Prescription patterns for diabetes mellitus and therapeutic implications: a population-based analysis

Objective: To analyze drug prescriptions for insulin and oral antidiabetic drugs in type 1 and type 2 diabetes mellitus patients seen in the Brazilian Public Healthcare System (Unified Health System - SUS) in Ribeirao Preto, SP, Brazil. Subjects and methods: All the patients with diabetes seen in the SUS in the western district of Ribeirao Preto, SP, Brazil between March/2006 and February/2007 were included in the study. Results: A total of 3,982 patients were identified. Mean age of the patients was 60.6 years, and 61.0% were females. Sixty percent of the patients were treated with monotherapy. Doses of oral antidiabetic drugs were lower in monotherapy than in polytherapy. Ten patients received doses of glibenclamide or metformin above the recommended maximum doses, and in elderly patients there was no reduction in drug doses. Conclusion: Monotherapy with oral antidiabetic drugs was the predominant procedure, and the doses were not individualized according to age. Arq Bras Endocrinol Metab. 2012;56(2):120-7

Intervalo hídrico ótimo e grau de compactação de um latossolo vermelho após 30 anos sob plantio direto

A qualidade física do solo é um dos fatores determinantes da sustentabilidade agronômica, econômica e ambiental no sistema plantio direto (SPD). A compactação do solo tem sido apontada como um dos fatores de redução da qualidade física em solos sob SPD. Contudo, com a utilização do SPD, pode haver o incremento de matéria orgânica do solo e o desenvolvimento de um sistema poroso contínuo e estável, que atenuam os impactos negativos da compactação. O objetivo deste trabalho foi avaliar a qualidade física de um Latossolo Vermelho distroférrico sob SPD durante 30 anos, utilizando o intervalo hídrico ótimo (IHO) e o grau de compactação do solo (GC). Em uma área comercial com histórico de altas produtividades sob SPD, foram coletadas amostras de solo com estrutura preservada e deformada, para determinação da densidade do solo (Ds), do IHO e do GC. As amostras com estrutura preservada foram obtidas em três posições, relativas às linhas (L), entrelinhas (E) e posição intermediária entre as linhas e entrelinhas (PI) da cultura do milho. Foram determinadas as curvas de retenção de água e resistência do solo à penetração, bem como a Ds. A amostra de solo com estrutura deformada foi usada para obter a curva de compactação, utilizando o teste de Proctor. A Dmax foi obtida a partir da curva de compactação, e o GC foi determinado pela razão entre a Ds e a Dmax. Independentemente dos limites críticos de resistência à penetração (RP), verifica-se redução do IHO com o aumento da Ds. Os maiores valores do IHO foram verificados na posição de amostragem L, e a utilização de RP crítica maior que 2,0 MPa resultou em IHO condizente com a qualidade física desse solo sob SPD de longo tempo. A Dmax foi de 1,52 kg dm-3, e o GC variou de 64 a 87 %, sendo os maiores valores obtidos nas posições E e PI. Os valores de IHO e GC obtidos neste estudo indicam que a qualidade física desse solo não é limitante à produção das culturas após 30 anos de utilização do SPD.

Assessing Pathogenicity for Novel Mutation/Sequence Variants: The Value of Healthy Older Individuals

Improvement in DNA technology is increasingly revealing unexpected/unknown mutations in healthy persons and generating anxiety due to their still unknown health consequences. We report a 44-year-old healthy father of a 10-year-old daughter with bilateral coloboma and hearing loss, but without muscle weakness, in whom a whole-genome CGH revealed a deletion of exons 38-44 in the dystrophin gene. This mutation was inherited from her asymptomatic father, who was further clinically and molecularly evaluated for prognosis and genetic counseling (GC). This deletion was never identified by us in 982 Duchenne/Becker patients. To assess whether the present case represents a rare case of non-penetrance, and aiming to obtain more information for prognosis and GC, we suggested that healthy older relatives submit their DNA for analysis, to which several complied. Mutation analysis revealed that his mother, brother, and 56-year-old maternal uncle also carry the 38-44 deletion, suggesting it an unlikely cause of muscle weakness. Genome sequencing will disclose mutations and variants whose health impact are still unknown, raising important problems in interpreting results, defining prognosis, and discussing GC. We suggest that, in addition to family history, keeping the DNA of older relatives could be very informative, in particular for those interested in having their genome sequenced.

Top spoilage losses in maize silage sealed with plastic films with different permeabilities to oxygen

The quality of plastic films used for horizontal silos is important to limit losses in the upper silage layer. The aim of this work was to study the effectiveness of different plastic films in reducing the top losses in maize silage. The following treatments were evaluated: (i) coextruded polyethylene/polyamide oxygen barrier film (OB), (ii) polyethylene film (PE), (iii) polyvinyl chloride film (PVC), and (iv) coextruded PE/polyvinyl alcohol film (PVOH). These treatments differed according to oxygen permeability with values of 75, 722, 982 and 289 cm(3) m(-2) per 24 hour respectively. OB and PVOH films had better temperature and fermentation profiles than the more permeable films. The OB film was effective in reducing the dry-matter (DM) losses during storage (82 g kg(-1)), and the PVOH film had an intermediate value of DM loss (101 g kg(-1)). PE and PVC films had higher losses (138 and 145 g kg(-1) respectively). Oxygen permeability of the films promoted a positive correlation with DM losses (P < 0.05; r2 = 0.945). The results indicate that O2 permeability through the plastic film is a crucial factor for maintaining silage quality in the upper layer of the silo when it is perfectly sealed.

Gene expression profile during coffee fruit development and identification of candidate markers for phenological stages

The objective of this work was to identify genes that could be used as suitable markers for molecular recognition of phenological stages during coffee (Coffea arabica) fruit development. Four cultivars were evaluated as to their differential expression of genes associated to fruit development and maturation processes. Gene expression was characterized by both semi-quantitative and quantitative RT-PCR, in fruit harvested at seven different developmental stages, during three different seasons. No size polymorphisms or differential expression were observed among the cultivars for the evaluated genes; however, distinct expression profiles along fruit development were determined for each gene. Four out of the 28 evaluated genes exhibited a regular expression profile in all cultivars and harvest seasons, and, therefore, they were validated as candidate phenological markers of coffee fruit. The gene a-galactosidase can be used as a marker of green stage, caffeine synthase as a marker of transition to green and yellowish-green stages, and isocitrate lyase and ethylene receptor 3 as markers of late maturation.

Junction Field Effect on the Retention Time for One-Transistor Floating-Body RAM

One-transistor floating-body random access memory retention time distribution is investigated on silicon-on-insulator UTBOX devices. It is shown that the average retention time can be improved by two to three orders of magnitude by reducing the body-junction electric field. However, the retention time distribution, which is mainly caused by the generation-recombination center density variation, remains similar.

Influence of Helmet Use in Facial Trauma and Moderate Traumatic Brain Injury Victims of Motorcycle Accidents

Objective: The objective of this research was to study the influence of the use of helmet in facial trauma victims of motorcycle accidents with moderate traumatic brain injury. Methods: We retrospectively reviewed the incidence of facial injuries in helmeted and nonhelmeted victims with moderate traumatic brain injury at a referral trauma hospital. Results: The sample consisted of 272 patients predominantly men (94.5%) and between 21 and 40 years old (62.9%). The majority of patients were using helmet (80.1%). The occurrence of facial fractures was most frequent for zygomatic bone (51.8%), followed by mandible (18.8%) and nasal bones (9.2%). Conclusions: Individuals in the most productive age group are most affected, which causes a great loss to financial and labor systems. It is important to take measures to alert the public regarding the severity of injuries likely to occur in motorcycle-related accidents and ways to prevent them.

Theoretical models for the antitrypanosomal activity of thiosemicarbazone derivatives

Thiosemicarbazones are cruzain inhibitors which have been identified as potential antitrypanosomal agents. In this work, several molecular properties were calculated at the density functional theory (DFT)/B3LYP/6-311G* level for a set of 44 thiosemicarbazones. Unsupervised and supervised pattern recognition techniques (hierarchical cluster analysis, principal component analysis, kth-nearest neighbors, and soft independent modeling by class analogy) were used to obtain structureactivity relationship models, which are able to classify unknown compounds according to their activities. The chemometric analyses performed here revealed that 12 descriptors can be considered responsible for the discrimination between high and low activity compounds. Classification models were validated with an external test set, showing that predictive classifications were achieved with the selected variable set. The results obtained here are in good agreement with previous findings from the literature, suggesting that our models can be useful on further investigations on the molecular determinants for the antichagasic activity. (C) 2012 Wiley Periodicals, Inc.

Underlying Event measurements in pp collisions at root s=0.9 and 7 TeV with the ALICE experiment at the LHC

We present measurements of Underlying Event observables in pp collisions at root s = 0 : 9 and 7 TeV. The analysis is performed as a function of the highest charged-particle transverse momentum p(T),L-T in the event. Different regions are defined with respect to the azimuthal direction of the leading (highest transverse momentum) track: Toward, Transverse and Away. The Toward and Away regions collect the fragmentation products of the hardest partonic interaction. The Transverse region is expected to be most sensitive to the Underlying Event activity. The study is performed with charged particles above three different p(T) thresholds: 0.15, 0.5 and 1.0 GeV/c. In the Transverse region we observe an increase in the multiplicity of a factor 2-3 between the lower and higher collision energies, depending on the track p(T) threshold considered. Data are compared to PYTHIA 6.4, PYTHIA 8.1 and PHOJET. On average, all models considered underestimate the multiplicity and summed p(T) in the Transverse region by about 10-30%.

ROLE OF FOCAL ADHESION KINASE IN LUNG REMODELING OF ENDOTOXEMIC RATS

Despite significant advances in the care of critically ill patients, acute lung injury continues to be a complex problem with high mortality. The present study was designed to characterize early lipopolysaccharide (LPS)-induced pulmonary injury and small interfering RNA targeting focal adhesion kinase (FAK) as a possible therapeutic tool in the septic lung remodeling process. Male Wistar rats were assigned into endotoxemic group and control group. Total collagen deposition was performed 8, 16, and 24 h after LPS injection. Focal adhesion kinase expression, interstitial and vascular collagen deposition, and pulmonary mechanics were analyzed at 24 h. Intravenous injection of small interfering RNA targeting FAK was used to silence expression of the kinase in pulmonary tissue. Focal adhesion kinase, total collagen deposition, and pulmonary mechanics showed increased in LPS group. Types I, III, and V collagen showed increase in pulmonary parenchyma, but only type V increased in vessels 24 h after LPS injection. Focal adhesion kinase silencing prevented lung remodeling in pulmonary parenchyma at 24 h. In conclusion, LPS induced a precocious and important lung remodeling. There was fibrotic response in the lung characterized by increased amount in total and specific-type collagen. These data may explain the frequent clinical presentation during sepsis of reduced lung compliance, oxygen diffusion, and pulmonary hypertension. The fact that FAK silencing was protective against lung collagen deposition underscores the therapeutic potential of FAK targeting by small interfering RNA.

SMALL INTERFERING RNA TARGETING FOCAL ADHESION KINASE PREVENTS CARDIAC DYSFUNCTION IN ENDOTOXEMIA

Sepsis and septic shock are associated with cardiac depression. Cardiovascular instability is a major cause of death in patients with sepsis. Focal adhesion kinase (FAK) is a potential mediator of cardiomyocyte responses to oxidative and mechanical stress. Myocardial collagen deposition can affect cardiac compliance and contractility. The aim of the present study was to determine whether the silencing of FAK is protective against endotoxemia-induced alterations of cardiac structure and function. In male Wistar rats, endotoxemia was induced by intraperitoneal injection of lipopolysaccharide (10 mg/kg). Cardiac morphometry and function were studied in vivo by left ventricular catheterization and histology. Intravenous injection of small interfering RNA targeting FAK was used to silence myocardial expression of the kinase. The hearts of lipopolysaccharide-injected rats showed collagen deposition, increased matrix metalloproteinase 2 activity, and myocyte hypertrophy, as well as reduced 24-h +dP/dt and -dP/dt, together with hypotension, increased left ventricular end-diastolic pressure, and elevated levels of FAK (phosphorylated and unphosphorylated). Focal adhesion kinase silencing reduced the expression and activation of the kinase in cardiac tissue, as well as protecting against the increased collagen deposition, greater matrix metalloproteinase 2 activity, and reduced cardiac contractility that occur during endotoxemia. In conclusion, FAK is activated in endotoxemia, playing a role in cardiac remodeling and in the impairment of cardiac function. This kinase represents a potential therapeutic target for the protection of cardiac function in patients with sepsis.

Structure- and ligand-based drug design approaches for neglected tropical diseases

Drug discovery has moved toward more rational strategies based on our increasing understanding of the fundamental principles of protein-ligand interactions. Structure( SBDD) and ligand-based drug design (LBDD) approaches bring together the most powerful concepts in modern chemistry and biology, linking medicinal chemistry with structural biology. The definition and assessment of both chemical and biological space have revitalized the importance of exploring the intrinsic complementary nature of experimental and computational methods in drug design. Major challenges in this field include the identification of promising hits and the development of high-quality leads for further development into clinical candidates. It becomes particularly important in the case of neglected tropical diseases (NTDs) that affect disproportionately poor people living in rural and remote regions worldwide, and for which there is an insufficient number of new chemical entities being evaluated owing to the lack of innovation and R&D investment by the pharmaceutical industry. This perspective paper outlines the utility and applications of SBDD and LBDD approaches for the identification and design of new small-molecule agents for NTDs.

Treatment of malignant gastroduodenal obstruction with a nitinol self-expanding metal stent: An international prospective multicentre registry

Background: Duodenal stenting has become a broadly accepted first line of treatment for patients with advanced malignant gastroduodenal obstruction as these patients are difficult to treat and are poor surgical candidates. Aims: To document duodenal stent performance for palliative management of malignant gastroduodenal obstruction. Methods: Multicentre, single arm, prospective registry documenting peroral endoscopic duodenal stenting procedures in 202 patients. Results: Technical success achieved in 98% (CI. 95%, 99%) of stent placements. Increase of Gastric Outlet Obstruction Score by at least 1 point compared to baseline was achieved in 91% (CI, 86%, 95%) of patients persisting for a median of 184 days (CI, 109, 266). By day 5 (CI, 4,6) after stent placement, 50% of patients experienced a score increase of at least 1 point. Improvement from 14% of patients at baseline tolerating soft solids or low residue/normal diet to 84% at 15 days, 86% at 30 days, 81% at 90 days, 79% at 180 days, and 70% at 270 days. Complications included stent ingrowth and/or overgrowth (12.4%), transient periprocedural symptoms (3%), bleeding (3%), stent migration (1.5%), and perforation (0.5%). Conclusions: Safety and effectiveness of duodenal stenting for palliation of malignant gastroduodenal obstruction was confirmed in the largest international prospective series to date. (C) 2011 Editrice Gastroenterologica Italiana S.r.l. Published by Elsevier Ltd. All rights reserved.

Root and Root Canal Morphology of Four-rooted Maxillary Second Molars: A Micro-Computed Tomography Study

Introduction: This study examined the anatomy of 4-rooted maxillary second molars by using micro computed tomography. Methods: Twenty-five 4-rooted maxillary second molars were scanned to evaluate the size and curvature of the roots; the distance and spatial configuration between some anatomical landmarks; the number of root canals and the position of apical foramina; the occurrence of fusion of roots and enamel pearls; the configuration of the canal at the apical third; the cross-sectional appearance, the volume, and surface area of the root canals. Data were compared by using analysis of variance post hoc Tukey test (alpha = 0.05). Results: The specimens were classified as types I (n = 16), II (n = 7), and III (n = 2). The size of the roots was similar (P > .05), and most of them presented straight with 1 canal, except the mesiobuccal that showed 2 canals in 24% of the samples. The configuration of the pulp chamber was mostly irregular quadrilateral-shaped. The lowest mean distance of the orifices was observed between the buccal roots (P < .05). Accessory canals were present mostly in the apical third. Location of the apical foramina varied considerably. Fusion of roots and enamel pearls occurred in 44% and 8% of the samples, respectively. Mean distance from the pulp chamber floor to the furcation was 2.15 +/- 0.57 mm. No statistical differences were found in the bi-dimensional and 3-dimensional analyses (P > .05). Conclusions: All analyzed parameters showed differences between roots, except for the length of the roots, the configuration of the canals at the apical third, cross-sectional appearance, volume, and surface area of the canals. (J Endod 2012;38:977-982)

Synthesis, Biological Evaluation, And Molecular Modeling of Chalcone Derivatives As Potent Inhibitors of Mycobacterium tuberculosis Protein Tyrosine Phosphatases (PtpA and PtpB)

Tuberculosis (TB) is a major infectious disease caused by Mycobacterium tuberculosis (Mtb). According to the World Health Organization (WHO), about 1.8 million people die from TB and 10 million new cases are recorded each year. Recently, a new series of naphthylchalcones has been identified as inhibitors of Mtb protein tyrosine phosphatases (PTPs). In this work, 100 chalcones were designed, synthesized, and investigated for their inhibitory properties against MtbPtps. Structure-activity relationships (SAR) were developed, leading to the discovery of new potent inhibitors with IC50 values in the low-micromolar range. Kinetic studies revealed competitive inhibition and high selectivity toward the Mtb enzymes. Molecular modeling investigations were carried out with the aim of revealing the most relevant structural requirements underlying the binding affinity and selectivity of this series of inhibitors as potential anti-TB drugs.