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Heather L Gelhorn,1 Beatrice Osumili,2 Katelyn Brown,2 Melissa M Ross,1 Andrea Schulz,1 Gabriela Fernandez,1 Kristina S Boye2 1Patient-Centered Research, Evidera, Inc., Bethesda, MD, USA; 2Value, Evidence, and Outcomes, Eli Lilly and Company, Indianapolis, IN, USACorrespondence: Heather L Gelhorn, Patient-Centered Research, Evidera, Inc., 7101 Wisconsin Avenue, Suite 1400, Bethesda, MD, 20814, USA, Tel +1-970-363-7333, Email heather.gelhorn@evidera.comPurpose: To quantify the preferences of people with type 2 diabetes (T2D) for treatment attributes of a glucose-dependent insulinotropic polypeptide (GIP)/glucagon-like peptide-1 (GLP-1) receptor agonist (RA) versus an injectable GLP-1 RA medication profile.Patients and Methods: Injection-naive people taking oral medications for T2D in the US and UK completed a web survey including a discrete choice experiment to quantify patients’ preferences for five treatment attributes: delivery system, frequency of nausea, frequency of hypoglycemia, HbA1c reduction, and weight reduction. Attributes and levels were based on head-to-head clinical trial data of tirzepatide 5mg, 10mg, and 15mg versus semaglutide 1mg. Preference data were analyzed separately by country using multinomial mixed logit (MXL) models. MXL parameters were used to estimate the predicted preference for each tirzepatide dose versus semaglutide 1mg. Direct preferences for each dose of tirzepatide versus semaglutide 1mg were elicited.Results: Participants (N=620) in the US (N=301) and UK (N=319) were 50.8% and 50.5% female with mean ages of 60.7 years and 58.9 years, respectively. The order and magnitude of relative attribute importance (RAI) scores differed between countries. HbA1c reduction (26.3%) had the greatest impact on US participants’ preferences, and hypoglycemia (32.8%) did among UK participants. Attribute-level marginal utility results indicated preferences for greater HbA1c improvements, the single-use pre-filled pen, lower hypoglycemia, greater weight reductions, and lower frequency of nausea. Assuming the availability of only tirzepatide or semaglutide 1mg, the predicted preference for tirzepatide (5, 10, and 15mg) in the US is 95.6% (vs 4.4% for semaglutide 1mg) and in the UK was 86.3% (vs 13.7% for semaglutide 1mg).Conclusion: HbA1c reduction, frequency of hypoglycemia, and weight reduction are key drivers of preferences among people with T2D when considering medication options. Overall, people with T2D are likely to prefer the tirzepatide over the semaglutide 1mg medication profiles.Keywords: patient preferences, discrete choice experiment, patient perspective, incretin

A relação entre alterações na composição corporal e o desenvolvimento de comorbidades já era observada por Hipócrates há mais de 2000 anos. O objetivo foi investigar o impacto agudo causado por teste de corrida em esteira em atletas de alto nível. Além de identificar alterações agudas ocorridas em diferentes lipoproteínas plasmáticas, na concentração plasmática de TNF (Fator de Necrose Tumoral) e observar possível correlação entre TNF e composição corporal em atletas de corrida. Trata-se de estudo transversal, descritivo e observacional, partindo de uma estratégia esportômica, com atletas jovens de alto nível. A amostra foi composta por 10 indivíduos do gênero masculino, atletas de alto rendimento de atletismo da associação de atletismo de Barra do Garças, MT. O protocolo de exercício esteira foi incrementado progressivamente até exaustão, utilizando analisador de gases. A variação nos níveis do TNF apresentou correlação com a variação dos fosfolipídeos (1,0), com variação do colesterol total (1,0), com variação de lipídeos totais (1,0), variação da Lipoproteína de Baixa Densidade (0,9), lipoproteína essa que também apresentou correlação com o valor do TNF pós exercício (0,9). Já TNF pré exercício apresentou coeficiente de correlação com o peso dos indivíduos (-0,9) e variação do TNF com o índice de Massa Corporal (-0,928). Usar testes estatísticos de correlação e apresentação dos resultados com mapas de calor (heat maps) pode ser uma ferramenta de mineração de dados (data-mining) para avaliação de biomarcadores e diferentes variáveis em estudos do imunometabolismo. O presente estudo apresenta novas perspectivas para relação da composição corporal com imunometabolismo.

The present study aimed to investigate the possible correlations between the cytokine and adipokine Tumour Necrosis Factor Alpha with parameters of body composition and lipid metabolism in young, high-level athletes after an incremental treadmill test observed in a sample of five individuals, male, high-level running athletes who the difficulty of treating large databases with different individuals, multiple biomarkers, and collection times, in addition to physical parameters and sample characteristics, added to the decrease in new findings induced by the application of statistical tools of univariate analysis, indicate the need to apply exploratory machine learning strategies, generating holistic and integrated analysis of the results. The present study showed a negative correlation between TNF and HDL and a similarity between the same TNF and LDL. These findings do not indicate a cause-and-effect relationship but suggest a possible modulation of the immune system, lipid metabolism, and exercise that requires further investigation.

Cutaneous aging is a complex and continuous biological process characterized by cellular and molecular alterations, with progressive reduction of the bodyʼs capacity to maintain the homeostasis, senescence, and/or apoptosis of the dermal cells. Fibroblast growth factors (FGF) have elicited studies to evaluate their role of repair and remodeling of the dermis during the skin anti-aging process, since they are regulatory proteins that mediate important signaling pathways and act on cell regeneration and repair processes. FGF acts primarily through binding to tyrosine kinase receptors through the autophosphorylation of their residues, promoting the phosphorylation of serine, threonine, and tyrosine residues of specific target proteins such as Raf-1, MAPK/Erk kinase, and extracellular signal-regulated kinase-1, which are part of the cascade of MAP kinases (mitogen-activated protein kinase). Then, FGF initiate signaling cascades inside the cell, where each kinase activates the following by phosphorylation, resulting in alterations of cellular functions. In addition, the FGF has a relevant role in anti-aging therapy because it is related to collagen and elastin synthesis activation responsible for skin resistance and elasticity, characteristics that are diminished with skin aging. Thus, the present article aims to review several scientific studies that demonstrated the cell signaling involved with the action of FGF on skin aging.

Background and objectives: Acne scars are one of the most distressing and long-term consequences of acne vulgaris, with damaging effect on a person’s physical, mental, and social well-being. Numerous treatment options are available including surgical and nonsurgical techniques, depending on the clinical presentation. Although considerable advances in the development of new treatment technologies and applications have been made in the last decade, international treatment guidelines and reimbursement schemes have not yet caught up with current knowledge and practice in many centers. The authors intend to highlight the potential utility of energy-based devices (EBDs) for acne scarring, offer recommendations for safe and efficacious treatment, and provide consensus-based EBD treatment options based on varying presentations demonstrated in a series of real-life clinical photographs. Study design/materials and methods: An international panel of 24 dermatologists and plastic surgeons from 12 different countries and a variety of practice backgrounds was self-assembled to develop updated consensus recommendations for the treatment of acne scars. A two-step modified Delphi method took place between March 2020 and February 2021 consisting of two rounds of emailed questionnaires. The panel members approved the final manuscript via email correspondence. Results: The manuscript includes a comprehensive discussion and panel recommendations regarding the following topics: 1. the role of EBD in mitigating and treating acne scars in a patient with active acne, 2. the use of various EBDs for the treatment of different acne scar types with special focus on commonly used laser platform such as vascular lasers, ablative fractional lasers (AFLs) and non-AFLs (NAFLs), 3. treatment combinations, and 4. acne scar treatments in skin of color. The last part comprised of 10 photos of real-life clinical cases with the panel recommendation treatment plan to achieve best aesthetic outcome. Conclusion: Panel members were unanimous in their view that EBDs have a role in the management of acne scars, with AFLs, NAFLs, vascular lasers, and RF devices preferentially selected by most of the panel experts. EBDs are considered a first-line treatment for a variety of acne scar types and patients without access to these treatments may not be receiving the best available care for optimal cosmetic results. Future high-quality research and updated international treatment guidelines and reimbursement schemes should reflect this status.

Objective:To evaluate the efficacy and safety of photodynamic therapy (PDT) with the novel 10% aminolevulinic acid (ALA) hydrochloride gel (10% ALA gel) and BF-RhodoLED® light (635 nm; 37 J/cm2 ) in combination with intense pulsed light (IPL) to augment the medical and aesthetic improvement of photodamaged skin of the décolleté. Methods:This was a single-site prospective, randomized, intraindividual split chest pilot study with 20 female subjects with moderate to severe photodamage of the décolleté. Subjects were randomized to ALA-PDT + IPL to one split-side of the chest and ALA-PDT only to the contralateral side. Three blinded raters assessed aesthetic improvement using the global aesthetic improvement scale (GAIS). Results:Eighteen subjects completed the study. Superior GAIS results were achieved on the ALA-PDT + IPL treatment side than on the ALA-PDT only treatment side (p < 0.001) after 24 weeks of follow-up. Conclusions:ALA-PDT using 10% ALA hydrochloride gel and BF-RhodoLED® light had superior rejuvenation effects on the décolleté when combined with IPL compared to ALA-PDT alone.

* DOI: 10.18312/connectionline.v0i23.1593 RESUMO O objetivo foi apresentar os passos para a construcao de um instrumento de avaliacao da qualidade de restaurantes segundo o Guia Alimentar para a Populacao Brasileira. Assim, trata-se de um estudo metodologico realizado com o intuito de construir um instrumento para avaliacao da qualidade de restaurantes utilizando-se o Guia Alimentar para a Populacao Brasileira. Optou-se por um questionario com vinte questoes em que buscouse incluir os principais questionamentos acerca do assunto, na tentativa de melhorar a analise global de um restaurante segundo as novas propostas do Guia, mas e reconhecivel a limitacao do instrumento mediante os varios questionamentos do Guia. Assim, o instrumento foi intitulado “Instrumento de Avaliacao da Qualidade de Restaurantes segundo o Guia Alimentar para a Populacao Brasileira (IAQR-Guia)”. O instrumento possui como opcoes de resposta “Sim”, “Nao” e “Nao se aplica”, pontuando 1,0 ponto para cada resposta “Sim”, devendo este valor ser recalculado mediante respostas “nao se aplica”. Sendo criado um ponto de corte para classificacao, entretanto, destaca-se que quanto maior a pontuacao, mais adequado esta o restaurante segundo o Guia Alimentacao para a Populacao Brasileira. Os passos para a construcao do Instrumento de IAQR-Guia foram concluidos sendo descrita a importância de cada questionamento. Palavras-chave: Guia Alimentar para a Populacao Brasileira. Sustentabilidade. Questionario. Restaurante

Objective: To describe the population assisted in a genetics outpatient clinic, in a medium-sized town, with respect to diagnosis, type of inheritance, and local impact of genetic care. Methods: Medical records and genetic consultation forms from 2006 to 2018 were reviewed. The variables analyzed were age, sex, origin, current residence, reason for consultation, professional who requested evaluation, final diagnosis, additional exams and their results. Results: A total of 609 patients were seen, 65.9% aged 0 to 12 years. Genetic syndromes were suspected in 15.1%, and 11% presented developmental delay. Neurogenetic disorders stood out among adults. Mendelian inheritance was more prevalent (17.8%). Requests for genetic consultation have doubled in the last 5 years, with 44.4% due to suspected genetic syndrome. Conclusion: Genetic consultations have shown to be an important tool for inpatient care, reducing the waiting time to initiate treatment, attenuating potential associated costs, and guiding the families of patients. Outpatient care provided diagnosis and genetic counseling for users from the city and surrounding region, decreased costs and offered a training environment in medical genetics. RESUMO Objetivo: Descrever a população atendida em um ambulatório de genética, em uma cidade de médio porte, em relação a diagnóstico, tipo de herança e impacto local do atendimento. Métodos: Foram revisados os prontuários e formulários do serviço de genética entre 2006 e 2018. As variáveis analisadas foram idade, sexo, procedência e atual residência, motivo de referência/consultoria, profissional que encaminhou, diagnóstico final, exames complementares e seus resultados. Resultados: Foram atendidos 609 pacientes, 65,9% com idade de zero a 12 anos. Houve suspeita de síndromes genéticas em 15,1%, e 11% apresentaram atraso no desenvolvimento. Distúrbios neurogenéticos destacaram-se entre os adultos. A herança mendeliana teve maior frequência (17,8%). As solicitações de consultorias genéticas duplicaram nos últimos 5 anos, sendo 44,4% por “suspeita de síndrome genética”. Conclusão: As consultorias genéticas mostraram-se ferramenta importante em nível hospitalar, reduzindo o tempo de espera até a instituição terapêutica, minimizando custos potenciais associados e norteando os familiares. O atendimento ambulatorial ofereceu diagnóstico e aconselhamento genético para usuários da cidade e região, diminuiu custos, além de propiciar um ambiente de ensino em genética médica.

Background: Inadvertent intra-arterial injection of dermal fillers including calcium hydroxylapatite (CaHA) can result in serious adverse events including soft tissue necrosis, permanent scarring, visual impairment, and blindness. When intra-arterial injection occurs, immediate action is required for optimal outcomes, but the infrequency of this event means that many physicians may never have experienced this scenario. The aim of this document is to provide evidence-based and expert opinion recommendations for the recognition and management of vascular compromise following inadvertent injection of CaHA. Subjects and methods: An international group of experts with experience in injection of CaHA and management of vascular complications was convened to develop a consensus on the optimal management of vascular compromise following intra-arterial CaHA injection. The consensus members were asked to provide preventative advice for the avoidance of intravascular injection and to produce a treatment protocol for acute and delayed presentation. To ensure all relevant treatment options were included, the recommendations were supplemented with a PubMed search of the literature. Results: For prevention of intra-arterial CaHA injection, consensus members outlined the importance of a thorough knowledge of facial vascular anatomy and patient history, as well as highlighting potential risk zones and optimal injection techniques. Individual sections document how to recognize the symptoms of vascular occlusion leading to vision loss and tissue necrosis as well as detailed treatment protocols for the management of these events. For impending tissue necrosis, recommendations are provided for early and delayed presentations with treatment protocols for acute and follow-up treatment. A separate section details the treatment options for open and closed wounds. Conclusion: All physicians should be prepared for the eventuality of intra-arterial injection of a dermal filler, despite its rarity. These consensus recommendations combine advice from aesthetic experts with the latest reports from the published literature to provide an up-to-date office-based protocol for the prevention and treatment of complications arising from intra-arterial CaHA injection.

Background: The novel coronavirus (COVID-19) pandemic is expected to last for an extended time, making strict safety precautions for office procedures unavoidable. The lockdown is going to be lifted in many areas, and strict guidelines detailing the infection control measures for aesthetic clinics are going to be of particular importance. Methods: A virtual meeting was conducted with the members (n = 12) of the European Academy of Facial Plastic Surgery Focus Group to outline the safety protocol for the nonsurgical facial aesthetic procedures for aesthetic practices in order to protect the clinic staff and the patients from SARS-CoV-2 infection. The data analysis was undertaken by thematic and iterative approach. Results: Consensus guidelines for nonsurgical facial aesthetic procedures based on current knowledge are provided for three levels: precautions before visiting the clinic, precautions during the clinic visit, and precautions after the clinic visit. Conclusions: Sound infection control measures are mandatory for nonsurgical aesthetic practices all around the world. These may vary from country to country, but this logical approach can be customized according to the respective country laws and guidelines.

Background Second-generation antipsychotics (SGAs) used to treat patients with schizophrenia generally have lower risk of motor side effects (SEs) than first-generation antipsychotics, but they are associated with other well-known SEs. The goal of this study was to understand how specific SEs of SGAs impact daily functioning, emotional well-being, and overall quality of life of patients with schizophrenia from their own perspective. Methods This study was a cross-sectional, participant-reported web survey, conducted globally during 2017–2018. The survey captured participants’ socio-demographic information, and assessments using the Quality of Life Enjoyment and Satisfaction Questionnaire Short Form (Q-LES-Q-SF) instrument, and the Glasgow Antipsychotic Side-Effect Scale (GASS). Additionally, specific questions about functional and emotional impacts were developed for SEs recognized as being bothersome to patients,2 such as activating SEs (‘Feeling restless/unable to sit still’, ‘Shaky hands or arms’, and ‘Difficulty sleeping’) sedating SEs (‘Feeling sleepy during the day’, ‘Feeling drugged/like a zombie’) and metabolic or endocrine SEs (‘Weight gain’, ‘Problems enjoying sex’). Participants noted on a visual analog scale (VAS) the degree of impact on functioning, 0 indicating ‘no impact at all’ and 100 indicating the ‘largest degree of impact’. Participants with schizophrenia (≥18 years old) stable for at least one month, taking an SGA for 1–12 months, and self-reporting at least one SE were included. Results Of 6,556 respondents screened, 435 were included in the study – United States, n=180; Canada, n=99; Australia, n=28; and Europe, n=128 (Italy, n=90; Spain, n=22; Denmark, n=8; Norway, n=8). The majority of the participants were diagnosed within the last 5 years and nearly half were living with a spouse or partner. The employment rate (full time or part time) was 39.9% globally and 43.3% in Italy. Respondents in Italy were on ‘predominantly sedating’ (54.4%), and/or ‘similarly activating and sedating’ (43.3%) SGAs (as defined in Citrome, J Clin Psychopharmacol 2017). In Italy, Q-LES-Q-SF total score was (mean [standard deviation; SD]) 46.6 [9.1], out of a possible score range of 14–70 (globally, 44.3 [9.8]). Similar to other countries, participants from Italy showed lowest satisfaction scores for Q-LES-Q-SF items of ‘Sexual drive, interest and/or performance’, ‘Economic status’, and ‘Work’. In Italy, the most prevalent SEs reported on the GASS were ‘Feeling sleepy during the day’, ‘Difficulty sleeping’, and ‘Problems enjoying sex’, while globally patients reported ‘Feeling sleepy during the day’, ‘Difficulty sleeping’, and ‘Dry mouth’ as the most common SEs. More than half of the participants stated they had experienced gaining weight as an SE (52.4% globally and 62.2% in Italy). Globally, SEs perceived as bothersome by patients were reported to impact participants’ functioning and emotions. These SEs had at least a moderate to severe impact (defined by a VAS score ≥50) on all aspects of functioning (physical, psychological, social, and vocational). The most common emotions associated with SEs reported by participants were feeling ‘Frustrated’, ‘Dissatisfied’, and ‘Ashamed/embarrassed’. Generally, the results from the survey in Italy were comparable to those of the global survey. Discussion Findings from this survey confirm that participants taking SGAs for the treatment of schizophrenia still have many SEs, including activating and sedating SEs, sexual SEs, and weight gain. These SEs have a considerable negative impact on participant’s daily functioning and quality of life satisfaction, including on work, and sexual drive, in addition to psychosocial effects.

The condensing effect of aminoglycoside antibiotics on the structure of double-stranded DNA was examined. The selective condensation of DNA by small molecules is an interesting approach in biotechnology. Here, we present the interaction between calf thymus DNA and three types of antibiotic molecules: tobramycin, kanamycin, and neomycin. Several techniques were applied to study this effect. Atomic force microscopy, transmission electron microscopy images, and nuclear magnetic resonance spectra showed that the interaction of tobramycin with double-stranded DNA caused the rod, toroid, and sphere formation and very strong condensation of DNA strands, which was not observed in the case of other aminoglycosides used in the experiment. Studies on the mechanisms by which small molecules interact with DNA are important in understanding their functioning in cells, in designing new and efficient drugs, or in minimizing their adverse side effects. Specific interactions between tobramycin and DNA double helix was modeled using molecular dynamics simulations. Simulation study shows the aminoglycoside specificity to bend DNA double helix, shedding light on the origins of toroid formation. This phenomenon may lighten the ototoxicity or nephrotoxicity issues, but also other adverse reactions of aminoglycoside antibiotics in the human body. Electronic supplementary material The online version of this article (doi:10.1007/s00249-015-1095-9) contains supplementary material, which is available to authorized users.

Chronic leg ulcers can be a challenge to treat and long-term therapy a significant cost factor in western public health budgets. Objective wound assessment assays enabling selection of appropriate wound therapy regimes would be desirable. Oxygenation status in ulcer tissue has obtained increased attention as a relevant factor in wound healing. To increase oxygenation in wounds, a topical hemoglobin spray was developed. Although favorable results have been noted, the link between clinical efficacy and the mode of action has not been demonstrated. The aims were to determine if changes in tissue oxygenation can be measured after topical application of hemoglobin on chronic wounds and to evaluate the findings in terms of therapy strategies. Photoacoustic imaging was used to measure the local oxygen saturation (StO2) in leg ulcers before and after hemoglobin spray treatment. Sclerosis of the leg ulcers was histopathologically graded and the change in wound size was documented in a follow-up examination. Measuring 49 patients, an increase in StO2 after topical hemoglobin application from on average 66.1 to 71 % (p = 0.017) after 20 min was observed. Depending on the increase in StO2 (>10 % or

Maltreatment of children is a major public-health and social-welfare problem but socio-demographic variability has received little attention. This work addresses such variability in a general population cohort and associations with depression. Analyses were based on the cross-sectional SHIP-LEGEND examination among 2265 adults (29–89 years). Childhood maltreatment was multi-dimensionally assessed with the German 28-item Childhood Trauma Questionnaire (CTQ): emotional neglect; emotional abuse; physical neglect; physical abuse; sexual abuse. Non-linear associations between CTQ responses and age were assessed with fractional polynomials and cubic splines. Scale properties were analysed with confirmatory factor analyses and item response models. Associations between childhood maltreatment domains and depression [Beck Depression Inventory-II (BDI-II)] were assessed. The majority (58.9%) reported events indicative of at least mild levels of childhood maltreatment. CTQ subscales showed characteristically different non-linear associations to age across the five studied domains, indicating methodological issues like recall bias and the influence of seminal events. Psychometric scale properties were acceptable to good for all subscales except for physical neglect. Associations to depression measures varied systematically across socio-demographic strata. We conclude that socio-demographic variability is a major issue when studying self-reported childhood maltreatment in a community sample. This needs to be taken into account for the study of associations to psychiatric key outcomes. Copyright © 2014 John Wiley & Sons, Ltd.

In vitro and in vivo models revealed that the somatotropic system exerts central effects on the central nervous system. Disturbances to this system such as in the case of growth hormone deficiency or growth hormone excess, are associated with a wide range of psychiatric disorders. Nonetheless, there is no epidemiological data available regarding the influence of growth hormone and its mediator, insulin-like growth factor I (IGF-I), on depressive disorders. The objective of this study was to investigate whether endogenous IGF-I levels may predict depression in humans. We included 4079 adult subjects from the Study of Health in Pomerania (SHIP), a population-based study with a 5-year follow-up period. The main predictor was the baseline IGF-I value categorized in three levels as10th percentile, between the 10th and the 90th percentile (the reference group) and90th percentile. The outcome measure was the incidence of depressive disorders according to the Composite International Diagnostic-Screener (CID-S). After adjustment for potential confounding variables, females with IGF-I levels below the 10th percentile had a higher incidence of depressive disorders during follow-up (OR 2.70 95% CI 1.38-5.28, p=0.004) compared to females within the reference group (10th-90th percentile). Among males, those with IGF-I levels above the 90th percentile had a higher risk of depressive disorder (OR 3.26 95% CI 1.52-6.98, p=0.002) than those within the 10th-90th percentile. In conclusion we can demonstrate that low IGF-I levels in females and high IGF-I levels in males predict the development of depressive disorders in this general adult population sample.

(2014). First Cornerstones of the eu Rules on Cross-Border Child Cases: The Jurisprudence of the Court of Justice of the European Union on the Brussels Iia Regulation From C to Health Service Executive. Journal of Private International Law: Vol. 10, No. 1, pp. 1-40.

Objective This work addresses the life-time-prevalence of mental disorders in the adult general population in a German region (Vorpommern). We address effects of attrition on prevalence estimates. Methods Analyses are based on a general population cohort study (29 - 89 years, Study of Health in Pomerania, N = 2400), using the M-CIDI to obtain life-time diagnoses of mental disorders according to ICD-10. Statistical weights were used to assess the effects of selective non-response on prevalence estimates related to baseline physical and psychological morbidity and sociodemographic variables, measured 10 years before. Results In total 44.6 % of the male and 55.2 % of the female participants fulfilled criteria for at least one ICD mental disorder including specific phobias and tobacco dependence. Physical but not psychological baseline morbidity showed relevant associations to participation in the psychological examination ten years later. Weighted and unweighted prevalence estimates for mental disorders were very similar. Conclusion Our results illustrate the high burden due to mental disorders. Most prevalence estimates seem robust to prior mental comorbidities.

Anliegen: Es sollen Schwellenwerte fur die Klassifikation von Vernachlassigung und Missbrauch mithilfe des CTS entwickelt und validiert werden. Methodik: Auf Basis zweier Bevolkerungsstudien werden Schwellenwerte bestimmt und anhand des Ausenkriteriums Depression validiert. Ergebnisse: Die bestimmten Schwellenwerte differenzieren gut hinsichtlich der Haufigkeit von Depressionen, und zeigen mit Ausnahme der Dimension „korperliche Vernachlassigung“ gute bis sehr gute Sensitivitaten und Spezifitaten zum Childhood Trauma Questionnaire. Schlussfolgerung: Die Schwellenwerte unterstutzen die Nutzung des CTS zur kategorialen Diagnostik.

Theoretische Modelle und empirische Befunde legen einen Zusammenhang zwischen Alexithymie, traumatischen Erlebnissen und der Diagnose einer posttraumatischen Belastungsstörung (PTSD) nahe, wobei die Befundlage nicht einheitlich ist und sich überwiegend auf klinische bzw. spezifische Populationen stützt. Vor diesem Hintergrund untersuchten wir 2098 Probanden aus der Allgemeinbevölkerung mit Selbstbeurteilungsinstrumenten zu Alexithymie (Toronto-Alexithymie-Skala; TAS-20) und aktueller Depressivität (Beck Depressions Inventar; BDI-II) sowie dem PTSD-Modul des Strukturierten Klinischen Interviews (SKID-I). Probanden mit einer PTSD hatten signifikant höhere Alexithymie-Werte in allen Dimensionen als traumatisierte Personen ohne PTSD und nicht-traumatisierte Erwachsene, auch unter Kontrolle relevanter konfundierender Variablen. Wurde zusätzlich Depressivität berücksichtigt, fanden sich diese Zusammenhänge nicht mehr. Diese Befunde werden in die bisherige Datenlage eingebettet und hinsichtlich der phänomenologischen Überschneidungen posttraumatischer Symptome wie abgeflachte emotionale Reagibilität, Depressivität und Alexithymie diskutiert.

In diesem Kapitel werden die Professionalisierungsmasnahmen im Rahmen des KOMPASS-Projektes in den Bildungsbereichen Sprache und Literacy, fruhe mathematische Bildung und sozial-emotionale Entwicklung beschrieben. Das in Kap. 2.4 dargestellte, gestufte Interventionsdesign umfasst fur die erste Interventionsgruppe (IG I) eine Grundlagenfortbildung, fachspezifische Fortbildungen sowie darauf aufbauende Individualcoachings. Die zweite Interventionsgruppe (IG II) erhielt lediglich die Grundlagenfortbildung sowie die fachspezifischen Fortbildungen.

Objective: To use a non-invasive measurement of oxygen saturation in chronic leg ulcers after the application of a topical haemoglobin spray to investigate if photoacoustic tomography is able to measure the oxygen saturation and if the stimulated oxygen increase can be demonstrated. Method: We measured the oxygen saturation of the ulcer tissue in five patients with chronic leg ulcers before application and 5 and 20 minutes after application of the haemoglobin spray, using photoacoustic tomography as a new method to assess oxygenation in real-time. Results: The average oxygen saturation showed a significant increase from 56.4% before to 69% (p=0.042) after 5 minutes and 78.8% (p=0.043) 20 minutes after the topical haemoglobin application. Conclusion: The oxygenation status of chronic, hard-to-heal wounds is gaining increasing interest in modern wound therapy. Topical haemoglobin spray is a new and effective method to increase the oxygenation in the ulcer tissue, but until now the link between clinical results and the mode of action was unclear. We were able to show for the first time that the use of a topical haemoglobin spray leads to an increase in oxygen saturation in vivo using photoacoustic tomography. Declaration of interest: Joachim Dissemond received financial support from the company SastoMed for several scientific projects as well as for lectures and as an advisor. The haemoglobin spray was provided by SastoMed GmbH (Georgsmarienhütte, Germany).

Anliegen: Ziel war die Entwicklung eines zeitokonomischen Screeninginstruments (Childhood Trauma Screener, CTS) zur Erfassung traumatischer Ereignisse in der Kindheit und Jugend. Methode: Auf der Basis einer Stichprobe der SHIP-LEGENDE-Studie (n = 1668) wurden 5 Items des „Childhood Trauma Questionnaire“ (CTQ, 28 Items) ermittelt, die die 5 Missbrauchs- und Vernachlassigungsdimensionen des CTQ am besten abbildeten. Ergebnisse: In der Validierung auf der Grundlage einer klinischen Stichprobe (n = 211) zeigten sich Korrelationen der 5 CTS Items mit der jeweils zugehorigen CTQ-Dimension von r = 0,55−0,87 sowie des CTS-Gesamtwerts zum CTQ-Gesamtwert von r = 0,88. Cronbachs α lag bei 0,757 (n = 499). Schlussfolgerungen: Der CTS ist ein reliables und sehr okonomisches Screeninginstrument zur Erfassung traumatischer Ereignisse in Kindheit und Jugend.

Background Based on biological interactions between the serotonergic system and the brain-derived neurotrophic factor (BDNF), BDNF is a plausible candidate for a gene–gene–environment interaction moderating the interaction between the s/l- promoter polymorphism of the serotonin transporter (5-HTTLPR) and childhood abuse. We tested the hypothesis of a three-way interaction with respect to depressive symptoms. Methods 2035 Caucasian subjects from the Study of Health in Pomerania (German general population) completed the Beck Depression Inventory (BDI-II) and the Childhood Trauma Questionnaire. All subjects were genotyped for the BDNF Val66Met (rs6265) and the s/l 5-HTTLPR polymorphisms. Results Tobit regression analyses revealed a three-way-interaction between the three genotypes of 5-HTTLPR and the BDNF genotypes and overall childhood abuse for the BDI-II score (p = 0.02). Emotional abuse carried the main effect of the interaction (p = 0.008). The s/s genotype of the 5-HTTLPR exerted its negative impact on mental health after childhood abuse only in the presence of the BDNF Val/Val genotype but not in the presence of the BDNF Met allele. In contrast, the l allele of the 5-HTTLPR also emerged as a genetic risk factor for depression in carriers of one or two Met alleles. Conclusions Our results point to a gene–gene–environment interaction that relevantly impacts on the role of the s/s genotype of the 5-HTTLPR in childhood abuse: Depending on the BDNF background (Val/Val versus Met allele) the s/s genotype showed either protective or risk properties with regard to depressive symptoms.

Childhood maltreatment and depressive disorders have both been associated with a dysregulation of the hypothalamic–pituitary–adrenal axis. The FKBP5 gene codes for a co-chaperone regulating the glucocorticoid-receptor sensitivity. Previous evidence suggests that subjects carrying the TT genotype of the FKBP5 gene single-nucleotide polymorphism (SNP) rs1360780 have an increased susceptibility to adverse effects of experimental stress. We therefore tested the hypothesis of an interaction of childhood abuse with rs1360780 in predicting adult depression. In all, 2157 Caucasian subjects from the Study of Health in Pomerania (German general population) completed the Beck Depression Inventory (BDI-II) and Childhood Trauma Questionnaire. The DSM-IV diagnosis of major depressive disorder (MDD) was assessed by interview. Genotypes of rs1360780 were taken from the Affymetrix Human SNP Array 6.0. Significant interaction (p=0.006) of physical abuse with the TT genotype of rs1360780 was found increasing the BDI-II score to 17.4 (95% confidence interval (CI)=12.0–22.9) compared with 10.0 (8.2–11.7) in exposed CC/CT carriers. Likewise, the adjusted odds ratio for MDD in exposed TT carriers was 8.2 (95% CI=1.9–35.0) compared with 1.3 (0.8–2.3) in exposed subjects with CC/CT genotypes. Relative excess risk due to interaction (RERI) analyses confirmed a significant additive interaction effect (RERI=6.8; 95% CI=0.64–33.7; p

Dysregulations of the hypothalamic-pituitary-adrenal (HPA) axis have been implicated in the pathogenesis of depressive disorders and the corticotropin-releasing hormone (CRH) was found to modulate emotional memory consolidation. Recently, two studies have reported an interaction between childhood abuse and the TAT-haplotype of the CRH-Receptor Gene (CRHR1) connecting childhood adversities and genetic susceptibility to adult depression. We tested the hypothesis of an interaction of childhood maltreatment with single nucleotide polymorphisms (SNPs) and haplotypes of the CRHR1 gene not previously investigated. Caucasian subjects (n = 1,638) from the German general population (Study of Health in Pomerania, SHIP) were analyzed. As in the previous studies, childhood abuse and neglect were assessed with the Childhood Trauma Questionnaire (CTQ) and depression with the Beck Depression Inventory (BDI-2). The CRHR1-SNPs were genotyped on the Affymetrix Genome-Wide Human SNP Array 6.0 platform. We identified an interaction between the TAT-haplotype and childhood physical neglect. The interaction with physical neglect showed significant (P < 0.05) results in 23 of the 28 SNPs, with rs17689882 (P = 0.0013) reaching "gene-wide" significance. Although we did not replicate the specific interaction of abuse and the TAT-haplotype of the CRHR1 gene we confirmed the relevance of an interplay between variants within the CRHR1 gene and childhood adversities in the modulation of depression in adults. The largest effect was found for rs17689882, a SNP previously not analyzed. Relevant sample differences between this and prior studies like lower BDI-2 scores, less childhood maltreatment and higher psychosocial functioning may account for the differences in gene-environment interaction findings. © 2010 Wiley-Liss, Inc.

RNA interference provides great opportunities for treating diseases from genetic disorders, infection, and cancer. The successful application of small interference RNA (siRNA) in cells with high transfection efficiency and low cytotoxicity is, however, a major challenge in gene-mediated therapy. Several pH-responsive core shell architectures have been designed that contain a nitrogen shell motif and a polyglycerol core, which has been prepared by a two-step protocol involving the activation of primary and secondary hydroxyl groups by phenyl chloroformate and amine substitution. Each polymer was analyzed by particle size and ζ potential measurements, whereas the respective polyplex formation was determined by ethidium bromide displacement assay, atomic force microscopy (AFM), and surface charge analysis. The in vitro gene silencing properties of the different polymers were evaluated by using a human epithelial carcinoma cell (HeLaS3) line with different proteins (Lamin, CDC2, MAPK2). Polyplexes yielded similar knockdown efficiencies as HiPerFect controls, with comparably low cytotoxicity. Therefore, these efficient and highly biocompatible dendritic polyamines are promising candidates for siRNA delivery in vivo.

A novel coordination oligo/polymer is synthesized by metal-directed self-assembly from equimolar amounts of the (dppp)M(OTf)2 precursor complexes (dppp = bis-(diphenylphosphino)-propane, OTf = triflate; M = PdII or M = PtII) and banana-shaped bidentate dipyridyl ligands. The assemblies were characterized by ESI mass spectrometry and NMR spectroscopy. The analysis of the cloudy suspension prepared by dissolving the coordination polymer in aqueous methanol solutions indicates nanosized spherical objects to form. Evidence for vesicle formation from these metallo-supramolecular oligomers comes from (cryogenic) transmission electron microscopy (TEM, cryo-TEM). Atomic force microscopy revealed stable nanospheres on hydrophilic mica and monolayer formation on hydrophobic highly oriented pyrolitic graphite (HOPG) substrates. On mica, also torus-shaped object were observed, which are rationalized by vesicles that opened during the drying procedure and released the internal solvent. Elemental analysis of the nanoas...

Two generations of dendritic nanoparticles were prepared, which contain ( E )-stilbene or ( E , E )-1,4-distyrylbenzene chromophores in the 4 or 8 terminal positions of the propylene imine dendrons. The compounds show a highly efficient photoreactivity. On prolonged irradiation all stilbenoid chromophores were destroyed by oligomerization (crosslinking) and the typical absorption and fluorescence of the chromophores disappeared completely.

An association between lower educational attainment (EA) and an increased risk for depression has been confirmed in various western countries. This study examines whether pleiotropic genetic effects contribute to this association. Therefore, data were analyzed from a total of 9662 major depressive disorder (MDD) cases and 14 949 controls (with no lifetime MDD diagnosis) from the Psychiatric Genomics Consortium with additional Dutch and Estonian data. The association of EA and MDD was assessed with logistic regression in 15 138 individuals indicating a significantly negative association in our sample with an odds ratio for MDD 0.78 (0.75-0.82) per standard deviation increase in EA. With data of 884 105 autosomal common single-nucleotide polymorphisms (SNPs), three methods were applied to test for pleiotropy between MDD and EA: (i) genetic profile risk scores (GPRS) derived from training data for EA (independent meta-analysis on similar to 120 000 subjects) and MDD (using a 10-fold leave-one-out procedure in the current sample), (ii) bivariate genomic-relationship-matrix restricted maximum likelihood (GREML) and (iii) SNP effect concordance analysis (SECA). With these methods, we found (i) that the EA-GPRS did not predict MDD status, and MDD-GPRS did not predict EA, (ii) a weak negative genetic correlation with bivariate GREML analyses, but this correlation was not consistently significant, (iii) no evidence for concordance of MDD and EA SNP effects with SECA analysis. To conclude, our study confirms an association of lower EA and MDD risk, but this association was not because of measurable pleiotropic genetic effects, which suggests that environmental factors could be involved, for example, socioeconomic status. Refereed/Peer-reviewed

A supramolecular carbohydrate-functionalized two-dimensional (2D) surface was designed and synthesized by decorating thermally reduced graphene sheets with multivalent sugar ligands. The formation of host-guest inclusions on the carbon surface provides a versatile strategy, not only to increase the intrinsic water solubility of graphene-based materials, but more importantly to let the desired biofunctional binding groups bind to the surface. Combining the vital recognition role of carbohydrates and the unique 2D large flexible surface area of the graphene sheets, the addition of multivalent sugar ligands makes the resulting carbon material an excellent platform for selectively wrapping and agglutinating Escherichia coli (E. coli). By taking advantage of the responsive property of supramolecular interactions, the captured bacteria can then be partially released by adding a competitive guest. Compared to previously reported scaffolds, the unique thermal IR-absorption properties of graphene derivatives provide a facile method to kill the captured bacteria by IR-laser irradiation of the captured graphene-sugar-E. coli complex.

Two types of dendritic nanoparticles were prepared, which contain ( E )-stilbene chromophores in the terminal positions of the dendrons. The compounds showed a highly efficient photoreactivity in the course of which statistical CC bond formations led to a crosslinking of the particles. Finally, all stilbene chromophores reacted and the typical ( E )-stilbene absorption and fluorescence disappeared completely.

BACKGROUND Ectropion repair is a challenge in plastic surgery. Depending on the etiology of the underlying problem, a variety of surgical techniques are available. The etiology, operative management, and recurrence rate are presented. OBJECTIVE An improvement of the deformity or, in the ideal case, a functional and aesthetic restoration should be accomplished. MATERIAL AND METHODS In this study, 58 patients with ectropion treated from June 2002 until March 2004 were analyzed, 33 with scar contractures, 13 with a tumor of the lid margin, 8 with facial paralysis, and 4 with senile ectropion. Surgical procedures included lateral or medial canthopexy, lateral tarsorrhaphy, wedge excision, skin graft, local flaps, cartilage graft, fascial slings, and combined procedures in one-third of the patients. RESULTS Postoperative complications included incomplete correction and others in 18.9% of the patients. Eight patients (13.8%) had to be reoperated. CONCLUSION Correction of the lower lid area including restoration of the lid margin in terms of shape and position is the surgical end point. The preoperative analysis is mandatory for a surgical solution to this severe problem, which is associated with a high incidence of recurrence, especially in difficult reconstructive cases. An individual sophisticated strategy combined with experience in the variety of surgical techniques is mandatory. Frequently, multiple procedures are necessary.