[Non-surgical peri-implantitis treatment with or without systemic antibiotics]. / Initiële behandeling van peri-implantitis met of zonder systemische antibiotica.

This study investigated the effect of initial nonsurgical treatment in patients with peri-implantitis with or without prescription of an antibiotic regimen consisting of amoxicillin and metronidazole. For this purpose, patients with peri-implantitis were randomized into a group of initial treatment with antibiotics and a group without antibiotics. They were re-evaluated 12 weeks after treatment. Analyses were performed at the patient level at 1 peri-implant pocket per patient. Both groups showed significant peri-implant pocket depth reductions after initial treatment. Treatment with antibiotics resulted in a higher mean reduction in peri-implant pocket depth than when no antibiotics were used, but this difference did not reach statistical significance. Only 2 implants, 1 in each group, showed a successful outcome of a peri-implant pocket depth ofunder ≤ 5 mm and with an absence of bleeding and pus after probing. Initial treatment with or without antibiotics is ultimately not sufficient to fully treat peri-implantitis; additional surgical procedures will often be required.

Methylene blue active substances in plaque of Bacillus subtilis subsp. subtilis and enrichment by supplemental calcium in culture media.

A series of experiments was conducted to identify the molecular species responsible for surface active emulsification (surfactant) bioactivity in Bacillus subtilis subsp. subtilis strain ATCC PTA-125135, and to describe culture conditions to support the enriched production of said bioactivity in cultured plaque of the strain. The assay for methylene blue active substances (MBAS) was found to be suitable for describing surfactant activity, where a solvent-extracted molecular fraction from the biofilm was found to retain surfactant activity and positively quantified as MBAS. Furthermore, an HPLC-refined protein fraction was found to quantify as MBAS with approximately 1·36-fold or greater surfactant activity per mol than sodium dodecyl sulphate, and a proteomic analysis of solvent extracted residues confirmed that biofilm surface layer protein BslA was a primary constituent of extracted residues. Surfactant bioactivity, quantified as MBAS, was enriched in cultured plaque by the supplementation of culture media with calcium chloride or calcium nitrate.

Silver Fluoride as a Treatment for Dental Caries.

Medical management of caries is a distinct treatment philosophy that employs topical minimally invasive therapies that treat the disease and is not merely prevention. This strategy is justified as an alternative or supplement to traditional care by significant disease recurrence rates following comprehensive operative treatment under general anesthesia. Silver diamine fluoride (SDF) is one agent to enable effective noninvasive treatment. The announcement of breakthrough therapy designation by the Food and Drug Administration (FDA) suggests that SDF may become the first FDA-approved drug for treating caries. Since our systematic review performed in April 2015, 4 clinical trials have been completed, which inform an update to the application protocol and frequency regimen. Suggestions from these studies are to skip the rinsing step due to demonstration of safety in young children, start patients with high disease severity on an intensive regimen of multiple applications over the first few weeks, and continue with semiannual maintenance doses as previously suggested. Breakthroughs in elucidating the impact of SDF on the dental plaque microbiome inform potential opportunities for understanding caries arrest. SDF can be added to the set of evidence-based noninvasive methods to treat caries lesions in primary teeth, such as the Hall crown technique and sealing lesions with accessible margins.

[Impact of medical TV series on surgical hospital patient's perception of reality]. / Einfluss von Arzt- und Krankenhausserien auf das Wirklichkeitsempfinden chirurgischer Krankenhauspatienten.

BACKGROUND: Medical TV series are very popular. Media research emphasizes that watching TV has an influence on patient's expectations and estimations concerning upcoming surgery. We analyzed these associations in our own patients. We suspected that reality as presented in the media and the actual reality of hospitals are not always conceived as two different worlds. METHODS: Over a 15-month period a standardized questionnaire was used to interview 162 in-house patients who had been admitted for an elective standard operation. They were interviewed 1-2 days prior to surgery and shortly before discharge from hospital. The questions aimed at their social situation and their TV viewing habits with special consideration of medical TV series. RESULTS: The knowledge of medical TV series is highly associated with a realistic assessment of these programs (p < 0.05). Furthermore, the knowledge of these programs is correlated with patient's unrealistic estimations of upcoming surgery. CONCLUSION: Medical TV series have a significant influence on surgical in-house patients. Patients with knowledge of many medical TV series believe that the medical setting in these shows is realistic. This can result in false estimations concerning real surgery.

Impact of Medical TV Shows on Preprocedural Fear of Surgical In-House Patients.

Background and Hypotheses: The growing number of medical television series and the increasing amount of time people spend watching TV will have an influence on what they expect from their treatment in a hospital. We suspect that reality as presented in the media and the actual reality of hospitals are not always conceived of as two different worlds. Many medical TV shows present dramatic, life-threatening operations much more often than they occur in reality. Patients who frequently watch such shows might be induced to believe that even routine operations are often dangerous, which could result in higher levels of fear before such an operation. We suspect then that there is a significant relation between preoperative levels of fear and TV viewing habits. METHODS: A standardized questionnaire was used to interview 162 in-house patients who had come to the hospital for an elective standard operation in a German hospital. They were interviewed 1-2 days prior to operation and shortly before discharge from hospital. The questions aimed at their social situation, their TV viewing habits with special consideration of medical TV shows, and the patients' preprocedural fear. RESULTS: The links between levels of education, age, and gender on the one hand, and viewing habits on the other, which have been shown in cultivation research, are supported by our findings. Approximately 50% reported a relevant anxiety level above 4 (on a scale of 0-10). There is a significant association between levels of fear and TV viewing habits. Thirteen subjects (8%) indicated that they suffered the highest imaginable degree of fear, all of them frequent watchers of medical TV shows. Frequent viewers of medical TV shows were definitely more scared than all other patients (p = 0.039). The preoperative level of fear was highest in the age group of under 40 years and significantly lower (p = 0.0042) in the age group of over 70 years. CONCLUSION: The assumed effects of cultivation with in-house patients caused by watching TV series could be shown to be statistically significant. Watching medical TV shows increases the patients' preoperative fear.

A survey of US and Canadian hospitals' paediatric massive transfusion protocol policies.

BACKGROUND: Trauma is the leading cause of death in children >1 year of age, with haemorrhage as the most common cause of medically preventable deaths. While massive transfusion protocols (MTPs) have been investigated and used in adults to reduce death from haemorrhage, there are a paucity of published data on MTP practices and outcomes in children. This study aimed to survey current MTP policies and the frequency of activation at paediatric care centres. STUDY DESIGN AND METHODS: We conducted a survey of MTPs at hospitals in the United States and Canada, including children's general hospitals, children's specialty hospitals and children's units in general hospitals. We collected information on how the MTP is activated, what therapeutics are given, frequency of its use, and how it is audited for compliance. RESULTS: Forty-six survey responses were analysed. Physician discretion was the most common activation criteria (89%). A majority of sites (78%) targeted a 'high' (≥1 : 2) ratio of plasma to red blood cells (RBC). Fifteen percent of sites use antifibrinolytics in their MTPs. Eighty nine percent of sites have type-O RBC units and 48% of sites had thawed plasma units stored in an immediately available location. CONCLUSION: There is a wide variation in MTPs among paediatric hospitals with regard to both activation criteria and products administered. This underscores the need for future prospective studies to determine the most effective resuscitation methods for paediatric populations to improve outcomes and therapeutic safety for massive bleeding.

Transmission optical coherence tomography based measurement of optical material properties.

We present transmission optical coherence tomography (transmission OCT) as a versatile tool to measure optical material properties of turbid media. The transmission OCT signal is described in detail and it is demonstrated how the group refractive index (n(g)), group velocity dispersion (GVD) and optical attenuation can be determined from this signal. We experimentally validate the refractive index properties of glasses, liquids and glucose water solutions in terms of n(g) and GVD. Measurements of scattering coefficients are determined using transmission OCT for suspensions of silica particles. Quantitative agreement is obtained with a dependent scattering model, both for the average as well as the wavenumber resolved optical attenuation coefficient. Good agreement is observed between our measurements and literature values.

Severe Quetiapine Withdrawal Syndrome with Nausea and Vomiting in a 65-year-old Patient with Psychotic Depression.

A 65-year old patient suffering from severe psychotic depression obtained quetiapine for roughly one year. Several attempts to discontinue quetiapine by tapering the dose provoked severe withdrawal symptoms with nausea and vomitus. Pretreatment with domperidone largely prevented withdrawal so that he finally could successfully discontinue quetiapine administration.

[Concept of an additional physical education lesson in English ("moving words") per week in a secondary school: Results of controlled investigation]. / Konzept einer zusätzlichen Sportstunde pro Woche in englischer Sprache ("moving words") in einer Mittelschule : Ergebnisse einer kontrollierten Studie.

BACKGROUND: Physical exercise improves physical fitness of children and pupils may also benefit from sports with regard to cognitive competence. However, timetable and syllabus often give little scope so that alternatives such as combined lessons in English and sports may be suited to integrate the desire for exercise and leaning. METHOD: Parallel classes of a secondary school (form V; 39 pupils) were determined by random as control group (CG: age 10.5 ys, m 11, f 10) or intervention group (IG: age 10.7 ys, m 7, f 11). All pupils got regular physical education of 3 hours per week. In the IG one English lesson was relocated into the sports hall according to the "moving words" concept for one year. Both physical fitness (Munich fitness test) and concentration (d2-test) were assessed before and 3 times with intervals of 3 months. Moreover, 6-month marks were documented. All data were analyzed descriptively in addition to confirmative statistics (Repeated Measures ANOVA). RESULTS: Neither physical fitness nor concentration showed significant differences between the two groups. Both groups improved both criteria within one year, girls of the IG tended to work exacter with fewer mistakes (d2-Test), but dropped behind with regard to physical fitness. Otherwise, boys in the IG ameliorated rate of mistakes, tempo and exactness in the d2-test (p < 0.05) including a positive trend in physical fitness. Whereas English marks in the reports of the IG improved (0.4 versus 0.1), in both groups marks in sports did not change substantially. CONCLUSIONS: Particularly, boys benefit from the "moving-words" concept improving both their physical fitness as well as concentration. Why girls aged 10 to 11 years, on the contrary, do not benefit from the combined learning to the same degree is an interesting issue for further studies.

A radish seed antifungal peptide with a high amyloid fibril-forming propensity.

The amyloid fibril-forming ability of two closely related antifungal and antimicrobial peptides derived from plant defensin proteins has been investigated. As assessed by sequence analysis, thioflavin T binding, transmission electron microscopy, atomic force microscopy and X-ray fiber diffraction, a 19 amino acid fragment from the C-terminal region of Raphanus sativus antifungal protein, known as RsAFP-19, is highly amyloidogenic. Further, its fibrillar morphology can be altered by externally controlled conditions. Freezing and thawing led to amyloid fibril formation which was accompanied by loss of RsAFP-19 antifungal activity. A second, closely related antifungal peptide displayed no fibril-forming capacity. It is concluded that while fibril formation is not associated with the antifungal properties of these peptides, the peptide RsAFP-19 is of potential use as a controllable, highly amyloidogenic small peptide for investigating the structure of amyloid fibrils and their mechanism of formation.

Radiomics-based prediction of local control in patients with brain metastases following postoperative stereotactic radiotherapy.

BACKGROUND: Surgical resection is the standard of care for patients with large or symptomatic brain metastases (BMs). Despite improved local control after adjuvant stereotactic radiotherapy, the risk of local failure (LF) persists. Therefore, we aimed to develop and externally validate a pre-therapeutic radiomics-based prediction tool to identify patients at high LF risk. METHODS: Data were collected from A Multicenter Analysis of Stereotactic Radiotherapy to the Resection Cavity of Brain Metastases (AURORA) retrospective study (training cohort: 253 patients from two centers; external test cohort: 99 patients from five centers). Radiomic features were extracted from the contrast-enhancing BM (T1-CE MRI sequence) and the surrounding edema (FLAIR sequence). Different combinations of radiomic and clinical features were compared. The final models were trained on the entire training cohort with the best parameter set previously determined by internal 5-fold cross-validation and tested on the external test set. RESULTS: The best performance in the external test was achieved by an elastic net regression model trained with a combination of radiomic and clinical features with a concordance index (CI) of 0.77, outperforming any clinical model (best CI: 0.70). The model effectively stratified patients by LF risk in a Kaplan-Meier analysis (p < 0.001) and demonstrated an incremental net clinical benefit. At 24 months, we found LF in 9% and 74% of the low and high-risk groups, respectively. CONCLUSIONS: A combination of clinical and radiomic features predicted freedom from LF better than any clinical feature set alone. Patients at high risk for LF may benefit from stricter follow-up routines or intensified therapy.

Development and external validation of an MRI-based neural network for brain metastasis segmentation in the AURORA multicenter study.

BACKGROUND: Stereotactic radiotherapy is a standard treatment option for patients with brain metastases. The planning target volume is based on gross tumor volume (GTV) segmentation. The aim of this work is to develop and validate a neural network for automatic GTV segmentation to accelerate clinical daily routine practice and minimize interobserver variability. METHODS: We analyzed MRIs (T1-weighted sequence ± contrast-enhancement, T2-weighted sequence, and FLAIR sequence) from 348 patients with at least one brain metastasis from different cancer primaries treated in six centers. To generate reference segmentations, all GTVs and the FLAIR hyperintense edematous regions were segmented manually. A 3D-U-Net was trained on a cohort of 260 patients from two centers to segment the GTV and the surrounding FLAIR hyperintense region. During training varying degrees of data augmentation were applied. Model validation was performed using an independent international multicenter test cohort (n = 88) including four centers. RESULTS: Our proposed U-Net reached a mean overall Dice similarity coefficient (DSC) of 0.92 ± 0.08 and a mean individual metastasis-wise DSC of 0.89 ± 0.11 in the external test cohort for GTV segmentation. Data augmentation improved the segmentation performance significantly. Detection of brain metastases was effective with a mean F1-Score of 0.93 ± 0.16. The model performance was stable independent of the center (p = 0.3). There was no correlation between metastasis volume and DSC (Pearson correlation coefficient 0.07). CONCLUSION: Reliable automated segmentation of brain metastases with neural networks is possible and may support radiotherapy planning by providing more objective GTV definitions.

Identifying core MRI sequences for reliable automatic brain metastasis segmentation.

BACKGROUND: Many automatic approaches to brain tumor segmentation employ multiple magnetic resonance imaging (MRI) sequences. The goal of this project was to compare different combinations of input sequences to determine which MRI sequences are needed for effective automated brain metastasis (BM) segmentation. METHODS: We analyzed preoperative imaging (T1-weighted sequence ± contrast-enhancement (T1/T1-CE), T2-weighted sequence (T2), and T2 fluid-attenuated inversion recovery (T2-FLAIR) sequence) from 339 patients with BMs from seven centers. A baseline 3D U-Net with all four sequences and six U-Nets with plausible sequence combinations (T1-CE, T1, T2-FLAIR, T1-CE + T2-FLAIR, T1-CE + T1 + T2-FLAIR, T1-CE + T1) were trained on 239 patients from two centers and subsequently tested on an external cohort of 100 patients from five centers. RESULTS: The model based on T1-CE alone achieved the best segmentation performance for BM segmentation with a median Dice similarity coefficient (DSC) of 0.96. Models trained without T1-CE performed worse (T1-only: DSC = 0.70 and T2-FLAIR-only: DSC = 0.73). For edema segmentation, models that included both T1-CE and T2-FLAIR performed best (DSC = 0.93), while the remaining four models without simultaneous inclusion of these both sequences reached a median DSC of 0.81-0.89. CONCLUSIONS: A T1-CE-only protocol suffices for the segmentation of BMs. The combination of T1-CE and T2-FLAIR is important for edema segmentation. Missing either T1-CE or T2-FLAIR decreases performance. These findings may improve imaging routines by omitting unnecessary sequences, thus allowing for faster procedures in daily clinical practice while enabling optimal neural network-based target definitions.

Sex differences in fear memory and extinction of mice with forebrain-specific disruption of the mineralocorticoid receptor.

Previous studies showed that the mineralocorticoid receptor (MR) is needed for behavioral flexibility in a fear conditioning paradigm. Female mice with forebrain-specific deletion of the MR gene (MR(CaMKCre) ) were unable to show extinction of contextual fear, and could not discriminate between cue and context fear unlike control mice. In the present study, male and female (MR(CaMKCre) ) mice and control littermates were used to study sex-specific fear conditioning, memory performance and extinction. The fear conditioning paradigm assessed both context- and cue-related fear within one experimental procedure. We observed that at the end of the conditioning all mice acquired the fear-motivated response. During the first minutes of the memory test, both male and female MR(CaMKCre) mice remembered and feared the context more than the control mice. Furthermore, female MR(CaMKCre) mice were not able to extinguish this memory even on the second day of memory testing. The female mutants also could not discriminate between cue (more freezing) and context periods (less freezing). In contrast, male MR(CaMKCre) mice and the controls showed extinction and were capable to discriminate, although the MR(CaMKCre) mice needed more time before they started extinction. These findings further support the relevance of MR for behavioral flexibility and extinction of fear-motivated behavior. In conclusion, the loss of MR in the forebrain results in large differences in emotional and cognitive behaviors between female and male mice, which suggests a role of this receptor in the female prevalence of stress- and anxiety-regulated disorders.

Stress or no stress: mineralocorticoid receptors in the forebrain regulate behavioral adaptation.

Corticosteroid effects on cognitive abilities during behavioral adaptation to stress are mediated by two types of receptors. While the glucocorticoid receptor (GR) is mainly involved in the consolidation of memory, the mineralocorticoid receptor (MR) mediates appraisal and initial responses to novelty. Recent findings in humans and mice suggest that under stress, the MR might be involved in the use of different learning strategies. Here, we used male mice lacking the MR in the forebrain (MR(CaMKCre)), which were subjected to 5-10 min acute restraint stress, followed 30 min later by training trials on the circular hole board. Mice had to locate an exit hole using extra- and intra-maze cues. We assessed performance and the use of spatial and stimulus-response strategies. Non-stressed MR(CaMKCre) mice showed delayed learning as compared to control littermates. Prior stress impaired performance in controls, but did not further deteriorate learning in MR(CaMKCre) mice. When stressed, 20-30% of both MR(CaMKCre) and control mice switched from a spatial to a stimulus-response strategy, which rescued performance in MR(CaMKCre) mice. Furthermore, MR(CaMKCre) mice showed increased GR mRNA expression in all CA areas of the hippocampus and an altered basal and stress-induced corticosterone secretion, which supports their role in the modulation of neuroendocrine activity. In conclusion, our data provide evidence for the critical role of MR in the fast formation of spatial memory. In the absence of forebrain MR spatial learning performance was under basal circumstances impaired, while after stress further deterioration of performance was rescued by switching behavior increasingly to a stimulus-response strategy.

Relevance of stress and female sex hormones for emotion and cognition.

There are clear sex differences in incidence and onset of stress-related and other psychiatric disorders in humans. Yet, rodent models for psychiatric disorders are predominantly based on male animals. The strongest argument for not using female rodents is their estrous cycle and the fluctuating sex hormones per phase which multiplies the number of animals to be tested. Here, we will discuss studies focused on sex differences in emotionality and cognitive abilities in experimental conditions with and without stress. First, female sex hormones such as estrogens and progesterone affect emotions and cognition, contributing to sex differences in behavior. Second, females respond differently to stress than males which might be related to the phase of the estrous cycle. For example, female rats and mice express less anxiety than males in a novel environment. Proestrus females are less anxious than females in the other estrous phases. Third, males perform in spatial tasks superior to females. However, while stress impairs spatial memory in males, females improve their spatial abilities, depending on the task and kind of stressor. We conclude that the differences in emotion, cognition and responses to stress between males and females over the different phases of the estrous cycle should be used in animal models for stress-related psychiatric disorders.

Comparing culture, real-time PCR and fluorescence resonance energy transfer technology for detection of Porphyromonas gingivalis in patients with or without peri-implant infections.

BACKGROUND AND OBJECTIVE: The aim of the study was to compare the detection of Porphyromonas gingivalis using a fluorescence resonance energy transfer (FRET) technology with commonly used diagnostic methods in salivary and subgingival plaque samples from subjects with dental implants. P. gingivalis was considered as a marker for a pathogenic microbiota. MATERIAL AND METHODS: Ninety-seven adult subjects were recruited, including periodontally healthy controls with no dental implants, implant controls with no peri-implant disease and patients with peri-implant disease. Saliva and subgingival/submucosal plaque samples were collected from all subjects and were analyzed using culture, real-time PCR and FRET technology employing P. gingivalis-specific substrates. RESULTS: It was found that the P. gingivalis-specific substrates were highly suitable for detecting the presence of P. gingivalis in saliva and in subgingival plaque samples, showing comparable specificity to culture and real-time PCR. CONCLUSION: We applied the FRET technology to detect P. gingivalis in implant patients with or without an implant condition and in controls without implants. The technique seems suitable for detection of P. gingivalis in both plaque and saliva samples. However, with all three techniques, P. gingivalis was not very specific for peri-implantitis cases. Future work includes fine-tuning the FRET technology and also includes the development of a chair-side application.

Strategic protein target analysis for developing drugs to stop dental caries.

Dental caries is the most common disease to cause irreversible damage in humans. Several therapeutic agents are available to treat or prevent dental caries, but none besides fluoride has significantly influenced the disease burden globally. Etiologic mechanisms of the mutans group streptococci and specific Lactobacillus species have been characterized to various degrees of detail, from identification of physiologic processes to specific proteins. Here, we analyze the entire Streptococcus mutans proteome for potential drug targets by investigating their uniqueness with respect to non-cariogenic dental plaque bacteria, quality of protein structure models, and the likelihood of finding a drug for the active site. Our results suggest specific targets for rational drug discovery, including 15 known virulence factors, 16 proteins for which crystallographic structures are available, and 84 previously uncharacterized proteins, with various levels of similarity to homologs in dental plaque bacteria. This analysis provides a map to streamline the process of clinical development of effective multispecies pharmacologic interventions for dental caries.

[Quality management in psychiatry: evaluation of an ergotherapeutical questionnaire before and after treatment]. / Qualitätsmanagement der psychiatrischen Behandlung: Evaluation ergotherapeutischer Befundbögen bei Aufnahme und Entlassung.

In analogy to somatic medicine, modern psychiatry strives to measure the outcome of treatment and care. In order to warrant an effective therapy, this request is reasonable from the standpoint of both the therapist and the patient as well as hospitals or insurance companies. However, how can I measure friendliness, empathy or humanity, the "being available for somebody"? For sure, psychiatric DRGs, which connote efficacy based on periods of time, are by no means suitable. The present study analyses routine clinical data of an ergotherapeutic questionnaire, as an aid to estimating treatment quality. The naturalistic character of this data collection during daily routine may be an advantage to assessing the quality of results in psychiatry.

The role of temperature in nucleation processes.

Heat and mass transfers are coupled processes, also in nucleation. In principle, a nucleating cluster would have a different temperature compared to the surrounding supersaturated old phase because of the heat release involved with attaching molecules to the cluster. In turn a difference in temperature across the cluster surface is a driving force for the mass transfer to and from the cluster. This coupling of forces in nonisothermal nucleation is described using mesoscopic nonequilibrium thermodynamics, emphasizing measurable heat effects. An expression was obtained for the nonisothermal nucleation rate in a one-component system, in the case where a temperature difference exists between a cluster distribution and the condensed phase. The temperature is chosen as a function of the cluster size only, while the temperature of the condensed phase is held constant by a bath. The generally accepted expression for isothermal stationary nucleation is contained as a limiting case of the nonisothermal stationary nucleation rate. The equations for heat and mass transport were solved for stationary nucleation with the given cluster distribution and with the temperature controlled at the boundaries. A factor was defined for these conditions, determined by the heat conductivity of the surrounding phase and the phase transition enthalpy, to predict the deviation between isothermal and nonisothermal nucleation. For the stationary state described, the factor appears to give small deviations, even for primary nucleation of droplets in vapor, making the nonisothermal rate smaller than the isothermal one. The set of equations may lead to larger and different thermal effects under different boundary conditions, however.