The relevance of a right scale for sampling when studying high-resolution behavioral dynamics.

Many species used in behavioral studies are small vertebrates with high metabolic rates and potentially enhanced temporal resolution of perception. Nevertheless, the selection of an appropriate scales to evaluate behavioral dynamics has received little attention. Herein, we studied the temporal organization of behaviors at fine-grain (i.e. sampling interval ≤1s) to gain insight into dynamics and to rethink how behavioral events are defined. We statistically explored high-resolution Japanese quail (Coturnix japonica) datasets encompassing 17 defined behaviors. We show that for the majority of these behaviors, events last predominately <300ms and can be shorter than 70ms. Insufficient sampling resolution, even in the order of 1s, of behaviors that involve spatial displacement (e.g. walking) yields distorted probability distributions of event durations and overestimation of event durations. Contrarily, behaviors without spatial displacement (e.g. vigilance) maintain non-Gaussian, power-law-type distributions indicative of long-term memory, independently of the sampling resolution evaluated. Since data probability distributions reflect underlying biological processes, our results highlight the importance of quantification of behavioral dynamics based on the temporal scale pertinent to the species, and data distribution. We propose a hierarchical model that links diverse types of behavioral definitions and distributions, and paves the way towards a statistical framework for defining behaviors.

Effects of a differentiating therapy on cancer-stem-cell-driven tumors.

The growth of many solid tumors has been found to be driven by chemo- and radiotherapy-resistant cancer stem cells (CSCs). A suitable therapeutic avenue in these cases may involve the use of a differentiating agent (DA) to force the differentiation of the CSCs and of conventional therapies to eliminate the remaining differentiated cancer cells (DCCs). To describe the effects of a DA that reprograms CSCs into DCCs, we adapt a differential equation model developed to investigate tumorspheres, which are assumed to consist of jointly evolving CSC and DCC populations. We analyze the mathematical properties of the model, finding the equilibria and their stability. We also present numerical solutions and phase diagrams to describe the system evolution and the therapy effects, denoting the DA strength by a parameter adif. To obtain realistic predictions, we choose the other model parameters to be those determined previously from fits to various experimental datasets. These datasets characterize the progression of the tumor under various culture conditions. Typically, for small values of adif the tumor evolves towards a final state that contains a CSC fraction, but a strong therapy leads to the suppression of this phenotype. Nonetheless, different external conditions lead to very diverse behaviors. For microchamber-grown tumorspheres, there is a threshold in therapy strength below which both subpopulations survive, while high values of adif lead to the complete elimination of the CSC phenotype. For tumorspheres grown on hard and soft agar and in the presence of growth factors, the model predicts a threshold not only in the therapy strength, but also in its starting time, an early beginning being potentially crucial. In summary, our model shows how the effects of a DA depend critically not only on the dosage and timing of the drug application, but also on the tumor nature and its environment.

Coracoid tunnels in open and arthroscopic treatment of acromioclavicular dislocation: an experimental cadaveric study.

PURPOSE: Treatment of acromioclavicular joint (ACJ) dislocation is not encoded uniquely. Type I and II injuries are usually treated conservatively, while types IV, V and VI surgically. Controversy still exists over the treatment of type III injuries. In the operative approach, there is no agreement on the best surgical technique. Our purpose is to compare the mini-open and arthroscopic approach focusing on the evaluation of the anatomical precision of the coracoid drilling. METHODS: This is a controlled laboratory study. Ten fresh-frozen cadaveric shoulders were randomly assigned to the two techniques in order to compare them. We performed essential surgical gestures to drill the tunnel using MINAR® System (mini-open) and Dog-Bone® (ARTHREX, arthroscopic). The anatomical specimens were then subjected to CT-scan investigation. We statistically evaluated the precision of these two techniques analyzing DICOM files using two parameters. Parameter 1 evaluates the tunnel entry area on the superior side of the coracoid. Parameter 2 describes the orientation of the tunnel. RESULTS: There are no statistically significant differences (95% confidence level) between arthroscopic and mini-open approach about the precision in the location of the coracoid hole, regarding the entry area (p = 1.00) and the orientation (p = 0.196). CONCLUSION: The evidences collected enable the orthopedic surgeon to choose equally between the two techniques in the treatment of AC joint dislocation toward precision.

Joint fitting reveals hidden interactions in tumor growth.

Tumor growth is often the result of the simultaneous development of two or more cancer cell populations. Crucial to the system evolution are the interactions between these populations. To obtain information about these interactions we apply the recently developed vector universality (VUN) formalism to various instances of competition between tumor populations. The formalism allows us (a) to quantify the growth mechanisms of a HeLa cell colony, describing the phenotype switching responsible for its fast expansion, (b) to reliably reconstruct the evolution of the necrotic and viable fractions in both in vitro and in vivo tumors using data for the time dependences of the total masses alone, and (c) to show how the shedding of cells leading to subspheroid formation is beneficial to both the spheroid and subspheroid populations, suggesting that shedding is a strong positive influence on cancer dissemination.

Curative effect of the probiotic strain Lactobacillus fermentum L23 in a murine model of vaginal infection by Gardnerella vaginalis.

UNLABELLED: Bacterial vaginosis is a common vaginal infection characterized by changes in the vaginal microbiota. The objective of this work was to evaluate the colonization ability and curative effect of Lactobacillus fermentum L23 after vaginal administration in female BALB/c mice infected with Gardnerella vaginalis. One dose of Lact. fermentum L23 containing 10(9 ) CFU ml(-1) was administered locally in a murine vaginal model. L23 colonized the vaginal tract of BALB-c mice after one inoculation. The infection by G. vaginalis in a murine model was induced by vaginal administration of a 1 × 10(6 ) CFU ml(-1) suspension. Infection with the pathogen was observed in the vaginal tract for 4 days. At 144 h after inoculation, levels of 4 log10 CFU ml(-1) were observed. The curative effect of L23 was evaluated with one administration at 1 × 10(9 ) CFU ml(-1) 72 h after the inoculation with G. vaginalis. Lactobacillus fermentum L23 inhibited the growth of G. vaginalis. The results of suppression of G. vaginalis using different concentrations of L23 were favourable due that these concentrations are normally used in commercial formulas. The obtained results indicate that Lact. fermentum L23 inhibited the growth of G. vaginalis. Therefore, L23 might be used as a potential biotherapeutic agent for the elimination of this bacterium. SIGNIFICANCE AND IMPACT OF THE STUDY: The use of the probiotic strain Lactobacillus fermentum L23 as a biotherapeutic agent can be expected to prevent and treat genital infections, particularly recurrent bacterial vaginosis, with similar concentrations to those normally used in commercial formulas. It is likely that the use of this probiotic strain for the treatment of bacterial vaginosis will provide a natural and nontoxic treatment modality.

Effect of two probiotic strains of Lactobacillus on in vitro adherence of Listeria monocytogenes, Streptococcus agalactiae, and Staphylococcus aureus to vaginal epithelial cells.

The lactobacilli probiotics maintain a normal vaginal biota and prevent disease recurrence. This microorganisms form a pellicle on the vaginal epithelium that acts as a biologic barrier against colonization by pathogenic bacteria. In this paper were realized assays of exclusion, competition, and displacement. For these test, vaginal epithelial cells, two strains of lactobacilli and pathogenic bacteria (Staphylococcus aureus, Streptococcus agalactiae and Listeria monocytogenes) were used. The lactobacilli strains showed a great capacity of adherence, with a mean of 83.5 ± 26.67 Lactobacillus fermentum cells and 56.2 ± 20.87 Lactobacillus rhamnosus cells per vaginal epithelial cells. L. fermentum and L. rhamnosus were able to reduce the adherence of S. aureus, S. agalactiae and L. monocytogenes in a significant level in this assay (P < 0.01). The lactobacilli used in this study protect the vaginal epithelium through a series of barriers and interference mechanisms. The aim of present study was to assess the ability of vaginal Lactobacillus strains, selected for their probiotic properties, to block the adherence of pathogenic microorganisms in vitro by displacement, competition, and exclusion mechanisms.

Survey of Aspergillus section Flavi and aflatoxin B(1) in brewer's grain used as pig feedstuff in Córdoba, Argentina.

Brewing industry by-products are important animal feedstuff alternatives for local swine producers in Córdoba, Argentina. The high content of nutrients makes these by-products vulnerable to bacterial and fungal contamination. The objectives of the present study were (1) to determine the presence of Aspergillus section Flavi in brewer's grain used to feed pigs and (2) to evaluate the incidence of aflatoxin B(1) in the substrate. Total fungal count of most samples exceeded the levels proposed as feed quality limits, and most Aspergillus section Flavi strains found were able to produce high amounts of AFB(1) in vitro. However, the incidence of AFB(1) was low. The presence of contamination by aflatoxicogenic species in feedstuff might affect the productivity of swine producers and indirectly represents a public health issue.

Neonatal cutaneous disseminated aspergillosis in a preterm extremely-low-birth-weight infant with favourable outcome at 3-year follow-up: a case report.

Invasive disseminated neonatal aspergillosis is an uncommon disease, with only scattered reports in literature in the last few years. Here we report on a 25-week gestational age, 730 g at birth preterm female infant who developed on day-of-life 10 multiple cutaneous exhulcerative lesions in her right arm, trunk and abdomen. Early recognition and diagnosis of these lesions as a due to cutaneous initial symptom of cutaneous disseminated aspergillosis, as well as prompt treatment with Liposomal amphotericin B + Itraconazole, secured successful recovery from the systemic infection. Skin lesions healed without any surgical treatment. The infant was discharged in good health. Long-term follow-up at three years of age revealed normality of all neurodevelopmental and cognitive parameters. To our knowledge, this is one of the very few cases of survival, free from sequelae, for a preterm infant affected by neonatal cutaneous disseminated aspergillosis.

Ureaplasma urealyticum and Mycoplasma hominis sensitivity to bacteriocins produced by two Lactobacilli strains.

The purpose of the present study was to determine the inhibitory activities of two bacteriocins, produced by lactobacilli, against genital mycoplasmas. In this study, infections produced by genital mycoplasmas were studied; of these, 1.3% were caused by Mycoplasma hominis, 10.7% by Ureaplasma urealyticum and 5.6% by U. urealyticum + M. hominis. U. urealyticum was isolated from 75 out of 123 patients with genital mycoplasmas, while M. hominis was isolated from 9 patients (7.3%) and both U. urealyticum and M. hominis from 39 patients (31.7%). Bacteriocins, L23 and L60, produced by Lactobacillus fermentum and L. rhamnosus, respectively, appear to be two novel inhibitors of bacterial infection with potential antibacterial activity. Both bacteriocins proved to be active against 100% of strains tested; MICs of bacteriocin L23 ranged between 320 and 160 UA ml(-1) for 78% of the M. hominis strains and between 320 and 80 UA ml(-1) for 95% of the U. urealyticum strains. In addition, bacteriocin L60 was still active at 160 UA ml(-1) for a high percentage (56%) of M. hominis strains, and at 80 UA ml(-1) for 53% of the U. urealyticum strains. Interestingly, these antimicrobial substances produced by lactobacilli showed an inhibitory activity against genital mycoplasmas even when diluted. Altogether, our study indicates that the bacteriocins, L23 and L60, are good candidates for the treatment or prevention of genital infections in women.

Concurrent growth of phenotypic features: a phenomenological universalities approach.

Different physical features of an organism are often measured concurrently, because their correlations can be used as predictors of longevity, future health, or adaptability to an ecological niche. Since, in general, we do not know a priori if the temporal variations in the measured quantities are causally related, it may be useful to have a method that could help us to identify possible correlations and to obtain parameters that may vary from population to population. In this paper we develop a procedure that may detect underlying relationships. We do this by generalizing the recently introduced concept of phenomenological universalities to the complex field. In this generalization, allometric growth is described by a complex function, whose real and imaginary parts represent two phenotypic traits of the same organism. As particular solutions of the resulting problem, we obtain generalizations of the Gompertz and the von Bertalanffy-West growth equations. We then apply the procedure to two biological systems in order to show how to determine the existence of mutual interference between trait variations.

Neonatal lupus in triplet pregnancy of a patient with undifferentiated connective tissue disease evolving to systemic lupus erythematosus.

Pregnancy in patients suffering from undifferentiated connective tissue disease (UCTD) represents a risk situation for both the mother and the child. SSA/SSB autoantibodies can determine neonatal lupus (NL) in the foetus, regardless of the maternal disease. Furthermore, pregnancy increases the risk of flares and evolution to differentiated connective tissue disease (CTD). We report an uncommon case in which these complications occurred in a mother and in her foetuses. A 37-year-old woman affected by UCTD developed systemic lupus erythematosus (SLE) after her triplet pregnancy. The only manifestation of neonatal lupus we observed in the three newborns was SSA positivity associated with asymptomatic transient neutropenia.

Malignant pleural effusions: review of treatment and our experience.

More than half of patients with malignancy present with a pleural effusion at some time in their course. Recurrent malignant pleural effusions (MPE) impair functions and worsen the quality of life. Once a patient develops MPE, only mechanical drainage relieves pulmonary compression and dyspnea. Optimal treatment is however, still controversial. During January 2001 to January 2006, our group treated 48 patients with outpatient insertion of chronic indwelling pleural catheter (IPC), Pleurx (Pleurx, Surgimedics, Denver Biomaterials, Denver, CO, USA). Primary malignancy of 48 patients included: 27 lung cancers, 11 mesotheliomas, 5 breast cancers, 3 colon cancers, 2 pancreas cancers and 1 ovarian cancer. Eligibility for IPC required prior thoracentesis with histological confirmation of malignancy and chest roentgenogram evidence of effusion. All patients treated were made aware of their prior malignancy and positive cytology for MPE. Major complications, as systemic or pleural infections, were not registered. Permanence mean time of IPC was estimated as 88 days. Median time of draining interval was 7.0 days with maximum amount of effusion drained off being 1000 ml. Pleurodesis occurred in 23 of 48 (47.92%) patients with a mean time of pleurodesis being 43 days. IPC allows ambulatory treatment with a safe and effective drainage of MPE and is an alternative treatment to procedures in use.

Proton NMR relaxation of the dipolar quasi-invariants of nematic methyl deuterated para-azoxyanisole within the high-temperature Redfield relaxation theory.

The high-temperature Redfield spin-lattice relaxation theory is used for calculating the relaxation times of the different dipolar quasi-invariants in an eight-spin system which represents methyl deuterated para-azoxyanisole (PAAd6) in the nematic phase. According to previous experiments, this system can be considered as composed of weakly coupled pairs of strongly interacting spins, the ortho protons of the aromatic rings, thus, it possesses four quasi-invariants of the motion: Zeeman, dipolar intrapair and interpair, and singlet orders. We write the set of coupled differential equations which describe the relaxation of the generalized inverse spin temperatures of the four quasi-invariants. The relaxation constants are then calculated in terms of experimental two-spin spectral densities of the lattice motions. The relation between the multispin and the two-spin spectral densities is also deduced. Calculation shows that the Zeeman and singlet quasi-invariants are uncoupled from the dipolar ones, and that the relaxation time of the singlet order is much longer than those of the Zeeman and dipolar orders. The calculated cross relaxation rate between the dipolar orders through the lattice is small enough to be observable in the experiment. We also show that the nonsecular term associated with the collective motions dominates relaxation of the intrapair and interpair energies in PAAd6, while the local motions do not play a significant role, in qualitative agreement with the reported experimental behavior. The dipolar relaxation times predicted by the theory are significantly larger than the experimental ones, the difference being even more pronounced for the interpair quasi-invariant. We show that the discrepancy cannot be overcome neither by resorting to a realistic model for the spin system nor considering the various possible cross-relaxation pathways among the quasi-invariants. This feature points out the high- temperature approximation as a source of the discrepancy. We discuss the effect that slow and ultraslow molecular modes could have on the relaxation of the dipolar order.

Asymmetry alters immune-partner relationship.

Ambiguity in the mutual manipulation between the immune system, more appropriately termed integrated defense system, on the one hand and microbes and incipient tumors on the other, is to be taken into account. Such ambiguity may also apply to autoimmune infighting. Here we consider the association of its increased incidence with modern ways of living. Indifference about fate implies that longstanding, evolutionary regulated, immune/tissue relationships are no impediment for asymmetric estrangement promoted by ongoing globalization.

A possible relationship between Beckwith-Wiedemann syndrome and prune belly syndrome.

A new case of the association of the Beckwith-Wiedemann and prune belly syndrome is reported and the aetiology of the syndromes discussed.

High dose intravenous immunoglobulin repertoire versus anti-D. Disproportions in quantity and quality.

Here we consider certain therapeutic effects that intravenous administration of pooled high dose immunoglobulin and anti-D IgG share. Despite million-fold difference in doses such an effect occurs at least in idiopathic thrombocytopenic purpura (ITP). We postulate that spontaneous bleeding events may remit even when platelet numbers show refractoriness. We also mention the possible sparing of anti-D antibody-coated red blood cell (RBC) destruction and, finally, an acceleration of fibrotic involution. Fc receptors (FcRs) play a central role; beyond the well-established interactions with the immunoglobulin Fc fragment, FcRs are supposed to display special cognitive properties that enable them to pick out the therapeutic molecules from the recipient's IgG pool. Such subtle selection suggests some disarray in the host. On the other hand it may explain why the often-encouraging outcome of IVIG therapy remains unpredictable.

[Theory of training and quality of safety in health]. / Teoria della formazione e qualità della sicurezza in Sanità.

This article aims to define the concept of security, particularly in relation to concepts of risk, error, danger and adverse events. The authors go on to analyse the latest theory of adult training, applying it to healthcare safety whilst recognising that this is a complex facility. By using tools such as guidelines and risk management, the authors propose a new kind of corporate culture that enables certain initiatives, such as clinical governance and therefore learning organisation, to develop. This strategic organisation the company allows vital knowledge and experience, which lead to problem-solving and an increased guarantee of security for both internal and external clients, to become the common knowledge and property of the company as a whole and of all who operate in and around it.

Unconventional medicine teaching at the Universities of the European Union.

CONTEXT: The recent rapid increase in demand for and use of unconventional medicine requires an adequate medical education. In the United States, 64% of medical schools offer undergraduate courses. No information is available about similar courses at European universities. OBJECTIVES: To document the incidence of educational courses on unconventional medicine offered by the European universities and their topic content. DESIGN: Mail survey, which consisted of two questionnaires and was conducted in 1999 (January-June). The first questionnaire was sent to the universities' Rectorats, the second one to the faculties or lecturers indicated by the replies to the first questionnaire. PARTICIPANTS: The Universities listed by the Confederation of European Union Rectors' Conference. MAIN OUTCOME MEASURES: Courses offered at European Universities, both at medical faculties and at other faculties. RESULTS: Five hundred and fifty (550) universities were contacted. Replies were received from 326 (59%); 141 have a faculty of medicine and 107 (76%) of them replied. We also received answers from 29 faculties of health sciences. In addition we received 190 (50%) answers from 380 other miscellaneous universities. Courses on unconventional medicine were offered by 43 (40%) medical schools, 21 (72%) health sciences faculties, and by 15 (8%) other faculties. Topics covered encompassed a wide range of techniques (33), from homeopathy to shamanism. CONCLUSIONS: Unconventional medicine courses are widely represented at European universities. They cover a wide range of therapies. Many of them are used clinically. Research work is underway at several faculties.

Integrin function and regulation in development.

Integrins are a large family of membrane receptors, consisting of alpha and beta subunits, that play a pivotal role in the interaction of cells with the extracellular matrix. Such interaction regulates the organization of cells in organs and tissues during development as well as cell differentiation and proliferation. We have shown that unfertilized oocytes express integrins that might be important during fertilization. We also analyzed nervous system and muscle tissue development showing that integrin expression is precisely regulated during organization of these tissues. The results indicate that two distinct integrin alpha subunits mediate the outgrowth of processes in nerve and glial cells. Alpha1 integrin, a laminin receptor, is up-regulated by nerve growth factor and other differentiation stimuli and is involved in neurite extension by nerve cells. In contrast, process extension by glial cells is likely to involve the alphaV integrin. Moreover, the latter integrin subunit is also transiently expressed in muscle of the embryo body where it localizes predominantly at developing myotendinous junctions. After birth this integrin disappears and is substituted by the alpha7 subunit. At the same time, important changes also occur in the expression of the associated beta subunit. In fact, the beta1A isoform which is expressed in fetal muscles, is substituted by beta1D. These isoforms are generated by alternative splicing and differ in only a few amino acid residues at the COOH terminus of the protein. This region of the molecule is exposed at the cytoplasmic face of the plasma membrane and is connected to the actin filaments. Our results show that beta1D, which is expressed only in striated muscle tissues, binds to both cytoskeletal and extracellular matrix proteins with an affinity higher than beta1A. Thus, beta1D provides a stronger link between the cytoskeleton and extracellular matrix necessary to support mechanical tension during muscle contraction. These results indicate that cells can regulate their interactions with the extracellular matrix by changing their expression of alpha integrin subunits and thus ligand specificity, or by more subtle changes involving alternative usage of different cytoplasmic domains. The important role of both alpha and beta integrin subunit cytoplasmic domains during development is further illustrated by the analysis of targeted mutations which we have generated by homologous recombination in mice.

Distinct roles of the adaptor protein Shc and focal adhesion kinase in integrin signaling to ERK.

It has been proposed that integrins activate ERK through the adaptor protein Shc independently of focal adhesion kinase (FAK) or through FAK acting on multiple target effectors, including Shc. We show that disruption of the actin cytoskeleton by cytochalasin D causes a complete inhibition of FAK but does not inhibit Shc signaling and activation of ERK. We have then generated primary fibroblasts carrying a targeted deletion of the segment of beta(1) subunit cytoplasmic domain required for activation of FAK. Analysis of these cells indicates that FAK is not necessary for efficient tyrosine phosphorylation of Shc, association of Shc with Grb2, and activation of ERK in response to matrix adhesion. In addition, integrin-mediated activation of FAK does not appear to be required for signaling to ERK following growth factor stimulation. To examine if FAK could contribute to the activation of ERK in a cell type-specific manner through the Rap1/B-Raf pathway, we have used Swiss-3T3 cells, which in contrast to primary fibroblasts express B-Raf. Dominant negative studies indicate that Shc mediates the early phase and peak, whereas FAK, p130(CAS), Crk, and Rap1 contribute to the late phase of integrin-dependent activation of ERK in these cells. In addition, introduction of B-Raf enhances and sustains integrin-mediated activation of ERK in wild-type primary fibroblasts but not in those carrying the targeted deletion of the beta(1) cytoplasmic domain. Thus, the Shc and FAK pathways are activated independently and function in a parallel fashion. Although not necessary for signaling to ERK in primary fibroblasts, FAK may enhance and prolong integrin-mediated activation of ERK through p130(CAS), Crk, and Rap1 in cells expressing B-Raf.