Pericardial effusion in oncological patients: current knowledge and principles of management.

BACKGROUND: This article provides an up-to-date overview of pericardial effusion in oncological practice and a guidance on its management. Furthermore, it addresses the question of when malignancy should be suspected in case of newly diagnosed pericardial effusion. MAIN BODY: Cancer-related pericardial effusion is commonly the result of localization of lung and breast cancer, melanoma, or lymphoma to the pericardium via direct invasion, lymphatic dissemination, or hematogenous spread. Several cancer therapies may also cause pericardial effusion, most often during or shortly after administration. Pericardial effusion following radiation therapy may instead develop after years. Other diseases, such as infections, and, rarely, primary tumors of the pericardium complete the spectrum of the possible etiologies of pericardial effusion in oncological patients. The diagnosis of cancer-related pericardial effusion is usually incidental, but cancer accounts for approximately one third of all cardiac tamponades. Drainage, which is mainly attained by pericardiocentesis, is needed when cancer or cancer treatment-related pericardial effusion leads to hemodynamic impairment. Placement of a pericardial catheter for 2-5 days is advised after pericardial fluid removal. In contrast, even a large pericardial effusion should be conservatively managed when the patient is stable, although the best frequency and timing of monitoring by echocardiography in this context are yet to be established. Pericardial effusion secondary to immune checkpoint inhibitors typically responds to corticosteroid therapy. Pericardiocentesis may also be considered to confirm the presence of neoplastic cells in the pericardial fluid, but the yield of cytological examination is low. In case of newly found pericardial effusion in individuals without active cancer and/or recent cancer treatment, a history of malignancy, unremitting or recurrent course, large effusion or presentation with cardiac tamponade, incomplete response to empirical therapy with nonsteroidal anti-inflammatory, and hemorrhagic fluid at pericardiocentesis suggest a neoplastic etiology.

Fluorescence labeling methods influence the aggregation process of α-syn in vitro differently.

In a previous study, the coexistence of different aggregation pathways of insulin and ß-amyloid (Aß) peptides was demonstrated by correlative stimulated emission depletion (STED) microscopy and atomic force microscopy (AFM). This had been explained by suboptimal proteins labeling strategies that generate heterogeneous populations of aggregating species. However, because of the limited number of proteins considered, the failure of the fluorescent labeling that occurs in a large portion of the aggregating fibrils observed for insulin and Aß peptides, could not be considered a general phenomenon valid for all molecular systems. Here, we investigated the aggregation process of α-synuclein (α-syn), an amyloidogenic peptide involved in Parkinson's disease, which is significantly larger (MW ∼14 kDa) than insulin and Aß, previously investigated. The results showed that an unspecific labeling procedure, such as that previously adopted for shorter proteins, reproduced the coexistence of labeled/unlabeled fibers. Therefore, a site-specific labeling method was developed to target a domain of the peptide scarcely involved in the aggregation process. Correlative STED-AFM illustrated that all fibrillar aggregates derived from the aggregation of α-syn at the dye-to-protein ratio of 1 : 22 were fluorescent. These results, demonstrated here for the specific case of α-syn, highlight that the labeling artifacts can be avoided by careful designing the labeling strategy for the molecular system under investigation. The use of a label-free correlative microscopy technique would play a crucial role in the control of the setting of these conditions.

Effects of ensiling time on corn silage starch ruminal degradability evaluated in situ or in vitro.

Accurate measurements of concentration and ruminal degradability of corn silage starch is necessary for formulation of diets that meet the energy requirements of dairy cows. Five corn silage hybrids ensiled for 0 (unfermented), 30, 60, 120, and 150 d were used to determine the effects of ensiling time on starch degradability of corn silage. In addition, the effects of grind size of silage samples on 7-h in vitro starch degradability and the relationship between in vitro, in situ and near-infrared reflectance spectroscopy (NIRS) starch degradability were studied. In situ disappearance of corn silage starch increased from 0 to 150 d of ensiling, primarily as a result of an increase in the washout or rapidly degraded fraction of starch, particularly during the first 60 d of ensiling. When analyzed in vitro and by NIRS, ensiling time increased corn silage starch degradability either linearly or to a greater extent during the first 2 mo of ensiling. Differences in in situ starch disappearance among corn silage hybrids were apparent during the first 2 mo of ensiling but were attenuated as silages aged. No differences among hybrids were detected using a 7-h in vitro starch digestibility approach. Results from the in vitro subexperiment indicate that 7-h in vitro starch degradability was increased by reducing grind size of corn silage from 4 to 1 mm, regardless of ensiling duration. Fine grinding corn silages samples (i.e., 1-mm sieve) allowed distinguishing low- from medium- and high-starch degradability rated hybrids. Correlations among in situ, in vitro and NIRS measurements for starch degradability were medium to high (r ≥0.57); however, agreement among methods was low (concordance correlation coefficient ≤0.15). In conclusion, ensiling time linearly increased degradation rate of corn silage resulting in greater in situ starch disappearance after 150 d of ensiling. Reductions in grind size from 4 to 1 mm resulted in greater in vitro starch degradability, regardless of ensiling duration. Strong correlation but low agreement between starch degradability methods suggest that absolute estimations of corn silage starch degradability will vary, but all methods can be used to assess the effect of ensiling time on starch degradability.

Psychobiological evidence of the stress resilience fostering properties of a cosmetic routine.

Everyday life psychosocial stressors contribute to poor health and disease vulnerabilty. Means alternative to pharmacotherapy that are able to foster stress resilience are more and more under the magnifying glass of biomedical research. The aim of this study was to test stress resilience fostering properties of the self-administration of a cosmetic product enriched with essential oils. On day 0, fourty women, 25-50 years old, self-administered both the enriched cosmetic product (ECP) and a placebo one (PCP). Then, women were randomized for daily self-administration (from day 1 to 28) of either ECP (n = 20) or PCP (n = 20). On day 29, subjects underwent a psychosocial stress test (PST). Autonomic (heart rate and its variability) and neuroendocrine (salivary cortisol) parameters were assessed both on day 0 and 29. All subjects filled a number of psychological questionnaires in order to quantify anxiety, perceived stress, and mood profile, and were videorecorded during PST for non-verbal behavior evaluation. A single application of ECP produced an acute potentiation of cardiac parasympathetic modulation, which was not observed when placebo was used. Prolonged self-administration of ECP induced: (i) a dampening of the cortisol rise produced by PST, (ii) a reduction of state anxiety, (iii) a favorable change in mood profile, and (iv) a reduction of non-verbal behavior patterns that signal anxiety, motivational conflict and avoidance. In conclusion, this study suggests that the self-administration of a cosmetic cream enriched with essential oils should be considered as a stress resilience fostering strategy due to its favorable physiological, neuroendocrine and psychological effects.

Effects of ensiling time on corn silage neutral detergent fiber degradability and relationship between laboratory fiber analyses and in vivo digestibility.

Accurate analysis of degradability of silage neutral detergent fiber (NDF) is important for diet formulation and to predict lactational performance of dairy cows. In this study, 5 corn silage hybrids ensiled for 0 (unfermented), 30, 60, 120, and 150 d were used to determine the effects of ensiling time on silage neutral detergent fiber degradability (NDFD) and to assess the relationships between near-infrared reflectance spectroscopy (NIR) NDF-related analyses and in situ NDFD variables. In addition, the relationships between dietary concentration of indigestible NDF, 288-h incubation (iNDF288), or undegraded NDF, 240-h incubation (uNDF240), and in vivo total-tract apparent organic matter and NDF digestibility were studied in total mixed ration samples from 16 experiments with lactating dairy cows. Ensiling time had no effect on silage NDF concentration; however, the ratio of acid detergent fiber ÷ NDF increased, and estimated hemicellulose concentration decreased quadratically with ensiling time. Also, concentration of NDF-bound protein decreased, and that of lignin increased linearly with ensiling time. These changes in silage fiber composition resulted in a linear decrease in in situ effective degradability of silage NDF with increasing ensiling time. The indigestible fraction of NDF and concentration of structural carbohydrates were not affected by ensiling time. Correlations of in situ NDFD variables with laboratory NIR NDFD analyses were weak to moderate. The relationship of corn silage uNDF240 with lignin concentration or 30-h NDFD (all NIR analyses) was remarkably good (R2 = 0.73 and 0.88, respectively). The relationship between in situ iNDF288 concentration (but not uNDF240) and in vivo total-tract apparent digestibility of dietary organic matter and NDF was good (R2 = 0.72 and 0.80, respectively). In conclusion, in situ degradability of silage NDF linearly decreased from 0 to 150 d ensiling time, primarily caused by a decrease in concentrations of hemicellulose and NDF-bound protein. In situ NDF degradability measurements and common laboratory NIR NDF-related analyses were generally poorly correlated. We found a good relationship between in vivo NDF digestibility and dietary concentration of iNDF288 determined in situ, but the relationship with uNDF240 was poor.

Influence of substrate stiffness on human induced pluripotent stem cells: preliminary results.

Skeletal muscle differentiation was proven to be influenced by changes in the substrate stiffness. However, a lack of knowledge features this field, concerning skeletal muscle tissues obtained from human induced pluripotent stem cells. Here we report the fabrication of polydimethylsiloxane-based substrates in a range of stiffness values from 3.5 to 141 kPa and the response of human induced pluripotent stem cells cultured on them for 5 days. The substrates were able to sustain cell adhesion and proliferation throughout the whole period. An inversely proportional relationship (although not significant) was found between the proliferation rate and the substrate stiffness. Initial analyses of iPSCs skeletal muscle differentiation shown no influences on markers of the early stages. These results lay the foundations for further studies on the influence of extrinsic mechanical stimuli on induced pluripotent stem cells-derived skeletal muscle tissues.

GRP78 clustering at the cell surface of neurons transduces the action of exogenous alpha-synuclein.

Mutation or multiplication of the alpha-synuclein (Syn)-encoding gene is frequent cause of early onset Parkinson's disease (PD). Recent evidences point to the pathogenic role of excess Syn also in sporadic PD. Syn is a cytosolic protein, which has been shown to be released from neurons. Here we provide evidence that extracellular Syn induces an increase in surface-exposed glucose-related protein of 78 kDa (GRP78), which becomes clustered in microdomains of the neuronal plasma membrane. Upon interacting with Syn, GRP78 activates a signaling cascade leading to cofilin 1 inactivation and stabilization of microfilaments, thus affecting morphology and dynamics of actin cytoskeleton in cultured neurons. Downregulation of GRP78 abolishes the activity of exogenous Syn, indicating that it is the primary target of Syn. Inactivation of cofilin 1 and stabilization of actin cytoskeleton are present also in fibroblasts derived from genetic PD patients, which show a dramatic increase in stress fibers. Similar changes are displayed by control cells incubated with the medium of PD fibroblasts, only when Syn is present. The accumulation of Syn in the extracellular milieu, its interaction with the plasma membrane and Syn-driven clustering of GRP78 appear, therefore, responsible for the dysregulation of actin turnover, leading to early deficits in synaptic function that precede neurodegeneration.

AFM characterization of biomolecules in physiological environment by an advanced nanofabricated probe.

Many relevant questions in biology and medicine require both topography and chemical information with high spatial resolution. Several biological events that occur at the nanometer scale level need to be investigated in physiological conditions. In this regard Atomic Force Microscopy (AFM) is one of the most powerful tools for label-free nanoscale characterization of biological samples in liquid environment. Recently, the coupling of Raman spectroscopy to scanning probe microscopies has opened new perspectives on this subject; however, the coupling of quality AFM spectroscopy with Raman spectroscopy in the same probe is not trivial. In this work we report about the AFM capabilities of an advanced high-resolution probe that has been previously nanofabricated by our group for coupling with Raman spectroscopy applications. We investigate its use for liquid AFM measurements on biological model samples like lipid bilayers, amyloid fibrils, and titin proteins. We demonstrate topography resolution down to nanometer level, force measurement and stable imaging capability. We also discuss about its potential as nanoscale chemical probe in liquid phase.

Inhibiting effect of α(s1)-casein on Aß(1-40) fibrillogenesis.

BACKGROUND: α(s1)-Casein is one of the four types of caseins, the largest protein component of bovine milk. The lack of a compact folded conformation and the capability to form micelles suggest a relationship of α(s1)-casein with the class of the intrinsically disordered (or natively unfolded) proteins. These proteins are known to exert a stabilizing activity on biomolecules through specific interaction with hydrophobic surfaces. In the present work we focused on the effect of α(s1)-casein on the fibrillogenesis of 1-40 ß-amyloid peptide, involved in Alzheimer's disease. METHODS: The aggregation kinetics of ß-peptide in presence and absence of α(s1)-casein was followed under shear at 37°C by recording the Thioflavine fluorescence, usually taken as an indicator of fibers formation. Measurements of Static and Dynamic Light Scattering, Circular Dichroism, and AFM imaging were done to reveal the details of α(s1)-casein-Aß(1-40) interaction. RESULTS AND DISCUSSIONS: α(s1)-Casein addition sizably increases the lag-time of the nucleation phase and slows down the entire fibrillization process. α(s1)-Casein sequesters the amyloid peptide on its surface thus exerting a chaperone-like activity by means a colloidal inhibition mechanism. GENERAL SIGNIFICANCE: Insights on the working mechanism of natural chaperones in preventing or controlling the amyloid aggregation.

The grey mouse lemur: a non-human primate model for ageing studies.

The use of non-human primate models is required to understand the ageing process and evaluate new therapies against age-associated pathologies. The present article summarizes all the contributions of the grey mouse lemur Microcebus murinus, a small nocturnal prosimian primate, to the understanding of the mechanisms of ageing. Results from studies of both healthy and pathological ageing research on the grey mouse lemur demonstrated that this animal is a unique model to study age-dependent changes in endocrine systems, biological rhythms, thermoregulation, sensorial, cerebral and cognitive functions.

Force spectroscopy as a tool to investigate the properties of supported lipid membranes.

Solid supported lipid bilayers (SLB) are extensively used as a model for the investigation of cell membranes in a variety of spectroscopic and biophysical methods. It is nevertheless well known that the interaction with the solid substrate, such as mica or silicon, influences the properties of the membranes. In this article we have employed atomic force microscopy (AFM) in force spectroscopy mode (FS) to investigate the local mechanical properties of lipid membranes supported on mica and on polymer cushion. The lipid double layers were obtained by fusion of unilamellar vesicle of phospholipids. The polymer support was created by self-assembly of charged polyelectrolytes. Force spectroscopy provided information about the breakthrough force, the breakthrough depth, and the sample adhesion. A batch analysis algorithm to process high-resolution force mapping was developed. The breakthrough force to indent the bilayers down to the support and the adhesion force were measured as a function of the membrane charge. The comparison of the data obtained from SLB on mica and from bilayers on polymer cushion provides direct evidence about the influence of the substrate on the local mechanic properties of the membrane. As a major result, the yield force distribution of membranes on polymer cushion was bimodal, compared to the unimodal distribution obtained on mica.

Contaminación de fórmulas infantiles en polvo / Contaminations the formula infant power

En los últimos años se han reportado un número importante de infecciones severas por la bacteria Enterobacter Sakazakii. La mayoría de los casos ha sido descripta en neonatos, asociados a sepsis, meningitis o enterocolitis necrotizante y con elevados índices de mortalidad. Aunque el reservorio es desconocido, en el análisis de los factores de riesgo solamente el uso de fórmulas infantiles en polvo ha tenido una asociación significativa con la infección o colonización por dicha bacteria. A la luz de estos hallazgos epidemiológicos, la FDA ha recomendado a los profecionales de la salud evitar el uso de fórmulas infantiles en polvo en unidades de cuidado intensivo neonatal

Contaminación de fórmulas infantiles en polvo / Contaminations the formula infant power

En los últimos años se han reportado un número importante de infecciones severas por la bacteria Enterobacter Sakazakii. La mayoría de los casos ha sido descripta en neonatos, asociados a sepsis, meningitis o enterocolitis necrotizante y con elevados índices de mortalidad. Aunque el reservorio es desconocido, en el análisis de los factores de riesgo solamente el uso de fórmulas infantiles en polvo ha tenido una asociación significativa con la infección o colonización por dicha bacteria. A la luz de estos hallazgos epidemiológicos, la FDA ha recomendado a los profecionales de la salud evitar el uso de fórmulas infantiles en polvo en unidades de cuidado intensivo neonatal

Contaminación de fórmulas infantiles en polvo / Contamination of infant formulas in powder

En los últimos años se han reportado un número importante de infecciones severas por la bacteria Enterobacter Sakazakii. La mayoría de los casos ha sido descripta en neonatos, asociados a sepsis, meningitis o enterocolitis necrotizante y con elevados índices de mortalidad. Aunque el reservorio es deconocido, en el análisis de los factores de riesgo solamente el uso de fórmulas infantiles en polvo ha tenido una asociación significativa con la infección o colonización por dicha bacteria. A la luz de estos hallazgos epidemiológicos, la FDA ha recomendado a los profesionales de la salud evitar el uso de fórmulas infantiles en polvo en unidades de cuidado intensivo neonatal.

Contaminación de fórmulas infantiles en polvo / Contamination of infant formulas in powder

En los últimos años se han reportado un número importante de infecciones severas por la bacteria Enterobacter Sakazakii. La mayoría de los casos ha sido descripta en neonatos, asociados a sepsis, meningitis o enterocolitis necrotizante y con elevados índices de mortalidad. Aunque el reservorio es deconocido, en el análisis de los factores de riesgo solamente el uso de fórmulas infantiles en polvo ha tenido una asociación significativa con la infección o colonización por dicha bacteria. A la luz de estos hallazgos epidemiológicos, la FDA ha recomendado a los profesionales de la salud evitar el uso de fórmulas infantiles en polvo en unidades de cuidado intensivo neonatal. (AU)

[Quality of life in patients with temporomandibular disorders]. / Qualità della vita nei pazienti affetti da disordini temporomandibolari.

AIM: Oral disorders have a psycho-social impact on the quality of life, that can be measured with instruments as the Oral Health Impact Profile questionnaire (OHIP). Using the OHIP, we evaluated if and how the orofacial pain can affect the quality of life in temporomandibular disorders (TMD) patients. METHODS: A transversal case-control study was carried out. Study subjects were patients referred to the Section of Prosthetic Dentistry and Temporomandibular Disorders of the University of Pavia (Italy). Subjects were recruited sequentially until the target of 124. The controls were 61 "pain free" subjects, who were recruited from the same clinic. In analyzing the data, the chi squared test was used for categorical data, and t test and one-way analysis of variance were used for numerical scores. RESULTS: The subjects in this study were predominantly females (83.9%). The mean age of subjects was 35.1 years (standard deviation= 14.0). The most frequently reported symptoms were pain in the temporomandibular joint (TMJ) (87.1%). The data showed that orofacial pain had an important impact on daily life (p<0.05) and that its most common outcomes were psychological. CONCLUSIONS: Comparison with a "pain free" population clearly indicated that orofacial pain and associated symptoms negatively affect the quality of life of TMD patients.

Expression of adhesion molecules and functional stimulation in human neutrophils: modulation by GM-CSF and role of the Bcr gene.

Although devoid of proliferative capacity, polymorphonuclear neutrophils (PMN) express receptors for haemopoietic growth factors and need growth factors for survival and functional stimulation. This study showed that in vitro treatment of human PMN with GM-CSF for up to 48 h increases cell surface expression of the beta 2-integrin molecules CD11b/CD18 and CD11c/CD18 and of the receptor for the chemotactic peptide fMLP. Such modifications are usually expression of PMN activation. PMN treated with GM-CSF also displayed increased phagocytosis of latex particles and enhanced oxidative burst and superoxide anion release. Since integrins mediate PMN adhesion to endothelium, homotypic adhesion, chemotaxis/phagocytosis and the triggering of respiratory burst, our results suggested that functional stimulation of PMN persisted following prolonged exposure of PMN to growth factors and that it was not a temporary phenomenon which lasted only for the first 12-24 h of treatment. We also used oligonucleotides antisense to the Bcr gene mRNA to inhibit expression of the gene and evaluate its function in PMN, following the recent observation that PMN from Bcr-null mutant mice produced increased amounts of reactive oxygen metabolites upon activation. The antisense oligonucleotides had no effect on the parameters investigated. This may indicate that increased production of O2 by neutrophils in which the Bcr gene is not expressed requires either that gene expression is absent in the earlier stages of myeloid differentiation/maturation, so that when inhibition occurs in the terminally differentiated neutrophils their functional status is no longer influenced, or that the residual low-level expression of the gene which may be present in the antisense-treated cells is sufficient to provide a normal response to stimulation.

Increased expression of CD11b/CD18 on phagocytes in ischaemic disease: a bridge between inflammation and coagulation.

The aim of this study was to assess the expression of CD11b/CD18 integrin adhesion molecules on the phagocytes of patients with ischaemic diseases, and to evaluate the concentration of soluble adhesion molecules that are released from endothelium (sICAM-1) and from phagocytes (sL-selectin). A total of 370 patients were enrolled: 120 with coronary artery disease (CAD); 50 with peripheral artery occlusive disease (PAOD); and 200 control subjects with no clinical manifestations of ischaemic disease. CD11b/CD18 integrin was detected by flow cytometry, whereas sL-selectin and sICAM-1 concentrations were detected using a sandwich-type immunoassay. CD11b/CD18 integrin expression was found to be higher in the patients with ischaemic disease than in the control subjects (P < 0.001). The PAOD patients had higher values of CD11b/CD18 integrin than the CAD ones (P < 0.01). The concentration of soluble adhesion molecules did not show any significant differences within the three groups (P = NS). The high expression of CD11b/CD18 integrin in ischaemic disease patients may depend on the increased, but probably stable, cytokine network that has been demonstrated to occur in chronic ischaemic diseases: the difference observed between PAOD and CAD patients could be the consequence of higher inflammatory activation probably resulting from the greater extent of the atherosclerotic process in PAOD, or of the more localized ischaemic area in CAD patients. CD11b/CD18 can therefore be considered a marker of chronic phagocyte activation during ischaemic disease. On the other hand, sICAM and sL-selectin concentrations were found to be within the normal range; they have recently been considered as a marker for acute ischaemic events and acute inflammatory process activation. Our results confirm that in uncomplicated atherosclerosis no acute inflammatory process activation should occur.