Frustraevo: a web server to localize and quantify the conservation of local energetic frustration in protein families.

According to the Principle of Minimal Frustration, folded proteins can only have a minimal number of strong energetic conflicts in their native states. However, not all interactions are energetically optimized for folding but some remain in energetic conflict, i.e. they are highly frustrated. This remaining local energetic frustration has been shown to be statistically correlated with distinct functional aspects such as protein-protein interaction sites, allosterism and catalysis. Fuelled by the recent breakthroughs in efficient protein structure prediction that have made available good quality models for most proteins, we have developed a strategy to calculate local energetic frustration within large protein families and quantify its conservation over evolutionary time. Based on this evolutionary information we can identify how stability and functional constraints have appeared at the common ancestor of the family and have been maintained over the course of evolution. Here, we present FrustraEvo, a web server tool to calculate and quantify the conservation of local energetic frustration in protein families.

Pain in High-Dose-Rate Brachytherapy for Cervical Cancer: A Retrospective Cohort Study.

High-dose-rate brachytherapy (HDR) is part of the main treatment for locally advanced uterine cervical cancer. Our aim was to evaluate the incidence and intensity of pain and patients' satisfaction during HDR. Risk factors for suffering pain were also analyzed. A retrospective study was carried out by extracting data from patients who had received HDR treatment for five years. Postoperative analgesia had been administered using pre-established analgesic protocols for 48 h. Pain assessment was collected according to a protocol by the acute pain unit. Analgesic assessment was compared according to analgesic protocol administered, number of needles implanted, and type of anesthesia performed during the procedure. From 172 patients treated, data from 247 treatments were analyzed. Pain was considered moderate in 18.2% of the patients, and 43.3% of the patients required at least one analgesic rescue. Patients receiving major opioids reported worse pain control. No differences were found regarding the analgesic management according to the intraprocedural anesthesia used or the patients' characteristics. The number of inserted needles did not influence the postoperative analgesic assessment. Continuous intravenous infusion of tramadol and metamizole made peri-procedural pain during HDR mild in most cases. Many patients still suffered from moderate pain.

Looking in a mirror, laparoscopic gastric sleeve in situs inversus patient: a case report.

Laparoscopic sleeve gastrectomy has been widely accepted and adopted as a weight loss procedure for obesity. Although technically demanding, it is feasible and can improve patients' overall health. However, any variation from normal anatomy can be challenging for any surgery, especially bariatric surgery, where a mistake could mean going from a life-saving opportunity to costing the patient's life. We present the case of an obese patient who sought medical attention and decided on bariatric surgery. During her preoperative evaluation, situs inversus totalis was discovered. After careful planning, the surgical team completed the surgery without complications, and the patient recovered completely.

Situs inversus and bariatric surgery: A challenge for the surgical team.

INTRODUCTION AND IMPORTANCE: Obesity is a worldwide pandemic and is closely associated with an increased risk of comorbidities and overall mortality. Surgery has emerged as an essential strategy to ameliorate obesity-attributable comorbidities and as a powerful weight-loss tool. Due to the increasing number of obese patients predicted to elect surgery, individuals with rare anomalies such as situs inversus can be expected. CASE PRESENTATION: We present the case of a 49-year-old woman with situs inversus with levocardia. She had a high BMI and was admitted for bariatric surgery. After several adjustments to our technique, the procedure was completed without complications. CLINICAL DISCUSSION: Laparoscopic bariatric surgeries are highly demanding; variations from the normal anatomy could challenge the medical team. CONCLUSION: Preoperative diagnosis and highly trained surgeons is of paramount importance to adequately treat every patient.

Laparoscopic sleeve gastrectomy alters 1H-NMR-measured lipoprotein and glycoprotein profile in patients with severe obesity and nonalcoholic fatty liver disease.

Patients with morbid obesity frequently present non-alcoholic fatty liver (NAFL) and non-alcoholic steatohepatitis (NASH) associated with pro-atherogenic alterations. Laparoscopic sleeve gastrectomy (LSG) is an effective treatment for weight reduction, and for the remission of hepatic alterations. Using 1H-nuclear magnetic resonance (1H-NMR), we investigated the effects of LSG on lipoprotein and glycoprotein profile in patients with morbid obesity and liver disease. We included 154 patients with morbid obesity (49 non-NASH, 54 uncertain NASH, 51 definite NASH). A blood sample was obtained before surgery and, in patients with definite NASH, one year after surgery. Patients with NASH had increased concentrations of medium and small VLDL particles, VLDL and IDL cholesterol concentrations, IDL, LDL, and HDL triglyceride concentrations, and elevated glycoprotein levels. These changes were more marked in patients with type 2 diabetes mellitus. LSG produced significant decreases in the concentration of VLDL particles, VLDL cholesterol and triglycerides, an increase in the concentration LDL particles and LDL cholesterol concentrations, and a decrease in protein glycation. We conclude that patients with obesity and NASH had significant alterations in circulating levels of lipoproteins and glycoproteins that were associated with the severity of the disease. Most of these changes were reversed post-LSG.

Lipid Profile Rather Than the LCAT Mutation Explains Renal Disease in Familial LCAT Deficiency.

Renal complications are the major cause of morbidity and mortality in patients with familial lecithin-cholesterol acyltransferase (LCAT) deficiency (FLD). We report three FLD patients, two of them siblings-only one of whom developed renal disease-and the third case being a young man with early renal disease. The aim of this study was to analyze the clinical characteristics and possible mechanisms associated with renal disease in these patients. Plasma lipid levels, LCAT activity, lipoprotein particle profile by NMR and FPLC, free and esterified cholesterol, presence of lipoprotein X (LpX) and DNA sequencing in the three FLD patients have been determined. The three cases presented clinical characteristics of FLD, although only one of the siblings developed renal disease, at 45 years of age, while the other patient developed the disease in his youth. Genetic analysis revealed new missense homozygous mutations, p.(Ile202Thr) in both siblings and p.(Arg171Glu) in the other patient. Lipoprotein particle analysis showed that the two patients with renal disease presented higher numbers of small very low-density lipoprotein (VLDL) and a higher concentration of triglycerides in VLDL. This study reports three new cases of LCAT deficiency, not previously described. Renal disease is not only dependent on LCAT deficiency, and could be due to the presence of VLDL particles, which are rich in triglycerides, free cholesterol and LpX.

Lipid Profiling Using 1H NMR Spectroscopy.

Lipid profiling, which includes fatty acids, phospholipids, glycerides, and cholesterols is extremely important because of the essential role lipids play in the regulation of metabolism in animals. 1H-NMR-based protocols for high-throughput lipid analysis in complex mixtures have been developed and applied to biological systems. Many classes of lipids can be quantitatively analyzed in many sample matrices including serum, cells, and tissues using a simple 1H NMR experiment. In this chapter, we provide protocols for NMR-based lipid profiling including sample preparation, NMR experiments, and quantification using the LipSpin software tool.

Serum Paraoxonase-1-Related Variables and Lipoprotein Profile in Patients with Lung or Head and Neck Cancer: Effect of Radiotherapy.

We investigated alterations in the levels of the antioxidant paraoxonase-1 (PON1) and the lipoprotein profile (analyzed by nuclear magnetic resonance) in patients with lung cancer (LC) or head and neck cancer (HNC), and the effects produced thereon by radiotherapy (RT). We included 33 patients with LC and 28 patients with HNC. Before irradiation, and one month after completion of RT, blood samples were obtained. The control group was composed of 50 healthy subjects. Patients had significantly lower serum PON1 activity and concentration before RT than the control group. PON1-related variables were good predictors of the presence of LC or HNC, with analytical sensitivities and specificities greater than 80%. Patients showed a significant increase in the number of particles of all subclasses of very-low-density lipoproteins (large, medium and small). However, these changes were not maintained when adjusted for age, sex, and other clinical and demographic variables. Irradiation was associated with a significant increase in PON1 concentration and, only in patients with HNC, with an increase in high-density lipoprotein-cholesterol concentration. Our results suggest that determinations of the levels of PON1-related variables may constitute good biomarkers for the evaluation of these diseases. Studies with a larger number of patients are needed to fully confirm this hypothesis.

HDL Triglycerides: A New Marker of Metabolic and Cardiovascular Risk.

While cholesterol content in high-density lipoproteins (HDLs) is a well-established inverse marker of cardiovascular risk, the importance of HDL-triglyceride (HDL-TG) concentration is not well known. We aim to examine plasma HDL-TG concentrations, assessed by 1H-NMR, in patients with metabolic diseases and their association with classical biomarkers. In this cross-sectional study, we included 502 patients with type 2 diabetes or metabolic syndrome attending the lipid unit of our University Hospital. The presence of arteriosclerotic plaques was assessed by ultrasonography. A complete lipoprotein profile was performed by 1H-NMR (Liposcale test). HDL-TG was strongly positively correlated with total triglycerides, glycerol, and fatty liver index, while a strong negative correlation was observed with HDL-cholesterol (HDL-C) and HDL-particle number (HDL-P). HDL-TG was associated with all triglyceride-rich lipoprotein parameters and had an opposite association with HDL-C and HDL-P. It was also significantly correlated with circulating cholesterol ester transfer protein (CETP). HDL-TG concentrations were higher as metabolic syndrome components increased. HDL-TG was also higher with worsening glucose metabolism. Patients with carotid plaques also showed higher HDL-TG. In contrast to HDL-C, HDL-TG is directly associated with metabolism and arteriosclerotic vascular alterations. HDL-TG should be considered a biomarker of metabolic and cardiovascular risk and could be a marker of HDL dysfunction.

LipSpin: A New Bioinformatics Tool for Quantitative 1H NMR Lipid Profiling.

The structural similarity among lipid species and the low sensitivity and spectral resolution of nuclear magnetic resonance (NMR) have traditionally hampered the routine use of 1H NMR lipid profiling of complex biological samples in metabolomics, which remains mostly manual and lacks freely available bioinformatics tools. However, 1H NMR lipid profiling provides fast quantitative screening of major lipid classes (fatty acids, glycerolipids, phospholipids, and sterols) and some individual species and has been used in several clinical and nutritional studies, leading to improved risk prediction models. In this Article, we present LipSpin, a free and open-source bioinformatics tool for quantitative 1H NMR lipid profiling. LipSpin implements a constrained line shape fitting algorithm based on voigt profiles and spectral templates from spectra of lipid standards, which automates the analysis of severely overlapped spectral regions and lipid signals with complex coupling patterns. LipSpin provides the most detailed quantification of fatty acid families and choline phospholipids in serum lipid samples by 1H NMR to date. Moreover, analytical and clinical results using LipSpin quantifications conform with other techniques commonly used for lipid analysis.

Estudio de resistencia secundaria a las drogas antituberculosas. Informe de algunos hallazgos epidemiológicos, clínicos y radiológicos en estos pacientes

La resistencia secundaria del Mycobacterium tuberculosis a las drogas comúnmente utilizadas para su tratamiento es un problema creciente que requiere de mucha atención por parte del mundo científico. Con el fin de ir caracterizando el problema en nuestro medio se inicio un estudio de resistencia secundario a las drogas antituberculosas en los pacientes del departamento de Antioquia remitidos al Laboratorio Departamental de Salud Pública por haber presentado fallas tanto en el tratamiento inicial como en el segundo tratamiento. Se presentaron 102 pacientes con algún tipo de resistencia; la combinación isoniazida con rifampicina y otras drogas fue la más común. Se destacan algunos hallazgos clínicos, radiológicos y epidemiológicos que pudieran estar asociados con la aparición de resistencia.