily living, worse memory and mood, lower physical activity, poorer diet, worsening function, risk of social isolation, hazardous alcohol use, having no emergency carer, and multiple falls in the previous 12 months. After adjustment for age, sex, income, and educational attainment, living alone remained associated with multiple falls, functional impairment, poor diet, smoking status, risk of social isolation, and three self-reported chronic conditions: arthritis and/or rheumatism, glaucoma, and cataracts. CONCLUSION: Clinicians working with independently-living older people living alone should anticipate higher levels of disease and disability in these patients, and higher health and social risks, much of which will be due to older age, lower educational status, and female sex. Living alone itself appears to be associated with higher risks of falling, and constellations of pathologies, including visual loss and joint disorders. Targeted population screening using lone status may be useful in identifying older individuals at high risk of falling.

Alveolar echinococcosis: from a deadly disease to a well-controlled infection. Relative survival and economic analysis in Switzerland over the last 35 years

BACKGROUND/AIMS: Alveolar echinococcosis (AE) is a serious liver disease. The aim of this study was to explore the long-term prognosis of AE patients, the burden of this disease in Switzerland and the cost-effectiveness of treatment. METHODS: Relative survival analysis was undertaken using a national database with 329 patient records. 155 representative cases had sufficient details regarding treatment costs and patient outcome to estimate the financial implications and treatment costs of AE. RESULTS: For an average 54-year-old patient diagnosed with AE in 1970 the life expectancy was estimated to be reduced by 18.2 and 21.3 years for men and women, respectively. By 2005 this was reduced to approximately 3.5 and 2.6 years, respectively. Patients undergoing radical surgery had a better outcome, whereas the older patients had a poorer prognosis than the younger patients. Costs amount to approximately Euro108,762 per patient. Assuming the improved life expectancy of AE patients is due to modern treatment the cost per disability-adjusted life years (DALY) saved is approximately Euro6,032. CONCLUSIONS: Current treatments have substantially improved the prognosis of AE patients compared to the 1970s. The cost per DALY saved is low compared to the average national annual income. Hence, AE treatment is highly cost-effective in Switzerland.

Living and dying for inflammation: neutrophils, eosinophils, basophils

Neutrophils, eosinophils, and basophils play essential roles during microbe-induced and sterile inflammation. The severity of such inflammatory processes is controlled, at least in part, by factors that regulate cell death and survival of granulocytes. In recent years, major progress has been made in understanding the molecular mechanisms of granulocyte cell death and in identifying novel damage- and pathogen-associated molecular patterns as well as regulatory cytokines impacting granulocyte viability. Furthermore, an increased interest in innate immunity has boosted our overall understanding of granulocyte biology. In this review, we describe and compare factors and mechanisms regulating neutrophil, eosinophil, and basophil lifespan. Because dysregulation of death pathways in granulocytes can contribute to inflammation-associated immunopathology, targeting granulocyte lifespan could be therapeutically promising.

Incision length for kidney transplantation does not influence short- or long-term outcome: a prospective randomized controlled trial

BACKGROUND: While previous studies suggest advantages of minimally invasive surgery in living donor nephrectomy, similar data are lacking for kidney transplant recipients. Our aim was to prospectively evaluate short- and long-term outcome for kidney transplant recipients, comparing a short transverse (ST) to a classical hockey-stick (HS) incision. METHODS: Sixty-six patients were randomized into two groups: ST vs. HS from January 2008 to May 2010. ST was defined as incision length ≤9 cm and HS as >14 cm. Perioperative data were collected, with evaluation of intra- and postoperative complications and quality of recovery (QoR) score. RESULTS: There were no significant differences in patient demographics, early or long-term postoperative pain. There were no significant differences in QoR scores between the ST and HS group. Predictive for a worse QoR was persisting incisional pain at the 30-month follow-up. Thirty-days mortality, morbidity, and long-term kidney function did not differ between the two groups (p = 1.00, p = 0.62 and p = 0.66, respectively). CONCLUSIONS: Patient satisfaction as well as graft function and patient mortality was not influenced by incision length. With patient and graft safety being paramount, especially in times of organ shortage, incision length should reflect the requirement for a successful transplantation and not be a measure of feasibility.

Development of light-responsive porous polycarbonate membranes for controlled caffeine delivery

For controlled caffeine release, light-responsive membranes were developed. It was possible to produce membranes that reduced their caffeine permeability resistance by about 97% when irradiated with UV-light compared to measurements at daylight. This was achieved by grafting polymers possessing photochromic units onto track-edged polycarbonate membranes. Covalently linked coatings on porous polycarbonate membranes were obtained by plasma activation of the membrane surface followed by plasma-induced graft polymerization. Copolymerization of spiro-compounds during the coating process as well as postmodification of preformed coatings with spiropyran resulted in photochromic membranes. For the copolymerization process, the synthesis of five photochromic methacrylic and acrylic spiropyrans and spirooxazines was successfully performed. Additionally, a spiropyran with carboxylic acid functionality was synthesized for the postmodification process. This enabled us to postmodify polymeric materials containing alcohol or amine groups to obtain photochromic materials. UV-irradiation of these light-responsive membranes resulted in a strong colouration of the membrane, in a reduction of surface tension, which resulted in a decreased caffeine permeability resistance. The membranes were characterized using XPS for the elemental composition of the coating, contact angle measurements for the surface tension, solid-state UV/VIS measurements for the determination of the kinetic and stability properties, and two-photon microscopy for the localisation of the photochromic substance in the porous membrane.

Home-based training to improve manual dexterity in patients with multiple sclerosis: A randomized controlled trial.

BACKGROUND Impaired manual dexterity is frequent and disabling in patients with multiple sclerosis (MS), affecting activities of daily living (ADL) and quality of life. OBJECTIVE We aimed to evaluate the effectiveness of a standardized, home-based training program to improve manual dexterity and dexterity-related ADL in MS patients. METHODS This was a randomized, rater-blinded controlled trial. Thirty-nine MS patients acknowledging impaired manual dexterity and having a pathological Coin Rotation Task (CRT), Nine Hole Peg Test (9HPT) or both were randomized 1:1 into two standardized training programs, the dexterity training program and the theraband training program. Patients trained five days per week in both programs over a period of 4 weeks. Primary outcome measures performed at baseline and after 4 weeks were the CRT, 9HPT and a dexterous-related ADL questionnaire. Secondary outcome measures were the Chedoke Arm and Hand Activity Inventory (CAHAI-8) and the JAMAR test. RESULTS The dexterity training program resulted in significant improvements in almost all outcome measures at study end compared with baseline. The theraband training program resulted in mostly non-significant improvements. CONCLUSION The home-based dexterity training program significantly improved manual dexterity and dexterity-related ADL in moderately disabled MS patients. Trial Registration NCT01507636.