Crystallization and preliminary X-ray diffraction analysis of prephenate dehydratase from Mycobacterium tuberculosis H37Rv

Tuberculosis remains the leading cause of mortality arising from a bacterial pathogen ( Mycobacterium tuberculosis). There is an urgent need for the development of new antimycobacterial agents. The aromatic amino-acid pathway is essential for the survival of this pathogen and represents a target for structure-based drug design. Accordingly, the M. tuberculosis prephenate dehydratase has been cloned, expressed, purified and crystallized by the hanging-drop vapour-diffusion method using PEG 400 as a precipitant. The crystal belongs to the orthorhombic space group I222 or I2(1)2(1)2(1), with unit-cell parameters a = 98.26, b = 133.22, c = 225.01 angstrom, and contains four molecules in the asymmetric unit. A complete data set was collected to 3.2 angstrom resolution using a synchrotron-radiation source.

β-carotene attenuates the paradoxical effect of tobacco smoke on the mortality of rats after experimental myocardial infarction

The objective of this study was to investigate the effects of exposure to tobacco smoke (ETS) in rats that were or were not supplemented with dietary β-carotene (BC), on ventricular remodeling and survival after myocardial infarction (Ml). Rats (n = 189) were allocated to 4 groups: the control group, n = 45; group BC administered 500 mg/kg diet, n = 49, BC supplemented rats; group ETS, n - 55, rats exposed to tobacco smoke; and group BC+ETS, n = 40. Wistar rats weighing 10O g were administered one of the treatments until they weighed 200 to 250 g (∼5 wk). The ETS rats were exposed to cigarette smoke for 30 min 4 times/d, in a chamber connected to a smoking device. After reaching a weight of 200-250 g, rats were subjected to experimental MI (coronary artery occlusion) and mortality rates were determined over the next 105 d. In addition, echocardiographic, isolated heart, morphometrical, and biochemical studies were performed. Mortality data were tested using Kaplan-Meyer curves and other data by 2-way ANOVA. Survival rates were greater in the ETS group (58.2%) than in the control (33.3%) (P = 0.001) and BC+ETS rats (30.0%) (P = 0.007). The groups did not differ in the other comparisons. Left ventricular end-diastolic diameter normalized to body weight was greater and maximal systolic pressures were lower in the ETS groups than in non-ETS groups. Previous exposure to tobacco smoke induced a process of cardiac remodeling after MI. There is a paradoxical protector effect with tobacco smoke exposure, characterized by lower mortality, which is offset by BC supplementation. © 2005 American Society for Nutritional Sciences.

Oral cancer mortality trends in Brazilian geographical regions from 1996-2001

The purpose of this study was to analyse the oral cancer mortality trends in Brazil by geographic region, age and sex, from 1996 to 2001. The Brazilian Ministry of Health database DATASUS and the Brazilian Institute of Geography and Statistics were used as the source of data. Oral cancer mortality rates per 100,000 population were estimated. Statistical analyses comprised estimates of oral cancer mortality rates, grouped according to the study variables, in 1996, 1997, 1998, 1999, 2000 and 2001; also, the three-year periods 1996-1998 and 1999-2001 were analysed, allowing the oral cancer mortality trends between these two periods to be calculated. For comparison, in each geographical region, the ratio between two death rates (related to period or sex) was calculated. In the period 1996-2001, a total of 25,972 deaths due to oral cancer were reported, giving a mortality rate of 2.67. The rates for the periods 1996-1998 and 1999-2001 were 2.53 and 2.73, respectively, showing a slight increase in the rate. There was a predominance of oral cancer in males with a male/female ratio of approximately 4. All regions exhibited an increase in mortality rates, with the exception of the Southeast region. From 1996 to 2001, the average mortality rates were 3.55 and 3.58 for the Southeast and South regions, and 1.94, 1.41, and 0.86 for the Mid-West, Northeast, and North regions, respectively. Over the age of 40, oral cancer mortality rates were seen to increase rapidly with age. Oral cancer mortality increased in all regions, except in the Southeast, and was considerably higher among males and older individuals.

Profile of cardiovascular risk factors and mortality in patients with symptomatic peripheral arterial disease

Introduction: The present study examines cardiovascular risk factor profiles and 24-month mortality in patients with symptomatic peripheral arterial disease. Design Study: Prospective observational study including 75 consecutive patients with PAD (67 ± 9.7 years of age; 52 men and 23 women) hospitalized for planned peripheral vascular reconstruction. Doppler echocardiograms were performed before surgery in 54 cases. Univariate analyses were performed using Student's t-test or Fisher's exact test. Survival analysis at 24-month follow-up was performed using the Cox regression model and Kaplan-Meier method including age and chronic use of aspirin as covariates. Survival curves were compared using the log-rank test. Results: Hypertension and smoking were the most frequent risk factors (52 cases and 51 cases, respectively), followed by diabetes (32 cases). Undertreated dyslipidemia was found in 26 cases. Fasting glycine levels (131 ± 69.1 mg/dl) were elevated in 29 cases. Myocardial hypertrophy was found in 18 out of 54 patients. Thirty-four patients had been treated with aspirin. Overall mortality over 24 months was 24% and was associated with age (HR: 0.064; CI95: 0.014-0.115; p=0.013) and lack of use of aspirin, as no deaths occurred among those using this drug (p<0.001). No association was found between cardiovascular death (11 cases) and the other risk factors. Conclusion: There is a high prevalence of uncontrolled (treated or untreated) cardiovascular risk factors in patients undergoing planned peripheral vascular reconstruction, and chronic use of aspirin is associated with reduced all-cause mortality in these patients.

Could albumin level explain the higher mortality in hemodialysis patients with pulmonary hypertension?

Background: The pathogenesis of pulmonary hypertension (PH) in hemodialysis is still unclear. The aim of thisstudy was to identify the risk factors associated with the presence of PH in chronic hemodialysis patients and toverify whether these factors might explain the highest mortality among them.Methods: We conducted a retrospective study of hemodialysis patients who started treatment from August 2001to October 2007 and were followed up until April 2011 in a Brazilian referral medical school. According to theresults of echocardiography examination, patients were allocated in two groups: those with PH and those withoutPH. Clinical parameters, site and type of vascular access, bioimpedance, and laboratorial findings were comparedbetween the groups and a logistic regression model was elaborated. Actuarial survival curves were constructed andhazard risk to death was evaluated by Cox regression analysis.Results: PH > 35 mmHg was found in 23 (30.6%) of the 75 patients studied. The groups differed in extracellularwater, ventricular thickness, left atrium diameter, and ventricular filling. In a univariate analysis, extracellular waterwas associated with PH (relative risk = 1.194; 95% CI of 1.006 1.416; p = 0.042); nevertheless, in a multiple model,only left atrium enlargement was independently associated with PH (relative risk =1.172; 95% CI of 1.010 1.359;p = 0.036). PH (hazard risk = 3.008; 95% CI of 1.285 7.043; p = 0.011) and age (hazard risk of 1.034 per year of age;95% CI of 1.000 7.068; p = 0.047) were significantly associated with mortality in a multiple Cox regression analysis.However, when albumin was taken in account the only statistically significant association was between albuminlevel and mortality (hazard risk = 0.342 per g/dL; 95% CI of 0.119 0.984; p = 0.047) while the presence of PH lost itsstatistical significance (p = 0.184). Mortality was higher in patients with PH (47.8% vs 25%) who also had astatistically worse survival after the sixth year of follow up.Conclusions: PH in hemodialysis patients is associated with parameters of volume overload that sheds light on itspathophysiology. Mortality is higher in hemodialysis patients with PH and the low albumin level can explain thisassociation.© 2012 Greenfield et al.; licensee BioMed Central Ltd.

Serum Metalloproteinases 2 and 9 as Predictors of Gait Status, Pressure Ulcer and Mortality after Hip Fracture

Introduction: The aim of this study is to evaluate the serum activity of metalloproteinases (MMPs) -2 and -9 as predictors of pressure ulcer (PU), gait status and mortality 6 months after hip fracture. Methods: Eighty-seven patients over the age of 65 admitted to the orthopedic unit from January to December 2010 with hip fracture were prospectively evaluated. Upon admission, patient demographic information, including age, gender and concomitant diseases, was recorded. Blood samples were taken for analysis of MMP -2 and -9 activity by gel zymography and for biochemical examination within the first 72 hours of the patient's admission, after clinical stabilization. The fracture pattern (neck, trochanteric or subtrochanteric), time from admission to surgery, surgery duration and length of hospital stay were also recorded. Results: Two patients were excluded due to the presence of pathological fractures (related to cancer), and three patients were excluded due to the presence of PU before admission. Eighty-two patients, with a mean age of 80.4 ± 7.3 years, were included in the analysis. Among these patients, 75.6% were female, 59.8% had PU, and 13.4% died 6 months after hip fracture. All patients underwent hip fracture repair. In a univariate analysis, there were no differences in serum MMP activity between hip fracture patients with or without PU. In addition, the multiple logistic regression analysis models, which were adjusted by age, gender, length of hospital stay and C-reactive protein, showed that the pro-MMP-9 complexed with neutrophil gelatinase-associated lipocalin form (130 kDa) was associated with gait status recovery 6 months after hip fracture. Conclusions: In conclusion, serum pro-MMP-9 is a predictor of gait status recovery 6 months after hip fracture. © 2013 Gumieiro et al.

Demographic bottlenecks in tropical plant regeneration: A comparative analysis of causal influences

Mortality factors that act sequentially through the demographic transitions from seed to sapling may have critical effects on recruitment success. Understanding how habitat heterogeneity influences the causal factors that limit propagule establishment in natural populations is central to assess these demographic bottlenecks and their consequences. Bamboos often influence forest structure and dynamics and are a major factor in generating landscape complexity and habitat heterogeneity in tropical forests. To understand how patch heterogeneity influences plant recruitment we studied critical establishment stages during early recruitment of Euterpe edulis, Sloanea guianensis and Virola bicuhyba in bamboo and non-bamboo stands in the Brazilian Atlantic forest. We combined observational studies of seed rain and seedling emergence with seed addition experiments to evaluate the transition probabilities among regeneration stages within bamboo and non-bamboo stands. The relative importance of each mortality factor was evaluated by determining how the loss of propagules affected stage-specific recruitment success. Our results revealed that the seed addition treatment significantly increased seedling survivorship for all three species. E. edulis seedling survival probability increased in the addition treatment in the two stand types. However, for S. guianensis and V. bicuhyba this effect depended strongly on artificially protecting the seeds, as both species experienced increased seed and seedling losses due to post-dispersal seed predators and herbivores. Propagules of all three species had a greater probability of reaching subsequent recruitment stages when protected. The recruitment of large-seeded V. bicuhyba and E. edulis appears to be much more limited by post-dispersal factors than by dispersal limitation, whereas the small-seeded S. guianensis showed an even stronger effect of post-dispersal factors causing recruitment collapse in some situations. We demonstrated that E. edulis, S. guianensis and V. bicuhyba are especially susceptible to predation during early compared with later establishment stages and this early stage mortality can be more crucial than stand differences as determinants of successful regeneration. Among-species differences in the relative importance of dispersal vs. establishment limitation are mediated by variability in species responses to patch heterogeneity. Thus, bamboo effects on the early recruitment of non-bamboo species are patchy and species-specific, with successional bamboo patches exerting a far-reaching influence on the heterogeneity of plant species composition and abundance. © 2012 Perspectives in Plant Ecology, Evolution and Systematics.

Mini Nutritional Assessment predicts gait status and mortality 6 months after hip fracture.

The aim of the present study was to evaluate the Mini Nutritional Assessment (MNA), the Nutritional Risk Screening (NRS) 2002 and the American Society of Anesthesiologists Physical Status Score (ASA) as predictors of gait status and mortality 6 months after hip fracture. A total of eighty-eight consecutive patients over the age of 65 years with hip fracture admitted to an orthopaedic unit were prospectively evaluated. Within the first 72 h of admission, each patient's characteristics were recorded, and the MNA, the NRS 2002 and the ASA were performed. Gait status and mortality were evaluated 6 months after hip fracture. Of the total patients, two were excluded because of pathological fractures. The remaining eighty-six patients (aged 80·2 (sd 7·3) years) were studied. Among these patients 76·7 % were female, 69·8 % walked with or without support and 12·8 % died 6 months after the fracture. In a multivariate analysis, only the MNA was associated with gait status 6 months after hip fracture (OR 0·773, 95 % CI 0·663, 0·901; P= 0·001). In the Cox regression model, only the MNA was associated with mortality 6 months after hip fracture (hazard ratio 0·869, 95 % CI 0·757, 0·998; P= 0·04). In conclusion, the MNA best predicts gait status and mortality 6 months after hip fracture. These results suggest that the MNA should be included in the clinical stratification of patients with hip fracture to identify and treat malnutrition in order to improve the outcomes.

Clinical, serological, and parasitological analysis of snakes naturally infected with Cryptosporidium serpentis

Infection by Cryptosporidium serpentis is one of the most important diseases in reptiles and is characterized by chronic clinical or subclinical infection and the presence of hypertrophic gastritis, food regurgitation, progressive weight loss, mortality, and intermittent or continuous shedding of oocysts in the feces. The objectives of this study were to standardize an indirect enzyme-linked immunosorbent assay (ELISA) to detect antibodies against C. serpentis and to evaluate the clinical, parasitological, and humoral immune response in snakes naturally infected with C. serpentis. Twenty-one snakes naturally infected with C. serpentis and housed at the Butantan Institute, São Paulo, Brazil, underwent clinical and parasitological analyses for C. serpentis infection through daily records of clinical signs and a monthly survey of fecal shedding of oocysts using the Kinyoun's acid-fast staining. The serological evaluation was performed monthly by indirect ELISA using crude total antigen from oocysts of C. serpentis to detect anti-C. serpentis antibodies. Clinical symptoms consisted of food regurgitation, inappetence, and progressive weight loss. The parasitological analysis revealed intermittent fecal shedding of a variable number of oocysts in all snakes, with positivity in 85.32% (157/184) of the samples. The indirect ELISA was positive in 68.25% (86/126) of the samples. A humoral immune response was observed in most animals; however, fluctuating antibodies levels, leading to alternating positive and negative results, were observed in most snakes. © 2013 Elsevier B.V. All rights reserved.

Analysis of selected millennium development goals in Nicaragua

Includes bibliography

Enhanced Recovery after Elective Open Surgical Repair of Abdominal Aortic Aneurysm: A Complementary Overview through a Pooled Analysis of Proportions from Case Series Studies

Objectives: To evaluate the efficacy and safety of enhanced recovery after surgery (ERAS) programs in elective open surgical repair (OSR) of abdominal aortic aneurysm (AAA).Background: Open surgical repair of AAA is associated with high morbidity and mortality, prolonged hospital stay and high costs. ERAS programs contribute to the optimization of treatment by reducing hospital stay and improving clinical outcomes.Methods: A review of PubMed, EMBASE and LILACS databases was conducted. As only one randomized controlled trial was found, a pooled analysis of proportions from case series was conducted, considering it a complementary overview of the topic. Inclusion criteria were case series with more than five cases reported, adult patients who underwent an elective OSR of AAA and use of an ERAS program. ERAS was compared to conventional perioperative care. The pooled proportion and the confidence interval (CI) are shown for each outcome. The overlap of the CI suggests similar effect of the interventions studied.Results: Thirteen case series studies with ERAS involving 1,250 patients were compared to six case series with conventional care with a total of 1,429 patients. The pooled, respective proportions for ERAS and conventional care were: mortality, 1.51% [95% CI: 0.0091, 0.0226] and 3.0% [95% CI 0.0183, 0.0445]; and incidence of complications, 3.82% [95% CI 0.0259, 0.0528] and 4.0% [95% CI 0.03, 0.05].Conclusion: This review shows that ERAS and conventional care therapies have similar mortality and complication rates in OSR of AAA.

Temporal, spatial and spatiotemporal analysis of the occurrence of visceral leishmaniasis in humans in the City of Birigui, State of São Paulo, from 1999 to 2012

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Nutritional parameters are associated with mortality in acute kidney injury

OBJECTIVE: The objective of this study was to perform a nutritional assessment of acute kidney injury patients and to identify the relationship between nutritional markers and outcomes.METHOD: This was a prospective and observational study. Patients who were hospitalized at the Hospital of Botucatu School of Medicine were evaluated between January 2009 and December 2011. We evaluated a total of 133 patients with a clinical diagnosis of acute kidney injury and a clinical presentation suggestive of acute tubular necrosis. We explored the associations between clinical, laboratory and nutritional markers and in hospital mortality. Multivariable logistic regression was used to adjust for confounding and selection bias.RESULTS: Non-survivor patients were older (67 +/- 14 vs. 59 +/- 16 years) and exhibited a higher prevalence of sepsis (57.1 vs. 21.4%) and higher Acute Tubular Necrosis-Individual Severity Scores (0.60 +/- 0.22 vs. 0.41 +/- 0.21) than did survivor patients. Based on the multivariable analysis, laboratorial parameters such as blood urea nitrogen and C-reactive protein were associated with a higher risk of death (OR: 1.013, p = 0.0052; OR: 1.050, p = 0.01, respectively), and nutritional parameters such as low calorie intake, higher levels of edema, lower resistance based on bioelectrical impedance analysis and a more negative nitrogen balance were significantly associated with a higher risk of death (OR: 0.950, p = 0.01; OR: 1.138, p = 0.03; OR: 0.995, p = 0.03; OR: 0.934, p = 0.04, respectively).CONCLUSIONS: In acute kidney injury patients, a nutritional assessment seems to identify nutritional markers that are associated with outcome. In this study, a low caloric intake, higher C-reactive protein levels, the presence of edema, a lower resistance measured during a bioelectrical impedance analysis and a lower nitrogen balance were significantly associated with risk of death in acute kidney injury patients.

Low serum potassium levels increase the infectious-caused mortality in peritoneal dialysis patients: a propensity-matched score study

Background and ObjectivesHypokalemia has been consistently associated with high mortality rate in peritoneal dialysis. However, studies investigating if hypokalemia is acting as a surrogate marker of comorbidities or has a direct effect in the risk for mortality have not been studied. Thus, the aim of this study was to analyze the effect of hypokalemia on overall and cause-specific mortality.Design, Setting, Participants and MeasurementsThis is an analysis of BRAZPD II, a nationwide prospective cohort study. All patients on PD for longer than 90 days with measured serum potassium levels were used to verify the association of hypokalemia with overall and cause-specific mortality using a propensity match score to reduce selection bias. In addition, competing risks were also taken into account for the analysis of cause-specific mortality.ResultsThere was a U-shaped relationship between time-averaged serum potassium and all-cause mortality of PD patients. Cardiovascular disease was the main cause of death in the normokalemic group with 133 events (41.8%) followed by PD-non related infections, n=105 (33.0%). Hypokalemia was associated with a 49% increased risk for CV mortality after adjustments for covariates and the presence of competing risks (SHR 1.49; CI95% 1.01-2.21). In contrast, in the group of patients with K < 3.5mEq/L, PD-non related infections were the main cause of death with 43 events (44.3%) followed by cardiovascular disease (n=36; 37.1%). For PD-non related infections the SHR was 2.19 (CI95% 1.52-3.14) while for peritonitis was SHR 1.09 (CI95% 0.47-2.49).ConclusionsHypokalemia had a significant impact on overall, cardiovascular and infectious mortality even after adjustments for competing risks. The causative nature of this association suggested by our study raises the need for intervention studies looking at the effect of potassium supplementation on clinical outcomes of PD patients.