Bond strength of adhesives to dentin contaminated with smoker's saliva.

The purpose of this study was to determine the effects of contamination with smoker's and non-smoker's saliva on the bond strength of resin composite to superficial dentin using different adhesive systems. The interfacial structure between the resin and dentin was evaluated for each treatment using environmental scanning electron microscopy (ESEM). Freshly extracted human molars were ground with 600-grit SiC paper to expose the superficial dentin. Adhesives [One-Up-Bond-F-Plus (OUFP) and Adper-Prompt-L-Pop (APLP)] and resin composite (TPHSpectrum) were bonded to the dentin (n = 8/group, 180 total specimens) under five surface conditions: control (adhesive applied following manufacturers' instructions); saliva, then 5-s air dry, then adhesive; adhesive, saliva, 5-s air dry; adhesive, saliva, 5-s water rinse, 5-s air dry (ASW group); and adhesive, saliva, 5-s water rinse, 5-s air dry, reapply adhesive (ASWA group). After storage in water at 37 degrees C for 24 h, the specimens were debonded under tension at a speed of 0.5 mm/min. ESEM photomicrographs of the dentin/adhesive interfaces were taken. Mean bond strength ranged from 8.1 to 24.1 MPa. Fisher's protected least significant difference (P = 0.05) intervals for critical adhesive, saliva, and surface condition differences were 1.3, 1.3, and 2.1 MPa, respectively. There were no significant differences in bond strength to dentin between contamination by smoker's and nonsmoker's saliva, but bond strengths were significantly different between adhesive systems, with OUFP twice as strong as APLP under almost all conditions. After adhesive application and contamination with either smoker's or nonsmoker's saliva followed by washing and reapplication of the adhesive (ASWA group), the bond strength of both adhesive systems was the same as that of the control group.

Non-acute myocardial infarction-related causes of elevated high-sensitive troponin T in the emergency room: a cross-sectional analysis

To systematically investigate putative causes of non-coronary high-sensitive troponin elevations in patients presenting to a tertiary care emergency department. In this cross-sectional analysis, patients who received serial measurements of high-sensitive troponin T between 1 August 2010 and 31 October 2012 at the Department of Emergency Medicine were included. The following putative causes were considered to be associated with non-acute coronary syndrome-related increases in high-sensitive troponin T: acute pulmonary embolism, renal insufficiency, aortic dissection, heart failure, peri-/myocarditis, strenuous exercise, rhabdomyolysis, cardiotoxic chemotherapy, high-frequency ablation therapy, defibrillator shocks, cardiac infiltrative disorders (e.g., amyloidosis), chest trauma, sepsis, shock, exacerbation of chronic obstructive pulmonary disease, and diabetic ketoacidosis. During the study period a total of 1,573 patients received serial measurements of high-sensitive troponin T. Of these, 175 patients were found to have acute coronary syndrome leaving 1,398 patients for inclusion in the study. In 222 (30 %) of patients, no putative cause described in the literature could be attributed to the elevation in high-sensitive troponin T observed. The most commonly encountered mechanism underlying the troponin T elevation was renal insufficiency that was present in 286 patients (57 %), followed by cerebral ischemia in 95 patients (19 %), trauma in 75 patients (15 %) and heart failure in 41 patients (8 %). Non-acute coronary syndrome-associated elevation of high-sensitive troponin T levels is commonly observed in the emergency department. Renal insufficiency and acute cerebral events are the most common conditions associated with high-sensitive troponin T elevation.

Cardiomyocyte PDGFR-beta signaling is an essential component of the mouse cardiac response to load-induced stress.

PDGFR is an important target for novel anticancer therapeutics because it is overexpressed in a wide variety of malignancies. Recently, however, several anticancer drugs that inhibit PDGFR signaling have been associated with clinical heart failure. Understanding this effect of PDGFR inhibitors has been difficult because the role of PDGFR signaling in the heart remains largely unexplored. As described herein, we have found that PDGFR-beta expression and activation increase dramatically in the hearts of mice exposed to load-induced cardiac stress. In mice in which Pdgfrb was knocked out in the heart in development or in adulthood, exposure to load-induced stress resulted in cardiac dysfunction and heart failure. Mechanistically, we showed that cardiomyocyte PDGFR-beta signaling plays a vital role in stress-induced cardiac angiogenesis. Specifically, we demonstrated that cardiomyocyte PDGFR-beta was an essential upstream regulator of the stress-induced paracrine angiogenic capacity (the angiogenic potential) of cardiomyocytes. These results demonstrate that cardiomyocyte PDGFR-beta is a regulator of the compensatory cardiac response to pressure overload-induced stress. Furthermore, our findings may provide insights into the mechanism of cardiotoxicity due to anticancer PDGFR inhibitors.

Intraoperative Mechanical Measurement of Bone Quality With the DensiProbe.

Reduced bone stock can result in fractures that mostly occur in the spine, distal radius, and proximal femur. In case of operative treatment, osteoporosis is associated with an increased failure rate. To estimate implant anchorage, mechanical methods seem to be promising to measure bone strength intraoperatively. It has been shown that the mechanical peak torque correlates with the local bone mineral density and screw failure load in hip, hindfoot, humerus, and spine in vitro. One device to measure mechanical peak torque is the DensiProbe (AO Research Institute, Davos, Switzerland). The device has shown its effectiveness in mechanical peak torque measurement in mechanical testing setups for the use in hip, hindfoot, and spine. In all studies, the correlation of mechanical torque measurement and local bone mineral density and screw failure load could be shown. It allows the surgeon to judge local bone strength intraoperatively directly at the region of interest and gives valuable information if additional augmentation is needed. We summarize methods of this new technique, its advantages and limitations, and give an overview of actual and possible future applications.

The Freedom SOLO bovine pericardial stentless valve

Abstract: The third-generation bovine pericardium Freedom SOLO (FS) stentless valve emerged in 2004 as a modified version of the Pericarbon Freedom stentless valve and as a very attractive alternative to stented bioprostheses. The design, choice of tissue, and anticalcification treatment fulfill most, if not all, requirements for an ideal valve substitute. The FS combines the single-suture, subcoronary implantation technique with the latest-generation bovine pericardial tissue and novel anticalcification treatment. The design allows imitation of the native healthy valve through unrestricted adaption to the patient's anatomy, reproducing a normal valve/root complex. However, despite hemodynamic performance superior to stented valves, we are approaching a critical observation period as superior durability, freedom from structural valve deterioration, and nonstructural failure has not been proven as expected. However, optimal performance and freedom from structural valve deterioration depend on correct sizing and perfect symmetric implantation, to ensure low leaflet stress. Any malpositioning can lead to tissue fatigue over time. Furthermore, the potential for better outcomes depends on optimal patient selection and observance of the limitations for the use of stentless valves, particularly for the FS. Clearly, stentless valve implantation techniques are less reproducible and standardized, and require surgeon-dependent experience and skill. Regardless of whether or not stentless valve durability surpasses third-generation stented bioprostheses, they will continue to play a role in the surgical repertoire. This review intends to help practitioners avoid pitfalls, observe limitations, and improve patient selection for optimal long-term outcome with the attractive FS stentless valve.

TM6SF2 rs58542926 influences hepatic fibrosis progression in patients with non-alcoholic fatty liver disease.

Non-alcoholic fatty liver disease (NAFLD) is an increasingly common condition, strongly associated with the metabolic syndrome, that can lead to progressive hepatic fibrosis, cirrhosis and hepatic failure. Subtle inter-patient genetic variation and environmental factors combine to determine variation in disease progression. A common non-synonymous polymorphism in TM6SF2 (rs58542926 c.449 C>T, p.Glu167Lys) was recently associated with increased hepatic triglyceride content, but whether this variant promotes clinically relevant hepatic fibrosis is unknown. Here we confirm that TM6SF2 minor allele carriage is associated with NAFLD and is causally related to a previously reported chromosome 19 GWAS signal that was ascribed to the gene NCAN. Furthermore, using two histologically characterized cohorts encompassing steatosis, steatohepatitis, fibrosis and cirrhosis (combined n=1,074), we demonstrate a new association, independent of potential confounding factors (age, BMI, type 2 diabetes mellitus and PNPLA3 rs738409 genotype), with advanced hepatic fibrosis/cirrhosis. These findings establish new and important clinical relevance to TM6SF2 in NAFLD.

The Initial Slope of the Variogram, Foundation of the Trabecular Bone Score, Is Not or Poorly Associated With Vertebral Strength

Trabecular bone score (TBS) rests on the textural analysis of DXA to reflect the decay in trabecular structure characterising osteoporosis. Yet, its discriminative power in fracture studies remains incomprehensible as prior biomechanical tests found no correlation with vertebral strength. To verify this result possibly due to an unrealistic set-up and to cover a wide range of loading scenarios, the data from three previous biomechanical studies using different experimental settings was used. They involved the compressive failure of 62 human lumbar vertebrae loaded 1) via intervertebral discs to mimic the in vivo situation (“full vertebra”), 2) via the classical endplate embedding (“vertebral body”) or 3) via a ball joint to induce anterior wedge failure (“vertebral section”). HR-pQCT scans acquired prior testing were used to simulate anterior-posterior DXA from which areal bone mineral density (aBMD) and the initial slope of the variogram (ISV), the early definition of TBS, were evaluated. Finally, the relation of aBMD and ISV with failure load (Fexp) and apparent failure stress (σexp) was assessed and their relative contribution to a multi-linear model was quantified via ANOVA. We found that, unlike aBMD, ISV did not significantly correlate with Fexp and σexp, except for the “vertebral body” case (r2 = 0.396, p = 0.028). Aside from the “vertebra section” set-up where it explained only 6.4% of σexp (p = 0.037), it brought no significant improvement to aBMD. These results indicate that ISV, a replica of TBS, is a poor surrogate for vertebral strength no matter the testing set-up, which supports the prior observations and raises a fortiori the question of the deterministic factors underlying the statistical relationship between TBS and vertebral fracture risk.

Report of the WPA section of pharmacopsychiatry on the relationship of antiepileptic drugs with suicidality in epilepsy

INTRODUCTION This report from the World Psychiatric Association Section on Pharmacopsychiatry examines the possible relationship of antiepileptic drugs with suicide-related clinical features and behaviors in patients with epilepsy. MATERIALS AND METHODS A systematic review of the MEDLINE search returned 1039 papers, of which only 8 were considered relevant. A critical analysis of the Food and Drug Administration (FDA) report on the increase risk for patients under antiepileptics to manifest suicidality is also included in this report. RESULTS The analysis of these studies revealed that the data are not supportive of the presence of a "class effect" on suicide-related behavior; on the contrary, there are some data suggesting such an effect concerning treatment with topiramate, lamotrigine, and levetiracetam for which further research is needed. DISCUSSION For the majority of people with epilepsy, anticonvulsant treatment is necessary and its failure for any reason is expected to have deleterious consequences. Therefore, clinicians should inform patients and their families of this increased risk of suicidal ideation and behavior, but should not overemphasize the issue. Specific subgroups of patients with epilepsy might be at a higher risk, and deserve closer monitoring and follow-up. Future research with antiepileptics should specifically focus on depression and suicidal thoughts.

Minimal residual disease in cancer therapy - Small things make all the difference

Minimal residual disease (MRD) is a major hurdle in the eradication of malignant tumors. Despite the high sensitivity of various cancers to treatment, some residual cancer cells persist and lead to tumor recurrence and treatment failure. Obvious reasons for residual disease include mechanisms of secondary therapy resistance, such as the presence of mutant cells that are insensitive to the drugs, or the presence of cells that become drug resistant due to activation of survival pathways. In addition to such unambiguous resistance modalities, several patients with relapsing tumors do not show refractory disease and respond again when the initial therapy is repeated. These cases cannot be explained by the selection of mutant tumor cells, and the precise mechanisms underlying this clinical drug resistance are ill-defined. In the current review, we put special emphasis on cell-intrinsic and -extrinsic mechanisms that may explain mechanisms of MRD that are independent of secondary therapy resistance. In particular, we show that studying genetically engineered mouse models (GEMMs), which highly resemble the disease in humans, provides a complementary approach to understand MRD. In these animal models, specific mechanisms of secondary resistance can be excluded by targeted genetic modifications. This allows a clear distinction between the selection of cells with stable secondary resistance and mechanisms that result in the survival of residual cells but do not provoke secondary drug resistance. Mechanisms that may explain the latter feature include special biochemical defense properties of cancer stem cells, metabolic peculiarities such as the dependence on autophagy, drug-tolerant persisting cells, intratumoral heterogeneity, secreted factors from the microenvironment, tumor vascularization patterns and immunosurveillance-related factors. We propose in the current review that a common feature of these various mechanisms is cancer cell dormancy. Therefore, dormant cancer cells appear to be an important target in the attempt to eradicate residual cancer cells, and eventually cure patients who repeatedly respond to anticancer therapy but lack complete tumor eradication.

Overcoming Liability of Newness through Socialization : How Legitimation Strategies of a New Venture evolve

Liability of newness, the tendency of new ventures to die early after market entry, results from lacking legitimacy in their new cultural context and according failure to acquire resources. Based on a longitudinal case study on repeated resource acquisition attempts of a new venture, we found that overcoming liability of newness depended on the socialization of the new venture to the normative environment on which it depended on for resources. Over time and across repeated resource acquisition attempts, socialization - the process of learning the use of legitimate symbols and their culturally contingent meanings - enabled the new venture to become the skillful cultural operator on which legitimation and resource acquisition was contingent. From our data, 'Accumulating a repertoire of legitimate symbols' and 'Assimilating the evaluations of resource-holders' emerged as the two primary mechanisms for new venture socialization. The study's contributions to related literature and its broader theoretical implications are discussed

Induction of endoplasmic reticular stress by bortezomib: A novel therapeutic strategy for pancreatic cancer

Bortezomib (VELCADE™, formerly known as PS-341) is a selective and potent inhibitor of the proteasome that was recently FDA-approved for the treatment of multiple myeloma. Despite its success in multiple myeloma and progression into clinical trials for other malignancies, bortezomib's exact mechanism of action remains undefined. The major objective of this study was to evaluate the anticancer activity of this drug using in vitro and in vivo pancreatic cancer models and determine whether bortezomib-induced apoptosis occurs via induction of endoplasmic reticular (ER) stress. The investigation revealed that bortezomib inhibited tumor cell proliferation via abrogation of cdk activity and induced apoptosis in pancreatic cancer cell lines. I hypothesized that bortezomib-induced apoptosis was triggered by a large accumulation ubiquitin-conjugated proteins that resulted in ER stress. My data demonstrated that bortezomib induced a unique type of ER stress in that it inhibited PKR-like ER kinase (PERK) and subsequent phosphorylation of eukaryotic initiation factor 2α (eif2α), a key event in translational suppression. The combined effects of proteasome inhibition and the failure to attenuate translation resulted in an accumulation of aggregated proteins (proteotoxicity), JNK activation, cytochrome c release, caspase-3 activation, and DNA fragmentation. Bortezomib also enhanced apoptosis induced by other agents that stimulated the unfolded protein response (UPR), demonstrating that translational suppression is a critical cytoprotective mechanism during ER stress. Tumor cells attempt to survive bortezomib-induced ER stress by sequestering aggregated proteins into large structures, termed aggresomes. Since histone deacetylase 6 (HDAC6) is essential for aggresome formation, tumor cells may be sensitized to bortezomib-induced apoptosis by blocking HDAC function. My results demonstrated that HDAC inhibitors disrupted aggresome formation and synergized with bortezomib to induce apoptosis in pancreatic cancer or multiple myeloma cells in vitro and in orthotopic pancreatic tumors in vivo. Taken together, my data establish a mechanistic link between bortezomib-induced aggresome formation, ER stress, and apoptosis and identify a novel therapeutic strategy for the treatment of pancreatic cancer and other hematologic and solid malignancies. ^

Factors associated with hospital admission of elder cardiovascular patients in an emergency center

Context. Healthcare utilization of elder cardiovascular patients in United States will increase in near future, due to an aging population. This trend could burden urban emergency centers, which have become a source of primary care. ^ Objective. The objective of this study was to determine the association of age, gender, ethnicity, insurance and other presenting variables on hospital admission in an emergency center for elder cardiovascular patients. ^ Design, setting and participants. An anonymous retrospective review of emergency center patient login records of an urban emergency center in the years 2004 and 2005 was conducted. Elder patients (age ≥ 65 years) with cardiovascular disease (ICD91 390-459) were included. Multivariate logistic regression analysis was used to identify independent factors for hospital admission. Four major cardiovascular reasons for hospitalisation – ischemic heart disease, heart failure, hypertensive disorders and stroke were analysed separately. ^ Results. The number of elder patients in the emergency center is increasing, the most common reason for their visit was hypertension. Majority (59%) of the 12,306 elder patients were female. Forty five percent were uninsured and 1,973 patients had cardiovascular disease. Older age (OR 1.10; CI 1.02-1.19) was associated with a marginal increase in hospital admission in elder stroke patients. Elder females compared to elder males were more likely to be hospitalised for ischemic heart disease (OR 2.71; CI 1.22-6.00) and heart failure (OR 1.58; CI 1.001-2.52). Furthermore, insured elder heart failure patients (OR 0.54; CI 0.31-0.93) and elder African American heart failure patients (OR 0.32; CI 0.13-0.75) were less likely to be hospitalised. Ambulance use was associated with greater hospital admissions in elder cardiovascular patients studied, except for stroke. ^ Conclusion. Appropriate health care distribution policies are needed for elder patients, particularly elder females, uninsured, and racial/ethnic minorities. These findings could help triage nurse evaluations in emergency centers to identify patients who were more likely to be hospitalised to offer urgent care and schedule appointments in primary care clinics. In addition, health care plans could be formulated to improve elder primary care, decrease overcrowding in emergency centers, and decrease elder healthcare costs in the future. ^

Restauración de incisivo inferior fracturado mediante procedimientos de invasión mínima : reporte de un caso clínico

La odontología está inmersa en un nuevo paradigma: no se puede pensar en ninguna técnica restauradora sin que participen fenómenos de adhesión. El desarrollo de pernos de fibra de vidrio, sumado a los procedimientos de restauraciones adhesivas puede utilizarse como uno de los tantos recursos de la odontología de invasión mínima. Los pernos de fibra de vidrio ofrecen varias ventajas: comportamiento anisótropo, módulo de elasticidad bajo, buena resistencia mecánica, el lecho que aloja al perno de fibra requiere de una mínima preparación y se cementan con cementos adhesivos con carga, permitiendo de esta manera obtener una superficie homogénea que se interpone entre el perno de fibra y los tejidos dentales, conectándolo a los tejidos del conducto y sustituyendo mecánicamente la dentina. El caso clínico que se reporta se presentó para su resolución en la Clínica Integrada III F. O. UNCuyo durante el año lectivo 2009. El paciente presentaba una fractura amelodentinaria desde hacía cuatro años, con compromiso de la vitalidad y un proceso periapical. Durante los procedimientos endodónticos se realizó una perforación de la pared del conducto que se selló mediante la colocación de hidróxido de calcio y la obturación del mismo con conos de gutapercha. Se efectuó el seguimiento clínico y radiográfico del caso en donde se constató la reparación del proceso apical y luego se procedió a la restauración del elemento dentario con resinas compuestas con la ayuda de un poste de fibra de vidrio cementado con cemento resinoso. Dadas las características del tratamiento endodóntico realizado, se decidió dejar más porción del cono de gutapercha a pesar de lo aconsejado por numerosos autores, ya que de esta manera se aseguró el sellado de la perforación radicular para evitar de esta manera la nanofiltración hacia el interior del elemento dentario.

Trazo de un encuentro : los límites de la teoría frente a la práctica política en la lectura althusseriana de Maquiavelo

La producción teórica de Louis Althusser forja una alianza entre materialismo y política que asedia los espacios comunes de la tradición teórica marxista. Para Althusser, las posibilidades de actualizar la teoría, de transformarla en una herramienta útil para el análisis y la formulación de estrategias acordes a los problemas planteados por la coyuntura, implica un trabajo sobre los conceptos tal como se encontraban en la teoría marxista clásica. En la crisis manifiesta del movimiento comunista internacional se expresa el correlato entre impotencia teórica y fracaso político. Por esta razón, y aun considerando los cambios de acento que se registran a lo largo de sus escritos, su discurso insiste en señalar los bloqueos e insuficiencias conceptuales de la teoría, los “límites absolutos" que anidan en la adherencia idealista de parte de las formulaciones de Marx. En los límites que traza sobre la teoría marxista y llevando la alianza entre materialismo y política más allá de Marx, Althusser encuentra a Maquiavelo. Nos proponemos indagar cómo este rodeo permite a Althusser replantear, no sin desplazamientos, la relación entre teoría y práctica política, en el horizonte de volver a la primera permeable a los matices que la coyuntura imprime sobre la segunda.

Combatir al “enemigo interno" : el caso de la provincia de Mendoza (1973-1976)

Hacia mediados de la década del 70, la crisis institucional, la conflictividad social y el fracaso del intento redistribucionista del tercer gobierno peronista, llevaron a que se produjera una generalización de distintos procedimientos autoritarios que incluyeron el accionar represivo paraestatal y otras estrategias tales como reformas legales de corte represivo, un operativo de “limpieza" de militantes de izquierda al interior del peronismo, y modificaciones doctrinarias de reglamentos militares. En este trabajo, desde el campo de la historia reciente, y a partir del uso de fuentes escritas y orales, analizaremos en la trama local, de qué manera dichos factores se inscribieron y articularon en el proceso de represión paraestatal previo a la dictadura, en pos de profundizar en el estudio de las redes de relaciones implicadas en la prácticas coercitivas llevadas a cabo durante el tercer gobierno peronista.