Evaluation der Prognose bei dünnen malignen Melanomen (0.8-1.0mm Tumordicke) anhand eines Datensatzes der Universitätshautklinik Tübingen 2000-2010

Das maligne Melanom steigt in der Inzidenz weiter an, so dass die Anzahl zu versorgender Patienten seit Jahren weiter zunimmt. Hierbei nimmt die Nachsorge einen großen Stellenwert ein, um Zweitmelanome in möglichst frühen Stadien – bei noch geringer Tumordicke – sowie deren Rezidive frühzeitig zu erkennen, um einen Progress zu verhindern. Die achte Version der AJCC führte eine neue Stadieneinteilung für Melanome ein. In der vorliegenden Dissertation wurde untersucht, ob sich durch die neue Klassifizierung Änderungen für das Nachsorgeschema bei Melanomen mit einer Tumordicke von bis zu 1 mm erforderlich machen. Hierzu wurden in der vorliegenden Arbeit anhand eines Datensatzes des Zentralregisters der Deutschen Dermatologischen Gesellschaft und ebenso der Universitätshautklinik Tübingen prognostische Faktoren und Verläufe bei dünnen Melanomen untersucht. Die Einschlusskriterien setzten sich zusammen aus invasiven, kutanen malignen Melanomen der Tumordicke ≤2.0mm, Erstdiagnose zwischen 2000-2010 mit der T-Subklassifikation T1a/T1b oder T2a und einer Nachsorgezeit (Follow-up Time) von >3 Monaten. So ergab sich ein Kollektiv aus 12.132 Patienten. Der Datensatz wurde stratifiziert nach Tumordicke, die gemäß der aktuellen Tumordickeneinteilung der AJCC klassifiziert wurde: Die drei Subgruppen <0.8mm (n=7324), 0.8-1.0mm (n=1879) und 1.01-2.0mm (n=2929) wurden hinsichtlich des Rezidivverhaltens, der Rezidivhäufigkeit, des Rezidivfreien Überlebens und des Melanomspezifischen Überlebens analysiert. Außerdem wurden Patientencharakteristika, Prognosefaktoren und Häufigkeitsverteilungen innerhalb des Kollektivs nach Tumordickeneinteilung bestimmt. Die Analysen erfolgten mittels IBM SPSS Statistics (Version 27). Statistische Methoden wie die Kaplan-Meier-Überlebensanalyse, Bestimmung der Hazard Raten und Cox-Regressionsanalysen wurden angewandt. In der vorliegenden Studie zeigten sich Tumordicke und Ulzeration als signifikante, unabhängige prognostische Faktoren mit einem relativen Risiko von 2.1 für die Tumordicke und 3.0 für die Ulzeration in der Cox-Regressionsanalyse. Mit steigender Tumordicke ergibt sich ein Anstieg der Rezidive von 3.7% bei <0.8mm, über 9.8% bei 0.8-1.0mm, bis 15.8% bei 1.01-2.0mm. Die mediane rezidivfreie Zeit beträgt 32 Monate. In allen drei Gruppen zeigen sich lokoregionäre Metastasen als häufigste Rezidivart mit 2.7% bei <0.8mm, 7.2% bei 0.8-1.0mm und 9.9% bei 1.01-2.0mm. Eine Fernmetastasierung konnte in allen drei Gruppen seltener beobachtet werden. Das Melanomspezifische Überleben liegt in den drei Gruppen nach Tumordicke (<0.8mm, 0.8-1.0mm, 1.01-2.0mm) bis zum 5-Jahres-Zeitpunkt bei über 94%. Beim 10-Jahres-Überleben zeigt die Gruppe mit 0.8-1.0mm eine Wahrscheinlichkeit von 89.8% und die Gruppe mit 1.01-2.0mm eine Wahrscheinlichkeit von 88.1%. Das Rezidivfreie Überleben (1-10-Jahres-Überleben) liegt bei der Gruppe mit <0.8mm zwischen 91.5%-99.4%, für die Gruppe mit 0.8-1.0mm bei 81.9%-98.1% und für die Gruppe mit 1.01-2.0mm bei 74.0%-97.0%. Hazard Raten für das Auftreten von Rezidiven zeigten bei Melanomen einer Tumordicke von 1.04mm zeigen ein vergleichbar hohes Risiko unter Berücksichtigung der Hazard Raten über 1:40 im 3- und 8-Jahresabstand mit ebenso vergleichbaren Überlebensdaten (RFS, MSS). Die Veränderungen durch die Anpassung der T-Klassifikation in der aktuellen AJCC Definition mit den Tumordicken <0.8mm, 0.8-1.0mm und 1.01-2.0mm und Änderung der Zusammensetzung in den Tumorstadien IA und IB, ergaben keine Hinweise, dass eine Änderung der Nachsorge in diesen Tumorstadien angepasst werden müsste

Cigarette Smoking Among Low-Income African Americans: A Serious Public Health Problem

Background This study examines the current prevalence of cigarette smoking and the number of cigarettes smoked in a community-based sample of 1021 low-income African-American men and women. Methods Participants were selected using a two-stage, area probability sample design. Data were collected in 2002–2003 in face-to-face interviews and analyzed in 2005. All data and analyses were weighted to account for the complex sampling design. Results Fifty-nine percent of men and 41% of women were current smokers, with younger individuals apparently initiating smoking at an earlier age than older individuals. Conclusions The high prevalence of cigarette use provides further evidence that the excess burden of tobacco-related disease among low-income African-American families may be on the rise. This is of great concern, and if confirmed by further research, indicates an urgent need for preventive intervention

Pain control following inguinal herniorrhaphy: current perspectives

Inguinal hernia repair is one of the most common surgeries performed worldwide. With the success of modern hernia repair techniques, recurrence rates have significantly declined, with a lower incidence than the development of chronic postherniorrhaphy inguinal pain (CPIP). The avoidance of CPIP is arguably the most important clinical outcome and has the greatest impact on patient satisfaction, health care utilization, societal cost, and quality of life. The etiology of CPIP is multifactorial, with overlapping neuropathic and nociceptive components contributing to this complex syndrome. Treatment is often challenging, and no definitive treatment algorithm exists. Multidisciplinary management of this complex problem improves outcomes, as treatment must be individualized. Current medical, pharmacologic, interventional, and surgical management strategies are reviewed

A novel and well-defined benchmarking method for second generation read mapping

Background Second generation sequencing technologies yield DNA sequence data at ultra high-throughput. Common to most biological applications is a mapping of the reads to an almost identical or highly similar reference genome. The assessment of the quality of read mapping results is not straightforward and has not been formalized so far. Hence, it has not been easy to compare different read mapping approaches in a unified way and to determine which program is the best for what task. Results We present a new benchmark method, called Rabema (Read Alignment BEnchMArk), for read mappers. It consists of a strict definition of the read mapping problem and of tools to evaluate the result of arbitrary read mappers supporting the SAM output format. Conclusions We show the usefulness of the benchmark program by performing a comparison of popular read mappers. The tools supporting the benchmark are licensed under the GPL and available from http://www.seqan.de/projects/rabema.html

The Consensus Coding Sequence (Ccds) Project: Identifying a Common Protein-Coding Gene Set for the Human and Mouse Genomes

Effective use of the human and mouse genomes requires reliable identification of genes and their products. Although multiple public resources provide annotation, different methods are used that can result in similar but not identical representation of genes, transcripts, and proteins. The collaborative consensus coding sequence (CCDS) project tracks identical protein annotations on the reference mouse and human genomes with a stable identifier (CCDS ID), and ensures that they are consistently represented on the NCBI, Ensembl, and UCSC Genome Browsers. Importantly, the project coordinates on manually reviewing inconsistent protein annotations between sites, as well as annotations for which new evidence suggests a revision is needed, to progressively converge on a complete protein-coding set for the human and mouse reference genomes, while maintaining a high standard of reliability and biological accuracy. To date, the project has identified 20,159 human and 17,707 mouse consensus coding regions from 17,052 human and 16,893 mouse genes. Three evaluation methods indicate that the entries in the CCDS set are highly likely to represent real proteins, more so than annotations from contributing groups not included in CCDS. The CCDS database thus centralizes the function of identifying well-supported, identically-annotated, protein-coding regions.National Human Genome Research Institute (U.S.) (Grant number 1U54HG004555-01)Wellcome Trust (London, England) (Grant number WT062023)Wellcome Trust (London, England) (Grant number WT077198

Structural and functional annotation of the porcine immunome

Background: The domestic pig is known as an excellent model for human immunology and the two species share many pathogens. Susceptibility to infectious disease is one of the major constraints on swine performance, yet the structure and function of genes comprising the pig immunome are not well-characterized. The completion of the pig genome provides the opportunity to annotate the pig immunome, and compare and contrast pig and human immune systems.[br/] Results: The Immune Response Annotation Group (IRAG) used computational curation and manual annotation of the swine genome assembly 10.2 (Sscrofa10.2) to refine the currently available automated annotation of 1,369 immunity-related genes through sequence-based comparison to genes in other species. Within these genes, we annotated 3,472 transcripts. Annotation provided evidence for gene expansions in several immune response families, and identified artiodactyl-specific expansions in the cathelicidin and type 1 Interferon families. We found gene duplications for 18 genes, including 13 immune response genes and five non-immune response genes discovered in the annotation process. Manual annotation provided evidence for many new alternative splice variants and 8 gene duplications. Over 1,100 transcripts without porcine sequence evidence were detected using cross-species annotation. We used a functional approach to discover and accurately annotate porcine immune response genes. A co-expression clustering analysis of transcriptomic data from selected experimental infections or immune stimulations of blood, macrophages or lymph nodes identified a large cluster of genes that exhibited a correlated positive response upon infection across multiple pathogens or immune stimuli. Interestingly, this gene cluster (cluster 4) is enriched for known general human immune response genes, yet contains many un-annotated porcine genes. A phylogenetic analysis of the encoded proteins of cluster 4 genes showed that 15% exhibited an accelerated evolution as compared to 4.1% across the entire genome.[br/] Conclusions: This extensive annotation dramatically extends the genome-based knowledge of the molecular genetics and structure of a major portion of the porcine immunome. Our complementary functional approach using co-expression during immune response has provided new putative immune response annotation for over 500 porcine genes. Our phylogenetic analysis of this core immunome cluster confirms rapid evolutionary change in this set of genes, and that, as in other species, such genes are important components of the pig’s adaptation to pathogen challenge over evolutionary time. These comprehensive and integrated analyses increase the value of the porcine genome sequence and provide important tools for global analyses and data-mining of the porcine immune response

The COMPARE Data Hubs

Data sharing enables research communities to exchange findings and build upon the knowledge that arises from their discoveries. Areas of public and animal health as well as food safety would benefit from rapid data sharing when it comes to emergencies. However, ethical, regulatory and institutional challenges, as well as lack of suitable platforms which provide an infrastructure for data sharing in structured formats, often lead to data not being shared or at most shared in form of supplementary materials in journal publications. Here, we describe an informatics platform that includes workflows for structured data storage, managing and pre-publication sharing of pathogen sequencing data and its analysis interpretations with relevant stakeholders

Assessing the impact of low level laser therapy (LLLT) on biological systems: a review

PURPOSE: Low level laser therapy (LLLT) in the visible to near infrared spectral band (390-1100 nm) is absorption of laser light at the electronic level, without generation of heat. It may be applied in a wide range of treatments including wound healing, inflammation and pain reduction. Despite its potential beneficial impacts, the use of lasers for therapeutic purposes still remains controversial in mainstream medicine. Whilst taking into account the physical characteristics of different qualities of lasers, this review aims to provide a comprehensive account of the current literature available in the field pertaining to their potential impact at cellular and molecular levels elucidating mechanistic interactions in different mammalian models. The review also aims to focus on the integral approach of the optimal characteristics of LLLT that suit a biological system target to produce the beneficial effect at the cellular and molecular levels. METHODS: Recent research articles were reviewed that explored the interaction of lasers (coherent sources) and LEDs (incoherent sources) at the molecular and cellular levels. RESULTS: It is envisaged that underlying mechanisms of beneficial impact of lasers to patients involves biological processes at the cellular and molecular levels. The biological impact or effects of LLLT at the cellular and molecular level could include cellular viability, proliferation rate, as well as DNA integrity and the repair of damaged DNA. This review summarizes the available information in the literature pertaining to cellular and molecular effects of lasers. CONCLUSIONS: It is suggested that a change in approach is required to understand how to exploit the potential therapeutic modality of lasers whilst minimizing its possible detrimental effects

Global monitoring of antimicrobial resistance based on metagenomics analyses of urban sewage

Antimicrobial resistance (AMR) is a serious threat to global public health, but obtaining representative data on AMR for healthy human populations is difficult. Here, we use meta-genomic analysis of untreated sewage to characterize the bacterial resistome from 79 sites in 60 countries. We find systematic differences in abundance and diversity of AMR genes between Europe/North-America/Oceania and Africa/Asia/South-America. Antimicrobial use data and bacterial taxonomy only explains a minor part of the AMR variation that we observe. We find no evidence for cross-selection between antimicrobial classes, or for effect of air travel between sites. However, AMR gene abundance strongly correlates with socio-economic, health and environmental factors, which we use to predict AMR gene abundances in all countries in the world. Our findings suggest that global AMR gene diversity and abundance vary by region, and that improving sanitation and health could potentially limit the global burden of AMR. We propose metagenomic analysis of sewage as an ethically acceptable and economically feasible approach for continuous global surveillance and prediction of AMR.Peer reviewe