Improvement in ARDS experimental model installation: Low mortality rate and maintenance of hemodynamic stability

Introduction: Many experimental models using lung lavage have been developed for the study of acute respiratory distress syndrome (ARDS). The original technique has been modified by many authors, resulting in difficulties with reproducibility. There is insufficient detail on the lung injury models used, including hemodynamic stability during animal preparation and drawbacks encountered such as mortality. The authors studied the effects of the pulmonary recruitment and the use of fixed tidal volume (Vt) or fixed inspiratory pressure in the experimental ARDS model installation. Methods: Adult rabbits were submitted to repeated lung lavages with 30 ml/kg warm saline until the ARDS definition (PaO2/FiO(2) <= 100) was reached. The animals were divided into three groups, according to the technique used for mechanical ventilation: 1) fixed Vt of 10 ml/kg; 2) fixed inspiratory pressure (IP) with a tidal volume of 10 ml/kg prior to the first lung lavage; and 3) fixed Vt of 10 ml/kg with pulmonary recruitment before the first lavage. Results: The use of alveolar recruitment maneuvers, and the use of a fixed Vt or IP between the lung lavages did not change the number of lung lavages necessary to obtain the experimental model of ARDS or the hemodynamic stability of the animals during the procedure. A trend was observed toward an increased mortality rate with the recruitment maneuver and with the use of a fixed IP. Discussion: There were no differences between the three study groups, with no disadvantage in method of lung recruitment, either fixed tidal volume or fixed inspiratory pressure, regarding the number of lung lavages necessary to obtain the ARDS animal model. Furthermore, the three different procedures resulted in good hemodynamic stability of the animals, and low mortality rate. (C) 2012 Elsevier Inc. All rights reserved.

Natriuretic Peptides and Long-Term Mortality in Patients with Severe Aortic Stenosis

Background and aim of the study: The natriuretic peptides, brain natriuretic peptide (BNP) and its N-terminal prohormone (NT-proBNP), can be used as diagnostic and prognostic markers for aortic stenosis (AS). However, the association between BNP, NT-proBNP, and long-term clinical outcomes in patients with severe AS remains uncertain. Methods: A total of 64 patients with severe AS was prospectively enrolled into the study, and underwent clinical and echocardiographic assessments at baseline. Blood samples were drawn for plasma BNP and NT-proBNP analyses. The primary outcome was death from any cause, through a six-year follow up period. Cox proportional hazards modeling was used to examine the association between natriuretic peptides and long-term mortality, adjusting for important clinical factors. Results: During a mean period of 1,520 681 days, 51 patients (80%) were submitted to aortic valve replacement, and 13 patients (20%) were medically managed without surgical interventions. Mortality rates were 13.7% in the surgical group and 62% in the medically managed group (p <0.001). Patients with higher plasma BNP (>135 pg/ml) and NT-proBNP (>1,150 pg/ml) levels at baseline had a greater risk of long-term mortality (hazard ratio [HR] 3.2, 95% confidence interval [CI] 1.1-9.1; HR 4.3, 95% CI 1.4-13.5, respectively). After adjusting for important covariates, both BNP and NT-proBNP remained independently associated with long-term mortality (HR 2.9, 95%CI 1.5-5.7; HR 1.8, 95%CI 1.1-3.1, respectively). Conclusion: In patients with severe AS, plasma BNP and NT-proBNP levels were associated with long-term mortality. The use of these biomarkers to guide treatment might represent an interesting approach that deserves further evaluation. The Journal of Heart Valve Disease 2012;21:331-336

BNP and Admission Glucose as In-Hospital Mortality Predictors in Non-ST Elevation Myocardial Infarction

Objectives. Admission hyperglycemia and B-type natriuretic peptide (BNP) are associated with mortality in acute coronary syndromes, but no study compares their prediction in-hospital death. Methods. Patients with non-ST-elevation myocardial infarction (NSTEMI), in-hospital mortality and two-year mortality or readmission were compared for area under the curve (AUC), sensitivity (SEN), specificity (SPE), positive predictive value (PPV), negative predictive value (NPV), and accuracy (ACC) of glycemia and BNP. Results. Respectively, AUC, SEN, SPE, PPV, NPV, and ACC for prediction of in-hospital mortality were 0.815, 71.4%, 84.3%, 26.3%, 97.4%, and 83.3% for glycemia = 200 mg/dL and 0.748, 71.4%, 68.5%, 15.2%, 96.8% and 68.7% for BNP = 300 pg/mL. AUC of glycemia was similar to BNP (P = 0.411). In multivariate analysis we found glycemia >= 200mg/dL related to in-hospital death (P = 0.004). No difference was found in two-year mortality or readmission in BNP or hyperglycemic subgroups. Conclusion. Hyperglycemia was an independent risk factor for in-hospital mortality in NSTEMI and had a good ROC curve level. Hyperglycemia and BNP, although poor in-hospital predictors of unfavorable events, were independent risk factors for death or length of stay >10 days. No relation was found between hyperglycemia or BNP and long-term events.

Stem cells in embryonic skin development

The skin is a complex stratified organ which acts not only as a permeability barrier and defense against external agents, but also has essential thermoregulatory, sensory and metabolic functions. Due to its high versatility and activity, the skin undergoes continuous self-renewal to repair damaged tissue and replace old cells. Consequently, the skin is a reservoir for adult stem cells of different embryonic origins. Skin stem cell populations reside in the adult hair follicle, sebaceous gland, dermis and epidermis. However, the origin of most of the stem cell populations found in the adult epidermis is still unknown. Far more unknown is the embryonic origin of other stem cells that populate the other layers of this tissue. In this review we attempt to clarify the emergence, structure, markers and embryonic development of diverse populations of stem cells from the epidermis, dermis and related appendages such as the sebaceous gland and hair follicle.

Temporal Trends of Asthma Mortality Rates in Brazil from 1980 to 2010

Objective. Mortality from asthma has varied among countries during the last several decades. This study aimed to identify temporal trends of asthma mortality in Brazil from 1980 to 2010. Method. We analyzed 6840 deaths of patients aged 5-34 years that occurred in Brazil with the underlying cause of asthma. We applied a log-linear model using Poisson regression to verify peaks and trends. We also calculated the point estimation and 95% confidence interval (CI 95%) of the annual percent change (APC) of the mortality rates, and the average annual percent change (AAPC) for 2001-2010. Results. A decline was observed from 1980 to 1992 [APC = -3.4 (-5.0 to -1.8)], followed by a nonsignificant rise until 1996 [APC = 6.8 (-1.4 to 15.6)], and a new downward trend from 1997 to 2010 [APC = -2.7 (-3.9 to -1.6)]. The APCs varied according to age strata: 5-14 years from 1980 to 2010 [-0.3 (-1.1 to 0.5)]; 15-24 years from 1980 to 1991 [-2.1 (-5.0 to 0.9)], from 1992 to 1996 [6.8 (-6.7 to 22.2)], and from 1997 to 2010 [-3.9 (-5.7 to -2.0)]; 24-25 years from 1980 to 1992 [-2.5 (-4.6 to -0.3)], from 1993 to 1995 [12.0 (-21.1 to 59.1)], and from 1996-2010 [-1.7 (-3.0 to -0.4)]. AAPC from 2001 to 2010 was -1.7 (-3.0 to -0.4); the decline for this period was significant for patients over 15 years old, women, and those living in the Southeast region. Conclusion. Asthma mortality rates in Brazil have been declining since the late 1990s.

Failure to reduce C-reactive protein levels more than 25% in the last 24 hours before intensive care unit discharge predicts higher in-hospital mortality: A cohort study

Purpose: To discharge a patient from the intensive care unit (ICU) is a complex decision-making process because in-hospital mortality after critical illness may be as high as up to 27%. Static C-reactive protein (CRP) values have been previously evaluated as a predictor of post-ICU mortality with conflicting results. Therefore, we evaluated the CRP ratio in the last 24 hours before ICU discharge as a predictor of in-hospital outcomes. Methods: A retrospective cohort study was performed in 409 patients from a 6-bed ICU of a university hospital. Data were prospectively collected during a 4-year period. Only patients discharged alive from the ICU with at least 72 hours of ICU length of stay were evaluated. Results: In-hospital mortality was 18.3% (75/409). Patients with reduction less than 25% in CRP concentrations at 24 hours as compared with 48 hours before ICU discharge had a worse prognosis, with increased mortality (23% vs 11%, P = .002) and post-ICU length of stay (26 [7-43] vs 11 [5-27] days, P = .036). Moreover, among hospital survivors (n = 334), patients with CRP reduction less than 25% were discharged later (hazard ratio, 0.750; 95% confidence interval, 0.602-0.935; P = .011). Conclusions: In this large cohort of critically ill patients, failure to reduce CRP values more than 25% in the last 24 hours of ICU stay is a strong predictor of worse in-hospital outcomes. (C) 2012 Elsevier Inc. All rights reserved.

The Real Importance of Pre-Existing Comorbidities on Long-Term Mortality after Acute Kidney Injury

Background: The causes of death on long-term mortality after acute kidney injury (AKI) have not been well studied. The purpose of the study was to evaluate the role of comorbidities and the causes of death on the long-term mortality after AKI. Methodology/Principal Findings: We retrospectively studied 507 patients who experienced AKI in 2005-2006 and were discharged free from dialysis. In June 2008 (median: 21 months after AKI), we found that 193 (38%) patients had died. This mortality is much higher than the mortality of the population of Sao Paulo City, even after adjustment for age. A multiple survival analysis was performed using Cox proportional hazards regression model and showed that death was associated with Khan's index indicating high risk [adjusted hazard ratio 2.54 (1.38-4.66)], chronic liver disease [1.93 (1.15-3.22)], admission to non-surgical ward [1.85 (1.30-2.61)] and a second AKI episode during the same hospitalization [1.74 (1.12-2.71)]. The AKI severity evaluated either by the worst stage reached during AKI (P=0.20) or by the need for dialysis (P=0.12) was not associated with death. The causes of death were identified by a death certificate in 85% of the non-survivors. Among those who died from circulatory system diseases (the main cause of death), 59% had already suffered from hypertension, 34% from diabetes, 47% from heart failure, 38% from coronary disease, and 66% had a glomerular filtration rate <60 previous to the AKI episode. Among those who died from neoplasms, 79% already had the disease previously. Conclusions: Among AKI survivors who were discharged free from dialysis the increased long-term mortality was associated with their pre-existing chronic conditions and not with the severity of the AKI episode. These findings suggest that these survivors should have a medical follow-up after hospital discharge and that all efforts should be made to control their comorbidities.

Household income, sex and respiratory mortality in Sao Paulo, Brazil, 1996-2010

SETTING: Respiratory mortality rates are declining in several countries, including Brazil; however, the effect of socio-economic indicators and sex is unclear. OBJECTIVE: To identify differences in mortality trends according to income and sex in the city of Sao Paulo, Brazil. DESIGN: We performed a time-trend analysis of all respiratory diseases, including chronic obstructive pulmonary disease (COPD), lung cancer and tuberculosis, using Joinpoint regression comparing high, middle and low household income levels from 1996 to 2010. RESULTS: The annual per cent change (APC) and 95% confidence intervals (95%CIs) for death rates from all respiratory disease in men in high-income areas was -1.1 (95%CI -2.7 to 0.5) in 1996-2002 and -4.3 (95%CI -5.9 to -2.8) in 2003-2009. In middle- and low-income areas, the decline was respectively -1.5 (95%CI -2.2 to -0.7) and -1.4 (95%CI -1.9 to -0.8). For women, the APC declined in high-income (-1.0, 95%CI -1.9 to -0.2) and low-income areas (0.8, 95%CI -1.3 to -0.2), but not in middle-income areas (-0.5, 95%CI -1.4 to 0.3) from 1996 to 2010. CONCLUSION: Death rates due to COPD and all respiratory disease declined more consistently in men from high-income areas. Mortality due to lung cancer decreased in men, but increased in women in middle- and low-income areas.

Nitrogen excretion during embryonic development of the green iguana, Iguana iguana (Reptilia; Squamata)

Development within the cleidoic egg of birds and reptiles presents the embryo with the problem of accumulation of wastes from nitrogen metabolism. Ammonia derived from protein catabolism is converted into the less toxic product urea or relatively insoluble uric acid. The pattern of nitrogen excretion of the green iguana, Iguana iguana, was determined during embryonic development using samples from allantoic fluid and from the whole homogenized egg, and in hatchlings and adults using samples of blood plasma. Urea was the major excretory product over the course of embryonic development. It was found in higher concentrations in the allantoic sac, suggesting that there is a mechanism present on the allantoic membrane enabling the concentration of urea. The newly hatched iguana still produced urea while adults produced uric acid. The time course of this shift in the type of nitrogen waste was not determined but the change is likely to be related to the water relations associated with the terrestrial habit of the adult. The green iguana produces parchment-shelled eggs that double in mass during incubation due to water absorption: the eggs also accumulate 0.02 mM of urea, representing 82% of the total measured nitrogenous residues that accumulate inside the allantois. The increase in egg mass and urea concentration became significant after 55 days of incubation then were unchanged until hatching. (C) 2012 Elsevier Inc. All rights reserved.

Propensity score matching approach to test the association of income inequality and mortality in Sao Paulo, Brazil

Background Support for the adverse effect of high income inequality on population health has come from studies that focus on larger areas, such as the US states, while studies at smaller geographical areas (eg, neighbourhoods) have found mixed results. Methods We used propensity score matching to examine the relationship between income inequality and mortality rates across 96 neighbourhoods (distritos) of the municipality of Sao Paulo, Brazil. Results Prior to matching, higher income inequality distritos (Gini >= 0.25) had slightly lower overall mortality rates (2.23 per 10 000, 95% CI -23.92 to 19.46) compared to lower income inequality areas (Gini <0.25). After propensity score matching, higher inequality was associated with a statistically significant higher mortality rate (41.58 per 10 000, 95% CI 8.85 to 73.3). Conclusion In Sao Paulo, the more egalitarian communities are among some of the poorest, with the worst health profiles. Propensity score matching was used to avoid inappropriate comparisons between the health status of unequal (but wealthy) neighbourhoods versus equal (but poor) neighbourhoods. Our methods suggest that, with proper accounting of heterogeneity between areas, income inequality is associated with worse population health in Sao Paulo.

Embryonic and Fetal Development in - Pigmy Rice Rat - Oligoryzomys sp (Rodentia, Sigmodontinae) and its Significance for Being a new Experimental Model

Oligoryzomys (Cricetidae, Sigmodontinae) is a common rodent genus from South America that includes a couple of very similar species. Related species have been used as experimental model for understanding several diseases for which these species are reservoirs. In order to provide a better understanding of the embryological aspects of this group, herein we showed data on the embryonic and fetal development in Oligoryzomys sp. Eight specimens of different stages of gestation were obtained from the Collection of the Zoology Museum of University of Sao Paulo, Brazil. Gestational ages were estimated by crown-rump-length according to Evans and Sack (1973). To address our analysis after examining the gross morphology, tissues from several organs were processed for light and scanning electron microscopy. Morphological data on the systems (nervous system, cardiorespiratory system, intestinal tract and urogenital system) were described in detail. Finally, the findings were compared with what is known about embryological aspects in other rodent species in order to establish similarities and differences during the organogenesis in different species.

Disparities in female breast cancer mortality rates in Brazil between 1980 and 2009

OBJECTIVE: To describe the temporal trends in female breast cancer mortality rates in Brazil in its macro-regions and states between 1980 and 2009. METHODS: This was an ecological time-series study using data on breast cancer deaths registered in the Mortality Data System (SIM/WHO) and census data on the resident population collected by the Brazilian Institute of Geography and Statistics (IBGE/WHO). Joinpoint regression analyses were used to identify the significant changes in trends and to estimate the annual percentage change (APC) in mortality rates. RESULTS: Female breast cancer mortality rates in Brazil tended to stabilize from 1994 onward (APC = 0.4%). Considering the Brazilian macro-regions, the annual mortality rates decreased in the Southeast, stabilized in the South and increased in the Northeast, North, and Midwest. Only the states of Sao Paulo (APC = -1.9%), Rio Grande do Sul (APC = -0.8%) and Rio de Janeiro (APC = -0.6%) presented a significant decline in mortality rates. The greatest increases were found in Maranhao (APC = 12%), Paraiba (APC = 11.9%), and Piaui (APC = 10.9%). CONCLUSION: Although there has been a trend toward stabilization in female breast cancer mortality rates in Brazil, when the mortality rate of each macro-region and state is analyzed individually, considerable inequalities are found, with rate decline or stabilization in states with higher socioeconomic levels and a substantial increase in those with lower socioeconomic levels.

Reprogramming of prostate cancer-associated stromal cells to embryonic stem-like

BACKGROUND CD90+ prostate cancer-associated (CP) stromal cells represent a diseased cell type found only in tumor tissue. They differ from their normal counterpart in gene expression and inductive signaling. Genetic reprogramming by induced pluripotent stem (iPS) cell technology can effectively change adult cells into stem-like cells through wholesale alteration of the gene expression program. This technology might be used to erase the abnormal gene expression of diseased cells. The resultant iPS cells would no longer express the disease phenotype, and behave like stem cells. METHODS CP stromal cells, isolated from tumor tissue of a surgically resected prostate by anti-CD90-mediated sorting and cultured in vitro, were transfected with in vitro packaged lentiviral expression vectors containing stem cell transcription factor genes POU5F1, LIN28, NANOG, and SOX2. RESULTS Alkaline phosphatase-positive iPS cells were obtained in about 3 weeks post-transfection at a frequency of 10-4. Their colony morphology was indistinguishable from that of human embryonic stem (ES) cells. Transcriptome analysis showed a virtually complete match in gene expression between the iPS and ES cells. CONCLUSIONS Genes of CP stromal cells could be fully inactivated by genetic reprogramming. As a consequence, the disease phenotype was cured. Prostate 72:14531463, 2012. (c) 2012 Wiley Periodicals, Inc.

The use of parthenotegenetic and IVF bovine blastocysts as a model for the creation of human embryonic stem cells under defined conditions

Clinical application of human embryonic stem cells will be possible, when cell lines are created under xeno-free and defined conditions. We aimed to establish methodologies for parthenogenetic activation, culture to blastocyst and mechanical isolation of the inner cell mass (ICM) using bovine oocytes, as a model for derivation and proliferation of human embryonic stem cells under defined xeno-free culture conditions. Cumulus-oocyte-complexes were in vitro matured and activated using Ca(2+)Ionophore and 6-DMAP or in vitro fertilized (IVF). Parthenotes and biparental embryos were cultured to blastocysts, when their ICM was mechanically isolated and placed onto a substrate of fibronectin in StemProA (R) medium. After attachment, primary colonies were left to proliferate and stained for pluripotency markers, alkaline phosphatase and Oct-4. Parthenogenesis and fertilization presented significantly different success rates (91 and 79 %, respectively) and blastocyst formation (40 and 43 %, respectively). ICMs from parthenogenetic and IVF embryos formed primary and expanded colonies at similar rates (39 % and 33 %, respectively). Six out of eight parthenogenetic colonies tested positive for alkaline phosphatase. Three colonies were analyzed for Oct-4 and they all tested positive for this pluripotency marker. Our data show that Ca2+ Ionophore, and 6-DMAP are efficient in creating large numbers of blastocysts to be employed as a model for human oocyte activation and embryo development. After mechanical isolation, parthenogetic derived ICMs showed a good rate of derivation in fibronectin and Stem-Pro forming primary and expanded colonies of putative embryonic stem cells. This methodology may be a good strategy for parthenogenetic activation of discarded human oocytes and derivation in defined conditions for future therapeutic interventions.