Advanced Ulcerated Squamous Cell Carcinoma of the Hand with Locoregional Axillary Lymph Node Metastasis – Case Report and Literature Review

BACKGROUND: Cutaneous squamous cell carcinoma (SCC) of the hand is the most common soft-tissue malignancy in this particular region. A literature survey suggested a higher rate of metastases in advanced SCC of the hand compared to head-and-neck cutaneous SCC. CASE REPORT: An 84-year-old man presented with an ulcerated firm tumour on the dorsum of his right hand. A diagnostic biopsy confirmed the diagnosis SCC. Imaging suggested an involvement of the tendons of digits 3 and 4. A diagnostic ultrasound suggested a loco-regional axillary lymph node metastasis. After discussion in the interdisciplinary tumour board, amputation of the affected digits followed by lymph node excision was recommended. CONCLUSIONS: Advanced SCC of the hand requires interdisciplinary management. Amputation is part of the surgical spectrum in advanced cases

Advanced Ulcerated Squamous Cell Carcinoma of the Hand with Locoregional Axillary Lymph Node Metastasis – Case Report and Literature Review

BACKGROUND: Cutaneous squamous cell carcinoma (SCC) of the hand is the most common soft-tissue malignancy in this particular region. A literature survey suggested a higher rate of metastases in advanced SCC of the hand compared to head-and-neck cutaneous SCC. CASE REPORT: An 84-year-old man presented with an ulcerated firm tumour on the dorsum of his right hand. A diagnostic biopsy confirmed the diagnosis SCC. Imaging suggested an involvement of the tendons of digits 3 and 4. A diagnostic ultrasound suggested a loco-regional axillary lymph node metastasis. After discussion in the interdisciplinary tumour board, amputation of the affected digits followed by lymph node excision was recommended. CONCLUSIONS: Advanced SCC of the hand requires interdisciplinary management. Amputation is part of the surgical spectrum in advanced cases

CapZ-lipid membrane interactions: a computer analysis

BACKGROUND: CapZ is a calcium-insensitive and lipid-dependent actin filament capping protein, the main function of which is to regulate the assembly of the actin cytoskeleton. CapZ is associated with membranes in cells and it is generally assumed that this interaction is mediated by polyphosphoinositides (PPI) particularly PIP(2), which has been characterized in vitro. RESULTS: We propose that non-PPI lipids also bind CapZ. Data from computer-aided sequence and structure analyses further suggest that CapZ could become partially buried in the lipid bilayer probably under mildly acidic conditions, in a manner that is not only dependent on the presence of PPIs. We show that lipid binding could involve a number of sites that are spread throughout the CapZ molecule i.e., alpha- and beta-subunits. However, a beta-subunit segment between residues 134–151 is most likely to be involved in interacting with and inserting into lipid membrane due to a slighly higher ratio of positively to negatively charged residues and also due to the presence of a small hydrophobic helix. CONCLUSION: CapZ may therefore play an essential role in providing a stable membrane anchor for actin filaments

H3K14ac is linked to methylation of H3K9 by the triple Tudor domain of SETDB1

SETDB1 is an essential H3K9 methyltransferase involved in silencing of retroviruses and gene regulation. We show here that its triple Tudor domain (3TD) specifically binds to doubly modified histone H3 containing K14 acetylation and K9 methylation. Crystal structures of 3TD in complex with H3K14ac/K9me peptides reveal that peptide binding and K14ac recognition occurs at the interface between Tudor domains (TD) TD2 and TD3. Structural and biochemical data demonstrate a pocket switch mechanism in histone code reading, because K9me1 or K9me2 is preferentially recognized by the aromatic cage of TD3, while K9me3 selectively binds to TD2. Mutations in the K14ac/K9me binding sites change the subnuclear localization of 3TD. ChIP-seq analyses show that SETDB1 is enriched at H3K9me3 regions and K9me3/K14ac is enriched at SETDB1 binding sites overlapping with LINE elements, suggesting that recruitment of the SETDB1 complex to K14ac/K9me regions has a role in silencing of active genomic regions

4MOST : the 4-metre multi-object spectroscopic telescope project in the assembly, integration, and test phase

4MOST is a new high-multiplex, wide-field spectroscopic survey facility under construction for ESO's 4m-VISTA telescope at Paranal, Chile. Its key specifications are: a large field of view of 4.4 square degrees, a high multiplex fibre positioner based on the tilting spine principle that positions 2436 science fibres in the focal surface of which 1624 fibres go to two low-resolution optical spectrographs (R = λ/Δλ ~ 6500) and 812 fibres transfer light to the high-resolution optical spectrograph (R ~ 20,000). Currently, almost all subsystems are completed and full testing in Europe will be finished in spring 2023, after which 4MOST will be shipped to Chile. An overview is given of instrument construction and capabilities, the planned science of the consortium and the recently selected community programmes, and the unique operational scheme of 4MOST

Bundeswehr - Waffe des Kapitals: Materialien zur Rolle der Bundeswehr im Gesellschaftssystem der BRD

Die vorliegende Arbeit ist als politisches Produkt einer bestimmten Phase der Studentenbewegung zu begreifen (1): 1m Sommer 1968 schlossen sich Hunderte von Bundeswehrreservisten, die an den Westberliner Universitäten studierten, zu einer Anti-Bundeswehr-Kampagne im Rahmen des Kampfes gegen die Verabschiedung der Notstandsgesetze zusammen. Die Kampagne kam über eine Resolution (2), einen Brief an das Bundesverteidigungsministerium und intensive Diskussionen iiber Fragen antimilitaristischer Taktik nicht hinaus. Ihre politische Unklarheit, mangelnde theoretische Grundlagen und die Abgehobenheit von der Praxis antimilitaristischer Arbeit in Westdeutschland lieben sie auf eine kleine Gruppe zusammenschrumpfen. Diese Gruppe unternahm es in der Folgezeit, die historischen, sozioökonomischen und politischen Aspekte der Rolle der Bundeswehr im Gesellschaftssystem der BRD herauszuarbeiten. Die unterschiedliche politische Zusammensetzung der Gruppe sowie der langwierige Erstellungsprozeß der Arbeit (vor allem dadurch bedingt, daß die Schwerpunkte des politischen Engagements der Beteiligten sich meist bald in andere Bereiche bewegten) erlaubte nur ansatzweise die Entwicklung einer durchgehenden, einheitlichen politischen und wissenschaftlichen Fragestellung und in ihrer Folge einer kollektiven Arbeitsweise. So stehen die einzelnen Teile der vorliegenden Arbeit oft relativ unverbunden nebeneinander. Vor allem konnten die neueren Fortschritte marxistischer Methode und Analyse nur teilweise aufgenommen werde

Social context for workplace health promotion: feasibility considerations in Costa Rica, Finland, Germany, Spain and Sweden

IRETWe constructed a simple, flexible procedure that facilitates the pre-assessment of feasibility of workplace health promotion (WHP) programmes. It evaluates cancer hazards, workers’ need for hazard reduction, acceptability of WHP, and social context. It was tested and applied in 16 workplace communities and among 1085 employees in industry, construction, transport, services, teaching and municipal works in Costa Rica, Finland, Germany, Spain and Sweden. Social context is inseparable from WHP. It covers workers’ organizations and representatives, management, safety committees, occupational health services, health and safety enforcement agencies, general health services, nongovernment organizations, insurance systems, academic and other institutions, regulatory stipulations pertaining WHP, and material resources. Priorities, risk definitions, attitudes, hazard profiles, motivations and assessment methods were highly contextual. Management preferred passive interventions, helping cover expert costs, participating in planning and granting time. Trade unions, workers’ representatives, safety committees and occupational health services appeared to be important operational partners. Occupational health services may however be loaded with curative and screening functions or be non-existent. We advocate participatory, multifaceted WHP based on the needs and empowerment of the workers themselves, integrating occupational and lifestyle hazards. Workforce in irregular and shift work, in agriculture, in small enterprises, in the informal sector, and immigrant, seasonal and temporary workers represent groups in need of particular strategies such as community health promotion. In a more general framework, social context itself may become a target for intervention.Construimos un procedimiento simple y flexible que facilita la evaluación previa de la viabilidad de los programas de promoción de la salud en el lugar de trabajo (WHP). Evalúa los peligros del cáncer, la necesidad de los trabajadores de reducir los peligros, la aceptabilidad de la WHP y el contexto social. Fue probado y aplicado en 16 comunidades laborales y entre 1085 empleados en la industria, construcción, transporte, servicios, docencia y obras municipales en Costa Rica, Finlandia, Alemania, España y Suecia. El contexto social es inseparable de WHP. Abarca las organizaciones y representantes de trabajadores, la dirección, los comités de seguridad, los servicios de salud ocupacional, las agencias de aplicación de la salud y la seguridad, los servicios de salud en general, las organizaciones no gubernamentales, los sistemas de seguros, las instituciones académicas y de otro tipo, las estipulaciones reglamentarias relativas a las WHP y los recursos materiales. Las prioridades, las definiciones de riesgo, las actitudes, los perfiles de peligro, las motivaciones y los métodos de evaluación eran muy contextuales. La gerencia prefirió las intervenciones pasivas, ayudando a cubrir los costos de los expertos, participando en la planificación y otorgando tiempo. Los sindicatos, los representantes de los trabajadores, los comités de seguridad y los servicios de salud en el trabajo parecían ser socios operativos importantes. Sin embargo, los servicios de salud ocupacional pueden estar cargados de funciones curativas y de detección o ser inexistentes. Abogamos por una WHP participativa y multifacética basada en las necesidades y el empoderamiento de los propios trabajadores, integrando los riesgos ocupacionales y de estilo de vida. La mano de obra en el trabajo irregular y por turnos, en la agricultura, en las pequeñas empresas, en el sector informal y los trabajadores inmigrantes, estacionales y temporales representan grupos que necesitan estrategias particulares como la promoción de la salud comunitaria. En un marco más general, el contexto social en sí mismo puede convertirse en un objetivo de intervención.Construímos um procedimento simples e flexível que facilita a pré-avaliação da viabilidade de programas de promoção da saúde no local de trabalho (WHP). Ele avalia os riscos de câncer, a necessidade dos trabalhadores de reduzir os riscos, a aceitabilidade do WHP e o contexto social. Foi testado e aplicado em 16 comunidades de locais de trabalho e entre 1.085 funcionários na indústria, construção, transporte, serviços, ensino e obras municipais na Costa Rica, Finlândia, Alemanha, Espanha e Suécia. O contexto social é inseparável do WHP. Abrange organizações e representantes de trabalhadores, gestão, comitês de segurança, serviços de saúde ocupacional, agências de fiscalização de saúde e segurança, serviços de saúde em geral, organizações não governamentais, sistemas de seguro, instituições acadêmicas e outras, estipulações regulamentares relativas a WHP e recursos materiais. Prioridades, definições de risco, atitudes, perfis de perigo, motivações e métodos de avaliação eram altamente contextuais. A administração preferiu intervenções passivas, ajudando a cobrir os custos de especialistas, participando do planejamento e concedendo tempo. Sindicatos, representantes dos trabalhadores, comitês de segurança e serviços de saúde ocupacional pareciam ser parceiros operacionais importantes. Os serviços de saúde ocupacional podem, entretanto, estar repletos de funções curativas e de triagem ou podem não existir. Defendemos o WHP participativo e multifacetado com base nas necessidades e na capacitação dos próprios trabalhadores, integrando riscos ocupacionais e de estilo de vida. A força de trabalho em trabalho irregular e por turnos, na agricultura, em pequenas empresas, no setor informal e os trabalhadores imigrantes, sazonais e temporários representam grupos que precisam de estratégias específicas, como a promoção da saúde comunitária. Em uma estrutura mais geral, o próprio contexto social pode se tornar um alvo para intervençãoFinnish Institute of Occupational Health, FinlandKarolinska Institute, SwedenBremen Institute for Prevention Research and Social Medicine, GermanyMunicipality of Sabadell, EspañaDirectorate General for Occupational Health, EspañaMunicipal Institute for Medical Research, EspañaNational Institute for Occupational Safety and Hygiene, EspañaUniversidad Nacional, Costa RicaTechnological University of Costa Rica, Costa RicaInstituto Regional de Estudios en Sustancias Tóxica

Consistent alterations in faecal microbiomes of patients with primary sclerosing cholangitis independent of associated colitis.

Background Single‐centre studies reported alterations of faecal microbiota in patients with primary sclerosing cholangitis (PSC). As regional factors may affect microbial communities, it is unclear if a microbial signature of PSC exists across different geographical regions. Aim To identify a robust microbial signature of PSC independent of geography and environmental influences. Methods We included 388 individuals (median age, 47 years; range, 15‐78) from Germany and Norway in the study, 137 patients with PSC (n = 75 with colitis), 118 with ulcerative colitis (UC) and 133 healthy controls. Faecal microbiomes were analysed by 16S rRNA gene sequencing (V1‐V2). Differences in relative abundances of single taxa were subjected to a meta‐analysis. Results In both cohorts, microbiota composition (beta‐diversity) differed between PSC patients and controls (P < 0.001). Random forests classification discriminated PSC patients from controls in both geographical cohorts with an average area under the curve of 0.88. Compared to healthy controls, many new cohort‐spanning alterations were identified in PSC, such as an increase of Proteobacteria and the bile‐tolerant genus Parabacteroides, which were detected independent from geographical region. Associated colitis only had minor effects on microbiota composition, suggesting that PSC itself drives the faecal microbiota changes observed. Conclusion Compared to healthy controls, numerous microbiota alterations are reproducible in PSC patients across geographical regions, clearly pointing towards a microbiota composition that is shaped by the disease itself and not by environmental factors. These reproducibly altered microbial populations might provide future insights into the pathophysiology of PSC