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Amyloid adhesins are β-sheet-rich extracellular proteins thought to contribute to bioflocculation. They are present in activated sludge to varying extent. However, it remains unclear which operational conditions promote their production. To this end, the abundance and distribution of amyloids and their potential producers were monitored in two lab-scale reactors operated in sequencing batch mode with an unaerated and aerated reaction phase. Various feeding regimes ranging from feast-famine to nearly continuous feeding were applied. Thioflavin T staining revealed more amyloids in the lab-scale reactors during all operational stages compared to the full-scale industrial and municipal inocula. Furthermore, the feeding regime impacted the distribution of produced amyloids from dense clusters during feast-famine conditions towards a dispersed distribution during nearly continuous feeding. This dispersed presence did not negatively impact the bioflocculation (towards average floc size and shear sensitivity). 16S rRNA sequencing detected several known EPS and amyloid producers. More continuous and, hence, partially aerobic feeding promoted the relative abundance of denitrifiers. Sequential Thioflavin T staining and fluorescence in situ hybridization identified Zoogloea and Ca . Competibacter as potential amyloid producers under the applied conditions. This experiment confirms that amyloid producers need to be triggered for production and that the feeding regime impacts the microbial community composition, which in turn influences the amyloid production and distribution., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper. The authors declare no competing interests., (© 2022 The Authors. Published by Elsevier Ltd.)

To investigate whether beta oscillations are causally related to motor inhibition, thirty-six participants underwent two concurrent transcranial alternating current stimulation (tACS) and electroencephalography (EEG) sessions during which either beta (20 Hz) or gamma (70 Hz) stimulation was applied while participants performed a stop-signal task. In addition, we acquired magnetic resonance images to simulate the electric field during tACS. 20 Hz stimulation targeted at the pre-supplementary motor area enhanced inhibition and increased beta oscillatory power around the time of the stop-signal in trials directly following stimulation. The increase in inhibition on stop trials followed a dose-response relationship with the strength of the individually simulated electric field. Computational modeling revealed that 20 and 70 Hz stimulation had opposite effects on the braking process. These results highlight that the effects of tACS are state-dependent and demonstrate that fronto-central beta activity is causally related to successful motor inhibition, supporting its use as a functional biomarker., Competing Interests: The authors declare no competing interests., (© 2022 The Authors.)

The long-term use of benzodiazepine receptor agonists (BZRAs) is associated with multiple side effects, such as increased sedation, hangover or an elevated risk of dependency and abuse. Unfortunately, the long-term use of BZRAs is reaching worrying intake rates, and therefore, the need for action is high. It was demonstrated already that the overall willingness of patients for deprescription increased when a slow dose reduction scheme with the possibility for dose increase, if needed, is employed. The current study aims to develop a flexible dosing platform of zolpidem hemitartrate (ZHT) to facilitate such withdrawal therapy. As this is the first report on the extrusion and 3D printing of ZHT, its thermal behaviour and sensitivity towards photolytic degradation was characterised. It was shown that ZHT possesses multiple polymorphs and was especially prone to oxidative photolysis. Next, a variety of immediate release polymers (Eudragit EPO, Kollidon VA64, Kollidon 12PF and Soluplus) were blended and extruded with Polyox WSR N10 to investigate their feedability and printability by mechanical and rheological analysis. The addition of PEO was shown to enable printing of these brittle pharmaceutical polymers, although the processing temperature was deemed critical to avoid surface defects on the resulting filaments. An EPO(70)PEO(30) system was selected based on its suitable mechanical properties and low hygroscopicity favoring ZHT stability. The matrix was blended with 1% or 10% API. The effect of certain printing parameters (caplet size, nozzle diameter, % overlap) on dissolution behaviour and caplet weight/dimensions/quality was assessed. A flexible dosing platform capable of delivering <1 mg and up to 10 mg of ZHT was created. Either caplet modification (incorporation of channels) or disintegrant addition (Primojel, Explotab, Ac-Di-Sol, Primellose and Polyplasdone-XL) failed to achieve an immediate release profile. This study provides the first report of a 3D-printed flexible dosing platform containing ZHT to aid in withdrawal therapy.

This article gives an update on how the composition of the influenza virus vaccine is determined, how the infection spreads, and what the consequences are of the disease. Next flu season for the first time a quadrivalent and intranasal vaccine will be available on the Belgian market. What is the difference with what we know until now? Is there an added value? How about the contraindications? Furthermore we elaborate on the composition of the influenza vaccine on the Belgian market for the season 2015-2016 and we give a reminder of the patient groups with a high risk for complications. As pharmacists we should motivate these patients to get themselves vaccinated. Finally, we discuss the reimbursement conditions of the National Institute for Health and Disability Insurance INIHDII.

Streptococcus pneumoniae is responsible for a large number of invasive infections and upper respiratory tract infections in infants, elderly and patients with high complication risk. Currently, two types of vaccine are available on the Belgian market. In the context of pharmaceutical care, it is important for pharmacists to know their specific characteristics and differences. In this article we try to explain these and to motivate their use in different patient populations. The 23-valent vaccine is different from the 13-valent vaccine, not only in number of serotypes, but also in its presentation as respectively polysaccharide- and conjugated vaccine which affects the immunogenicity. Moreover, their indication and use are also different. Finally we take a closer look at the specific use in infants and children at risk at one hand, and vaccination of eldery and adults with increased risk for severe pneumococcal infection on the other hand.

Unlabelled: Given the importance of angiogenesis for a tumor's survival and growth, several therapeutic strategies rely on the selective inhibition of angiogenesis and the destruction of existing tumor vasculature. These strategies raise the need for a noninvasive tool to evaluate tumor vasculature. We describe the radiosynthesis and evaluation of an imaging tracer that specifically binds tumor subendothelial collagen and thereby images tumor vasculature., Methods: (99m)Tc-tricarbonyl was prepared and labeled with His-collagen-binding adhesion protein 35 (CNA35). After in vitro specificity testing, in vivo biodistribution and dosimetric studies were performed in healthy nude mice via planar imaging. (99m)Tc-(CO)(3) His-CNA35 was evaluated for in vivo imaging of tumor vasculature in a HT29 colorectal carcinoma xenograft., Results: The labeling procedure yielded a compound with 95%-99% radiochemical purity and good in vitro stability. An in vitro binding test confirmed specificity and functionality. (99m)Tc-(CO)(3) His-CNA35 rapidly cleared from the blood and predominantly accumulated in the kidneys and liver. The effective dose for a proposed single injection of 500 MBq of (99m)Tc-(CO)(3) His-CNA35 is 3.70 mSv per organ or 2.01 mSv/g of tissue. Tumors were successfully visualized, and uptake correlated with ex vivo immunohistochemical staining of tumor vasculature., Conclusion: (99m)Tc-(CO)(3) His-CNA35 may be a useful radioligand for the in vivo detection of tumor vasculature through subendothelial collagen binding. A noninvasive method of imaging tumor vasculature that could provide a reliable assessment of tumor vasculature would allow evaluation of the effectiveness of commonly used antiangiogenic therapies and determination of their optimal dosing and scheduling.

Introduction: Apoptosis is one of the mechanisms behind successful chemotherapy and radiation treatment. Radiolabeled annexin A5 has been demonstrated to be a successful tool in the detection of apoptosis following chemotherapy in vivo., Methods: His-tagged annexin A5 was labeled with [(99m)Tc]-tricarbonyl and evaluated as apoptosis imaging radiotracer in vitro and in vivo. The binding of the radiotracer was evaluated in Colo205 cells stimulated with 5-FU (1 mM) for 4 and 24 h, and confirmed by flow cytometry. Biodistribution and dosimetric studies were performed in healthy nude mice (n=5) via planar scintigraphy. [(99m)Tc]-(CO)(3) His-annexin A5 was also evaluated for in vivo imaging of spontaneous apoptosis in Colo205-bearing mice (n=12)., Results: The labeling procedure yielded a compound with 95-99% radiochemical purity and good in vitro stability. In vitro binding experiments indicated that the radiotracer retained its PS-binding activity. [(99m)Tc]-(CO)(3) His-annexin A5 rapidly cleared from the blood and predominantly accumulated in the kidneys. Absorbed dose (per organ) was found to be 116 ± 64 μGy/MBq for the kidneys and 10.38 ± 0.50 μGy/MBq for the liver. The effective dose was 7.00 ± 0.28 μSv/MBq. Spontaneous apoptosis in Colo205-bearing mice was visualised by [(99m)Tc]-(CO)(3) His-annexin A5 SPECT and correlated well with caspase-3 immunostaining (R=0.867, P<.01)., Conclusion: [(99m)Tc]-(CO)(3) His-annexin A5 may be a useful novel radioligand for the in vivo detection of cell death associated with PS expression. A simple, noninvasive way of detecting apoptosis in vivo could have many applications including a better understanding of the extent and timing of apoptosis in response to cancer therapies and assessment of early tumor response., (Copyright © 2010 Elsevier Inc. All rights reserved.)

The use of radiolabeled antibodies that are able to target primary tumors as well as metastatic tumor sites with minimal reactivity to normal tissues is a promising approach for treating pancreatic cancer. In this study, the integrin alpha(v)beta(5) is studied as a target for the diagnosis of and potential therapy for human pancreatic cancer by using the radiolabeled murine monoclonal antibody (mAb) 14C5. Biopsy specimens from human pancreatic tumors were examined for the expression of the integrin alpha(v)beta(5). The pancreatic tumor cell line Capan-1 was used to test the in vitro targeting potency of mAb 14C5 labeled with 125/131-iodine and 111-indium. Internalization, retention, and metabolism were investigated in cellular radioimmunoassays. Biodistribution and tumor-targeting characteristics were studied in Capan-1 xenografts. All tumor sections were positive for the integrin alpha(v)beta(5), with an extensive positive staining of the stroma. Saturation binding experiments showed high affinity with comparable K(d)s. In vitro internalization experiments showed a longer intracellular retention of (111)In-p-benzyl isothiocyanate-1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid (p-SCN-Bz-DOTA)-14C5 in comparison to (125)I-14C5 and (111)In-p-isothiocyanatobenzyl diethylenetriaminepentaacetic acid (p-SCN-Bz-DTPA)-14C5. In vivo radioisotope tumor uptake was maximum at 48-72 hours, with the uptake of (111)In-p-SCN-Bz-DOTA-14C5 (35.84 +/- 8.64 percentage of injected dose per g [%ID/g]) being 3.9- and 2.2-folds higher than (131)I-14C5 (12.16 +/- 1.03%ID/g) and (111)In-p-SCN-Bz-DTPA-14C5 (14.30 +/- 3.76%ID/g), respectively. Planar gamma imaging with mAb 14C5 indicated clear localization of the pancreatic tumors versus minimal normal tissue uptake. mAb 14C5 is a promising new antibody for targeting the integrin alpha(v)beta(5) for the diagnosis of and potential therapy for pancreatic cancer.

The aim of this study was to collect information on dental health and dental care of German children and children of migrants for planning oral health promotion in the Rems-Murr-district. To meet this aim all first and fourth degree children in primary and special schools were examined. The dmft- and DMFT-Index, the number of fissure sealants, the filling material used and the children's nationality were recorded. The dmft of 6- and 7-year-olds was 1.50 among Germans, 4.61 among German migrants from Russia, 4.02 among Turks, 4.05 among children from former Yugoslavia, 2.35 among Italians, 1.95 among Greeks and 3.76 among children of other nationalities. At the age of 9 to 10 years Germans had an average of 0.31, German migrants from Russia 0.77, Turks 1.19, children from former Yugoslavia 1.32, Italians 0.64, Greeks 0.69 and children of other nationalities 0.57 DMF-teeth. In both age groups the proportion of caries-free children was highest among Germans and lowest among Turks. Also, more migrants than Germans were referred to a dentist for caries treatment. Compared to the Germans fewer migrants had at least one tooth sealed. The proportion of amalgam fillings to the total number of fillings was higher among 9- and 10-year-olds of Turkish, Italian or Yugoslavian origin than among other nationalities. The results of this study show that further development of oral health promotion programmes for children and parents with Turkish and Russian cultural background has the top-most priority.

The aim of this study was to collect information on the attitude to dentists and access to dental care by German and Turkish parents. To meet this aim, 829 parents attending a school medical inspection received a questionnaire. 811 (97.8%) questionnaires were returned and 778 (93.8%) could be used for analysis. Compared to German parents Turkish parents had a more negative attitude to the dentist. In particular, communication with the dentist was assessed more negatively by Turkish parents. Clearly more Turkish than German parents agreed that their dentist frequently made them feel guilty because of poor oral hygiene (31.2 vs. 5.6%). 7.7% of German but 23.9% of Turkish parents thought that their dentist did not give them enough information. Among the Turkish interviewees, language problems rather played a minor role in communication problems. 12.6% of German and 19.3% of Turkish interviewees thought they could not believe everything what the dentist said. Only 54.0% of the German and 28.9% of the Turkish parents knew that fissure sealants were paid by the statutory sickness fund. Dentists should be better trained in dealing with patients with a different social or cultural background. Also, dentists should be taught to consider health problems rather from a social than from an individual aspect. To improve cost transparency, dentists should publish the list of services not covered by the statutory sickness fund. Moreover, an independent patient consultation service should be offered.

Primed in situ Labelling, a technique based on primer mediated DNA synthesis, has become a useful tool in cytogenetics, especially for chromosome mapping, banding and the investigation of sequence organization in fresh metaphase preparations. Its application in the routine surgical pathology laboratory has been hampered by the fact that the technique did not work on paraffin-embedded, formalin-fixed tissue. We investigated cervical biopsies (n = 20) with morphological signs of HPV infection and found that the PRINS method is at least as sensitive as a classical in situ hybridization assay for detecting HPV DNA in paraffin-embedded, formalin-fixed tissue. In all investigated cases (n = 20), HPV DNA was found by both methods. The PRINS method was able to demonstrate HPV DNA not only in superficial koilocytotic squamous cells but also in non-koilocytotic cells in the deeper spinous cell layers, and even in some basal cells. We describe an economical protocol using conventional consensus HPV oligonucleotide DNA primers. The described method is rapid (approximately 3 hours) and easy to perform for screening and subtyping HPV infection in the routine surgical pathology laboratory.

The aim of this study was to collect data on catering at break in primary schools as a basis for planning health promotion activities. To meet this aim the principals of all schools were interviewed and the snacks and drinks that were sold at break were recorded in a checklist. The results show, that in 27.4% of the schools snacks or drinks were sold that cause damage to dental health or are not recommended for general health. Moreover nutritious products as school milk, wholemeal bread and fruits were frequently not available. In 55.8% of the schools no snacks and in 37.3% of them no drinks were sold at all. In 51% of the schools the children had the opportunity to have breakfast together in the classroom. The selling of not recommended snacks and drinks should be banned from schools, because they rather make healthy choices more difficult than easier and therefore undermine the effectiveness of health education. To change eating habits continuous and long-standing activities concerning breakfast at school are recommended.

The aim of this study is to explore the opinion of parents on dental screening in schools and kindergartens. A sample of 490 parents attending a school medical inspection was asked to fill in a self-administered questionnaire. The parents could express their level of agreement with five statements concerning dental screening and the recall system existing in Baden-Württemberg. The answers were conceived according to the Likert scale. The results of this study show that a large majority of the interviewees had a positive attitude towards screening and a less positive attitude towards the recall system. Compared to the Germans, the immigrants had a more positive attitude towards screening and a less positive attitude towards the recall system. Compared to the parents with lower education level, the parents with a higher educational level were more in favour of the recall system and less in favour of dental screening. The high acceptance of school dental inspections among parents should encourage the responsible authorities to expand dental screening, which is laid down in social legislation, to a greater number of schools and kindergartens.

After a dental examination at school a representative sample of 1244 schoolchildren in the Rems-Murr district received a questionnaire which had to be answered by their parents at home. The questions dealt with the use of fluorides and dental consultation of the children. Forty-nine per cent of the questionnaires were returned. The survey shows that fluoride supplementation by tablets enjoys an acceptance of more than 90% in early childhood, but loses much of its importance in later years. Eighty-eight per cent of the pupils brush teeth with a fluoridated dentifrice and ca. 39% of the households use fluorinated salt. Fluorides are frequently combined in an inappropriate way. This indicates that parents do not always know exactly how to use the products or simply confuse them with others. Dentists do not reserve topical fluoride applications for selected caries risk groups, as is fixed by law, but offer them to all their patients. More than 90% of the children see a dentist at least once and about 70% at least twice a year. Many children with untreated deciduous teeth had visited their dentist only a few weeks or months previous to the examination at school. Probably many dentists reject treatment of deciduous teeth for economic reasons. Consumers have to be instructed more intensively about the use of fluorides and should receive more specific advice adapted to their individual caries risk. To improve treatment of deciduous teeth modifications in the sickness insurance refund tariff system are necessary.

Based on an epidemiological caries study conducted in 1988, 1229 children of primary schools in the Rems-Murr-region were examined during autumn 1991 under identical conditions. The average DMF-T values vary from 0.2 for the children of 6 years of age to 1.7 for those of 10 years of age. Compared to 1988 and depending on age a caries reduction between 10 and 46% in permanent teeth was determined. In same period the percentage of caries-free children (df-t and DMF-T = 0) has clearly increased and the number of those who needed treatment in permanent teeth has been reduced by 50%. Especially in permanent teeth the state of treatment (MF-T:DMF-T x 100) has been improved considerably and vary now from 31 to 75% depending on age. Although different factors are responsible for the recent caries decline, the intensification of health education programmes probably plays a prominent role.

Within the framework of an averaging study (clinical examination combined with written questionnaire) an attempt was made to determine the extent to which theoretical and practical knowledge of caries prophylaxis influences the behaviour and dental health of school children. Mean DF and DMF levels, it was demonstrated, are significantly reduced in children who know more; also, a higher percentage of children reported brushing their teeth more than once a day. In spite of this, a considerable discrepancy is noticed between knowledge and behaviour. Improved integration of dental hygiene instruction in the school day could improve school children's motivation to change their behaviour on a lasting basis.

An epidemiological study on caries in 1,091 primary school pupils in the Rems-Murr area revealed improvement in oral health as compared with results of earlier studies in the Federal Republic of Germany. For example, 31.4% of first-form pupils and 16.1% of fourth-form pupils were shown to have naturally healthy teeth (DMF-T + dmf-t = 0). The average DMF-T(S) values were between 0.39 (0.5) for six-year-olds and 2.02 (2.74) for ten-year-olds. The average percent of treated permanent teeth in six (ten)-year-old pupils was determined to be 20.5 (46.5)%. The pronounced polarisation of the individual values is, however, of of ater significance in developing programmes for caries prophylaxis than are these average values: Only 22% of the children accounted for approx. 70% of the carious, missing or filled permanent teeth. Carious defects in the permanent teeth of six and seven-year-old pupils were found almost exclusively in the fissures and pits of the six-year molars. An improvement in the oral health of the above-named age groups can only be achieved by means of specific and individual prophylaxis programmes.