The aim of the present study was to assess the possibility to measure caries-induced laser fluorescence underneath a novel nano-filled fissure sealant. Sixty freshly extracted human teeth with occlusal dentine carious lesions were horizontally divided, exposing the respective lesion. Teeth were randomly assigned to three groups:(I) white fissure sealant with filler particles (Fissurit F, Voco),(II) clear fissure sealant without filler particles (Fissurit, Voco) and (III) novel experimental fissure sealant with nano-filler particles (Voco). Starting with a sealant thickness of 3 mm, laser fluorescence measurements (DIAGNOdent, KaVo) were performed after finishing the sealant surfaces with polishing papers, reducing the material at intervals of 0.5 mm until the sealant was removed completely. Evaluating a thickness of 0.5 mm, both the clear (83 % of the baseline fluorescence after fine grit polishing) and the white sealant (25 %) did not allow to measure baseline fluorescence (p < 0.05) with no fluorescence reduction in the experimental sealant group (p > 0.05). With increasing sealer thickness, fluorescence was influenced even by the experimental material (89 % of the baseline value at 1 mm). However, by using the experimental material, statistically significant higher fluorescence values than those for the other materials under study (p < 0.05) were obtained. Thicker sealant layers and coarse grit polishing caused a decrease of laser fluorescence in all groups (p < 0.05). Employing the experimental nano-filled sealant, laser fluorescence measurements for caries detection can be performed through thicker sealant layers compared to conventional sealant materials. Thus, it might be possible to use this material to assess a caries progression underneath the sealant and administer an appropriate therapy in due time.

Cryptococcus neoformans is an encapsulated yeast that primarily causes a life-threatening meningoencephalitis in immunosuppressed individuals especially those with HIV/AIDS. Its main virulence factor is its polysaccharide capsule which interferes with complement-mediated phagocytosis. C. neoformans infections ensue following inhalation of small desiccated less encapsulated propagules leading to pulmonary pneumonia or colonization of the host's respiratory tract. Numerous murine experimental studies have shown major discrepancies in cryptococcal cell and capsule enlargement between the lung and brain. In this report, we describe a nonmurine experimental model of the striking variability between cryptococcal cell and capsule size diameters in histology sections of postmortem lung and brain in a fatal cryptococcal infection in a heart transplant recipient.

PURPOSE In disseminated prostate cancer, expression of human epidermal growth factor receptor type 2 (HER2) is one of the pathways to androgen independence. Radionuclide molecular imaging of HER2 expression in disseminated prostate cancer might identify patients for HER2-targeted therapy. Affibody molecules are small (7 kDa) targeting proteins with high potential as tracers for radionuclide imaging. The goal of this study was to develop an optimal Affibody-based tracer for visualization of HER2 expression in prostate cancer. METHODS A synthetic variant of the anti-HER2 Z(HER2:342) Affibody molecule, Z(HER2:S1), was N-terminally conjugated with the chelators DOTA, NOTA and NODAGA. The conjugated proteins were biophysically characterized by electrospray ionization mass spectroscopy (ESI-MS), circular dichroism (CD) spectroscopy and surface plasmon resonance (SPR)-based biosensor analysis. After labelling with (111)In, the biodistribution was assessed in normal mice and the two most promising conjugates were further evaluated for tumour targeting in mice bearing DU-145 prostate cancer xenografts. RESULTS The HER2-binding equilibrium dissociation constants were 130, 140 and 90 pM for DOTA-Z(HER2:S1), NOTA-Z(HER2:S1) and NODAGA-Z(HER2:S1), respectively. A comparative study of (111)In-labelled DOTA-Z(HER2:S1), NOTA-Z(HER2:S1) and NODAGA-Z(HER2:S1) in normal mice demonstrated a substantial influence of the chelators on the biodistribution properties of the conjugates.(111)In-NODAGA-Z(HER2:S1) had the most rapid clearance from blood and healthy tissues.(111)In-NOTA-Z(HER2:S1) showed high hepatic uptake and was excluded from further evaluation.(111)In-DOTA-Z(HER2:S1) and (111)In-NODAGA-Z(HER2:S1) demonstrated specific uptake in DU-145 prostate cancer xenografts in nude mice. The tumour uptake of (111)In-NODAGA-Z(HER2:S1), 5.6 ± 0.4%ID/g, was significantly lower than the uptake of (111)In-DOTA-Z(HER2:S1), 7.4 ± 0.5%ID/g, presumably because of lower bioavailability due to more rapid clearance.(111)In-NODAGA-Z(HER2:S1) provided higher tumour-to-blood ratio, but somewhat lower tumour-to-liver, tumour-to-spleen and tumour-to-bone ratios. CONCLUSION Since distant prostate cancer metastases are situated in bone or bone marrow, the higher tumour-to-bone ratio is the most important. This renders (111)In-DOTA-Z(HER2:S1) a preferable agent for imaging of HER2 expression in disseminated prostate cancer.

OBJECTIVE Membrane endothelial protein C receptor (mEPCR) is highly expressed in peritubular capillaries of kidneys from patients with active and poorly responsive lupus nephritis (LN). We investigated the hypothesis that changes in the microvasculature are widespread with extension to the dermal vasculature. METHODS Skin biopsies from uninvolved skin (buttocks) were performed in 27 patients with LN and 5 healthy controls. Sections were stained with specific antibodies reactive with mEPCR, adiponectin, intercellular adhesion molecule-1 (ICAM-1), and CD31; then assessed by enumeration of stained blood vessels (percentage positive blood vessels) blinded to knowledge of clinical information. RESULTS There was a significant increase in the prevalence of blood vessels that stained for mEPCR and ICAM-1 in patients compared to controls [94% vs 59%(p = 0.045) and 81% vs 67%(p = 0.037), respectively]. Adiponectin staining and CD31 staining were similar between the groups (45% vs 43% and 98% vs 92%). Dermal staining for mEPCR was greater in patients with proliferative glomerulonephritis than in those with membranous disease (96% vs 60%; p = 0.029). A composite of poor prognostic renal markers and death was significantly associated with greater expression of mEPCR staining. CONCLUSION These data are consistent with the notion that in patients with LN, activation of the microvasculature extends beyond the clinically targeted organ. The insidious expression of this widespread vasculopathy may be a contributor to longterm comorbidities.

OBJECTIVE To assess clinical and microbiological outcomes of an Er:YAG laser in comparison with sonic debridement in the treatment of persistent periodontal pockets in a prospective randomized controlled multicentre study design. MATERIAL AND METHODS A total of 78 patients in supportive periodontal therapy with two residual pockets were included, 58 were available for the whole follow-up period. Root surfaces were instrumented either with a sonic scaler (Sonicflex(®) 2003 L) or with an Er:YAG laser (KEY Laser(®) 3). Clinical attachment levels (CAL), Probing depths (PD), Plaque control record (PCR) and Bleeding on probing (BOP) were assessed at baseline, 13 and 26 weeks after treatment. In addition, microbiological analysis was performed employing a DNA diagnostic test kit (micro-IDent(®) Plus). RESULTS Probing depths and CAL were significantly reduced in both groups over time (p < 0.05), without significant differences between the groups (p > 0.05). BOP frequency values decreased significantly within both groups (p < 0.05), with no difference between the laser and the sonic treatment (p > 0.05). PCR frequency values did not change during the observation period (p > 0.05). Microbiological analysis failed to expose any significant difference based on treatment group or period. CONCLUSION Employing both sonic and laser treatment procedures during supportive periodontal care, similar clinical and microbiological outcomes can be expected.

Pandemic and seasonal infectious diseases such as influenza may have serious negative health and economic consequences. Certain non-pharmaceutical intervention strategies - including school closures - can be implemented rapidly as a first line of defense against spread. Such interventions attempt to reduce the effective number of contacts between individuals within a community; yet the efficacy of closing schools to reduce disease transmission is unclear, and closures certainly result in significant economic impacts for caregivers who must stay at home to care for their children. Using individual-based computer simulation models to trace contacts among schoolchildren within a stereotypical school setting, we show how alternative school-based disease interventions have great potential to be as effective as traditional school closures without the corresponding loss of workforce and economic impacts.

Tooth colour matching of composite materials is often a common problem caused by a dark background from the oral cavity. Therefore, the aim of the study was to evaluate a novel aesthetic composite material and to assess the influence of white and black backgrounds. Tooth shades of 30 freshly extracted upper front teeth were determined using a spectrophotometer (SpectroShade™) both against a white and a black background. Two class IV cavities in each tooth were prepared and restored using three different composite resins: Arabesk™ (AB), Synergy™ (SE) and the novel material Amaris™ (AM). After water storage for 1 week, differences in hue, saturation and lightness were measured to assess changes from baseline. After thermocycling, teeth were evaluated once more to assess the reliability of the treatment outcomes. Compared to baseline, differences in hue were not statistically different for all restoration materials (p > 0.05) with respect to the white or black background. Delta values for saturation were not different in the AB and AM groups (p > 0.05) with higher values for SE (p < 0.05). Regarding lightness, values in the AB group were statistically higher (p < 0.05) than values for AM with no difference between AB and SE and with no difference between the AM and SE groups (p > 0.05). Employing the novel aesthetic composite resin, a minor impact of white and black backgrounds could be observed compared to conventional composites. Therefore, it might effectively mask the dark background from the oral cavity.

Background: Platelet adhesion, activation and aggregation at sites of vascular injury are essential processes for primary hemostasis. Elevation of the intracellular Ca(2+) concentration is a central event in platelet activation but the underlying mechanisms are not fully understood. Store-operated calcium entry (SOCE) through Orai1 was shown to be the main Ca(2+) influx pathway in murine platelets, but there are additional non-store-operated Ca(2+) (non-SOC) and receptor operated Ca(2+) (ROC) channels expressed in the platelet plasma membrane. Objective: Canonical transient receptor potential (TRPC) channel 6 is found both in human and murine platelets and has been proposed to mediate diacylglycerol (DAG) activated ROCE but also a role in the regulation of SOCE has been suggested. Methods: To investigate the function of TRPC6 in platelet Ca(2+) signaling and activation, we analyzed platelets from mice deficient in TRPC6 using wide range of in vitro and in vivo assays. Results: In the mutant platelets, DAG activated Ca(2+) influx was found to be abolished. However, this did not significantly affect SOCE or agonist induced Ca(2+) responses. Platelet function in vitro and in vivo was also unaltered in the absence of TRPC6. Conclusion: Our results indicate that DAG activated ROCE is mediated exclusively by TRPC6 in murine platelets, but this Ca(2+) influx has no major functional relevance for hemostasis and thrombosis. Further, in contrast to previous suggestions, based on studies with human platelets, TRPC6 appears to play an insignificant role in the regulation of SOCE in murine platelets.

A six-year-old Rottweiler with chronic ascites and moderate panhypoproteinaemia that had been treated with large volume paracentesis over several months duration was diagnosed with a large bi-atrial mass and hepatic fibrosis. For palliative treatment, a peritoneo-vesical automated fluid shunt system with an integrated chargeable battery and an integrated computer to control pump function and to transmit data transcutaneously was implanted by coeliotomy. The pump was left in place for 10 weeks, eliminating the need for further paracentesis during this time. At the end of this period, no ascites was discernible and serum protein concentrations had returned to their respective reference intervals. As a complication, decubitus with skin perforation had developed above the pump. Besides palliative treatment of chronic refractory ascites, this pump may have application in other conditions characterised by chronic cavity effusion or in peritoneal dialysis.