Personalized modeling for prediction with decision-path models

Deriving predictive models in medicine typically relies on a population approach where a single model is developed from a dataset of individuals. In this paper we describe and evaluate a personalized approach in which we construct a new type of decision tree model called decision-path model that takes advantage of the particular features of a given person of interest. We introduce three personalized methods that derive personalized decision-path models. We compared the performance of these methods to that of Classification And Regression Tree (CART) that is a population decision tree to predict seven different outcomes in five medical datasets. Two of the three personalized methods performed statistically significantly better on area under the ROC curve (AUC) and Brier skill score compared to CART. The personalized approach of learning decision path models is a new approach for predictive modeling that can perform better than a population approach

Aortic root enlargement does not increase the surgical risk and short-term patient outcome

Objective: To analyze the short-term outcome of aortic root enlargement (ARE) using death and adverse events as end points. Methods: From January 1999 through December 2009, 3339 patients were subjected to aortic valve replacement (AVR). A total of 678 were considered to have small aortic roots (SARs) in which an aortic prosthesis size 21mm or smaller was implanted. ARE using a bovine pericardial patch was performed in another 218 patients, who constitute the study population. This comprised 174 females (79.8%); the mean age was 69.4±13.4 years (8-87, median 74 years), the body surface area (BSA) was 1.59±0.15m(2) and the body mass index (BMI) 25.77±3.16kgm(-2), and 192 (88.5%) were in New York Heart Association (NYHA) II-III. Preoperative echocardiography revealed significant left ventricular (LV) dysfunction in 17 patients (8%), a mean aortic valve area of 0.57±0.27cm(2), and a mean gradient of 62.51±21.25mmHg. A septal myectomy was performed in 129 subjects (59.2%), and other associated procedures, mostly coronary artery bypass grafting (CABG), in 60 (27.5%). Bioprostheses were implanted in 161 patients (73.9%). The mean valve size was 21.9±1.0 (21-25). The mean extracorporeal circulation (ECC) and aortic clamping times were 82.8±19.8min and 56.8±12.5min, respectively. Results: Hospital mortality was 0.9% (n=2) for ARE as compared with 0.6% (n=4) for the SAR group (p=0.8). Inotropic support was required in only 13 (5.9%) patients and the first 24-h chest drainage was 336.2±202ml. Other complications included pacemaker implantation (7.8%), acute renal failure (10.6%), respiratory (4.1%), and CVA/transient ischemic attack (CVA/TIA) (3.2%). Postoperative echocardiographic evaluation showed a significant decrease in peak and mean aortic gradients (23.7±9.5 and 14±6.2mmHg, respectively, p<0.0001). The mean indexed effective orifice area (iEOA) was 0.92±0.01cm(2)m(-2) (vs 0.84±0.07cm(2)m(-2), in SAR, p<0.0001). Only 11% of patients (n=24) with ARE exhibited moderate patient-prosthesis mismatch (PPM) and none had severe PPM. Mean hospital stay was 9.7±9.29 days (median 7 days). Conclusions: With the growing number of patients with degenerative aortic valve pathology, mainly an older population, sometimes with calcified and fragile aortic wall, the issue of dealing with an SAR poses the dilemma of whether to implant a smaller prosthesis and admit some degree of PPM, or to enlarge the aortic root. This study demonstrates that the latter can be done in a safe and reproducible manner

TNF-α and IL-6 immunohistochemistry in rat renal tissue experimentaly infected with Leptospira interrogans serovar Canicola

Leptospirosis is a public health problem worldwide and its etiology remains unclear. Its pathogenesis involves a complex interaction between host and infecting microorganism. The inflammatory reaction that controls the infection process also underscores many pathophysiological events occurring in leptospirosis. We investigated the presence of tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6) in renal tissues by immunohistochemical and histopathological examination in animals experimentally inoculated with Leptospira serovar Canicola. All the tests were carried out 2, 7, 14, 21 or 28 days after inoculation. Although TNF-α and IL-6 had been detected in tissues throughout the observation period, these cytokines appeared more intensely during the initial phase of infection. Therefore, both TNF-α and IL-6 were associated with the immunopathogenesis of leptospirosis. This profile suggests a high immunocellular response throughout the early infection stages followed by subsequent humoral response.Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)São Paulo State University Dentistry School Department of Animal Health and ProductionSão Paulo State University Dentistry School Department of Clinics, Surgery and Animal ReproductionFederal University of São Paulo Department of MedicineUNIFESP, Department of MedicineSciEL

Coronary artery bypass surgery without cardioplegia: hospital results in 8515 patients†

OBJECTIVES: Cardioplegic myocardial protection is used in most cardiac surgical procedures. However, other alternatives have proved useful. We analysed the perioperative results in a large series of patients undergoing coronary artery bypass (CABG) using cardiopulmonary bypass (CPB) and non-cardioplegic methods. METHODS: From January 1992 to October 2013, 8515 consecutive patients underwent isolated CABG with CPB without cardioplegia, under hypothermic ventricular fibrillation and/or an empty beating heart. The mean age was 61.9 ± 9.5 years, 12.4% were women, 26.3% diabetic, 64% hypertensive; and 9.6% had peripheral vascular disease, 7.8% cerebrovascular disease and 54.3% previous acute myocardial infarction (AMI). One-third of patients were in Canadian Cardiovascular Society Class III/IV. Three-vessel disease was present in 76.5% of the cases and 10.9% had moderate/severe left ventricle (LV) dysfunction (ejection fraction <40%). A multivariate analysis was made of risk factors associated to in-hospital mortality and three major morbidity complications [cerebrovascular accident, mediastinitis and acute kidney injury (AKI)], as well as for prolonged hospital stay. RESULTS: The mean CPB time was 58.2 ± 20.7 min. The mean number of grafts per patient was 2.7 ± 0.8 (arterial: 1.2 ± 0.5). The left internal thoracic artery (ITA) was used in 99.4% of patients and both ITAs in 23.1%. The in-hospital mortality rate was 0.7% (61 patients), inotropic support was required in 6.6% and mechanical support in 0.8, and 2.0% were re-explored for bleeding and 1.3% for sternal complications (mediastinitis, 0.8%). AKI, the majority transient, occurred in 1595 patients (18.9%). The incidence rates of stroke/transient ischemic attack (TIA) and acute myocardial infarction (AMI) were 2.6 and 2.5%, respectively, and atrial fibrillation/flutter occurred in 22.6% of cases. Age, LV dysfunction, non-elective surgery, previous cardiac surgery, peripheral vascular disease and CPB time were independent risk factors for mortality and major morbidity. The mean hospital stay was 7.2 ± 5.7 days. CONCLUSIONS: Isolated CABG with CPB using non-cardioplegic methods proved very safe, with low mortality and morbidity. These methods are simple and expeditious and remain as very useful alternative techniques of myocardial preservation.info:eu-repo/semantics/publishedVersio

Introduction: “Engaging with the writings of Denise Ferreira da Silva”

This is the final version. Available from Berghahn Journals via the DOI in this record. This interdisciplinary forum convenes a wide-ranging conversation centred around the writings of Denise Ferreira da Silva, whose unrelenting inquiry locates the workings of raciality in the very constitution of the modern subject, and, relatedly, global and historical consciousness. Da Silva’s excavation of raciality is consequently expansive in its implications and fundamental in its focus. Throughout her oeuvre, including Unpayable Debt (2022) and Toward a Global Idea of Race (2007), the crucial role of ‘law’ in legitimizing the modern, global racial and economic order remains a central problem. Da Silva’s decolonial agenda will meet with immediate sympathy from many in anthropology – a discipline that has engaged in sustained auto-critique of its own complicity in racialized colonial rule for decades (see Asad 1975; Lewis 1973; Pels and Salemink 2000; for a contemporary instance, cf. Price 2011). However, da Silva shows that any narrow focus on specifc direct linkages to related problematics of knowledge production occludes the constitutive role of modern subjectivity in the globalization of modern juridical rule itself. The ambition of da Silva’s excavation addresses, among other things, such recurring questions for legal anthropology as: ‘who has law and in what sense can diferent populations be said to have law?’; ‘how has the idea of “law” helped to reproduce the very world wrought by the post-Enlightenment?’; and ‘How might we test the limits of law?

Pharmacological Inhibition of FAK-Pyk2 Pathway Protects Against Organ Damage and Prolongs the Survival of Septic Mice

Sepsis and septic shock are associated with high mortality and are considered one of the major public health concerns. The onset of sepsis is known as a hyper-inflammatory state that contributes to organ failure and mortality. Recent findings suggest a potential role of two non-receptor protein tyrosine kinases, namely Focal adhesion kinase (FAK) and Proline-rich tyrosine kinase 2 (Pyk2), in the inflammation associated with endometriosis, cancer, atherosclerosis and asthma. Here we investigate the role of FAK-Pyk2 in the pathogenesis of sepsis and the potential beneficial effects of the pharmacological modulation of this pathway by administering the potent reversible dual inhibitor of FAK and Pyk2, PF562271 (PF271) in a murine model of cecal ligation and puncture (CLP)-induced sepsis. Five-month-old male C57BL/6 mice underwent CLP or Sham surgery and one hour after the surgical procedure, mice were randomly assigned to receive PF271 (25 mg/kg, s.c.) or vehicle. Twenty-four hours after surgery, organs and plasma were collected for analyses. In another group of mice, survival rate was assessed every 12 h over the subsequent 5 days. Experimental sepsis led to a systemic cytokine storm resulting in the formation of excessive amounts of both pro-inflammatory cytokines (TNF-α, IL-1β, IL-17 and IL-6) and the anti-inflammatory cytokine IL-10. The systemic inflammatory response was accompanied by high plasma levels of ALT, AST (liver injury), creatinine, (renal dysfunction) and lactate, as well as a high, clinical severity score. All parameters were attenuated following PF271 administration. Experimental sepsis induced an overactivation of FAK and Pyk2 in liver and kidney, which was associated to p38 MAPK activation, leading to increased expression/activation of several pro-inflammatory markers, including the NLRP3 inflammasome complex, the adhesion molecules ICAM-1, VCAM-1 and E-selectin and the enzyme NOS-2 and myeloperoxidase. Treatment with PF271 inhibited FAK-Pyk2 activation, thus blunting the inflammatory abnormalities orchestrated by sepsis. Finally, PF271 significantly prolonged the survival of mice subjected to CLP-sepsis. Taken together, our data show for the first time that the FAK-Pyk2 pathway contributes to sepsis-induced inflammation and organ injury/dysfunction and that the pharmacological modulation of this pathway may represents a new strategy for the treatment of sepsis

Carvacrol, (-)-borneol and citral reduce convulsant activity in rodents

Carvacrol, a monoterpenic phenol present in essential oils of the Labiatae family, has been used through the ages as a source of flavor in food and for medicinal purposes. Borneol is a monoterpene found in several species of Artemisia and Dipterocarpaceae, used for anxiety, pain and anesthesia in traditional Chinese. Citral, a mixture of two geometrical isomers (neral and geranial), is one of the most important compounds in some citrus oils and has central nervous system (CNS) properties. The anticonvulsant effect of carvacrol (CARV), (-)-borneol (BOR) and citral (CIT) was investigated in two animal models of epilepsy. Mice were pretreated with CARV, BOR or CIT (50, 100, and 200 mg/kg, i.p.) 30 min before pentylenetetrazole (PTZ) or maximal electroshock (MES) tests, the two most important animal epilepsy tests. The latency for development of convulsions and protection percentage was recorded. In order to investigate the involvement of GABAergic system, flumazenil was utilized. These monoterpenes, CARV in a higher, but not in a lower dose (p &lt; 0.001), BOR and CIT in all doses (p &lt; 0.05 or p &lt; 0.001), were capable of promoting an increase of latency for the development of convulsions induced by PTZ. Additionally, these compounds were efficient in preventing the tonic convulsions (p &lt; 0.05) induced by MES. However, the GABAergic neurotransmitter system might be involved, at least in BOR effects. Henceforth, our results suggest that CARV, BOR and CIT possess anticonvulsant activity effect against PTZ-induced convulsions and MES.Key words: Carvacrol, (-)-borneol, citral, anticonvulsant activit

Characterization of mycobacteria and mycobacteriophages isolated from compost at the São Paulo Zoo Park Foundation in Brazil and creation of the new mycobacteriophage Cluster U

Background: A large collection of sequenced mycobacteriophages capable of infecting a single host strain of Mycobacterium smegmatis shows considerable genomic diversity with dozens of distinctive types (clusters) and extensive variation within those sharing evident nucleotide sequence similarity. Here we profiled the mycobacterial components of a large composting system at the São Paulo zoo. Results: We isolated and sequenced eight mycobacteriophages using Mycobacterium smegmatis mc2155 as a host. None of these eight phages infected any of mycobacterial strains isolated from the same materials. The phage isolates span considerable genomic diversity, including two phages (Barriga, Nhonho) related to Subcluster A1 phages, two Cluster B phages (Pops, Subcluster B1; Godines, Subcluster B2), three Subcluster F1 phages (Florinda, Girafales, and Quico), and Madruga, a relative of phage Patience with which it constitutes the new Cluster U. Interestingly, the two Subcluster A1 phages and the three Subcluster F1 phages have genomic relationships indicating relatively recent evolution within a geographically isolated niche in the composting system. Conclusions: We predict that composting systems such as those used to obtain these mycobacteriophages will be a rich source for the isolation of additional phages that will expand our view of bacteriophage diversity and evolution

Inhibition of Macrophage Migration Inhibitory Factor Activity Attenuates Haemorrhagic Shock-Induced Multiple Organ Dysfunction in Rats

OBJECTIVE: The aim of this study was to investigate (a) macrophage migration inhibitory factor (MIF) levels in polytrauma patients and rats after haemorrhagic shock (HS), (b) the potential of the MIF inhibitor ISO-1 to reduce multiple organ dysfunction syndrome (MODS) in acute (short-term and long-term follow-up) HS rat models and (c) whether treatment with ISO-1 attenuates NF-κB and NLRP3 activation in HS. BACKGROUND: The MODS caused by an excessive systemic inflammatory response following trauma is associated with a high morbidity and mortality. MIF is a pleiotropic cytokine which can modulate the inflammatory response, however, its role in trauma is unknown. METHODS: The MIF levels in plasma of polytrauma patients and serum of rats with HS were measured by ELISA. Acute HS rat models were performed to determine the influence of ISO-1 on MODS. The activation of NF-κB and NLRP3 pathways were analysed by western blot in the kidney and liver. RESULTS: We demonstrated that (a) MIF levels are increased in polytrauma patients on arrival to the emergency room and in rats after HS, (b) HS caused organ injury and/or dysfunction and hypotension (post-resuscitation) in rats, while (c) treatment of HS-rats with ISO-1 attenuated the organ injury and dysfunction in acute HS models and (d) reduced the activation of NF-κB and NLRP3 pathways in the kidney and liver. CONCLUSION: Our results point to a role of MIF in the pathophysiology of trauma-induced organ injury and dysfunction and indicate that MIF inhibitors may be used as a potential therapeutic approach for MODS after trauma and/or haemorrhage

Male urine signals social rank in the Mozambique tilapia (Oreochromis mossambicus)

<p>Abstract</p> <p>Background</p> <p>The urine of freshwater fish species investigated so far acts as a vehicle for reproductive pheromones affecting the behaviour and physiology of the opposite sex. However, the role of urinary pheromones in intra-sexual competition has received less attention. This is particularly relevant in lek-breeding species, such as the Mozambique tilapia (<it>Oreochromis mossambicus</it>), where males establish dominance hierarchies and there is the possibility for chemical communication in the modulation of aggression among males. To investigate whether males use urine during aggressive interactions, we measured urination frequency of dye-injected males during paired interactions between size-matched males. Furthermore, we assessed urinary volume stored in the bladder of males in a stable social hierarchy and the olfactory potency of their urine by recording of the electro-olfactogram.</p> <p>Results</p> <p>Males released urine in pulses of short duration (about one second) and markedly increased urination frequency during aggressive behaviour, but did not release urine whilst submissive. In the stable hierarchy, subordinate males stored less urine than males of higher social rank; the olfactory potency of the urine was positively correlated with the rank of the male donor.</p> <p>Conclusion</p> <p>Dominant males store urine and use it as a vehicle for odorants actively released during aggressive disputes. The olfactory potency of the urine is positively correlated with the social status of the male. We suggest that males actively advertise their dominant status through urinary odorants which may act as a 'dominance' pheromone to modulate aggression in rivals, thereby contributing to social stability within the lek.</p