Comparative evaluation of the tendon-bone interface contact pressure in different single- versus double-row suture anchor repair techniques

The aim of the study was to evaluate the time zero contact pressure over a defined rotator cuff footprint using different repair and stitch techniques in an established sheep model. Forty fresh-frozen sheep shoulders were randomly assigned to five repair groups: single-row repair using simple stitches (SRA-s), single-row repair using horizontal mattress stitches (SRA-m), and single-row repair using arthroscopic Mason-Allen stitches (SRA-ama). Double-row repair was either performed with a combination of simple and horizontal mattress stitches (DRA-sm) or with arthroscopic Mason-Allen/horizontal mattress stitches (DRA-amam). Investigations were performed using a pressure-sensitive film system. The average contact pressure and pressure pattern were measured for each group. Contact pressure was lowest in SRA-m followed by SRA-s. SRA-ama showed highest contact pressure of all single-row treatment groups (P < 0.05). DRA-amam presented the highest overall contact pressure (P < 0.05), whereas DRA-sm exerted contact pressure equal to that of SRA-ama. Both double-row techniques showed the most expanded pressure pattern. Average contact pressures for the more complex single- and double-row techniques utilizing arthroscopic Mason-Allen stitches were greater than were those of the repair techniques utilizing simple and horizontal mattress stitches. However, the contact pattern between the anchors could be increased by using the double-row technique, resulting in more footprint coverage compared to patterns utilizing the single-row techniques. These results support the use of the more complex arthroscopic Mason-Allen stitches and may improve the environment for healing of the repaired rotator cuff tendon

Pretubulysin: From Hypothetical Biosynthetic Intermediate to Potential Lead in Tumor Therapy

Pretubulysin is a natural product that is found in strains of myxobacteria in only minute amounts. It represents the first enzyme-free intermediate in the biosynthesis of tubulysins and undergoes post-assembly acylation and oxidation reactions. Pretubulysin inhibits the growth of cultured mammalian cells, as do tubulysins, which are already in advanced preclinical development as anticancer and antiangiogenic agents. The mechanism of action of this highly potent compound class involves the depolymerization of microtubules, thereby inducing mitotic arrest. Supply issues with naturally occurring derivatives can now be circumvented by the total synthesis of pretubulysin, which, in contrast to tubulysin, is synthetically accessible in gram-scale quantities. We show that the simplified precursor is nearly equally potent to the parent compound. Pretubulysin induces apoptosis and inhibits cancer cell migration and tubulin assembly in vitro. Consequently, pretubulysin appears to be an ideal candidate for future development in preclinical trials and is a very promising early lead structure in cancer therapy

Cdc45 Limits Replicon Usage from a Low Density of preRCs in Mammalian Cells

Little is known about mammalian preRC stoichiometry, the number of preRCs on chromosomes, and how this relates to replicon size and usage. We show here that, on average, each 100-kb of the mammalian genome contains a preRC composed of approximately one ORC hexamer, 4–5 MCM hexamers, and 2 Cdc6. Relative to these subunits, ∼0.35 total molecules of the pre-Initiation Complex factor Cdc45 are present. Thus, based on ORC availability, somatic cells contain ∼70,000 preRCs of this average total stoichiometry, although subunits may not be juxtaposed with each other. Except for ORC, the chromatin-bound complement of preRC subunits is even lower. Cdc45 is present at very low levels relative to the preRC subunits, but is highly stable, and the same limited number of stable Cdc45 molecules are present from the beginning of S-phase to its completion. Efforts to artificially increase Cdc45 levels through ectopic expression block cell growth. However, microinjection of excess purified Cdc45 into S-phase nuclei activates additional replication foci by three-fold, indicating that Cdc45 functions to activate dormant preRCs and is rate-limiting for somatic replicon usage. Paradoxically, although Cdc45 colocalizes in vivo with some MCM sites and is rate-limiting for DNA replication to occur, neither Cdc45 nor MCMs colocalize with active replication sites. Embryonic metazoan chromatin consists of small replicons that are used efficiently via an excess of preRC subunits. In contrast, somatic mammalian cells contain a low density of preRCs, each containing only a few MCMs that compete for limiting amounts of Cdc45. This provides a molecular explanation why, relative to embryonic replicon dynamics, somatic replicons are, on average, larger and origin efficiency tends to be lower. The stable, continuous, and rate-limiting nature of Cdc45 suggests that Cdc45 contributes to the staggering of replicon usage throughout S-phase, and that replicon activation requires reutilization of existing Cdc45 during S-phase

PAX8 promotes tumor cell growth by transcriptionally regulating E2F1 and stabilizing RB protein

The retinoblastoma protein (RB)–E2F1 pathway has a central role in regulating the cell cycle. Several PAX proteins (tissue-specific developmental regulators), including PAX8, interact with the RB protein, and thus regulate the cell cycle directly or indirectly. Here, we report that PAX8 expression is frequent in renal cell carcinoma, bladder, ovarian and thyroid cancer cell lines, and that silencing of PAX8 in cancer cell lines leads to a striking reduction in the expression of E2F1 and its target genes, as well as a proteasome-dependent destabilization of RB protein, with the RB1 mRNA level remaining unaffected. Cancer cells expressing PAX8 undergo a G1/S arrest and eventually senesce following PAX8 silencing. We demonstrate that PAX8 transcriptionally regulates the E2F1 promoter directly, and E2F1 transcription is enhanced after RB depletion. RB is recruited to the PAX8-binding site, and is involved in PAX8-mediated E2F1 transcription in cancer cells. Therefore, our results suggest that, in cancer, frequent and persistent expression of PAX8 is required for cell growth control through transcriptional activation of E2F1 expression and upregulation of the RB–E2F1 pathway

Mortes evitáveis em vítimas com traumatismos

OBJETIVO: Descrever métodos e estimativas de mortalidade proporcional por mortes evitáveis e tipos de não conformidades do atendimento relacionadas a esses eventos. MÉTODOS: Revisão sistemática de publicações sobre mortes evitáveis em vítimas com traumatismos entre 2000 e 2009. Foi realizada pesquisa nas bases de dados Lilacs, SciELO e Medline utilizando-se a estratégia de busca com as palavras-chave "trauma", "avoidable", "preventable", "interventions" e "complications", e os descritores em ciências da saúde "death", "cause of death" e "hospitals". RESULTADOS: Identificaram-se 29 artigos publicados no período, com predomínio de estudos retrospectivos (96,5%). Os métodos mais comumente utilizados para definir a evitabilidade do óbito foram painel de especialistas ou pontuação de índices de gravidade, tendo sido empregadas as seguintes categorias: evitável, potencialmente evitável e não evitável. A média da mortalidade proporcional por mortes evitáveis dos estudos foi de 10,7% (dp 11,5%). As não conformidades mais comumente relatadas nas publicações foram sistema inadequado de atendimento ao traumatizado e erro na avaliação e tratamento. CONCLUSÕES: Observaram-se falhas na uniformização dos termos empregados para categorizar as mortes e as não conformidadades encontradas. Portanto, sugere-se a padronização da taxonomia da classificação das mortes e dos tipos de não conformidades observadas

Lawson criterion for ignition exceeded in an inertial fusion experiment

For more than half a century, researchers around the world have been engaged in attempts to achieve fusion ignition as a proof of principle of various fusion concepts. Following the Lawson criterion, an ignited plasma is one where the fusion heating power is high enough to overcome all the physical processes that cool the fusion plasma, creating a positive thermodynamic feedback loop with rapidly increasing temperature. In inertially confined fusion, ignition is a state where the fusion plasma can begin "burn propagation" into surrounding cold fuel, enabling the possibility of high energy gain. While "scientific breakeven" (i.e., unity target gain) has not yet been achieved (here target gain is 0.72, 1.37 MJ of fusion for 1.92 MJ of laser energy), this Letter reports the first controlled fusion experiment, using laser indirect drive, on the National Ignition Facility to produce capsule gain (here 5.8) and reach ignition by nine different formulations of the Lawson criterion

Baixa percepção de risco entre adolescentes espanhóis em relação ao consumo de álcool

Según los estudios recientes, los adolescentes españoles muestran una baja percepción del riesgo asociado al consumo de alcohol. El objetivo de la presente investigación es analizar los factores que favorecen esta baja percepción a partir de la opinión de un grupo de 32 profesionales/expertos en adolescencia, familia, escuela, medios de comunicación y políticas locales. Se utilizó una metodología cualitativa, fundamentada en Grounded Theory, a partir de la información obtenida mediante 5 grupos de discusión guiados por entrevistas semiestructuradas. Se identificaron 12 factores o subcategorías agrupados en 4 categorías generales: riesgo a corto plazo, inmediatez y percepción de invulnerabilidad (categoría ¿pensamiento adolescente¿); concepción benévola del alcohol, normalización del consumo y binomio alcohol-diversión (categoría ¿normas sociales¿); consumo habitual en los padres, inconsistencia verbal-no verbal en el modelado parental, consumo sin riesgo en los medios, consumo con resultados positivos en los medios (categoría ¿modelos sociales¿); excesivo contenido sanitario, riesgo a largo plazo (categoría ¿discurso preventivo¿). Tras discutir los resultados en el contexto de la literatura científica actual, se realizan varias propuestas con el objetivo de aumentar la percepción del riesgo en los adolescentes: incidir con mayor fuerza en contenidos sobre los riesgos a corto plazo del alcohol; orientar las estrategias educativas dirigidas al adolescente, también hacia los agentes de socialización, especialmente los padres; incidir en políticas centradas en la sustancia y en reducir la oferta.According to recent studies, Spanish adolescents show low perception of risk in alcohol consumption. The current study aims to analyze the factors that favor this low perception based on the opinion of a group of 32 professional experts on adolescence, family, school, mass media, and local policies. A qualitative methodology was used, based on Grounded Theory, using information from 5 focus groups guided by semi-structured interviews. Twelve factors or subcategories were identified, grouped in 4 general categories: short-term risk, immediacy, and perception of invulnerability (¿adolescent thinking¿ category); benevolent view of alcohol, normalization of consumption, and alcohol-entertainment binomial (¿social norms¿ category); parents¿ habitual consumption, verbal/non-verbal inconsistency in parental model, risk-free consumption depicted in the mass media, consumption with positive results in the media (¿social models¿ category); and excessive health content, long-term risk (¿preventive discourse¿ category). After discussing the results in the context of the current scientific literature, the article offers various proposals for increasing risk perception in adolescents: stronger impact of contents on short-term risks of alcohol; educational strategies targeted to adolescents to include agents of socialization, especially parents; and policies centered on the substance and reduction of supply.De acordo com estudos recentes, os adolescentes espanhóis mostram baixa percepção de risco em relação ao consumo de álcool. O estudo tem como objetivo analisar os fatores associados com a baixa percepção de risco, com base nas opiniões de um grupo de 32 especialistas em adolescência, família, escola, mídia e políticas locais. Foi utilizada uma metodologia qualitativa, baseada na Teoria Fundamentada, usando informações de cinco grupos focais orientados por entrevistas semi-estruturadas. Foram identificados 12 fatores ou subcategorias, agrupados em quatro categorias gerais: risco no curto prazo, imediatismo e percepção de invulnerabilidade (categoria de ¿pensamento adolescente¿); visão benevolente em relação ao álcool, normalização do consumo e binômio álcool-entretenimento (categoria de ¿normas sociais¿); consumo habitual pelos pais, inconsistência na comunicação verbal versus não verbal no modelo representado pelos pais, consumo isento de risco retratado pela mídia, consumo com resultados positivos na mídia (categoria de ¿modelos sociais¿) e excesso de conteúdo relacionado à saúde, risco no longo prazo (categoria de ¿discurso preventivo¿). Depois de discutir os resultados no contexto da literatura científica atual, o artigo oferece várias propostas para aumentar a percepção de risco entre os adolescentes: impacto mais forte de conteúdos sobre os riscos do álcool no curto prazo; estratégias educativas orientadas aos adolescentes para incluir os agentes da socialização, especialmente os pais, além de políticas centradas na substância e na redução da oferta.Departamento de Educación y Psicología SocialVersión del edito