Proyecto de desarrollo de modelo de negocio Trendlab

Proyecto de emprendimiento llevado a través de la metodología de lean startup con la finalidad de probar la factibilidad de implementar un modelo de negocio que se centra en la vinculación de individuos con necesidades específicas de desarrollo de habilidades competitivas laborales y un experto que pueda ofrecer ampliar dichas destrezas

Changes in capsular serotype alter the surface exposure of pneumococcal adhesins and impact virulence

We examined the contribution of serotype on Streptococcus pneumoniae adhesion and virulence during respiratory tract infection using a panel of isogenic TIGR4 (serotype 4) mutants expressing the capsule types 6A (+6A), 7F (+7F) and 23F (+23F) as well as a deleted and restored serotype 4 (+4) control strain. Immunoblots, bacterial capture assays with immobilized antibody, and measurement of mean fluorescent intensity by flow cytometry following incubation of bacteria with antibody, all determined that the surface accessibility, but not total protein levels, of the virulence determinants Pneumococcal surface protein A (PspA), Choline binding protein A (CbpA), and Pneumococcal serine-rich repeat protein (PsrP) changed with serotype. In vitro, bacterial adhesion to Detroit 562 pharyngeal or A549 lung epithelial cells was modestly but significantly altered for +6A, +7F and +23F. In a mouse model of nasopharyngeal colonization, the number of +6A, +7F, and +23F pneumococci in the nasopharynx was reduced 10 to 100-fold versus +4; notably, only mice challenged with +4 developed bacteremia. Intratracheal challenge of mice confirmed that capsule switch strains were highly attenuated for virulence. Compared to +4, the +6A, +7F, and +23F strains were rapidly cleared from the lungs and were not detected in the blood. In mice challenged intraperitoneally, a marked reduction in bacterial blood titers was observed for those challenged with +6A and +7F versus +4 and +23F was undetectable. These findings show that serotype impacts the accessibility of surface adhesins and, in particular, affects virulence within the respiratory tract. They highlight the complex interplay between capsule and protein virulence determinants

Demand Management Based on Model Predictive Control Techniques

Demand management (DM) is the process that helps companies to sell the right product to the right customer, at the right time, and for the right price. Therefore the challenge for any company is to determine how much to sell, at what price, and to which market segment while maximizing its profits. DM also helps managers efficiently allocate undifferentiated units of capacity to the available demand with the goal of maximizing revenue. This paper introduces control system approach to demand management with dynamic pricing (DP) using the model predictive control (MPC) technique. In addition, we present a proper dynamical system analogy based on active suspension and a stability analysis is provided via the Lyapunov direct method

Normal aortic diameters within the Mexican population and the impact of gender and ethnicity

Background: There is a lack of studies describing the normal size of the aorta in Mexican population. Objective: To analyze aortic measurements in Mexican patients and to compared them with patients from five different countries. Methods: Measurements of the aorta were divided in Mexicans and controls. Comparisons between ethnicities and groups were performed using Mann Whitney rank sum test. Results: The registry included 166 patients, 106 (63.8%) were enrolled in Mexico and 60 (36.1%) in the control group. Mexican patients had smaller aortic diameters compared to the control group, at the level of the right renal artery ostium, inferior mesenteric artery, and aortic bifurcation. The Hispanic population had significantly smaller aortic diameters from the level of the celiac artery to the aortic bifurcation. Conclusion: The normal aortic diameters in the Mexican population are smaller compared to other countries.</p

Neuraminidase A exposed galactose promotes Streptococcus pneumoniae biofilm formation during colonization.

Streptococcus pneumoniae is an opportunistic pathogen that colonizes the nasopharynx. Herein we show that carbon availability is distinct between the nasopharynx and bloodstream of adult humans: glucose being absent in the nasopharynx whereas galactose being abundant. We demonstrate that pneumococcal neuraminidase A (NanA), which cleaves terminal sialic acid residues from host glycoproteins, exposed galactose on the surface of septal epithelial cells thereby increasing its availability during colonization. We observed that mutants of S. pneumoniae deficient in NanA and β-galactosidase A (BgaA) failed to form biofilms in vivo despite normal biofilm-forming abilities in vitro Subsequently, we observed that glucose, sucrose, and fructose were inhibitory for biofilm formation, whereas galactose, lactose and low concentrations of sialic acid were permissive. Together these findings suggested that the genes involved in biofilm formation were under some form of carbon catabolite repression (CCR), a regulatory network during which genes involved in the uptake and metabolism of less-preferred sugars are silenced during growth with preferred sugars. Supporting this notion, we observed that a mutant deficient in pyruvate oxidase, which converts pyruvate to acetyl-phosphate during non-CCR inducing growth conditions, was unable to form biofilms. Subsequent comparative RNA-seq analyses of planktonic- and biofilm-grown pneumococci showed that metabolic pathways involving the conversion of pyruvate to acetyl-phosphate and subsequently leading to fatty acid biosynthesis were consistently up-regulated during diverse biofilm growth conditions. We conclude carbon availability in the nasopharynx impacts pneumococcal biofilm formation in vivo Additionally, biofilm formation involves metabolic pathways not previously appreciated to play an important role

Pneumococcal Gene Complex Involved in Resistance to Extracellular Oxidative Stress

Streptococcus pneumoniae is a Gram-positive bacterium which is a member of the normal human nasopharyngeal flora but can also cause serious disease such as pneumonia, bacteremia, and meningitis. Throughout its life cycle, S. pneumoniae is exposed to significant oxidative stress derived from endogenously produced hydrogen peroxide (H2O2) and from the host through the oxidative burst. How S. pneumoniae, an aerotolerant anaerobic bacterium that lacks catalase, protects itself against hydrogen peroxide stress is still unclear. Bioinformatic analysis of its genome identified a hypothetical open reading frame belonging to the thiol-specific antioxidant (TlpA/TSA) family, located in an operon consisting of three open reading frames. For all four strains tested, deletion of the gene resulted in an approximately 10-fold reduction in survival when strains were exposed to external peroxide stress. However, no role for this gene in survival of internal superoxide stress was observed. Mutagenesis and complementation analysis demonstrated that all three genes are necessary and sufficient for protection against oxidative stress. Interestingly, in a competitive index mouse pneumonia model, deletion of the operon had no impact shortly after infection but was detrimental during the later stages of disease. Thus, we have identified a gene complex involved in the protection of S. pneumoniae against external oxidative stress, which plays an important role during invasive disease.

Moderate-High Disease Activity in Patients with Recent-Onset Psoriatic Arthritis-Multivariable Prediction Model Based on Machine Learning

The aim was to identify patient- and disease-related characteristics predicting moderate-to-high disease activity in recent-onset psoriatic arthritis (PsA). We performed a multicenter observational prospective study (2-year follow-up, regular annual visits) in patients aged ≥18 years who fulfilled the CASPAR criteria and had less than 2 years since the onset of symptoms. The moderate-to-high activity of PsA was defined as DAPSA > 14. We trained a logistic regression model and random forest-type and XGBoost machine learning algorithms to analyze the association between the outcome measure and the variables selected in the bivariate analysis. The sample comprised 158 patients. At the first follow-up visit, 20.8% of the patients who attended the clinic had a moderate-to-severe disease. This percentage rose to 21.2% on the second visit. The variables predicting moderate-high activity were the PsAID score, tender joint count, level of physical activity, and sex. The mean values of the measures of validity of the machine learning algorithms were all high, especially sensitivity (98%; 95% CI: 86.89-100.00). PsAID was the most important variable in the prediction algorithms, reinforcing the convenience of its inclusion in daily clinical practice. Strategies that focus on the needs of women with PsA should be considered

Severe Pneumococcal Pneumonia Causes Acute Cardiac Toxicity and Subsequent Cardiac Remodeling

Rationale: Up to one-third of patients hospitalized with pneumococcal pneumonia experience major adverse cardiac events (MACE) during or after pneumonia. In mice, Streptococcus pneumoniae caninvade themyocardium, induce cardiomyocyte death, and disrupt cardiac function following bacteremia, but it is unknown whether the same occurs in humans with severe pneumonia. Objectives: We sought to determine whether S. pneumoniae can (1) translocate the heart, (2) induce cardiomyocyte death, (3) causeMACE, and (4) induce cardiac scar formation after antibiotic treatment during severe pneumonia using a nonhuman primate (NHP) model. Methods: We examined cardiac tissue from six adult NHPs with severe pneumococcal pneumonia and three uninfected control animals. Three animals were rescued with antibiotics (convalescent animals). Electrocardiographic, echocardiographic, and serum biomarkers of cardiac damage were measured (troponin T, N-terminal pro-brain natriuretic peptide, and heart-type fatty acid binding protein). Histological examination included hematoxylin and eosin staining, immunofluorescence, immunohistochemistry, picrosirius red staining, and transmission electron microscopy. Immunoblots were used to assess the underlying mechanisms. Measurements and Main Results: Nonspecific ischemic alterations were detected by electrocardiography and echocardiography. Serum levels of troponin T and heart-type fatty acid binding protein were increased (P,0.05) after pneumococcal infection in both acutely ill and convalescent NHPs. S. pneumoniae was detected in the myocardium of all NHPs with acute severe pneumonia. Necroptosis and apoptosis were detected in the myocardium of both acutely ill and convalescent NHPs. Evidence of cardiac scar formation was observed only in convalescent animals by transmission electron microscopy and picrosirius red staining. Conclusions: S. pneumoniae invades the myocardium and induces cardiac injury with necroptosis and apoptosis, followed by cardiac scarring after antibiotic therapy, in anNHP model of severe pneumonia

Routine management of locally advanced cervical cancer with concurrent radiation and cisplatin. Five-year results

BACKGROUND: Globally, cervical cancer primarily affects socially disadvantaged women. Five randomized trials were the foundation for adopting cisplatin-based chemotherapy during radiation as the standard of care for high-risk patients after primary radical hysterectomy who require adjuvant radiation and for locally advanced patients treated with definitive radiation. These results were obtained in clinical trials performed in carefully prepared academic centers; hence, we sought to determine whether these results could be reproduced when patients were treated on an out-of-protocol basis. METHODS: We reviewed the files of 294 patients with locally advanced cervical cancer who received radiation plus weekly cisplatin as routine management between 1999 to 2003, and analyzed treatment compliance, response rate, toxicity, and survival. RESULTS: A total of 294 patients who received radiation and cisplatin were analyzed. Mean age was 43.8 years (range, 26–68 years). The majority of cases were squamous cell carcinoma (87.8%), and distribution according to International Federation of Gynecology and Obstetrics (FIGO) stage was as follows: IB2-IIA, 23%; IIB, 53.3%, and IIIB, 23%; there were only two IVA cases. Overall, 96% of patients completed external beam, and intracavitary therapy. The majority of patients (67%) received the planned six courses of weekly cisplatin. Complete responses were achieved in 243 (83%) patients, whereas 51 (17%) had either persistent (32 patients, 10.8%) or progressive (19 patients, 6.4%) disease. At median follow-up (28 months; range, 2–68 months), 36 patients (12.2%) have relapsed (locally 30.5, and systemically, 69.5%). The most common toxicities were hematologic and gastrointestinal, in the majority of cases considered mild-moderate. At median follow-up (28 months; range, 2–68 months), overall and progression-free survival are 76.5 and 67%, respectively. CONCLUSION: Our results support use of chemoradiation with six weekly applications of cisplatin at 40 mg/m(2 )during external radiation for routine management of locally advanced cervical cancer

Acute pulmonary embolism as a complication in a young male patient with a left popliteal venous aneurysm

Abstract Venous aneurysms are rare and have a prevalence of 0.1 to 0.2% in the reported series. Typically, patients do not present any symptoms, but are prone to develop deep venous thrombosis (DVT) and the most feared complication, pulmonary embolism (PE). We present the case of a previously healthy 36-year-old man who presented at the emergency department with tachycardia, dyspnea, and pleuritic pain. A thoracic computed tomography angiography (CTA) confirmed the diagnosis of acute pulmonary embolism. He was treated with systemic thrombolysis and anticoagulation. In the further workup of the cause of the embolism, computed tomography revealed a fusiform dilation of the left popliteal vein measuring 3 by 3 centimeters (cm) with an incomplete filling defect because of thrombus presence. The patient underwent open surgical repair. At one month follow-up, he was asymptomatic, and an ultrasound revealed complete patency of the popliteal vein without dilatation or thrombus