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Despite the need for specific weaning strategies in neurological patients, evidence is generally insufficient or lacking. We aimed to describe the evolution over time of weaning and extubation practices in patients with acute brain injury compared with patients who are mechanically ventilated (MV) due to other reasons.We performed a secondary analysis of three prospective, observational, multicenter international studies conducted in 2004, 2010, and 2016 in adults who had need of invasive MV for more than 12 h. We collected data on baseline characteristics, variables related to management ventilator settings, and complications while patients were ventilated or until day 28.Among the 20,929 patients enrolled, we included 12,618 (60%) who started the weaning from MV, of whom 1722 (14%) were patients with acute brain injury. In the acutely brain-injured cohort, 538 patients (31%) did not undergo planned extubation, defined as the need for a tracheostomy without an attempt of extubation, accidental extubation, and death. Among the 1184 planned extubated patients with acute brain injury, 202 required reintubation (17%). Patients with acute brain injury had a higher odds for unplanned extubation (odds ratio [OR] 1.35, confidence interval for 95% [CI 95%] 1.19-1.54; p 0.001), a higher odds of failure after the first attempt of weaning (spontaneous breathing trial or gradual reduction of ventilatory support; OR 1.14 [CI 95% 1.01-1.30; p = 0.03]), and a higher odds for reintubation (OR 1.41 [CI 95% 1.20-1.66; p 0.001]) than patients without brain injury. Patients with hemorrhagic stroke had the highest odds for unplanned extubation (OR 1.47 [CI 95% 1.22-1.77; p 0.001]), of failed extubation after the first attempt of weaning (OR 1.28 [CI 95% 1.06-1.55; p = 0.009]), and for reintubation (OR 1.49 [CI 95% 1.17-1.88; p 0.001]). In relation to weaning evolution over time in patients with acute brain injury, the risk for unplanned extubation showed a downward trend; the risk for reintubation was not associated to time; and there was a significant increase in the percentage of patients who underwent extubation after the first attempt of weaning from MV.Patients with acute brain injury, compared with patients without brain injury, present higher odds of undergoing unplanned extubated after weaning was started, lower odds of being extubated after the first attempt, and a higher risk of reintubation.

BACKGROUND: Driving pressure (ΔP) has been described as a risk factor for mortality in patients with ARDS. However, the role of ΔP in the outcome of patients without ARDS and on mechanical ventilation has received less attention. Our objective was to evaluate the association between ΔP on the first day of mechanical ventilation with the development of ARDS. METHODS: This was a post hoc analysis of a multicenter, prospective, observational, international study that included subjects who were on mechanical ventilation for > 12 h. Our objective was to evaluate the association between ΔP on the first day of mechanical ventilation with the development of ARDS. To assess the effect of ΔP, a logistic regression analysis was performed when adjusting for other potential risk factors. Validation of the results obtained was performed by using a bootstrap method and by repeating the same analyses at day 2. RESULTS: A total of 1,575 subjects were included, of whom 65 (4.1%) developed ARDS. The ΔP was independently associated with ARDS (odds ratio [OR] 1.12, 95% CI 1.07–1.18 for each cm H(2)O of ΔP increase, P < .001). The same results were observed at day 2 (OR 1.14, 95% CI 1.07–1.21; P < .001) and after bootstrap validation (OR 1.13, 95% CI 1.04–1.22; P < .001). When taking the prevalence of ARDS in the lowest quartile of ΔP (≤9 cm H(2)O) as a reference, the subjects with ΔP > 12–15 cm H(2)O and those with ΔP > 15 cm H(2)O presented a higher probability of ARDS (OR 3.65, 95% CI 1.32–10.04 [P = .01] and OR 7.31, 95% CI, 2.89–18.50 [P < .001], respectively). CONCLUSIONS: In the subjects without ARDS, a higher level of ΔP on the first day of mechanical ventilation was associated with later development of ARDS. (ClinicalTrials.gov registration NCT02731898.)

Phenolic lipids components of the cashew nutshell liquid (CNSL) have molecular structures capable of chemical signalling that regulate gene expression, metabolism and inflammation. This study sets out to assess how CNSL derivatives impact oral bacteria, from an antibacterial and anti-collagenolytic perspective, as well as its biocompatibility with dental pulp stem cells. Two hemi-synthetic saturated CNSL derivative compounds were selected (LDT11-Anacardic Acids-derivative and LDT409-cardanol-derivative). Bacteriostatic activity was tested against Streptococcus mutans and Veillonella parvula. Antimicrobial capacity against preformed S. mutans biofilms was investigated using a collagen-coated Calgary Biofilm Device and confocal microscopy. Clostridium histolyticum, P. gingivalis and S. mutans biofilms were used to assess anti-collagenolytic activity. Biocompatibility with human dental pulp stromal cells (HDPSCs) was investigated (MTT for viability proportion, LDH assays for cell death rate). LDTs inhibited the bacterial growth, as well as partially inhibited bacterial collagenases in concentrations higher than 5 μg/mL. Dose–response rates of biofilm cell death was observed (LDT11 at 20, 50, 100 μg/mL = 1.0 ± 0.4, 0.7 ± 0.3, 0.6 ± 0.03, respectively). Maximum cytotoxicity was 30%. After 1 week, LDT409 had no HDPSCs death. HDPSCs viability was decreased after 24 h of treatment with LDT11 and LDT409, but recovered at 72 h and showed a massive increase in viability and proliferation after 1 week. LDTs treatment was associated with odontoblast-like morphology. In conclusion, LDT11 multifunctionality and biocompatibility, stimulating dental pulp stem cells proliferation and differentiation, indicates a potential as a bio-based dental material for regenerative Dentistry. Its potential as a bacterial collagenases inhibitor to reduce collagen degradation in root/dentinal caries can be further explored.

The multifactorial nature of Alzheimer's disease (AD) is a reason for the lack of effective drugs as well as a basis for the development of "multi-target-directed ligands" (MTDLs). As cases increase in developing countries, there is a need of new drugs that are not only effective but also accessible. With this motivation, we report the first sustainable MTDLs, derived from cashew nutshell liquid (CNSL), an inexpensive food waste with anti-inflammatory properties. We applied a framework combination of functionalized CNSL components and well-established acetylcholinesterase (AChE)/butyrylcholinesterase (BChE) tacrine templates. MTDLs were selected based on hepatic, neuronal, and microglial cell toxicity. Enzymatic studies disclosed potent and selective AChE/BChE inhibitors (5, 6, and 12), with subnanomolar activities. The X-ray crystal structure of 5 complexed with BChE allowed rationalizing the observed activity (0.0352 nM). Investigation in BV-2 microglial cells revealed antineuroinflammatory and neuroprotective activities for 5 and 6 (already at 0.01 mu M), confirming the design rationale.

To date, it is unknown whether systematic biopsies can be safely omitted in patients with unsuspicious MRI findings or if systematic biopsies should be required when targeting focal lesions (PI-RADS 3-5).A series of 366 patients (249 without a previous biopsy) were examined in a 1.5 Tesla MRI scanner. All patients were submitted to systematic biopsies (12-14 regions) with additional targeted biopsies (by cognitive fusion) of focal PI-RADS lesions (PI-RADS 3-5).In our series, patients with PI-RADS 1/2 findings had rates of adenocarcinoma of any grade,GG1 and GG4/5 of 34%, 14% and 3%, respectively. The use of MRI prior to biopsy in our series increased the detection of clinically significant prostate cancer (CSPCa) in 28% of patients with focal lesions, and focal lesions were present in 293/366 (80%) of all patients. For CSPCa (GG1), targeted biopsies improved the diagnosis in 28% of patients, while systematic biopsies resulted in an additional 19% of cancer cases in the series.Systematic biopsies should still be considered in patients with PI-RADS 1/2 findings. Our findings also suggest a stronger benefit of the combined strategy of targeted and systematic biopsies than the findings of previous studies concerning the detection of CSPCa in biopsy-naïve patients.

Purpose Variations in clinical characteristics and management and in the mortality of mechanically ventilated patients have not been sufficiently evaluated. We hypothesized that mortality shows a variability associated with country after adjustment for clinical characteristics and management. Methods Analysis of four studies carried out at 6-year intervals over an 18-year period. The studies included 26,024 patients (5183 in 1998, 4968 in 2004, 8108 in 2010, and 7765 in 2016) admitted to 1253 units from 38 countries. The primary outcome was 28-day mortality. We performed analyses using multilevel logistic modeling with mixed-random effects, including country as a random variable. To evaluate the effect of management strategies on mortality, a mediation analysis was performed. Results Adjusted 28-day mortality decreased significantly over time (first study as reference): 2004: odds ratio 0.82 (95% confidence interval [CI] 0.72–0.93); 2010: 0.63 (95% CI 0.53–0.75); 2016: 0.49 (95% CI 0.39–0.61). A protective ventilatory strategy and the use of continuous sedation mediated a moderate fraction of the effect of time on mortality in patients with moderate hypoxemia and without hypoxemia, respectively. Logistic multilevel modeling showed a significant effect of country on mortality: median odds ratio (MOR) in 1998: 2.02 (95% CI 1.57–2.48); in 2004: 1.76 (95% CI 1.47–2.06); in 2010: 1.55 (95% CI 1.37–1.74), and in 2016: 1.39 (95% CI 1.25–1.54). Conclusions These findings suggest that country could contribute, independently of confounder variables, to outcome. The magnitude of the effect of country decreased over time. Clinical trials registered with http://www.clinicaltrials.gov (NCT02731898). Electronic supplementary material The online version of this article (10.1007/s00134-019-05867-9) contains supplementary material, which is available to authorized users.

Acute respiratory distress syndrome (ARDS) is a life-threatening disease. We evaluated the prognostic utility of Model for End-stage Liver Disease excluding INR (MELD-XI) score for predicting mortality in a cohort of critically ill patients on mechanical ventilation.In total, 11,091 mechanically ventilated patients were included in our post-hoc retrospective analysis, a subgroup of the VENTILA study (NCT02731898). Evaluation of associations with mortality was done by logistic and Cox regression analysis, an optimal cut-off was calculated using the Youden Index. We divided the cohort in two sub-groups based on their MELD-XI score at the optimal cut-off (12 score points).Peak-, plateau- and positive end-expiratory pressure were higher in patients with MELD-XI12. Patients with MELD-XI12 had higher driving pressures (14 ± 6 cmH2O versus 13 ± 6; p 0.001). MELD-XI was associated with 28-day mortality after correction for relevant cofounders including SAPS II and ventilation pressures (HR 1.04 95%CI 1.03-1.05; p 0.001. Patients with MELD-XI12 evidenced both increased hospital (46% versus 27%; p 0.001) and 28-day mortality (39% versus 22%).MELD-XI is independently associated with mortality and constitutes a useful and easily applicable tool for risk stratification in critically ill patients receiving mechanical ventilation.NCT02731898, registered 4 April 2016.

BACKGROUND: The growing proportion of elderly intensive care patients constitutes a public health challenge. The benefit of critical care in these patients remains unclear. We compared outcomes in elderly versus very elderly subjects receiving mechanical ventilation. METHODS: In total, 5,557 mechanically ventilated subjects were included in our post hoc retrospective analysis, a subgroup of the VENTILA study. We divided the cohort into 2 subgroups on the basis of age: very elderly subjects (age ≥ 80 y; n = 1,430), and elderly subjects (age 65–79 y; n = 4,127). A propensity score on being very elderly was calculated. Evaluation of associations with 28-d mortality was done with logistic regression analysis. RESULTS: Very elderly subjects were clinically sicker as expressed by higher SAPS II scores (53 ± 18 vs 50 ± 18, P < .001), and their rates of plateau pressure < 30 cm H(2)O were higher, whereas other parameters did not differ. The 28-d mortality was higher in very elderly subjects (42% vs 34%, P < .001) and remained unchanged after propensity score adjustment (adjusted odds ratio 1.31 [95% CI 1.16–1.49], P < .001). CONCLUSIONS: Age was an independent and unchangeable risk factor for death in mechanically ventilated subjects. However, survival rates of very elderly subjects were > 50%. Denial of critical care based solely on age is not justified. (ClinicalTrials.gov registration NCT02731898.)

The coronavirus disease 2019 (COVID-19) is caused by the Severe Acute Respiratory Syndrome Coronavirus-2 (SARS- CoV-2) with an estimated fatality rate of less than 1%. The SARS-CoV-2 accessory proteins ORF3a, ORF6, ORF7a, ORF7b, ORF8, and ORF10 possess putative functions to manipulate host immune mechanisms. These involve interferons, which appear as a consensus function, immune signaling receptor NLRP3 (NLR family pyrin domain-containing 3) inflammasome, and inflammatory cytokines such as interleukin 1β (IL-1β) and are critical in COVID-19 pathology. Outspread variations of each of the six accessory proteins were observed across six continents of all complete SARS-CoV-2 proteomes based on the data reported before November 2020. A decreasing order of percentage of unique variations in the accessory proteins was determined as ORF3a > ORF8 > ORF7a > ORF6 > ORF10 > ORF7b across all continents. The highest and lowest unique variations of ORF3a were observed in South America and Oceania, respectively. These findings suggest that the wide variations in accessory proteins seem to affect the pathogenicity of SARS-CoV-2.

The origin of the severe acute respiratory syndrome-coronavirus 2 (SARS-CoV-2) virus causing the COVID-19 pandemic has not yet been fully determined. Despite the consensus about the SARS-CoV-2 origin from bat CoV RaTG13, discrepancy to host tropism to other human Coronaviruses exist. SARS-CoV-2 also possesses some differences in its S protein receptor-binding domain, glycan-binding N-terminal domain and the surface of the sialic acid-binding domain. Despite similarities based on cryo-EM and biochemical studies, the SARS-CoV-2 shows higher stability and binding affinity to the ACE2 receptor. The SARS-CoV-2 does not appear to present a mutational "hot spot" as only the D614G mutation has been identified from clinical isolates. As laboratory manipulation is highly unlikely for the origin of SARS-CoV-2, the current possibilities comprise either natural selection in animal host before zoonotic transfer or natural selection in humans following zoonotic transfer. In the former case, despite SARS-CoV-2 and bat RaTG13 showing 96% identity some pangolin Coronaviruses exhibit very high similarity to particularly the receptor-binding domain of SARS-CoV-2. In the latter case, it can be hypothesized that the SARS-CoV-2 genome has adapted during human-to-human transmission and based on available data, the isolated SARS-CoV-2 genomes derive from a common origin. Before the origin of SARS-CoV-2 can be confirmed additional research is required.

PURPOSE: To analyze the relationship between hypercapnia developing within the first 48 h after the start of mechanical ventilation and outcome in patients with acute respiratory distress syndrome (ARDS). PATIENTS AND METHODS: We performed a secondary analysis of three prospective non-interventional cohort studies focusing on ARDS patients from 927 intensive care units (ICUs) in 40 countries. These patients received mechanical ventilation for more than 12 h during 1-month periods in 1998, 2004, and 2010. We used multivariable logistic regression and a propensity score analysis to examine the association between hypercapnia and ICU mortality. MAIN OUTCOMES: We included 1899 patients with ARDS in this study. The relationship between maximum PaCO2 in the first 48 h and mortality suggests higher mortality at or above PaCO2 of ≥50 mmHg. Patients with severe hypercapnia (PaCO2 ≥50 mmHg) had higher complication rates, more organ failures, and worse outcomes. After adjusting for age, SAPS II score, respiratory rate, positive end-expiratory pressure, PaO2/FiO2 ratio, driving pressure, pressure/volume limitation strategy (PLS), corrected minute ventilation, and presence of acidosis, severe hypercapnia was associated with increased risk of ICU mortality [odds ratio (OR) 1.93, 95% confidence interval (CI) 1.32 to 2.81; p = 0.001]. In patients with severe hypercapnia matched for all other variables, ventilation with PLS was associated with higher ICU mortality (OR 1.58, CI 95% 1.04-2.41; p = 0.032). CONCLUSIONS: Severe hypercapnia appears to be independently associated with higher ICU mortality in patients with ARDS. info:eu-repo/semantics/publishedVersion

Context: Plants of the Piperaceae family produce piplartine that was used to synthesize the cinnamides. Objective: To assess the effects of piplartine (1) and cinnamides (2–5) against the protozoa responsible for malaria and leishmaniasis, and peritoneal cells of Swiss mice. Materials and methods: Cultures of Leishmania amazonensis, Plasmodium falciparum-infected erythrocytes, and peritoneal cells were incubated, in triplicate, with different concentrations of the compounds (0 to 256 μg/mL). The inhibitory concentration (IC50) in L. amazonensis and cytotoxic concentration (CC50) in peritoneal cell were assessed by the MTT method after 6 h of incubation, while the IC50 for P. falciparum-infected erythrocytes was determined by optical microscopy after 48 or 72 h of incubation; the Selectivity Index (SI) was calculated by CC50/IC50. Results: All compounds inhibited the growth of microorganisms, being more effective against P. falciparum after 72 h of incubation, especially for the compounds 1 (IC50 = 3.2 μg/mL) and 5 (IC50 = 6.6 μg/mL), than to L. amazonensis (compound 1 = 179.0 μg/mL; compound 5 = 106.0 μg/mL). Despite all compounds reducing the viability of peritoneal cells, the SI were 10 for the piplartine (>37.4) and cinnamides 4 (>10.7) and 5 (= 38.4). Discussion and conclusion: The potential of piplartine and cinnamides 4 and 5 in the treatment of malaria suggest further pre-clinical studies to evaluate their effects in murine malaria and to determine their mechanisms in cells of the immune system.

In a search for effective and sustainable treatments for trypanosomiasis, we developed a library of hybrid compounds by merging the structural features of a previously synthesized quinone hit (4) with those of long‐chain phenolic constituents from cashew nut shell liquid (CNSL). CNSL is an agro‐waste product from cashew nut processing factories with great potential as a precursor for the production of drugs. The synthesized compounds were tested against Trypanosoma brucei brucei, including three multi‐drug resistant strains (B48, ISMR1, and aqp2/aqp3‐KO), T. congolense, and a human cell line (HFF). The most potent activity was found against T. b. brucei, the causative agent of African trypanosomiasis. Shorter‐chain derivatives were more active than the starting hit in parasite growth inhibition, displaying rapid trypanocidal activity with low micromolar EC50 values, but no discernable toxicity on human cell lines. Preliminary studies probing their mode of action on trypanosomes showed depletion of cellular ATP, followed by the depolarization of the mitochondrial membrane and ultrastructural damage to the mitochondrion. This was accompanied by the production of high levels of reactive oxygen species. We envisage that such hybrid compounds, obtained from renewable and inexpensive material, might be promising bio‐based, sustainable hits for anti‐trypanosomatid drug discovery.

Arylpiperazines 2 – 11 were synthesized, and their biological profiles at α1-adrenergic receptors (α1-ARs) assessed by binding assays in CHO cells expressing human cloned subtypes and by functional experiments in isolated rat vas deferens (α1A), spleen (α1B), and aorta (α1D). Modifications at the 1,3-benzodioxole and phenyl phamacophoric units resulted in the identification of a number of potent compounds (moderately selective with respect to the α1b-AR), in binding experiments. Notably, compound 7 (LDT451) showed a subnanomolar p K i of 9.41 towards α1a-AR. An encouragingly lower α1B-potency was a general trend for all the series of compounds, which showed α1A/D over α1B selectivity in functional assays. If adequately optimized, such peculiar selectivity could have relevance for a potential LUTS/BPH therapeutic application.

Cardanol is a phenolic lipid component of cashew nut shell liquid (CNSL), obtained as the byproduct of cashew nut food processing. Being a waste product, it has attracted much attention as a precursor for the production of high-value chemicals, including drugs. On the basis of these findings and in connection with our previous studies on cardanol derivatives as acetylcholinesterase (AChE) inhibitors, we designed a novel series of analogues by including a protonable amino moiety belonging to different systems. Properly addressed docking studies suggested that the proposed structural modifications would allow the new molecules to interact with both the catalytic active site (CAS) and the peripheral anionic site (PAS) of AChE, thus being able to act as dual binding inhibitors. To disclose whether the new molecules showed the desired profile, they were first tested for their cholinesterase inhibitory activity towards EeAChE and eqBuChE. Compound 26, bearing an N-ethyl-N-(2-methoxybenzyl)amine moiety, showed the highest inhibitory activity against EeAChE, with a promising IC50 of 6.6 μM, and a similar inhibition profile of the human isoform (IC50 = 5.7 μM). As another positive feature, most of the derivatives did not show appreciable toxicity against HT-29 cells, up to a concentration of 100 μM, which indicates drug-conform behavior. Also, compound 26 is capable of crossing the blood-brain barrier (BBB), as predicted by a PAMPA-BBB assay. Collectively, the data suggest that the approach to obtain potential anti-Alzheimer drugs from CNSL is worth of further pursuit and development.

PURPOSE: In neurologically critically ill patients with mechanical ventilation (MV), the development of acute respiratory distress syndrome (ARDS) is a major contributor to morbidity and mortality, but the role of ventilatory management has been scarcely evaluated. We evaluate the association of tidal volume, level of PEEP and driving pressure with the development of ARDS in a population of patients with brain injury. MATERIALS AND METHODS: We performed a secondary analysis of a prospective, observational study on mechanical ventilation. RESULTS: We included 986 patients mechanically ventilated due to an acute brain injury (hemorrhagic stroke, ischemic stroke or brain trauma). Incidence of ARDS in this cohort was 3%. Multivariate analysis suggested that driving pressure could be associated with the development of ARDS (odds ratio for unit increment of driving pressure 1.12; confidence interval for 95%: 1.01 to 1.23) whereas we did not observe association for tidal volume (in ml per kg of predicted body weight) or level of PEEP. ARDS was associated with an increase in mortality, longer duration of mechanical ventilation, and longer ICU length of stay. CONCLUSIONS: In a cohort of brain-injured patients the development of ARDS was not common. Driving pressure was associated with the development of this disease. info:eu-repo/semantics/publishedVersion

Benign prostatic hyperplasia (BPH) is a progressive disease related to the imbalance of cell growth and apoptosis, and it plays a key role in the development of lower urinary tract symptoms (LUTS). The main pharmacological treatment is based on α1A-adrenoceptor blockers, but in several cases monotherapy has failed. Recent studies of prostate pathophysiology have noted the role of α1D-adrenoceptors and 5-HT1A receptors in prostate cell proliferation in addition to the usual role of α1A-adrenoceptors in prostate contraction. N-phenylpiperazine is a scaffold structure that may confer drug affinity for these three receptors. Therefore, the present work aimed to investigate the pharmacological characteristics of N1-(2-methoxyphenyl)-N4-hexylpiperazine (LDT66). Using isometric contraction assays with rat prostate and aorta, LDT66 reduced phenylephrine-induced contractions and showed K B values of 3.4 and 2.2 nM for α1A- and α1D-adrenoceptors, respectively. According to the functional binding assays data, LDT66 showed a high affinity (nanomolar range) for the 5-HT1A receptors, behaving as an antagonist. LDT66 also showed a low affinity (micromolar range) for receptors unrelated to BPH such as α1B-adrenoceptors, α2A-adrenoceptors, muscarinic and 5-HT2A receptors, which is a desirable profile in order to prevent putative side effects. Accordingly, LDT66 (100 μg/kg) showed a marginal hypotensive effect. Using the DU-145 prostate cells, control experiments characterized the α1D-adrenoceptor- and 5-HT1A receptor-mediated cell growth by phenylephrine and 5-HT, respectively. LDT66 (50 nM) prevented both effects similarly. In conclusion, LDT66 is a high-affinity multi-target antagonist of relevant receptors for BPH, and it may be a new starting point for multi-target drug development to treat BPH and LUTS.

This paper deals with molecular modeling of new therapeutic agents for treating the Alzheimer's disease. The therapeutic line adopted for this study is the cholinergic hypothesis. To modulate positively the cholinergic function through the inhibition of the acetylcholinesterase, a set of candidates was designed from a natural compound extracted from the cashew nutshell liquid, anacardic acid. In silico screening of this chemical library revealed a ligand that is more promising once it is correlated with an active drug through specific topological and electronic descriptors. The protein-ligand docking showed stable binding modes and the binding free energy computed for the active site of the receptor suggests that our ligand presents a potential biological response. Graphical Abstract Representation of the three dimensional structure of the AChE, showing the important binding sites of the Gorge and the conformation of the ligand.

This study aimed to estimate the absorption, distribution, metabolism and excretion (ADME) properties and safety of LDT5, a lead compound for oral treatment of benign prostatic hyperplasia that has previously been characterized as a multi-target antagonist of α1A-, α1D-adrenoceptors and 5-HT1A receptors. The preclinical characterization of this compound comprised the evaluation of its in vitro properties, including plasma, microsomal and hepatocytes stability, cytochrome P450 metabolism and inhibition, plasma protein binding, and permeability using MDCK-MDR1 cells. De-risking and preliminary safety pharmacology assays were performed through screening of 44 off-target receptors and in vivo tests in mice (rota-rod and single dose toxicity). LDT5 is stable in rat and human plasma, human liver microsomes and hepatocytes, but unstable in rat liver microsomes and hepatocytes (half-life of 11 min). LDT5 is highly permeable across the MDCK-MDR1 monolayer (Papp ∼32×10-6 cm/s), indicating good intestinal absorption and putative brain penetration. LDT5 is not extensively protein-bound and is a substrate of human CYP2D6 and CYP2C19 but not of CYP3A4 (half-life >60 min), and did not significantly influence the activities of any of the human cytochrome P450 isoforms screened. LDT5 was considered safe albeit new studies are necessary to rule out putative central adverse effects through D2, 5-HT1A and 5-HT2B receptors, after chronic use. This work highlights the drug-likeness properties of LDT5 and supports its further preclinical development.

© 2015 Sutherasan et al., [Introduction]: The aim of this study was to describe and compare the changes in ventilator management and complications over time, as well as variables associated with 28-day hospital mortality in patients receiving mechanical ventilation (MV) after cardiac arrest. [Methods]: We performed a secondary analysis of three prospective, observational multicenter studies conducted in 1998, 2004 and 2010 in 927 ICUs from 40 countries. We screened 18,302 patients receiving MV for more than 12 hours during a one-month-period. We included 812 patients receiving MV after cardiac arrest. We collected data on demographics, daily ventilator settings, complications during ventilation and outcomes. Multivariate logistic regression analysis was performed to calculate odds ratios, determining which variables within 24 hours of hospital admission were associated with 28-day hospital mortality and occurrence of acute respiratory distress syndrome (ARDS) and pneumonia acquired during ICU stay at 48 hours after admission. [Results]: Among 812 patients, 100 were included from 1998, 239 from 2004 and 473 from 2010. Ventilatory management changed over time, with decreased tidal volumes (V) (1998: mean 8.9 (standard deviation (SD) 2) ml/kg actual body weight (ABW), 2010: 6.7 (SD 2) ml/kg ABW; 2004: 9 (SD 2.3) ml/kg predicted body weight (PBW), 2010: 7.95 (SD 1.7) ml/kg PBW) and increased positive end-expiratory pressure (PEEP) (1998: mean 3.5 (SD 3), 2010: 6.5 (SD 3); P, The VENTILA study was supported by Centro de Investigación Biomédica en Red de Enfermedades Respiratorias (CIBERES), Instituto de Salud Carlos III, Madrid, Spain. Dr Ferguson is supported by a Canadian Institutes of Health Research New Investigator Award (Ottawa, Canada).

We have theoretically studied new potential candidates of acetylcholinesterase (AChE) inhibitors designed from cardanol, a non-isoprenoid phenolic lipid of cashew Anacardium occidentale nut-shell liquid. The electronic structure calculations of fifteen molecule derivatives from cardanol were performed using B3LYP level with 6-31G, 6-31G(d), and 6-311 + G(2d,p) basis functions. For this study we used the following groups: methyl, acetyl, N,N-dimethylcarbamoyl, N,N-dimethylamine, N,N-diethylamine, piperidine, pyrrolidine, and N,N-methylbenzylamine. Among the proposed compounds we identified that the structures with substitution by N,N-dimethycarbamoyl, N,N-dimethylamine, and pyrrolidine groups were better correlated to rivastigmine, and represent possible AChE inhibitors against Alzheimer disease.

Benign prostatic hyperplasia (BPH) is characterized by stromal cell proliferation and contraction of the periurethral smooth muscle, causing lower urinary tract symptoms. Current BPH treatment, based on monotherapy with α1A-adrenoceptor antagonists, is helpful for many patients, but insufficient for others, and recent reports suggest that stimulation of α1D-adrenoceptors and 5-hydroxytryptamine (serotonin) (5-HT)1A receptors contributes to cell proliferation. In this study, we investigated the potential of three N-phenylpiperazine derivatives (LDT3, LDT5, and LDT8) as multi-target antagonists of BPH-associated receptors. The affinity and efficacy of LDTs were estimated in isometric contraction and competition-binding assays using tissues (prostate and aorta) and brain membrane samples enriched in specific on- or off-target receptors. LDTs' potency was estimated in intracellular Ca(2+) elevation assays using cells overexpressing human α1-adrenoceptor subtypes. The antiproliferative effect of LDTs on prostate cells from BPH patients was evaluated by viable cell counting and 3-(4,5-dimethythiazol-2-yl)-2,5-diphenyl tetrazolium bromide assays. We also determined LDTs' effects on rat intraurethral and arterial pressure. LDT3 and LDT5 are potent antagonists of α1A-, α1D-adrenoceptors, and 5-HT1A receptors (Ki values in the nanomolar range), and fully inhibited phenylephrine- and 5-HT-induced proliferation of BPH cells. In vivo, LDT3 and LDT5 fully blocked the increase of intraurethral pressure (IUP) induced by phenylephrine at doses (ED50 of 0.15 and 0.09 μg.kg(-1), respectively) without effect on basal mean blood pressure. LDT3 and LDT5 are multi-target antagonists of key receptors in BPH, and are capable of triggering both prostate muscle relaxation and human hyperplastic prostate cell growth inhibition in vitro. Thus, LDT3 and LDT5 represent potential new lead compounds for BPH treatment.

To compare stresses in the peri-implant bone produced by fixed partial prostheses with mesial and distal cantilevers, when cemented or screwed onto implants.The experimental design consisted of four 3D models obtained by volumetric computerized tomography and analyzed using finite element analysis (FEA). Stresses were simulated in two stages. Stage 1 consisted of application of the preload. A 288 N load was applied to pillar screws of the cemented prosthesis, resulting in 389 MPa peak; 257 N was applied to the intermediate screw (multi-unit) resulting in 390 MPa peak; and 111 N was applied to the prosthesis infrastructure screw in the screwed prostheses, resulting in 390 MPa peak. In stage 2, the axial and oblique loads were applied. The axial load consisted of 50 N for molar implants and 30 N for premolar implants. The oblique load (on the buccal slope of the buccal cusp of each crown) consisted of 30 N for premolar implants and 50 N for molar implants, with a buccolingual vector at a 45° angle with the occlusal plane. The response variables were the axial and oblique stresses on the peri-implant bone, according to the following groups: group 1-models of fixed partial prostheses cemented onto implants with mesial or distal cantilevers; group 2-models of fixed partial denture screwed onto implants with mesial or distal cantilevers. Data were recorded, evaluated, and compared.Oblique loads produced higher peak values than axial loads, and were located at the bone crest of the implant closest to the cantilever, regardless of the prosthesis type. In the cemented prosthesis models, oblique loads produced the highest peaks in the primary implant region when compared with the screwed prosthesis models.The screwed fixed prostheses caused less stress on peri-implant bone regardless of whether the cantilever was located mesially or distally.

There are limited data available about the role of sedation and analgesia during noninvasive positive pressure ventilation (NPPV). The objective of study was to estimate the effect of analgesic or sedative drugs on the failure of NPPV. We studied patients who received at least 2 h of NPPV as first-line therapy in a prospective observational study carried out in 322 intensive care units from 30 countries. A marginal structural model (MSM) was used to analyze the association between the use of analgesic or sedative drugs and NPPV failure (defined as need for invasive mechanical ventilation). 842 patients were included in the analysis. Of these, 165 patients (19.6 %) received analgesic or sedative drugs at some time during NPPV; 33 of them received both. In the adjusted analysis, the use of analgesics (odds ratio 1.8, 95 % confidence interval 0.6–5.4) or sedatives (odds ratio 2.8, 95 % CI 0.85–9.4) alone was not associated with NPPV failure, but their combined use was associated with failure (odds ratio 5.7, 95 % CI 1.8–18.4). Slightly less than 20 % of patients received analgesic or sedative drugs during NPPV, with no apparent effect on outcome when used alone. However, the simultaneous use of analgesics and sedatives may be associated with failure of NPPV.

background The need for reintubation after extubation and discontinuation of mechanical ventilation is not uncommon and is associated with increased mortality. Noninvasive positivepressure ventilation has been suggested as a promising therapy for patients with respiratory failure after extubation, but a single-center, randomized trial recently found no benefit. We conducted a multicenter, randomized trial to evaluate the effect of noninvasive positive-pressure ventilation on mortality in this clinical setting. methods Patients in 37 centers in eight countries who were electively extubated after at least 48 hours of mechanical ventilation and who had respiratory failure within the subsequent 48 hours were randomly assigned to either noninvasive positive-pressure ventilation by face mask or standard medical therapy. results A total of 221 patients with similar baseline characteristics had been randomly assigned to either noninvasive ventilation (114 patients) or standard medical therapy (107 patients) when the trial was stopped early, after an interim analysis. There was no difference between the noninvasive-ventilation group and the standard-therapy group in the need for reintubation (rate of reintubation, 48 percent in both groups; relative risk in the noninvasive-ventilation group, 0.99; 95 percent confidence interval, 0.76 to 1.30). The rate of death in the intensive care unit was higher in the noninvasive-ventilation group than in the standard-therapy group (25 percent vs. 14 percent; relative risk, 1.78; 95 percent confidence interval, 1.03 to 3.20; P=0.048), and the median time from respiratory failure to reintubation was longer in the noninvasive-ventilation group (12 hours vs. 2 hours 30 minutes, P=0.02). conclusions Noninvasive positive-pressure ventilation does not prevent the need for reintubation or reduce mortality in unselected patients who have respiratory failure after extubation.

O suporte ventilatório artificial invasivo e não invasivo ao paciente crítico tem evoluído e inúmeras evidências têm surgido, podendo ter impacto na melhora da sobrevida e da qualidade do atendimento oferecido nas unidades de terapia intensiva no Brasil. Isto posto, a Associação de Medicina Intensiva Brasileira (AMIB) e a Sociedade Brasileira de Pneumologia e Tisiologia (SBPT) - representadas pelo seus Comitê de Ventilação Mecânica e Comissão de Terapia Intensiva, respectivamente, decidiram revisar a literatura e preparar recomendações sobre ventilação mecânica objetivando oferecer aos associados um documento orientador das melhores práticas da ventilação mecânica na beira do leito, baseado nas evidencias existentes, sobre os 29 subtemas selecionados como mais relevantes no assunto. O projeto envolveu etapas visando distribuir os subtemas relevantes ao assunto entre experts indicados por ambas as sociedades que tivessem publicações recentes no assunto e/ou atividades relevantes em ensino e pesquisa no Brasil na área de ventilação mecânica. Esses profissionais, divididos por subtemas em duplas, responsabilizaram-se por fazer revisão extensa da literatura mundial sobre cada subtema. Reuniram-se todos no Forum de Ventilação Mecânica na sede da AMIB em São Paulo, em 03 e 04 de agosto de 2013 para finalização conjunta do texto de cada subtema e apresentação, apreciação, discussão e aprovação em plenária pelos 58 participantes, permitindo a elaboração de um documento final. Perspectives on invasive and noninvasive ventilatory support for critically ill patients are evolving, as much evidence indicates that ventilation may have positive effects on patient survival and the quality of the care provided in intensive care units in Brazil. For those reasons, the Brazilian Association of Intensive Care Medicine (Associação de Medicina Intensiva Brasileira - AMIB) and the Brazilian Thoracic Society (Sociedade Brasileira de Pneumologia e Tisiologia - SBPT), represented by the Mechanical Ventilation Committee and the Commission of Intensive Therapy, respectively, decided to review the literature and draft recommendations for mechanical ventilation with the goal of creating a document for bedside guidance as to the best practices on mechanical ventilation available to their members. The document was based on the available evidence regarding 29 subtopics selected as the most relevant for the subject of interest. The project was developed in several stages, during which the selected topics were distributed among experts recommended by both societies with recent publications on the subject of interest and/or significant teaching and research activity in the field of mechanical ventilation in Brazil. The experts were divided into pairs that were charged with performing a thorough review of the international literature on each topic. All the experts met at the Forum on Mechanical Ventilation, which was held at the headquarters of AMIB in São Paulo on August 3 and 4, 2013, to collaboratively draft the final text corresponding to each sub-topic, which was presented to, appraised, discussed and approved in a plenary session that included all 58 participants and aimed to create the final document.

Perspectives on invasive and noninvasive ventilatory support for critically ill patients are evolving, as much evidence indicates that ventilation may have positive effects on patient survival and the quality of the care provided in intensive care units in Brazil. For those reasons, the Brazilian Association of Intensive Care Medicine (Associação de Medicina Intensiva Brasileira - AMIB) and the Brazilian Thoracic Society (Sociedade Brasileira de Pneumologia e Tisiologia - SBPT), represented by the Mechanical Ventilation Committee and the Commission of Intensive Therapy, respectively, decided to review the literature and draft recommendations for mechanical ventilation with the goal of creating a document for bedside guidance as to the best practices on mechanical ventilation available to their members. The document was based on the available evidence regarding 29 subtopics selected as the most relevant for the subject of interest. The project was developed in several stages, during which the selected topics were distributed among experts recommended by both societies with recent publications on the subject of interest and/or significant teaching and research activity in the field of mechanical ventilation in Brazil. The experts were divided into pairs that were charged with performing a thorough review of the international literature on each topic. All the experts met at the Forum on Mechanical Ventilation, which was held at the headquarters of AMIB in São Paulo on August 3 and 4, 2013, to collaboratively draft the final text corresponding to each sub-topic, which was presented to, appraised, discussed and approved in a plenary session that included all 58 participants and aimed to create the final document.

We described herein the discovery of 1-(2-(benzo[d] [1,3]dioxol-6-yl)ethyl)-4-(2-methoxyphenyl) piperazine (LASSBio-772), as a novel potent and selective alpha 1A/1D adrenoceptor (AR) antagonist selected after screening of functionalized N-phenylpiperazine derivatives in phenylephrine-induced vasoconstriction of rabbit aorta rings. The affinity of LASSBio-772 for alpha 1A and alpha 1B AR subtypes was determined through displacement of [(3)H]prazosin binding. We obtained Ki values of 0.14 nM for the alpha 1A-AR, similar to that displayed by tamsulosin (K(i) = 0.13 nM) and 5.55 nM for the alpha 1B-AR, representing a 40-fold higher affinity for alpha 1A-AR. LASSBio-772 also presented high affinity (K(B) = 0.025 nM) for the alpha 1D-AR subtype in the functional rat aorta assay, showing to be equipotent to tamsulosin (K(B) = 0.017 nM).

The objective of the study was to estimate the prevalence of generics and their associated factors in a population of adults aged 20 to 59 years. The sample consisted of 374 individuals from the catchment area of a Family Health Unit in Ponta Grossa, PR, Brazil. Data were collected in home interviews. Study variables were divided into 3 groups: sociodemographic, health status and the use of health services. The chi-square test was used for statistical analysis. The prevalence of generics was 9.9%. Of those interviewed, 96.5% claimed to know about generic drugs, 64.3% believed they had the same quality as brand-name drugs and 88.9% reported they were cheaper. The most commonly-used groups of drugs were those for the nervous system and those for the cardiovascular system. After univariate analysis, the following factors were found to be statistically significant: economic status, employment status, health insurance, presence of chronic disease, medical consultation in the previous three months and hospitalization within the previous 12 months. The low prevalence of the use of generic drugs emphasizes the fact that stronger policies are needed to make generics available to the public, especially through the Family Health Strategy, since it is the studied population's principal form of access to these medications.

This work is part of a large program, which seeks to discover new antitumor isobenfuranones designed from anacardic acids. The synthetic strategy for the construction of the title compounds takes into consideration the use of inexpensive anacardic acids (2), the major natural cashew (Anacardium occidentale) nut-shell phenolic lipid, and features one-pot construction of fused-ring aromatic gamma-lactones, phthalides. The cytotoxicity screening in different human cancer cell lines (HL-60 leukemia, SF295 glioblastoma and MDA-MB435 melanoma) by the MTT assay showed that acyclic precursor (6), and isobenfuranones (1a and 1b) are active compounds. Interestingly, 1a exhibits significant antiproliferative effect against HL-60 cells and moderate activity against SF295 and MDA-MB435 cell lines. Analysis of mechanisms involved in the cytotoxic activity showed that active compounds were leading to DNA damage, triggering apoptosis or necrosis induction.

OBJECTIVES: Our primary aim was to compare the long‐term survivorship rates and the rates of successful osseointegration between two different types of uncemented acetabular components. INTRODUCTION: Two types of alloys have primarily been used for the manufacture of the uncemented acetabular components: titanium‐based and cobalt‐based alloys. A titanium‐based alloy appears to be more effective with regard to interface stress transfer to the host bone because of its lower elastic modulus relative to a cobalt‐based alloy. This supposed mechanical advantage of a titanium‐based alloy component motivated this comparative study. METHODS: Two uncemented acetabular components, a porous‐coated acetabulum and a Plasmacup®, were compared with a focus on long‐term prosthesis survivorship and the development of acetabular osseointegration. Five radiographic signs of osseointegration were evaluated at the last follow‐up appointment: (1) absence of radiolucent lines, (2) presence of a superolateral buttress, (3) medial stress‐shielding, (4) radial trabeculae, and (5) an inferomedial buttress. We considered the presence of any three of these radiographic signs, in the absence of acetabular dislocation or symptoms, to be indicative of successful acetabular osseointegration. RESULTS: Among 70 patients implanted with the porous‐coated acetabulum, 80% achieved osseointegration over a mean follow‐up time of 11.9 years versus 75.3% of the 73 patients who received a Plasmacup insert over a mean of 10.7 years. Prosthesis survivorship rates were not different between the two groups. Revision surgery due to mild or severe acetabular osteolysis, polyethylene wear, and aseptic loosening occurred in eight patients (11.4%) with a PCA versus nine (12.3%) with a Plasmacup. CONCLUSIONS: We conclude that, during the first ten years after surgery, there is no significant difference between these two types of uncemented cups with regard to either prosthesis survivorship or successful osseointegration.

The objective of this study was to identify risk factors associated with pre-term birth among live births in a hospital in Londrina, Paraná State, Brazil. Cases consisted of 328 pre-term births, and controls were 369 births with gestational age greater than 37 weeks. A multiple hierarchical logistic regression analysis was carried out. There was a significant correlation (p0.05) between pre-term birth and the following variables: socioeconomic status (slum residence); low age of head-of-family; maternal BMI19 or30 kg/m2; history of prematurity; history of assisted reproduction; mothers in a relationship for less than two years; maternal stress; weekly maternal alcohol consumption; insufficient prenatal care; gestational complications such as bleeding, genital tract infection, altered amniotic fluid volume, high blood pressure, and hospital admission; and twin pregnancy. Regular walks during pregnancy were a protective factor. Improved quality of prenatal care and the identification of the above factors during pregnancy may help reduce premature birth.

There are few studies about the consumption of medication by adults in Brazil. Therefore, the purpose of this research was to identify the profile of medication consumption and associated factors among adults aged 29 to 59 years old. This is a cross-sectional study. The sample included 374 individuals from the area of a family health unit in the city of Ponta Grossa, State of Paraná. The interviews were conducted from December 2006 to January 2007, with a 7-day recall. The medications were classified according to the Anatomical Therapeutic Chemical Classification. Qui-square test and logistic regression were used for statistical analysis. The prevalence of medication consumption was 67.1%. The use varied from 1 to 17 drugs. Analgesics were the therapeutic class most consumed. After multivariate analysis, the variables which remained significantly associated to use were: gender, self-perception of health, presence of chronic diseases, and access to a health plan. Commercial pharmacy was the main place for obtaining medicines (63.6%). The prevalence of medication consumption was similar to that found in national and international studies. The findings in this research may be a guide for the actions of family health teams.

The reduction in morbidity and mortality rates from diseases of the circulatory system (DCS) is one of the greatest challenges in primary care, and the implementation of the Family Health Program provides access to the multisectoral and integrated measures required for dealing with these diseases.To analyze DCS mortality and hospitalization rates before and after the implementation of the Family Health Program, in Londrina, Paraná.This was an ecological study, comparing DCS, cerebrovascular disease (CbVD) and ischemic heart disease (IHD) mortality rates and hospitalization rates by the SUS, in residents of Londrina, in two 4-year periods: 1997 to 2000, and 2002 to 2005. The data were obtained from the Mortality Information System and the Hospital Information System of the SUS. The ratios between the rates were calculated for both periods at 95% confidence interval.The DCS was the first cause of death in the city, in both quadrennia. The CbVD and IHD accounted for more than 63% of DCS deaths. In comparing the two quadrennia, there was a reduction in CbVD mortality rates, which was significant only for subjects over 59 years, in both genders, and the hospitalization rates increased by 10%. For IHD, no significant change occurred in mortality rates, and there was a 40% increase in hospitalization rates.The significant reduction only in CbVD mortality in the elderly suggests the need for expanding health assistance coverage to different population groups and the development of preventive and health promotion measures.

To analyze the coverage and quality of the data on hospitalizations due to external causes in the Hospital Information System of the Brazilian National Health System.Hospitalizations recorded in the Hospital Information System of 11 hospitals in two municipalities (Londrina and Maringá, Southern Brazil), in 2004, were compared with hospitalizations identified as consequences of external causes through investigating medical records, complemented with mortality and pre-hospital data. The crude agreement rate, sensitivity and positive predictive value were calculated. The profile of groups of hospitalization causes recorded in the System was compared with that obtained from investigations.In Londrina, 3,002 hospitalizations due to external causes were recorded in the System and, in Maringá, 1,403. The investigations found 4,018 and 2,370, respectively. The System presented high positive predictive values for hospitalizations due to external causes in both municipalities: 97.7% in Londrina and 98.6% in Maringá. However, the sensitivity was low: 57.3% in Maringá and 73% in Londrina, thus denoting underrecording of these causes. Comparison between the profiles of the types of causes revealed that there was underestimation of some causes in the System, especially regarding accidents due to exposure to inanimate mechanical forces, assaults and intentional self-harm.Underrecording of hospitalizations due to external causes and some distortions regarding the types of causes occurred in the Hospital Information System in both municipalities. Detection of these deficiencies may contribute towards the process of improving the quality of the information in this System.

Homicides are the main cause of non-natural death in Brazil and studies about them may contribute to their control. The objective of this study was to verify mortality rates due to homicides and legal interventions among young men in the State of Paraná, Brazil, and to identify correlated municipal characteristics. An ecological study was conducted, having the municipalities of the State as units of analysis. Mortality rates of homicides and legal interventions among men from 15 to 29 years of age were calculated for the years 2002-2004 and demographic and social municipal indicators were obtained. Mortality rate in the State was 94.8 per one hundred thousand. The size of the population, the proportion of young people aged 15 to 24 years, the proportion of enrollments in universities and the Gini index were the main indicators correlated to homicide mortality (p0.0001). Mortality rates were highest in municipalities of metropolitan regions, in those located at the border with Paraguay and in those located in the way between them and the Southeast Region of Brazil. Mortality rates and the proportion of deaths due to firearms increased with the size of the municipality. The greater number of youth and easier access to firearms and illicit drugs in such places may be influencing on these rates.

This cross-sectional study focused on motorcycle couriers (work profile, work conditions, and traffic accidents) in Londrina and Maringá, Paraná State, Brazil. Data were collected from self-completed questionnaires in 2005-2006. In Londrina and Maringá, respectively, 377 and 500 motorcycle couriers completed the questionnaire, with mean ages of 28 and 29 years. Londrina showed a higher proportion of couriers that earned per delivery, worked both day and night or on night shifts only, and who worked more than 10 hours a day (p0.05). Despite greater exposure to hazardous work and traffic conditions in Londrina, there was no significant difference in the accident rates during the 12 months prior to the survey in Londrina and Maringá (2.89 and 2.80 per 100 person-months, respectively). The study detected precarious work conditions, high exposure to hazardous traffic conditions, and high accident rates among motorcycle couriers.

To assess through high-resolution computed tomography the pulmonary parenchyma of children prematurely born with both very low birth weight and patent ductus arteriosus submitted to medical or surgical treatment that developed bronchopulmonary dysplasia.Between December 2006 and January 2007, 14 children prematurely born with a weight less than 1500 g with bronchopulmonary dysplasia (BPD) and patent ductus arteriosus (PDA) were submitted to high-resolution computed tomography (HRCT). All of them underwent surgical closure of the canal divided into two groups: A - medical (n=6) and B - surgical (n=8). The pool of patients comprised 9 baby boys and 5 girls who were 36.5+/-4.3 month-old. The HRCT were analyzed by two independent observers and quantified in each patient. The statistical analyses were assessed using the Mann-Whitney test, and p0.05 was considered statistically significant.Three patients presented normal tomographies, being two of A group and one of B. In A, the most frequent finding was multifocal ground-glass opacity. In B, multifocal ground-glass opacity, atelectasis, and low attenuation areas with relatively decreased number and caliber of vessels were prevalent (62.5%). There was a statistically significant difference between both groups, with B having higher averages in the intubation times, use of oxygen, and admission. However, as to the number of injuries found on HRCT there was no statistically significant difference (p=0.0787).The lately use of HRCT have shown no significant difference between both medical and surgical treatment aiming at to occlude the PDA in pulmonary parenchyma injuries of premature with PDA that developed bronchopulmonary dysplasia.

This objective of this paper was to verify the relations between the living and infrastructure conditions of municipalities in the State of Paraná, Brazil, and infant mortality rate and its components. An ecological study was carried out having the 399 municipalities of the State being classified into five clusters of living conditions. Infant, neonatal and postneonatal rates were calculated for the period 1997/2001. The mean infant, neonatal and postneonatal mortality rates in the State were, respectively, 19.3, 12.0 and 7.3 per 1,000 live births. Postneonatal mortality rates ranged from 8.7 (cluster of worst living conditions) to 6.3 per 1,000 live births (in the cluster classified as having the best living conditions). Regarding the neonatal component, clusters classified as holding the best and the worst living conditions presented the lowest values: 11.8 and 11.4 per 1,000 live births, respectively. We conclude that the postneonatal component still adequately discriminate living conditions in the State of Paraná. However, there is a need of complementary studies that aim to clarify the causes of similar neonatal mortality rates observed in the richest and in the poorest cluster of municipalities.

Traffic accidents are one of the most frequent cause of mortality among Brazilian youths. Therefore, this study aimed at detecting the prevalence of risk factors for such accidents in a young population.Questionnaires containing questions about risky behavior for traffic accidents were answered by students from the first to the fourth year of the Medical course of the State University of Londrina, Paraná State, Brazil, during October and November, 2000. The chi-square test was used to detect differences between the sexes, with a 5% significance level.Compared to women, male students reported a statistically significant higher frequency of transportation as a car driver, owning a driver license, to have learnt to drive a car under the age of 16 and to have drunk alcoholic beverages before driving a vehicle during the last 30 days. Among regular drivers, a lower proportion of desirable behavior was also noted among male students. Lack of attention (59.3%), disregarding traffic signals (33.5%) and speeding (22.5%) were the main factors cited as determinants for the occurrence of the last accident, with no gender difference.These results point out for the need to implement measures in order to reduce factors that favors the occurrence of traffic accidents among these youths, especially among males.

To describe helmet use among motorcyclists injured in traffic accidents in Londrina, a medium-sized city in Paraná, a state in southern Brazil, and to identify factors associated with not wearing a helmet at the time of the accident.We analyzed data concerning motorcycle users (drivers and passengers) who received care in 1998 from the only pre-hospitalization trauma and emergency care ambulance service in Londrina. The following variables were assessed: helmet use at the time of the accident; age; sex; seating position (driver or passenger); smell of alcohol on the breath; time of the day, day of the week, and month when the accident happened; and location of the accident (in the downtown area or outside of it).The average rate of helmet use was 63.2%. Factors independently associated with not using a helmet were (according to strength of association): being younger than 18 years of age (odds ratio (OR) = 6.61), having alcohol on the breath (OR = 3.93), accident occurring at night (OR = 2.51), accident happening outside the city's downtown area (OR = 2.27), and accident taking placing during the weekend (OR = 2.25).It is imperative to implement public policies aimed at promoting safety for motorcyclists, ongoing education in defensive driving, and the use of helmets and other safety equipment. Interventions should take into account that driving behaviors depend not just on individuals but also on the overall social and historical context.

We report two children who presented with multiple renal cysts involving only one kidney and in whom there was no family history of renal disease and who did not have syndromes known to be associated with renal cystic disease. This unilateral involvement may represent a distinct entity, which has only been previously described in three cases; however, long-term follow-up will be needed to confirm this hypothesis. We illustrate the sonographic and computed tomographic findings, and the differential diagnosis is discussed.