Assessing oral health-related quality of life among older people in home-based care - survey results of the InSEMaP study in Germany.

BACKGROUND: Older people receiving home-based care (HBC) often face barriers to access preventive oral health care (OHC) and dental treatments. Leading to deterioration of their oral healthcare. It is further deteriorated by factors such as increasing burden of systemic diseases, medicinal side effects, limited mobility, financial constraints and lack of professional OHC at home. Older people also struggle to maintain necessary daily oral hygiene, leading to malnutrition, weight loss, and a risk of a further health degradation. This cross-sectional survey aimed to investigate the oral health-related quality of life (OHRQoL) and their associated factors in HBC recipients. METHODS: 5,280 older people (≥ 60 years) living in Hamburg, who were in need of care and insured with statutory health insurance DAK-Gesundheit received the questionnaire, which included the German version of the Oral Health Impact Profile (OHIP G-14) and, the EQ-5D health-related quality of life (HRQoL) measure as well as further questions regarding the extent of informal social support, subjective oral health status, oral health behaviour, subjective cognitive status, and socio-demographic variables. RESULTS: The participants (n = 1,622) had a median age of 83.2 years, with 72.0% of the sample being female. Nearly two thirds of the sample reported that their independence or abilities were significantly impaired (care level 2). Regarding oral health impacts, 40.0% of the participants reported experiencing at least one of the fourteen possible prevalent impacts of the OHIP-G14 fairly often or very often. A multivariate regression model on the severity of oral health impacts revealed, that a better HRQoL, a positive perception of one's own dental status, fewer visits to dental practices, and no need for support in OHC were associated with better OHRQoL. Conversely, respondents with a negative perception of their oral health status, more frequent visits to a dental practice, a need for support in OHC, and subjective memory impairment showed poorer OHRQoL. CONCLUSIONS: The results highlight the risk for poor oral health among older people in HBC. We conclude that there is an urgent need to prioritise oral health, especially as poor oral health can further compromise the systemic wellbeing of these already care dependent population.

A narrative review of the socioeconomic burden associated with generalised pustular psoriasis.

Generalised pustular psoriasis (GPP) is a rare, chronic and life-threatening inflammatory skin disease characterised by widespread eruption of sterile pustules. With the approval of a GPP flare treatment in several countries occurring only recently, the socioeconomic burden associated with GPP is not well established. To highlight current evidence for patient burden, healthcare resource utilization (HCRU) and costs associated with GPP. Patient burden results from serious complications including sepsis and cardiorespiratory failure causing hospitalization and death. HCRU is driven by high hospitalization rates and treatment costs. The mean duration of a GPP hospital stay ranges from 10 to 16 days. A quarter of patients require intensive care, and the mean intensive care stay is 18 days. In comparison to patients with plaque psoriasis (PsO), patients with GPP have: a 64% higher score on the Charlson Comorbidity Index; higher hospitalization rates (≤36.3% vs. ≤23.3%); lower overall quality of life, and higher symptom scores for pain, itch, fatigue, anxiety and depression; direct costs associated with treatment 1.3- to 4.5-fold higher; higher rates of disabled work status (20.0% vs. 7.6%); and increased presenteeism (i.e. worse impairment at work), impaired daily activities, and medically related absenteeism. Current medical management and drug treatment utilising non-GPP-specific therapies impose a significant patient and direct economic burden. GPP also imposes an indirect economic burden by increasing work productivity impairment and medically related absenteeism. This high level of socioeconomic burden reinforces the need for new therapies with proven efficacy in the treatment of GPP.

Estimated frequency of somatic symptom disorder in general practice: cross-sectional survey with general practitioners.

BACKGROUND: Somatic symptom disorder (SSD) is the successor diagnosis of somatoform disorder in the 5th Edition of the Diagnostic and Statistical Manual of Mental Disorders (DSM-5). Relevance and frequency of SSD and its clinical symptoms in general practice are still unknown. We estimate frequencies of patients fulfilling the diagnostic criteria of SSD in general practice. METHODS: Mailed and online survey with general practitioners (GP) in Germany using a cross-sectional representative sample from registries of statutory health insurance physicians. GPs estimated percentages of their patients who show the clinical symptoms of SSD according to DSM-5; that is, one or more burdensome somatic symptoms (A criterion), excessive symptom- or illness-related concern, anxiety, or behaviour (B criterion), and persistence of the symptoms over at least 6 months (C criterion). Statistical analysis used means and confidence intervals of estimated patient proportions showing SSD symptoms. Frequency of full-blown SSD was based on the products of these proportions calculated for each GP. RESULTS: Responses from 1728 GPs were obtained. GPs saw the clinical symptoms of SSD fulfilled (A and B criteria) in 21.5% (95% CI: 20.6 to 22.3) of their patients. They further estimated that in 24.3% (95% CI: 23.3 to 25.2) of patients, symptoms would persist, yielding a total of 7.7% (95% CI: 7.1 to 8.4) of patients to have a full-blown SSD. CONCLUSIONS: We estimate a frequency of 7.7% of patients in general practice to fulfil the diagnostic criteria of SSD. This number may figure as a reference for the yet to be uncovered prevalence of SSD and it indicates a high clinical relevance of the clinical symptoms of SSD in general practice. REGISTRATION: German Clinical Trials Register (Deutschen Register Klinischer Studien, DRKS). DRKS-ID: DRKS00012942. The date the study was registered: October 2nd 2017. The date the first participant was enrolled: February 9th 2018.

Remote interpreting in primary care settings: a feasibility trial in Germany.

BACKGROUND: Global migration trends have led to a more diverse population in health care services everywhere, which in turn has set off a paradigm shift away from medical paternalism toward more patient autonomy. Consequently, physicians need to provide a more precise patient-centred healthcare. Professional interpreting appears to play a crucial part in tackling the challenges of language barriers adequately. The aim of this study was to conduct process evaluation through the implementing of video remote interpreting (VR) and telephone remote interpreting (TR) within primary care facilities in the northern German metropolis of Hamburg. METHODS: We conducted a three-armed exploratory pilot trial, which compared VR to TR and to a control group (CG) in different primary care settings. We assessed feasibility of implementation, as well as the acceptance of interpreting tools among their users. In addition, we compared the quality of communication as perceived by patients and physicians, as well as the enabling of patient-centred medicine over all three study groups using quantitative questionnaires. RESULTS: 13 practices (7 GPs, 3 Gynaecologists, 3 Paediatricians) took part in this trial. 183 interpreting calls were documented, 178 physicians as well as 127 patients answered their respective questionnaires. The implementation of the VR- und TR-tools went smoothly and they were broadly accepted by their users. However, the tools were used significantly less often than we had anticipated. With regards to quantitative questionnaires, VR scored significantly better than the control group in terms of the perceived quality of communication by both, patients and physicians and enabled of patient-centred medicine. CONCLUSION: Our main findings were the discrepancy between the assumed high demand of professional interpreting solutions on the one hand and the low willingness of practices to participate on the other. The rather low utilisation rates were also noteworthy. This discrepancy indicates a lack of awareness concerning the adverse effects of using informal or no interpreter in medical settings, which needs to be rectified. Due to the small sample size, all statistical results must be viewed with caution. However, our results show that remote interpreting represents a promising approach to tackling language barriers in primary care settings.

Large pneumatocele as a rare complication in SARS-CoV-2 infection of the lung.

In this paper, we present a case of SARS-CoV2-Virus a non-vaccinated 54-year-old male admitted with COVID-19 pneumonia and respiratory insufficiency requiring high-flow oxygen supplementation. CT-scan of the lung revealed multifocal bilateral ground-glass opacities and - as a rare complication - a large pneumatocele in the middle of the posterior part of the left lower lobe. In order to treat the pneumatocele, a 10 F was placed into the cavity. The resulting pneumothorax was successfully treated with a 20 F chest tube over a 9-day period. The pneumatocele shrank only slightly. This case demonstrates a unique radiologic finding in COVID-19, which is likely the result of severe inflammation secondary to SARS-CoV-2 including an unfruitful attempt at depressurisation.

Diagnostic and treatment barriers to persistent somatic symptoms in primary care - representative survey with physicians.

BACKGROUND: Many patients consult their primary care physician with persistent somatic symptoms such as pain or sickness. Quite often these consultations and further diagnostic measures yield no medical explanation for the symptoms - patients and physicians are left in uncertainty. In fact, diagnostic and treatment barriers in primary care hinder timely health-care provision for patients suffering from persistent somatic symptoms (PSS). The significance of individual barriers is still unknown. We compare and quantify these barriers from the perspective of primary care physicians and identify subpopulations of primary care physicians who experience particular barriers as most severe. METHODS: We mailed a questionnaire to primary care physicians (PCP) in Germany and asked them which barriers they consider most important. We invited a random sample of 12,004 primary care physicians in eight federal states in Germany. Physicians provided anonymous mailed or online responses. We also mailed a postcard to announce the survey and a mail reminder. Main measures were Likert rating scales of items relating to barriers in the diagnosis and treatment of PSS in primary care. Information on demography and medical practice were also collected. RESULTS: We analyzed 1719 data sets from 1829 respondents. PCPs showed strongest agreement with statements regarding (1.) their lack of knowledge about treatment guidelines, (2.) their perceptions that patients with PSS would expect symptom relief, (3.) their concern to overlook physical disease in these patients, and (4.) their usage of psychotropic drugs with these patients. More experienced PCPs were better able to cope with the possibility of overlooking physical disease than those less experienced. CONCLUSIONS: The PCPs in our survey answered that the obligation to rule out severe physical disease and the demand to relieve patients from symptoms belong to the most severe barriers for adequate treatment and diagnosis. Moreover, many physicians admitted to not knowing the appropriate treatment guidelines for these patients. Based on our results, raising awareness of guidelines and improving knowledge about the management of persistent somatic symptoms appear to be promising approaches for overcoming the barriers to diagnosis and treatment of persistent somatic symptoms in primary care. TRIAL REGISTRATION: German Clinical Trials Register (Deutschen Register Klinischer Studien, DRKS) https://www.drks.de/drks_web/setLocale_EN.do The date the study was registered: October 2nd 2017 The date the first participant was enrolled: February 9th 2018 DRKS-ID: DRKS00012942.

Catalytic H2O2 Activation by a Diiron Complex for Methanol Oxidation.

In nature, C-H bond oxidation of CH4 involves a peroxo intermediate that decays to the high-valent active species of either a "closed" {FeIV(µ-O)2FeIV} core or an "open" {FeIV(O)(µ-O)FeIV(O)} core. To mimic and to obtain more mechanistic insight in this reaction mode, we have investigated the reactivity of the bioinspired diiron complex [(susan){Fe(OH)(µ-O)Fe(OH)}]2+ [susan = 4,7-dimethyl-1,1,10,10-tetrakis(2-pyridylmethyl)-1,4,7,10-tetraazadecane], which catalyzes CH3OH oxidation with H2O2 to HCHO and HCO2H. The kinetics is faster in the presence of a proton. 18O-labeling experiments show that the active species, generated by a decay of the initially formed peroxo intermediate [(susan){FeIII(µ-O)(µ-O2)FeIII}]2+, contains one reactive oxygen atom from the µ-oxo and another from the µ-peroxo bridge of its peroxo precursor. Considering an FeIVFeIV active species, a "closed" {FeIV(µ-O)2FeIV} core explains the observed labeling results, while a scrambling of the terminal and bridging oxo ligands is required to account for an "open" {FeIV(O)(µ-O)FeIV(O)} core.

[Clinical trial of a stepped and collaborative care model for mental illnesses and comorbidities in the Hamburg Network for Health Services Research]. / Erprobung eines integrierten und gestuften Behandlungsmodells für psychische Störungen und Komorbiditäten im Hamburger Netzwerk für Versorgungsforschung.

Healthcare for mental disorders is a big challenge for the German healthcare system. In cases of comorbid mental diseases, patients suffer from an especially high burden of disease. So far, innovative care models for collaborative and stepped care have only been investigated with respect to their effectiveness for single mental disorders.The project "Collaborative and Stepped Care in Mental Health by Overcoming Treatment Sector Barriers" (COMET), which is being carried out by the Hamburg Network for Health Services Research (HAM-NET) from 2017 until 2020, examines an innovative, guideline-based healthcare model for the improvement of healthcare for patients with mental illnesses and their potential comorbidities. In this article this new stepped and collaborative care model for patients in primary care that integrates general practitioners, psychiatrists, psychotherapists, and hospitals is presented. For the implementation and facilitation of the model, guideline-based treatment pathways, a tablet-based computer program for screening, diagnostic and guideline-based treatment recommendations, as well as a web-based transferal platform were developed.The results of this project on the effectiveness and efficacy of the model can help determine if the model can be implemented in routine healthcare. This could represent a major step towards more integrated and cross-sectoral healthcare for patients with mental illnesses.

Reversible Carboxylate Shift in a µ-Oxo Diferric Complex in Solution by Acid-/Base-Addition.

A reversible carboxylate shift has been observed in a µ-oxo diferric complex in solution by UV-vis-NIR and FTIR spectroscopy triggered by the addition of a base or an acid. A terminal acetate decoordinates upon the addition of a proton, resulting in a shift of the remaining terminal acetato to a µ-η1:η1 bridge. The addition of a base restores the original structure containing only terminal acetates. The implications for metalloenzymes with carboxylate-bridged nonheme diiron active sites are discussed.

Two Unsupported Terminal Hydroxido Ligands in a µ-Oxo-Bridged Ferric Dimer: Protonation and Kinetic Lability Studies.

The dinuclear complex [(susan){FeIII(OH)(µ-O)FeIII(OH)}](ClO4)2 (Fe2(OH)2(ClO4)2; susan = 4,7-dimethyl-1,1,10,10-tetra(2-pyridylmethyl)-1,4,7,10-tetraazadecane) with two unsupported terminal hydroxido ligands and for comparison the fluorido-substituted complex [(susan){FeIIIF(µ-O)FeIIIF}](ClO4)2 (Fe2F2(ClO4)2) have been synthesized and characterized in the solid state as well in acetonitrile (CH3CN) and water (H2O) solutions. The Fe-OH bonds are strongly modulated by intermolecular hydrogen bonds (1.85 and 1.90 Å). UV-vis-near-IR (NIR) and Mössbauer spectroscopies prove that Fe2F22+ and Fe2(OH)22+ retain their structural integrity in a CH3CN solution. The OH- ligand induces a weaker ligand field than the F- ligand because of stronger π donation. This increased electron donation shifts the potential for the irreversible oxidation by 610 mV cathodically from 1.40 V in Fe2F22+ to 0.79 V versus Fc+/Fc in Fe2(OH)22+. Protonation/deprotonation studies in CH3CN and aqueous solutions of Fe2(OH)22+ provide two reversible acid-base equilibria. UV-vis-NIR, Mössbauer, and cryo electrospray ionization mass spectrometry experiments show conservation of the mono(µ-oxo) bridging motif, while the terminal OH- ligands are protonated to H2O. Titration experiments in aqueous solution at room temperature provide the p Ka values as p K1 = 4.9 and p K2 = 6.8. Kinetic studies by temperature- and pressure-dependent 17O NMR spectrometry revealed for the first time the water-exchange parameters [ kex298 = (3.9 ± 0.2) × 105 s-1, Δ H⧧ = 39.6 ± 0.2 kJ mol-1, Δ S⧧ = -5.1 ± 1 J mol-1 K-1, and Δ V⧧ = +3.0 ± 0.2 cm3 mol-1] and the underlying Id mechanism for a {FeIII(OH2)(µ-O)FeIII(OH2)} core. The same studies suggest that in solution the monoprotonated {FeIII(OH)(µ-O)FeIII(OH2)} complex has µ-O and µ-O2H3 bridges between the two Fe centers.

A Mixed-Valence Fluorido-Bridged FeIIFeIII Complex.

The reaction of the new dinucleating ligand susan6-Me with Fe(BF4)2·6H2O results in formation of the homovalent FeIIFeII complex [(susan6-Me){FeII(µ-F)2FeII}]2+ and the mixed-valence FeIIFeIII complex [(susan6-Me){FeIIF(µ-F)FeIIIF}]2+ depending on the absence or presence of dioxygen, respectively. Complex [(susan6-Me){FeIIF(µ-F)FeIIIF}]2+ is the first molecular mixed-valence complex with a fluorido bridge. The short FeIII-µ-F bond of 1.87 Å causes a large reorganization energy, resulting in a localized class II system with an intervalence charge-transfer band of high energy at 10000 cm-1.

Determination of aromatic amines in human urine using comprehensive multi-dimensional gas chromatography mass spectrometry (GCxGC-qMS).

Aromatic amines are an important class of harmful components of cigarette smoke. Nevertheless, only few of them have been reported to occur in urine, which raises questions on the fate of these compounds in the human body. Here we report on the results of a new analytical method, in situ derivatization solid phase microextraction (SPME) multi-dimensional gas chromatography mass spectrometry (GCxGC-qMS), that allows for a comprehensive fingerprint analysis of the substance class in complex matrices. Due to the high polarity of amino compounds, the complex urine matrix and prevalence of conjugated anilines, pretreatment steps such as acidic hydrolysis, liquid-liquid extraction (LLE), and derivatization of amines to their corresponding aromatic iodine compounds are necessary. Prior to detection, the derivatives were enriched by headspace SPME with the extraction efficiency of the SPME fiber ranging between 65 % and 85 %. The measurements were carried out in full scan mode with conservatively estimated limits of detection (LOD) in the range of several ng/L and relative standard deviation (RSD) less than 20 %. More than 150 aromatic amines have been identified in the urine of a smoking person, including alkylated and halogenated amines as well as substituted naphthylamines. Also in the urine of a non-smoker, a number of aromatic amines have been identified, which suggests that the detection of biomarkers in urine samples using a more comprehensive analysis as detailed in this report may be essential to complement the approach of the use of classic biomarkers.

Effectiveness, tolerability and acceptance of a low-dosed estradiol/dienogest formulation (Lafamme 1 mg/2 mg) for the treatment of menopausal complaints: a non-interventional observational study over 6 cycles of 28 days.

BACKGROUND: Concern and controversy characterize nowadays the use of hormone therapy for management of patients with menopausal complaints. This observational non-interventional study examined the use of a marketed oral formulation containing 1 mg estradiol valerate and 2 mg dienogest for treatment of menopausal symptoms in 1292 women visiting 243 gynecological practices in Germany. METHODS: Score changes in the Menopausal Rating Scale (MRS) after three and six 28-day cycles were primary endpoints. Subjective reports on skin- and hair-related complaints and satisfaction with treatment effects were assessed. The incidence of adverse drug reactions (ADRs), adverse events (AEs) and vaginal bleeding was evaluated. RESULTS: MRS total score decreased substantially and stronger than the clinically relevant change of 5 points (p < 0.0001) as compared with baseline. Subjective skin- and hair-related complaints declined. No unexpected ADRs were reported. AEs (including ADRs) were registered in 8.8% of the participants; most frequent AEs/ADRs were postmenopausal hemorrhage (2.9%) and drug ineffective (1.4%). Nearly 76% of the subjects remained amenorrheic. Approximately 90% of the patients rated the medication's effectiveness/tolerability as good/very good; 84% intended to continue the treatment. CONCLUSION: This low-dose estradiol/dienogest formulation proved efficient and well-tolerated option for the alleviation of menopausal symptoms associated with estrogen deficiency.

Effectiveness of a primary care based complex intervention to promote self-management in patients presenting psychiatric symptoms: study protocol of a cluster-randomized controlled trial.

BACKGROUND: Anxiety, Depression and Somatoform (ADSom) disorders are highly prevalent in primary care. Managing these disorders is time-consuming and requires strong commitment on behalf of the General Practitioners (GPs). Furthermore, the management of these patients is restricted by the high patient turnover rates in primary care practices, especially in the German health care system.In order to address this problem, we implement a complex, low-threshold intervention by an Advanced Practice Nurse (APN) using a mixture of case management and counseling techniques to promote self-management in these patients. Here we present the protocol of the "Self-Management Support for Anxiety, Depression and Somatoform Disorders in Primary Care" (SMADS)-Study. METHODS/DESIGN: The study is designed as a cluster-randomized controlled trial, comparing an intervention and a control group of 10 primary care practices in each case. We will compare the effectiveness of the intervention applied by an APN with usual GP-care. A total of 340 participants will be enrolled in the study, 170 in either arm. We use the Patient Health Questionnaire-German version (PHQ-D) as a screening tool for psychiatric symptoms, including patients with a score above 5 on any of the three symptom scales. The primary outcome is self-efficacy, measured by the General Self-Efficacy Scale (GSE), here used as a proxy for self-management. As secondary outcomes we include the PHQ-D symptom load and questionnaires regarding coping with illness and health related quality of life. Outcome assessments will be applied 8 weeks and 12 months after the baseline assessment. DISCUSSION: The SMADS-study evaluates a complex, low threshold intervention for ambulatory patients presenting ADSom-symptoms, empowering them to better manage their condition, as well as improving their motivation to engage in self-help and health-seeking behaviour. The benefit of the intervention will be substantiated, when patients can enhance their expected self-efficacy, reduce their symptom load and engage in more self-help activities to deal with their everyday lives. After successfully evaluating this psychosocial intervention, a new health care model for the management of symptoms of anxiety, depression and somatoform disorders for ambulatory patients could emerge, supplementing the work of the GP. TRIAL REGISTRATION: Clinicaltrials.gov Identifier: NCT01726387.

Effectiveness, tolerability and acceptance of an oral estradiol/levonorgestrel formulation for the treatment of menopausal complaints: a non-interventional observational study over six cycles of 28 days.

BACKGROUND: Use of hormone therapy for menopausal complaints is a subject of controversy and increased uncertainty and concerns. This non-interventional study aimed to investigate a marketed oral formulation containing 1 mg estradiol and 0.04 mg levonorgestrel for continuous treatment of menopausal symptoms for approximately 6 months in women visiting gynecological practices in Germany. METHODS: Changes in the menopause rating scale (MRS) total and sub-domain scores after three and six 28-d cycles served as primary endpoint. Skin- and hair-related complaints, quality of sexual life and subjective satisfaction with the treatment were assessed. Adverse drug reactions (ADRs), adverse events (AEs) and vaginal bleeding were evaluated. RESULTS: MRS scores improved significantly above 5 points of clinical relevance as compared to baseline (n = 736, p < 0.0001). Skin- and hair-related symptoms abated; quality of sexual life improved. AEs were registered in 9.9% of the participants. No unexpected ADRs were reported. Bleeding episodes consistently decreased; >75% of the subjects were amenorrheic throughout the study. Medication's effectiveness and tolerability was rated very good/good by >80% of the participants, who also continued treatment. CONCLUSION: This estradiol/low-dose levonorgestrel formulation safely alleviates menopausal symptoms in peri- and postmenopausal women with add-on benefits regarding dermatological and sexual life complaints.

Influence of cation concentration and valence on the structure and texture of spray-dried supraparticles from colloidal silica dispersions.

The structure and texture of supraparticles determine their properties and performance, thus playing a critical role in research studies as well as industrial applications. The addition of salts is a well-known strategy to manipulate the colloidal stability of nanoparticles. In this study, this approach is used to tune the structure of spray-dried supraparticles. Three different salts (NaCl, CaCl2, and AlCl3) were added to binary silica (SiO2) nanoparticle dispersions (of 40 and 400 nm in size) to change their colloidal stability by lowering the electrostatic repulsion or enhancing the cation bridging. Dependent on the cation valence of the added salt and the nanoparticle size, the critical salt concentration, which yields nanoparticle agglomeration, is reached at different salt amounts. This phenomenon is exploited to tune the final structure of supraparticles - obtained by spray-drying binary dispersions - from core-shell to Janus-like to well-mixed structures. This consequently also tunes textural properties, like surface roughness and the pore system of the obtained supraparticles. Our results provide insights for controlling the structure of spray-dried supraparticles by manipulating the stability of binary nanoparticle dispersions, and they establish a framework for composite particle design.

Nature-Inspired Regenerative Fine-Dust-Catching Coatings to Improve Air Quality.

Increased particulate matter (PM) concentrations in our ambient air are the cause of various life-threatening diseases and consequently need to be reduced to nonhazardous levels. The natural PM removal capabilities of leaves inspired the development of a low-cost coating technology that exploits natural weather phenomena for its PM catching and removal processes. The herein presented coating is based on microparticle-filled silicone with optimized chemical and physical surface properties. Its surface roughness was tuned using differently sized spray-dried particles, and its surface contact angle was adjusted through silicone tensides, polar ether groups incorporated in the silicon backbone, and the used amount of spray-dried particles. In such a way, optimized silicone coatings showed in laboratory experiments improved catching abilities (>300% relative to glass surfaces), a full retention of adsorbed PM during wind events, and the formation of large PM aggregates. Upon (simulated) rain events, these coatings were regenerated, and the content of harmful PM of various sizes dispersed in water was reduced between ∼73 and 100%. Furthermore, an outdoor test over 100 days showed the functioning of the coating under real-world conditions. These regenerative coatings are readily applicable on diverse surfaces and do not require any further technical infrastructure. Thus, they present an extension of the toolbox for PM reduction technologies.

Structure-Based Design and Synthesis of Covalent Inhibitors for Deubiquitinase and Acetyltransferase ChlaDUB1 of Chlamydia trachomatis.

Upon infection by an intracellular pathogen, host cells activate apoptotic pathways to limit pathogen replication. Consequently, efficient proliferation of the obligate intracellular pathogen Chlamydia trachomatis, a major cause of trachoma and sexually transmitted diseases, depends on the suppression of host cell apoptosis. C. trachomatis secretes deubiquitinase ChlaDUB1 into the host cell, leading among other interactions to the stabilization of antiapoptotic proteins and, thus, suppression of host cell apoptosis. Targeting the bacterial effector protein may, therefore, lead to new therapeutic possibilities. To explore the active site of ChlaDUB1, an iterative cycle of computational docking, synthesis, and enzymatic screening was applied with the aim of lead structure development. Hereby, covalent inhibitors were developed, which show enhanced inhibition with a 22-fold increase in IC50 values compared to previous work. Comprehensive insights into the binding prerequisites to ChlaDUB1 are provided, establishing the foundation for an additional specific antichlamydial therapy by small molecules.

Rationalizing the Binding Modes of PET Radiotracers Targeting the Norepinephrine Transporter.

PURPOSE: A new PET radiotracer 18F-AF78 showing great potential for clinical application has been reported recently. It belongs to a new generation of phenethylguanidine-based norepinephrine transporter (NET)-targeting radiotracers. Although many efforts have been made to develop NET inhibitors as antidepressants, systemic investigations of the structure-activity relationships (SARs) of NET-targeting radiotracers have rarely been performed. METHODS: Without changing the phenethylguanidine pharmacophore and 3-fluoropropyl moiety that is crucial for easy labeling, six new analogs of 18F-AF78 with different meta-substituents on the benzene-ring were synthesized and evaluated in a competitive cellular uptake assay and in in vivo animal experiments in rats. Computational modeling of these tracers was established to quantitatively rationalize the interaction between the radiotracers and NET. RESULTS: Using non-radiolabeled reference compounds, a competitive cellular uptake assay showed a decrease in NET-transporting affinity from meta-fluorine to iodine (0.42 and 6.51 µM, respectively), with meta-OH being the least active (22.67 µM). Furthermore, in vivo animal studies with radioisotopes showed that heart-to-blood ratios agreed with the cellular experiments, with AF78(F) exhibiting the highest cardiac uptake. This result correlates positively with the electronegativity rather than the atomic radius of the meta-substituent. Computational modeling studies revealed a crucial influence of halogen substituents on the radiotracer-NET interaction, whereby a T-shaped π-π stacking interaction between the benzene-ring of the tracer and the amino acid residues surrounding the NET binding site made major contributions to the different affinities, in accordance with the pharmacological data. CONCLUSION: The SARs were characterized by in vitro and in vivo evaluation, and computational modeling quantitatively rationalized the interaction between radiotracers and the NET binding site. These findings pave the way for further evaluation in different species and underline the potential of AF78(F) for clinical application, e.g., cardiac innervation imaging or molecular imaging of neuroendocrine tumors.

Incidence, Clinical Significance, and Longitudinal Signal Characteristics of Ischemic Lesions Related to Diagnostic Cerebral Catheter Angiography.

PURPOSE: Cerebral DSA is a routine procedure with few complications. However, it is associated with presumably clinically inapparent lesions detectable on diffusion-weighted MRI imaging (DWI lesions). However, there are insufficient data regarding incidence, etiology, clinical relevance, and longitudinal development of these lesions. This study prospectively evaluated subjects undergoing elective diagnostic cerebral DSA for the occurrence of DWI lesions, potentially associated clinical symptoms and risk factors, and longitudinally monitored the lesions using state-of-the-art MRI. MATERIALS AND METHODS: Eighty-two subjects were examined by high-resolution MRI within 24 h after elective diagnostic DSA and lesion occurrence was qualitatively and quantitatively evaluated. Subjects' neurological status was assessed before and after DSA by clinical neurological examination and a perceived deficit questionnaire. Patient-related risk factors and procedural DSA data were documented. Subjects with lesions received a follow-up MRI and were questioned for neurological deficits after a median of 5.1 months. RESULTS: After DSA, 23(28%) subjects had a total of 54 DWI lesions. Significantly associated risk factors were number of vessels probed, intervention time, age, arterial hypertension, visible calcified plaques, and less examiner experience. Twenty percent of baseline lesions converted to persistent FLAIR lesions at follow-up. After DSA, none of the subjects had a clinically apparent neurological deficit. Self-perceived deficits were nonsignificantly higher at follow-up. CONCLUSION: Cerebral DSA is associated with a considerable number of postinterventional lesions, some persisting as scars in brain tissue. Presumably because of the small lesion size and inconsistent location, no clinically apparent neurological deficits have been observed. However, subtle self-perceived changes may occur. Therefore, special attention is needed to minimize avoidable risk factors.