Pharmacologic disruption of Polycomb Repressive Complex 2 inhibits tumorigenicity and tumor progression in prostate cancer

<p>Abstract</p> <p>Background</p> <p>Polycomb repressive complex 2 (PRC2) mediates gene silencing through histone H3K27 methylation. PRC2 components are over-expressed in metastatic prostate cancer (PC), and are required for cancer stem cell (CSC) self-renewal. 3-Dezaneplanocin-A (DZNeP) is an inhibitor of PRC2 with broad anticancer activity.</p> <p>Method</p> <p>we investigated the effects of DZNeP on cell proliferation, tumorigenicity and invasive potential of PC cell lines (LNCaP and DU145).</p> <p>Results</p> <p>Exploring GEO and Oncomine databases, we found that specific PRC2 genes (EED, EZH2, SUZ12) predict poor prognosis in PC. Non-toxic DZNeP concentrations completely eradicated LNCaP and DU145 prostatosphere formation, and significantly reduced the expression of CSC markers. At comparable doses, other epigenetic drugs were not able to eradicate CSCs. DZNeP was also able to reduce PC cell invasion. Cells pre-treated with DZNeP were significantly less tumorigenic (LNCaP) and formed smaller tumors (DU145) in immunocompromised mice.</p> <p>Conclusion</p> <p>DZNeP is effective both in vitro and in vivo against PC cells. DZNeP antitumor activity is in part mediated by inhibition of CSC tumorigenic potential.</p

Perfil antropométrico dos pacientes internados em um hospital universitário

Introdução: Identificar precocemente o perfil antropométrico dos pacientes possibilita o conhecimento do estado nutricional e o planejamento de uma terapia nutricional adequada podendo reduzir o número e a gravidade das complicações e acelerar a sua recuperação.Objetivo: Identificar o perfil antropométrico dos pacientes na internação hospitalarMétodos: Estudo observacional descritivo, com pacientes adultos e idosos, que internaram no Hospital de Clínicas de Porto Alegre no período de julho de 2008 a dezembro de 2009.Resultados: Foram arrolados para o estudo 460 indivíduos com média de idade de 52 anos (± 16,14), sendo 164 (35,7%) idosos. Dos pacientes estudados, 152 (33%) chegaram ao hospital eutróficos, 216 (47%) com sobrepeso ou obesidade e 92 (20%) desnutridos. Entre os pacientes com sobrepeso e obesidade, 10 (4,6%) estavam com obesidade mórbida (IMC &gt; 40 kg/m²); e entre os desnutridos, 14 (15,2%) estavam com desnutrição grave (IMC &lt; 16 kg/m²). Os níveis assistenciais (NA) foram determinados conforme o diagnóstico nutricional, considerando percentual de perda de peso e IMC. Dos pacientes analisados, 12 (2,6%) foram classificados como NA 1, seguido por 325 (70,7%) como NA 2,  88 (19,1%) como NA 3 e 35 (7,6%) como NA 4. Pacientes idosos apresentaram maior percentual de desnutrição (26,2% vs 16,6%) quando comparados com os pacientes &lt; de 60 anos (p&lt; 0,014).Conclusão: A prevalência de risco e/ou desnutrição é elevada no ambiente hospitalar e demanda atenção dos profissionais da saúde responsáveis pela assistência do paciente, principalmente nos indivíduos com idade acima de 60 anos

PBAT/TPS Composite Films Reinforced with Starch Nanoparticles Produced by Ultrasound

The objective of the present work was to study the incorporation of starch nanoparticles (SNP) produced by ultrasound in blends of poly(butylene adipate-co-terephthalate) (PBAT) and thermoplastic starch (TPS). The films were produced by extrusion using varying percentages of SNP (1, 2, 3, 4, and 5% w/w). The SNP were prepared in water without the addition of any chemical reagent. The results revealed that ultrasound treatment results in the formation of SNP less than 100¿nm in size and of an amorphous character and lower thermal stability and low gelatinization temperature when compared with cassava starch. Scanning electron microscopy (SEM) showed that films presented some starch granules. The relative crystallinity (RC) of films decreases with increasing concentration of SNP. The addition of SNP slightly affected the thermal degradation of the films. The DSC results showed that the addition did not modify the interaction between the different components of the films. Mechanical tests revealed an increase in Young’s modulus (36%) and elongation-at-break (35%) with the incorporation of 1% SNP and this concentration reduced the water vapor permeability (53%) and significantly decreased the water absorption of the films, demonstrating that low concentrations of SNP can be used as reinforcement in a polymeric matrixPostprint (published version

Evaluation of nutritional care level in adult patients hospitalized at Hospital de Clínicas de Porto Alegre

Introdução: No momento da internação, é importante definir o diagnóstico nutricional, pois a hospitalização pode levar a uma piora do estado nutricional. Há evidências na literatura de que pacientes com intervenção nutricional precoce e adequada apresentam melhora nos resultados clínicos e nutricionais. Métodos: Este estudo teve um delineamento transversal, com o objetivo de identificar o estado nutricional de pacientes adultos avaliados em até 72 horas após a admissão hospitalar, por protocolo de avaliação utilizado para determinação do nível de assistência (NA) nutricional. Resultados: Foram avaliados 17.836 pacientes, sendo 59% clínicos e 41% cirúrgicos. Destes, 32% foram classificados como NA 3 e NA 4 (maior comprometimento nutricional) e 68% como NA 1A, NA e NA 2. Os dados de peso e altura foram registrados em 63% dos prontuários analisados. Conclusão: Concluímos que é possível avaliar todos os pacientes internados quando estabelecemos protocolos com condutas padronizadas, e identificar a gravidade do estado nutricional priorizando o atendimento de forma qualitativa baseado nos níveis assistenciais.Background: When a patient is admitted it is important to define his nutritional diagnosis, since hospital stay may lead to worsening of nutritional status. There is evidence in the literature that patients with early and adequate nutritional intervention have improvement in clinical and nutritional results. Methods: This study had a cross-sectional design, with the aim of identifying the nutritional status of adult patients evaluated up to 72 hours after hospital admission, using an evaluation protocol to determine the level of nutritional care (NC). Results: A total of 17,836 patients were evaluated, 59% clinical and 41% surgical. Of these, 32% were classified as NC 3 and NC 4 (higher nutritional impairment) and 68% as NC 1A, NC and NC 2. Weight and height data were recorded in 63% of medical records. Conclusion: In conclusion, it is possible to evaluate all hospitalized patients when there are protocols with standardized conducts, and to identify nutritional status severity by prioritizing care qualitatively based on care levels

Girls and Boys Born before 28 Weeks Gestation: Risks of Cognitive, Behavioral, and Neurologic Outcomes at Age 10 Years

To compare the prevalence of cognitive, neurological, and behavioral outcomes at 10 years of age in 428 girls and 446 boys who were born extremely preterm (EP)

Midwifery-led antenatal care models: mapping a systematic review to an evidence-based quality framework to identify key components and characteristics of care.

BACKGROUND: Implementing effective antenatal care models is a key global policy goal. However, the mechanisms of action of these multi-faceted models that would allow widespread implementation are seldom examined and poorly understood. In existing care model analyses there is little distinction between what is done, how it is done, and who does it. A new evidence-informed quality maternal and newborn care (QMNC) framework identifies key characteristics of quality care. This offers the opportunity to identify systematically the characteristics of care delivery that may be generalizable across contexts, thereby enhancing implementation. Our objective was to map the characteristics of antenatal care models tested in Randomised Controlled Trials (RCTs) to a new evidence-based framework for quality maternal and newborn care; thus facilitating the identification of characteristics of effective care. METHODS: A systematic review of RCTs of midwifery-led antenatal care models. Mapping and evaluation of these models' characteristics to the QMNC framework using data extraction and scoring forms derived from the five framework components. Paired team members independently extracted data and conducted quality assessment using the QMNC framework and standard RCT criteria. RESULTS: From 13,050 citations initially retrieved we identified 17 RCTs of midwifery-led antenatal care models from Australia (7), the UK (4), China (2), and Sweden, Ireland, Mexico and Canada (1 each). QMNC framework scores ranged from 9 to 25 (possible range 0-32), with most models reporting fewer than half the characteristics associated with quality maternity care. Description of care model characteristics was lacking in many studies, but was better reported for the intervention arms. Organisation of care was the best-described component. Underlying values and philosophy of care were poorly reported. CONCLUSIONS: The QMNC framework facilitates assessment of the characteristics of antenatal care models. It is vital to understand all the characteristics of multi-faceted interventions such as care models; not only what is done but why it is done, by whom, and how this differed from the standard care package. By applying the QMNC framework we have established a foundation for future reports of intervention studies so that the characteristics of individual models can be evaluated, and the impact of any differences appraised

The Relationship of Maternal Prepregnancy Body Mass Index and Pregnancy Weight Gain to Neurocognitive Function at Age 10 Years among Children Born Extremely Preterm

OBJECTIVE: To assess the association between maternal prepregnancy body mass index and adequacy of pregnancy weight gain in relation to neurocognitive function in school-aged children born extremely preterm. STUDY DESIGN: Study participants were 535 ten-year-old children enrolled previously in the prospective multicenter Extremely Low Gestational Age Newborns cohort study who were products of singleton pregnancies. Soon after delivery, mothers provided information about prepregnancy weight. Prepregnancy body mass index and adequacy of weight gain were characterized based on this information. Children underwent a neurocognitive evaluation at 10 years of age. RESULTS: Maternal prepregnancy obesity was associated with increased odds of a lower score for Differential Ability Scales-II Verbal IQ, for Developmental Neuropsychological Assessment-II measures of processing speed and visual fine motor control, and for Wechsler Individual Achievement Test-III Spelling. Children born to mothers who gained an excessive amount of weight were at increased odds of a low score on the Oral and Written Language Scales Oral Expression assessment. Conversely, children whose mother did not gain an adequate amount of weight were at increased odds of a lower score on the Oral and Written Language Scales Oral Expression and Wechsler Individual Achievement Test-III Word Reading assessments. CONCLUSION: In this cohort of infants born extremely preterm, maternal obesity was associated with poorer performance on some assessments of neurocognitive function. Our findings are consistent with the observational and experimental literature and suggest that opportunities may exist to mitigate risk through education and behavioral intervention before pregnancy

The impact of surgical delay on resectability of colorectal cancer: An international prospective cohort study

AIM: The SARS-CoV-2 pandemic has provided a unique opportunity to explore the impact of surgical delays on cancer resectability. This study aimed to compare resectability for colorectal cancer patients undergoing delayed versus non-delayed surgery. METHODS: This was an international prospective cohort study of consecutive colorectal cancer patients with a decision for curative surgery (January-April 2020). Surgical delay was defined as an operation taking place more than 4 weeks after treatment decision, in a patient who did not receive neoadjuvant therapy. A subgroup analysis explored the effects of delay in elective patients only. The impact of longer delays was explored in a sensitivity analysis. The primary outcome was complete resection, defined as curative resection with an R0 margin. RESULTS: Overall, 5453 patients from 304 hospitals in 47 countries were included, of whom 6.6% (358/5453) did not receive their planned operation. Of the 4304 operated patients without neoadjuvant therapy, 40.5% (1744/4304) were delayed beyond 4 weeks. Delayed patients were more likely to be older, men, more comorbid, have higher body mass index and have rectal cancer and early stage disease. Delayed patients had higher unadjusted rates of complete resection (93.7% vs. 91.9%, P = 0.032) and lower rates of emergency surgery (4.5% vs. 22.5%, P < 0.001). After adjustment, delay was not associated with a lower rate of complete resection (OR 1.18, 95% CI 0.90-1.55, P = 0.224), which was consistent in elective patients only (OR 0.94, 95% CI 0.69-1.27, P = 0.672). Longer delays were not associated with poorer outcomes. CONCLUSION: One in 15 colorectal cancer patients did not receive their planned operation during the first wave of COVID-19. Surgical delay did not appear to compromise resectability, raising the hypothesis that any reduction in long-term survival attributable to delays is likely to be due to micro-metastatic disease