Hypothermia at neonatal intensive care unit admission was not associated with respiratory disease or death in very preterm infants.

AIM: This study investigated the association between hypothermia and respiratory distress syndrome (RDS), bronchopulmonary dysplasia (BPD) or death in very preterm infants admitted to a Danish neonatal intensive care unit (NICU). METHODS: We studied 675 infants born at Aalborg University Hospital before 32 weeks and admitted to the NICU from April 1997 to December 2011. Hypothermia was defined as a core temperature of <36.5°C on admission. The primary outcome was severe RDS or death within the first three days of life, and the secondary outcome was BPD or death before 36 postmenstrual weeks. The multivariable logistic regression was adjusted for early-onset infection, gestational age, Apgar score, sex, treatment year and birth weight. RESULTS: Infants with hypothermia had a twofold increase (OR) in the odds for RDS or death (2.03), but the adjusted OR was not statistically significant (1.36). They also demonstrated a twofold increase (OR) in the odds for BPD or death (2.28), but again the adjusted OR was not statistically significant (1.03). CONCLUSION: After adjusting for confounders, we found that the association between hypothermia on admission to the NICU and RDS or death, or BPD or death was statistically insignificant.

HDAC1 and HDAC2 integrate the expression of p53 mutants in pancreatic cancer.

Mutation of p53 is a frequent genetic lesion in pancreatic cancer being an unmet clinical challenge. Mutants of p53 have lost the tumour-suppressive functions of wild type p53. In addition, p53 mutants exert tumour-promoting functions, qualifying them as important therapeutic targets. Here, we show that the class I histone deacetylases HDAC1 and HDAC2 contribute to maintain the expression of p53 mutants in human and genetically defined murine pancreatic cancer cells. Our data reveal that the inhibition of these HDACs with small molecule HDAC inhibitors (HDACi), as well as the specific genetic elimination of HDAC1 and HDAC2, reduce the expression of mutant p53 mRNA and protein levels. We further show that HDAC1, HDAC2 and MYC directly bind to the TP53 gene and that MYC recruitment drops upon HDAC inhibitor treatment. Therefore, our results illustrate a previously unrecognized class I HDAC-dependent control of the TP53 gene and provide evidence for a contribution of MYC. A combined approach targeting HDAC1/HDAC2 and MYC may present a novel and molecularly defined strategy to target mutant p53 in pancreatic cancer.

Confiabilidade da fotogrametria em relação a goniometria para avaliação postural de membros inferiores / Reliability of photogrammetry in relation to goniometry for postural lower limb assessment

CONTEXTUALIZAÇÃO: A avaliação postural bem como a mensuração da amplitude articular são instrumentos fundamentais para o diagnóstico, planejamento e acompanhamento da evolução e dos resultados de um tratamento fisioterapêutico. Elas podem ser realizadas tanto pela goniometria - método mais utilizado na clínica fisioterapêutica - como, com o avanço tecnológico, pela fotogrametria. OBJETIVOS: Verificar a confiabilidade paralela da fotogrametria computadorizada, utilizando dois softwares, o Corel Draw e o SAPo, em relação à goniometria para quatro ângulos nos membros inferiores. CASUÍSTICA E MÉTODOS:Foram estudados 26 voluntários de ambos os sexos, assintomáticos, com idade entre 18 e 45 anos, sem anisomelia de membros inferiores maior que 1 cm. Foram mensurados os ângulos tíbio-társico (TT), de flexo/extensão do joelho (flex/ext), ângulo Q (Q) e ângulo do retropé, inicialmente, com um goniômetro manual e, posteriormente, pela fotogrametria digital por meio dos softwares Corel Draw v. 12 e SAPo v.0.63. RESULTADOS: Os ângulos TT (p= 0,9991), do retropé (p= 0,2159) e de flexo/extensão do joelho (p= 0,4027) não foram estatisticamente diferentes entre os 3 métodos de avaliação. Já o ângulo Q foi significativamente diferente entre a goniometria e os dois softwares usados na fotogrametria (p= 0,0067), embora os valores obtidos pelos mesmos não tenham diferido entre si (p= 0,9920), demonstrando que os resultados da fotogrametria não foram influenciados pelos softwares utilizados. CONCLUSÃO: Para os ângulos avaliados em sujeitos jovens assintomáticos, a fotogrametria computadorizada é confiável paralelamente à goniometria, exceto para o ângulo Q. Portanto, na clínica fisioterapêutica, deve-se ter cautela no uso de medidas de ângulo Q provenientes de diferentes métodos de avaliação postural.

BACKGROUND: Postural assessment and joint range-of-motion measurements are fundamental in diagnosing, planning and following up the evolution and results from physical therapy treatment. These can be done with the aid of goniometry the most common method in physical therapy practice - and also, through technological advances, by means of photogrammetry. OBJECTIVE: To investigate the parallel reliability of computerized photogrammetry, using two software tools (Corel Draw and SAPo), in relation to goniometry, in four angles of the lower limbs. METHOD: Twenty-six asymptomatic volunteers of both sexes, aged between 18 and 45 years, were studied. None of them had leg length discrepancy greater than 1 cm. The tibiotarsal angle (TT), knee flexion/extension angle (F/E), quadriceps angle (Q) and subtalar angle (S) were measured. The measurement was done first with a manual goniometer and then with digital photogrammetry by means of the Corel Draw v. 12 and SAPo v.0.63 software. RESULTS: There were no statistical differences between the three evaluation methods for the TT (p= 0.9991), S (p= 0.2159) and F/E (p= 0.4027) angles. However, for the Q angle there was a significant difference between goniometry and the software used in photogrammetry (p= 0.0067), although there was no significant difference between two software tools (p= 0.9920). This showed that the photogrammetry results were not influenced by the software used. CONCLUSION: In these healthy young subjects, computerized photogrammetry showed good parallel reliability in comparison with goniometry, for all the angles evaluated except for the Q angle. Therefore, in physical therapy practice, caution is needed in using Q angle measurements coming from different postural assessment methods.

Potential antipsoriatic agents: lapacho compounds as potent inhibitors of HaCaT cell growth.

A number of lapacho compounds, representing the most common constituents of the inner bark of Tabebuia impetiginosa, together with some synthetic analogues, were evaluated in vitro against the growth of the human keratinocyte cell line HaCaT. With an IC(50) value of 0.7 microM, beta-lapachone (4) displayed activity comparable to that of the antipsoriatic drug anthralin. 2-Acetyl-8-hydroxynaphtho[2,3-b]furan-4,9-dione (7), which was prepared in a four-step synthesis from 2,8-dihydroxy-1, 4-naphthoquinone, was the most potent inhibitor among the known lapacho-derived compounds and inhibited cell growth with an IC(50) value of 0.35 microM. Furthermore, other active constituents of lapacho inhibited keratinocyte growth, with IC(50) values in the range of 0.5-3.0 microM. However, as already observed with anthralin, treatment of HaCaT cells with these potent lapacho compounds also caused remarkable damage to the plasma membrane. This was documented by leakage of lactate dehydrogenase into the culture medium, which significantly exceeded that of the vehicle control. Because of their potent activity against the growth of human keratinocytes, some lapacho-derived compounds appear to be promising as effective antipsoriatic agents.