Stereotactic body radiotherapy for early-stage non-small cell lung cancer: a multicentre study by the Oncologic Group for the Study of Lung Cancer (Spanish Radiation Oncology Society).

PURPOSE/OBJECTIVE(S): Stereotactic body radiotherapy (SBRT) has become the standard of care for patients with medically inoperable early-stage non-small cell lung cancer (NSCLC) and for patients who refuse surgery. The aim of this study was to evaluate the effectiveness and safety of primary SBRT in patients with early-stage NSCLC. MATERIALS/METHODS: Retrospective multicenter study of 397 patients (416 primary lung tumours) treated with SBRT at 18 centres in Spain. 83.2% were men. The median age was 74.4 years. In 94.4% of cases, the tumour was inoperable. The pathological report was available in 54.6% of cases. SPSS vs 22.0. was used to perform all statistical analyses. RESULTS: Complete response was obtained in 53.6% of cases. Significant prognostic factors were standard CT planning (p = 0.014) and 4D cone beam CT (p = 0.000). Acute and chronic toxicity ≥ grade 3 was observed in 1.2% of cases. At a median follow-up of 30 months, local relapse was 9.6%, lymph node relapse 12.8%, distant metastasis 16.6%, and another lung tumour 11.5%. Complete response was the only significant prognostic factor for local relapse (p = 0.012) and distant metastasis (p = 0.001). The local relapse-free survival was 88.7%. The overall survival was 75.7%. The cancer-specific survival was 92.7%. The disease-free survival was 78.7%. CONCLUSION: SBRT is an effective and well-tolerated treatment option for patients with early-stage lung cancer who are not suitable for surgery. The most important prognostic factor for local and distant recurrence was complete response, which in our sample depended on the type of CT planning and the IGRT technique.

Inflammaging as a link between autoimmunity and cardiovascular disease: the case of rheumatoid arthritis.

Currently, traditional and non-traditional risk factors for cardiovascular disease have been established. The first group includes age, which constitutes one of the most important factors in the development of chronic diseases. The second group includes inflammation, the pathophysiology of which contributes to an accelerated process of vascular remodelling and atherogenesis in autoimmune diseases. Indeed, the term inflammaging has been used to refer to the inflammatory origin of ageing, explicitly due to the chronic inflammatory process associated with age (in healthy individuals). Taking this into account, it can be inferred that people with autoimmune diseases are likely to have an early acceleration of vascular ageing (vascular stiffness) as evidenced in the alteration of non-invasive cardiovascular tests such as pulse wave velocity. Thus, an association is created between autoimmunity and high morbidity and mortality rates caused by cardiovascular disease in this population group. The beneficial impact of the treatments for rheumatoid arthritis at the cardiovascular level has been reported, opening new opportunities for pharmacotherapy.

Toward identifying reproducible brain signatures of obsessive-compulsive profiles: rationale and methods for a new global initiative.

BACKGROUND: Obsessive-compulsive disorder (OCD) has a lifetime prevalence of 2-3% and is a leading cause of global disability. Brain circuit abnormalities in individuals with OCD have been identified, but important knowledge gaps remain. The goal of the new global initiative described in this paper is to identify robust and reproducible brain signatures of measurable behaviors and clinical symptoms that are common in individuals with OCD. A global approach was chosen to accelerate discovery, to increase rigor and transparency, and to ensure generalizability of results. METHODS: We will study 250 medication-free adults with OCD, 100 unaffected adult siblings of individuals with OCD, and 250 healthy control subjects at five expert research sites across five countries (Brazil, India, Netherlands, South Africa, and the U.S.). All participants will receive clinical evaluation, neurocognitive assessment, and magnetic resonance imaging (MRI). The imaging will examine multiple brain circuits hypothesized to underlie OCD behaviors, focusing on morphometry (T1-weighted MRI), structural connectivity (Diffusion Tensor Imaging), and functional connectivity (resting-state fMRI). In addition to analyzing each imaging modality separately, we will also use multi-modal fusion with machine learning statistical methods in an attempt to derive imaging signatures that distinguish individuals with OCD from unaffected siblings and healthy controls (Aim #1). Then we will examine how these imaging signatures link to behavioral performance on neurocognitive tasks that probe these same circuits as well as to clinical profiles (Aim #2). Finally, we will explore how specific environmental features (childhood trauma, socioeconomic status, and religiosity) moderate these brain-behavior associations. DISCUSSION: Using harmonized methods for data collection and analysis, we will conduct the largest neurocognitive and multimodal-imaging study in medication-free subjects with OCD to date. By recruiting a large, ethno-culturally diverse sample, we will test whether there are robust biosignatures of core OCD features that transcend countries and cultures. If so, future studies can use these brain signatures to reveal trans-diagnostic disease dimensions, chart when these signatures arise during development, and identify treatments that target these circuit abnormalities directly. The long-term goal of this research is to change not only how we conceptualize OCD but also how we diagnose and treat it.

Non-coding RNA Expression, Function, and Variation during Drosophila Embryogenesis.

Long non-coding RNAs (lncRNAs) can often function in the regulation of gene expression during development; however, their generality as essential regulators in developmental processes and organismal phenotypes remains unclear. Here, we performed a tailored investigation of lncRNA expression and function during Drosophila embryogenesis, interrogating multiple stages, tissue specificity, nuclear localization, and genetic backgrounds. Our results almost double the number of annotated lncRNAs expressed at these embryonic stages. lncRNA levels are generally positively correlated with those of their neighboring genes, with little evidence of transcriptional interference. Using fluorescent in situ hybridization, we report the spatiotemporal expression of 15 new lncRNAs, revealing very dynamic tissue-specific patterns. Despite this, deletion of selected lncRNA genes had no obvious developmental defects or effects on viability under standard and stressed conditions. However, two lncRNA deletions resulted in modest expression changes of a small number of genes, suggesting that they fine-tune expression of non-essential genes. Several lncRNAs have strain-specific expression, indicating that they are not fixed within the population. This intra-species variation across genetic backgrounds may thereby be a useful tool to distinguish rapidly evolving lncRNAs with as yet non-essential roles.

Maize feedstocks with improved digestibility reduce the costs and environmental impacts of biomass pretreatment and saccharification.

BACKGROUND: Despite the recognition that feedstock composition influences biomass conversion efficiency, limited information exists as to how bioenergy crops with reduced recalcitrance can improve the economics and sustainability of cellulosic fuel conversion platforms. We have compared the bioenergy potential-estimated as total glucose productivity per hectare (TGP)-of maize cultivars contrasting for cell wall digestibility across processing conditions of increasing thermochemical severity. In addition, exploratory environmental impact and economic modeling were used to assess whether the development of bioenergy feedstocks with improved cell wall digestibility can enhance the environmental performance and reduce the costs of biomass pretreatment and enzymatic conversion. RESULTS: Systematic genetic gains in cell wall degradability can lead to significant advances in the productivity (TGP) of cellulosic fuel biorefineries under low severity processing; only if gains in digestibility are not accompanied by substantial yield penalties. For a hypothetical maize genotype combining the best characteristics available in the evaluated cultivar panel, TGP under mild processing conditions (~3.7 t ha(-1)) matched the highest realizable yields possible at the highest processing severity. Under this scenario, both, the environmental impacts and processing costs for the pretreatment and enzymatic saccharification of maize stover were reduced by 15 %, given lower chemical and heat consumption. CONCLUSIONS: Genetic improvements in cell wall composition leading to superior cell wall digestibility can be advantageous for cellulosic fuel production, especially if "less severe" processing regimes are favored for further development. Exploratory results indicate potential cost and environmental impact reductions for the pretreatment and enzymatic saccharification of maize feedstocks exhibiting higher cell wall degradability. Conceptually, these results demonstrate that the advance of bioenergy cultivars with improved biomass degradability can enhance the performance of currently available biomass-to-ethanol conversion systems.

Carcinoma neuroendocrino de vejiga en mujer con infección por VIH: presentación del primer caso mundial / Neuroendocrine carcinome of the bladder in a female with HIV infection: presentation of the first case worldwide

El carcinoma neuroendocrino primario de vejiga es una neoplasia infrecuente que representa el 0,5por ciento de todos los tumores vesicales. La asociación de carcinoma neuroendocrino de vejiga en un paciente con infección por VIH nunca hasta hoy había sido descrita. Presentamos el primer caso clínico español y mundial de esta desconocida y nunca descrita asociación. MATERIAL Y MÉTODOS: Se presenta el caso clínico de una paciente de 46 años con infección por VIH que desarrolló un carcinoma neuroendocrino de vejiga urinaria de evolución fatal. Se describe su clínica de presentación, métodos de diagnóstico utilizados y su tratamiento. La paciente debutó con retención urinaria aguda que rápidamente progresó a la instauración de una uropatía obstructiva alta con deterioro de la función renal. El diagnóstico se efectuó mediante TAC, resección transuretral y estudio histopatológico donde la clave del diagnóstico fue el estudio inmunohistoquímico intensamente positivo para la cromogranina A. El tratamiento adyuvante con quimioterapia le ocasionó una aplasia medular severa, falleciendo por fallo multiórganico a los 26 días de su diagnóstico. A propósito de este caso, se revisa la literatura inglesa en PubMed sobre carcinoma neuroendocrino de vejiga y sobre tumores vesicales en pacientes con infección VIH, no existiendo ningún caso publicado de carcinoma neuroendocrino de vejiga en un paciente con infección por VIH. CONCLUSIONES: El carcinoma neuroendocrino de vejiga es un tumor infrecuente y muy agresivo. Es un tumor que suele presentarse clínicamente en estadios avanzados o metastásicos donde ninguna terapia es eficaz. El tratamiento incluye resección trans-uretral (RTU), cistectomía parcial, cistectomía radical y quimioterapia. El estudio inmunohistoquímico (IHQ) y la tinción con cromogranina A dan la clave para su diagnóstico. Su presentación en pacientes VIH implica muy mal pronóstico. Éste caso es el primer caso mundial publicado de carcinoma neuroendocrino...

The primary neuroendocrine carcinome of the bladder is an infrequent neoplasm which represents 0.5 percent of all vesical tumors. The association of neuroendocrine carcinome of the bladder in a patient with HIV infection has never been described before today. We present the first clinical case in the Spanish-speaking world and worldwide, of this unknown and never written about association. MATERIAL AND METHODS: The clinical case of a 46-yearoldpatient with HIV infection who developed a neuroendocrine carcinoma of the urinary bladder with a fatal evolution, its clinical presentation, the diagnosis methods used and its treatment, are described. The patient started with a severe urinary retention which rapidly progressed to the establishment of a high obstructive uropathy with deterioration in the renal function. The diagnosis was done using TAC, transurethral resection and histopathological study where the key to diagnosis was the intensely positive immunohistochemical study for the chromogranin A. The adjuvant treatment with chemotherapy led to a severe medular aplasia, with the patient dying due to a multi-organ failure, 26 days after her diagnosis. As a result of this case, English literature on the matter in PubMed about neuroendocrine carcinome of the bladder and about vesical tumors in patients with HIV infection was revised, with no published case existing about neuroendocrine carcinome in a patient with HIV. CONCLUSIONS: The neuroendocrine carcinome of the bladder is an infrequent and very aggressive tumor. It is a tumor that tends to be clinically present in advanced or metastasic states, where no therapy is efficient. The treatment includes transurethral resection (TUR), partial cystectomy, radical cystectomy and chemotherapy. The immunohistochemical study (IHC), and the stain with chromogranin A are key for its diagnosis. Its presentation in HIV patients implies a very bad prognosis. This case is the first published case worldwide of neuroendocrine...

Receptor-dependent 4D-QSAR analysis of peptidemimetic inhibitors of Trypanosoma cruzi trypanothione reductase with receptor-based alignment.

Receptor-dependent four-dimensional quantitative structure-activity relationship (RD-4D-QSAR) studies were applied on a series of 21 peptides reversible inhibitors of Trypanosoma cruzi trypanothione reductase (TR) (Amino Acids, 20, 2001, 145). The RD-4D-QSAR (J Chem Inform Comp Sci, 43, 2003, 1591) approach can evaluate multiple conformations from molecular dynamics simulation and several superposition structure alignments inside a box composed by unitary cubic cells. The descriptors are the occupancy frequency of the atoms types inside the grid cells. We could develop 3D-QSAR models that were highly predictive (q(2) above 0.71). The 3D-QSAR models can be visualized as a spatial map of atom types that are important on the comprehension of the ligand-enzyme interaction mechanism, pointing main pharmacophoric groups and TR subsites described in the literature. We were able also to identify some TR subsites for further development in the drug discovery process against tropical diseases not yet studied.

"I felt so hurt and lonely": suicidal behavior in South Asian-Surinamese, Turkish, and Moroccan women in the Netherlands.

Young immigrant women in the Netherlands demonstrate disproportionate rates of suicidal behavior. This study investigated the origins of suicidal behavior in South Asian-Surinamese, Turkish, and Moroccan immigrant young women in order to identify ethnic- and gender-specific patterns of suicidal behavior. Based on life story interviews of women who had been enrolled in mental health care, we constructed five typical patterns in which social, cultural, and personal factors were interconnected. Suicidal behavior was influenced by the ability and right to act autonomously with regard to strategic life choices, as well as by the questioning of cultural values of self-sacrifice and protection of honor.

A finite element approach for modeling micro-structural discontinuities in the heart.

The presence of connective tissue as well as interstitial clefts forms a natural barrier to the electrical propagation in the heart. At a microscopic scale, such uncoupling structures change the pattern of the electrical conduction from uniform towards complex and may play a role in the genesis of cardiac arrhythmias. The anatomical diversity of conduction structures and their topology at a microscopic size scale is overwhelming for experimental techniques. Mathematical models have been often employed to study the behavior of the electrical propagation at a sub-cellular level. However, very fine and computationally expensive meshes are required to capture all microscopic details found in the cardiac tissue. In this work, we present a numerical technique based on the finite element method which allows to reproduce the effects of microscopic conduction barriers caused by the presence of uncoupling structures without actually resolving these structures in a high resolution mesh, thereby reducing the computational costs significantly.

Effect of insertion method on knoop hardness of high viscous glass ionomer cements.

The aim of this study was to assess the Knoop hardness of three high viscous glass ionomer cements: G1 - Ketac Molar; G2 - Ketac Molar Easymix (3M ESPE) and G3 - Magic Glass ART (Vigodent). As a parallel goal, three different methods for insertion of Ketac Molar Easymix were tested: G4 - conventional spatula; G5 - commercial syringe (Centrix) and G6 - low-cost syringe. Ten specimens of each group were prepared and the Knoop hardness was determined 5 times on each specimen with a HM-124 hardness machine (25 g/30 s dwell time) after 24 h, 1 and 2 weeks. During the entire test period, the specimens were stored in liquid paraffin at 37ºC. Significant differences were found between G3 and G1/G2 (two-way ANOVA and Tukey's post hoc test; p<0.01). There was no significant difference in the results among the multiple ways of insertion. The glass ionomer cement Magic Glass ART showed the lowest hardness, while the insertion technique had no significant influence on hardness.

4D-QSAR: perspectives in drug design.

Drug design is a process driven by innovation and technological breakthroughs involving a combination of advanced experimental and computational methods. A broad variety of medicinal chemistry approaches can be used for the identification of hits, generation of leads, as well as to accelerate the optimization of leads into drug candidates. The quantitative structure-activity relationship (QSAR) formalisms are among the most important strategies that can be applied for the successful design new molecules. This review provides a comprehensive review on the evolution and current status of 4D-QSAR, highlighting present challenges and new opportunities in drug design.

3D-Pharmacophore mapping of thymidine-based inhibitors of TMPK as potential antituberculosis agents.

Tuberculosis (TB) is the primary cause of mortality among infectious diseases. Mycobacterium tuberculosis monophosphate kinase (TMPKmt) is essential to DNA replication. Thus, this enzyme represents a promising target for developing new drugs against TB. In the present study, the receptor-independent, RI, 4D-QSAR method has been used to develop QSAR models and corresponding 3D-pharmacophores for a set of 81 thymidine analogues, and two corresponding subsets, reported as inhibitors of TMPKmt. The resulting optimized models are not only statistically significant with r(2) ranging from 0.83 to 0.92 and q(2) from 0.78 to 0.88, but also are robustly predictive based on test set predictions. The most and the least potent inhibitors in their respective postulated active conformations, derived from each of the models, were docked in the active site of the TMPKmt crystal structure. There is a solid consistency between the 3D-pharmacophore sites defined by the QSAR models and interactions with binding site residues. Moreover, the QSAR models provide insights regarding a probable mechanism of action of the analogues.

Effect of insertion method on knoop hardness of high viscous glass ionomer cements

The aim of this study was to assess the Knoop hardness of three high viscous glass ionomer cements: G1 - Ketac Molar; G2 - Ketac Molar Easymix (3M ESPE) and G3 - Magic Glass ART (Vigodent). As a parallel goal, three different methods for insertion of Ketac Molar Easymix were tested: G4 - conventional spatula; G5 - commercial syringe (Centrix) and G6 - low-cost syringe. Ten specimens of each group were prepared and the Knoop hardness was determined 5 times on each specimen with a HM-124 hardness machine (25 g/30 s dwell time) after 24 h, 1 and 2 weeks. During the entire test period, the specimens were stored in liquid paraffin at 37ºC. Significant differences were found between G3 and G1/G2 (two-way ANOVA and Tukey's post hoc test; p<0.01). There was no significant difference in the results among the multiple ways of insertion. The glass ionomer cement Magic Glass ART showed the lowest hardness, while the insertion technique had no significant influence on hardness.

O objetivo deste estudo foi avaliar a microdureza Knoop de três cimentos de ionômero de vidro de alta viscosidade: G1 - Ketac Molar; G2 - Ketac Molar Easymix (3M ESPE) and G3 - Magic Glass ART (Vigodent). Adicionalmente, como um co-objetivo, três diferentes formas de inserção do Ketac Molar Easymix foram avaliadas: G4 - espátula conventional; G5 - seringa comercial (Centrix) e G6 - seringa de baixo custo. Dez corpos de prova de cada grupo foram preparados e a microdureza Knoop foi determinada com 5 indentações por espécime com o aparelho HM-124 (25 g/30 s tempo de identação) após 24 h, 1 e 2 semanas. Durante todo o período de teste, os espécimes foram mantidos em parafina líquida a 37ºC. Diferenças estatísticas significantes foram encontradas entre G3 e G1 / G2 (ANOVA a 2 critérios e teste de Tukey post hoc; p<0,01). Não houve diferença nos resultados no que se refere às diferentes formas de inserção. O cimento de ionômero de vidro Magic Glass ART apresenta os valores mais baixos de dureza enquanto o método de inserção não influencia nos resultados de dureza.

The receptor-dependent QSAR paradigm: an overview of the current state of the art.

The original quantitative structure-activity relationship (QSAR) formulation was proposed by Hansch and Fujita in the 1960's and, since then QSAR analysis has evolved as a mature science, due mainly to the advances that occurred in the past two decades in the fields of molecular modeling, data analysis algorithms, chemoinformatics, and the application of graph theory in chemistry. Moreover, it is also worthy of note the exponential progress that have occurred in software and hardware development. In this context, a myriad of QSAR methods exist; from the considered "classical" approaches (known as two-dimensional (2D) QSAR), to three-dimensional (3D) and multidimensional (nD) QSAR ones. A distinct QSAR approach has been recently proposed, the receptor-dependent-QSAR, where explicit information regarding the receptor structure (usually a protein) is extensively used during modeling process. Indeed, a limited, but growing number of receptor-dependent QSAR methods are reported in the literature. With no intention to be comprehensive, an overview of receptor-dependent QSAR methods will be discussed along with an in-depth examination of their applications in drug design, virtual screen, and ADMET modeling in silico.

Rational design and 3D-pharmacophore mapping of 5'-thiourea-substituted alpha-thymidine analogues as mycobacterial TMPK inhibitors.

Thymidine monophosphate kinase (TMPK) has emerged as an attractive target for developing inhibitors of Mycobacterium tuberculosis growth. In this study the receptor-independent (RI) 4D-QSAR formalism has been used to develop QSAR models and corresponding 3D-pharmacophores for a set of 5'-thiourea-substituted alpha-thymidine inhibitors. Models were developed for the entire training set and for a subset of the training set consisting of the most potent inhibitors. The optimized (RI) 4D-QSAR models are statistically significant (r(2) = 0.90, q(2) = 0.83 entire set, r(2) = 0.86, q(2) = 0.80 high potency subset) and also possess good predictivity based on test set predictions. The most and least potent inhibitors, in their respective postulated active conformations derived from the models, were docked in the active site of the TMPK crystallographic structure. There is a solid consistency between the 3D-pharmacophore sites defined by the QSAR models and interactions with binding site residues. This model identifies new regions of the inhibitors that contain pharmacophore sites, such as the sugar-pyrimidine ring structure and the region of the 5'-arylthiourea moiety. These new regions of the ligands can be further explored and possibly exploited to identify new, novel, and, perhaps, better antituberculosis inhibitors of TMPKmt. Furthermore, the 3D-pharmacophores defined by these models can be used as a starting point for future receptor-dependent antituberculosis drug design as well as to elucidate candidate sites for substituent addition to optimize ADMET properties of analog inhibitors.

Free-energy force-field three-dimensional quantitative structure-activity relationship analysis of a set of p38-mitogen activated protein kinase inhibitors.

The p38-mitogen-activated protein kinases (p38-MAPKs) belong to a family of serine-threonine kinases activated by pro-inflammatory or stressful stimuli that are known to be involved in several diseases. Their biological importance, related to the release of inflammatory pro-cytokines such as tumor necrosis factor-alpha (TNF-alpha) and interleukin-1 (IL-1), has generated many studies aiming at the development of selective inhibitors for the treatment of inflammatory diseases. In this work, we developed receptor-based three dimensional (3D) quantitative structure-activity relationship (QSAR) models for a series of 33 pyridinyl imidazole compounds [Liverton et al. (1999) 42:2180], using a methodology named free-energy force-field (FEFF) [Tokarski and Hopfinger (1997) 37:792], in which scaled intra- and intermolecular energy terms of the Assisted Model Building Energy Refinement (AMBER) force field combined with a hydration-shell solvation model are the independent variables used in the QSAR studies. Multiple temperature molecular-dynamics simulations (MDS) of ligand-protein complexes and genetic-function approximation (GFA) were employed using partial least squares (PLS) as the fitting functions to develop FEFF-3D-QSAR models for the binding process. The best model obtained in the FEFF-3D-QSAR receptor-dependent (RD) method shows the importance of the van der Waals energy change upon binding and the electrostatic energy in the interaction of ligands with the receptor. The QSAR equations described here show good predictability and may be regarded as representatives of the binding process of ligands to p38-MAPK. Additionally, we have compared the top FEFF-3D-QSAR model with receptor independent (RI) 4D-QSAR models developed in a recent study [Romeiro et al. (2005) 19:385].

Construction of 4D-QSAR models for use in the design of novel p38-MAPK inhibitors.

The p38-mitogen-activated protein kinase (p38-MAPK) plays a key role in lipopolysaccharide-induced tumor necrosis factor-alpha (TNF-alpha) and interleukin-1 (IL-1) release during the inflammatory process, emerging as an attractive target for new anti-inflammatory agents. Four-dimensional quantitative structure-activity relationship (4D-QSAR) analysis [Hopfinger et al., J. Am. Chem. Soc., 119 (1997) 10509] was applied to a series of 33 (a training set of 28 and a test set of 5) pyridinyl-imidazole and pyrimidinyl-imidazole inhibitors of p38-MAPK, with IC50 ranging from 0.11 to 2100 nM [Liverton et al., J. Med. Chem., 42 (1999) 2180]. Five thousand conformations of each analogue were sampled from a molecular dynamics simulation (MDS) during 50 ps at a constant temperature of 303 K. Each conformation was placed in a 2 angstroms grid cell lattice for each of three trial alignments. 4D-QSAR models were constructed by genetic algorithm (GA) optimization and partial least squares (PLS) fitting, and evaluated by leave-one-out cross-validation technique. In the best models, with three to six terms, the adjusted cross-validated squared correlation coefficients, Q2adj, ranged from 0.67 to 0.85. Model D (Q2adj = 0.84) was identified as the most robust model from alignment 1, and it is representative of the other best models. This model encompasses new molecular regions as containing pharmacophore sites, such as the amino-benzyl moiety of pyrimidine analogs and the N1-substituent in the imidazole ring. These regions of the ligands should be further explored to identify better anti-inflammatory inhibitors of p38-MAPK.

Rational design of new antituberculosis agents: receptor-independent four-dimensional quantitative structure-activity relationship analysis of a set of isoniazid derivatives.

A 4D-QSAR analysis was carried out for a set of 37 hydrazides whose minimum inhibitory concentrations against M. tuberculosis var. bovis were evaluated. These ligands are thought to act like isoniazid in mycolic acid biosynthesis. Results indicate that nonpolar groups in the acyl moiety of ligands markedly decrease biological activity. Molecular modifications of the ligand NAD moiety, including nonpolar groups and hydrogen bond donor and acceptor groups, seemingly improve ligand interactions with amino acid residues of the InhA active site.

Colecistectomía: análisis de la experiencia personal 5 años antes y 5 años después de la cirugía laparoscópica / Cholecystectomy: five years before and five years after the advent of laparoscopic cholecystectomy

Se analiza la experiencia de los autores en cirugia de vesicula y vias biliares en dos periodos de 5 años, antes y despues del advenimiento de la Colecistectomia laparoscopica y se observa que el numero total de intervenciones aumento en un 30.09 por ciento, disminuyo en forma importante el numero de cirugias de urgencias, de colangiografias transoperatorias y de exploraciones de las vias biliares, y se acorto considerablemente el numero de dias de hospitalizacion. En tiempo operatorio, edad y sexo, no hubo diferencias. Las complicaciones disminuyeron del 4.86 por ciento en la cirugia tradicional al 3.06 por ciento en la cirugia laparoscopica. No se observa mortalidad en las 2 series. Se concluye que la cirugia laparoscopica ha cambiado radicalmente la manera de tratar la patologia de vesicula y vias biliares, beneficiando al paciente con todas las innumerables ventajas de la cirugia de invasion minima.