A viscoactive constitutive modeling framework with variational updates for the myocardium.

We present a constitutive modeling framework for contractile cardiac mechanics by formulating a single variational principle from which incremental stress-strain relations and kinetic rate equations for active contraction and relaxation can all be derived. The variational framework seamlessly incorporates the hyperelastic behavior of the relaxed and contracted tissue along with the rate - and length - dependent generation of contractile force. We describe a three-element, Hill-type model that unifies the active tension and active deformation approaches. As in the latter approach, we multiplicatively decompose the total deformation gradient into active and elastic parts, with the active deformation parametrizing the contractile Hill element. We adopt as internal variables the fiber, cross-fiber, and sheet normal stretch ratios. The kinetics of these internal variables are modeled via definition of a kinetic potential function derived from experimental force-velocity relations. Additionally, we account for dissipation during tissue deformation by adding a Newtonian viscous potential. To model the force activation, the kinetic equations are coupled with the calcium transient obtained from a cardiomyocyte electrophysiology model. We first analyze our model at the material point level using stress and strain versus time curves for different viscosity values. Subsequently, we couple our constitutive framework with the finite element method (FEM) and study the deformation of three-dimensional tissue slabs with varying cardiac myocyte orientation. Finally, we simulate the contraction and relaxation of an ellipsoidal left ventricular model and record common kinematic measures, such as ejection fraction, and myocardial tissue volume changes.

Statistical Physics of Viral Capsids with Broken Symmetry.

We present a model to understand quantitatively the role of symmetry breaking in assembly of macromolecular aggregates in general, and the protein shells of viruses in particular. A simple dodecahedral lattice model with a quadrupolar order parameter allows us to demonstrate how symmetry breaking may reduce the probability of assembly errors and, consequently, enhance assembly efficiency. We show that the ground state is characterized by large-scale cooperative zero-energy modes. In analogy with other models, this suggests a general physical principle: the tendency of biological molecules to generate symmetric structures competes with the tendency to break symmetry in order to achieve specific functional goals.

Theta oscillons in behaving rats.

Recently discovered constituents of the brain waves-the oscillons-provide high-resolution representation of the extracellular field dynamics. Here we study the most robust, highest-amplitude oscillons that manifest in actively behaving rats and generally correspond to the traditional θ-waves. We show that the resemblances between θ-oscillons and the conventional θ-waves apply to the ballpark characteristics-mean frequencies, amplitudes, and bandwidths. In addition, both hippocampal and cortical oscillons exhibit a number of intricate, behavior-attuned, transient properties that suggest a new vantage point for understanding the θ-rhythms' structure, origins and functions. We demonstrate that oscillons are frequency-modulated waves, with speed-controlled parameters, embedded into a noise background. We also use a basic model of neuronal synchronization to contextualize and to interpret the observed phenomena. In particular, we argue that the synchronicity level in physiological networks is fairly weak and modulated by the animal's locomotion.

Theta oscillons in behaving rats.

Recently discovered constituents of the brain waves-the oscillons-provide high-resolution representation of the extracellular field dynamics. Here we study the most robust, highest-amplitude oscillons that manifest in actively behaving rats and generally correspond to the traditional θ-waves. We show that the resemblances between θ-oscillons and the conventional θ-waves apply to the ballpark characteristics-mean frequencies, amplitudes, and bandwidths. In addition, both hippocampal and cortical oscillons exhibit a number of intricate, behavior-attuned, transient properties that suggest a new vantage point for understanding the θ-rhythms' structure, origins and functions. We demonstrate that oscillons are frequency-modulated waves, with speed-controlled parameters, embedded into a noise background. We also use a basic model of neuronal synchronization to contextualize and to interpret the observed phenomena. In particular, we argue that the synchronicity level in physiological networks is fairly weak and modulated by the animal's locomotion.

A novel HLA allele, HLA-A*02:393, identified in a two generation Italian family.

HLA-A*02:393 differs by a single nucleotide substitution from both A*02:26 (A524G) and from A*02:40:01 (T527A).

Discrete Structure of the Brain Rhythms.

Neuronal activity in the brain generates synchronous oscillations of the Local Field Potential (LFP). The traditional analyses of the LFPs are based on decomposing the signal into simpler components, such as sinusoidal harmonics. However, a common drawback of such methods is that the decomposition primitives are usually presumed from the onset, which may bias our understanding of the signal's structure. Here, we introduce an alternative approach that allows an impartial, high resolution, hands-off decomposition of the brain waves into a small number of discrete, frequency-modulated oscillatory processes, which we call oscillons. In particular, we demonstrate that mouse hippocampal LFP contain a single oscillon that occupies the θ-frequency band and a couple of γ-oscillons that correspond, respectively, to slow and fast γ-waves. Since the oscillons were identified empirically, they may represent the actual, physical structure of synchronous oscillations in neuronal ensembles, whereas Fourier-defined "brain waves" are nothing but poorly resolved oscillons.

Prophylactic antibiotics in soft-tissue procedures in children with cerebral palsy.

PURPOSE: Data on the benefits of perioperative prophylactic antibiotics in the paediatric population are lacking. In this study, we aimed to assess the rate of infection after isolated soft-tissue procedures in patients with cerebral palsy with and without preoperative prophylactic antibiotics between 2009 and 2015. METHODS: We reviewed the records of all children with cerebral palsy who underwent isolated soft-tissue procedures (on the upper and lower limb) at our hospital between 2009 and 2015. Children with at least 30-day postoperative follow-up were included. Children who had groin incisions were excluded. RESULTS: Two groups were identified: the antibiotic group (77 children with 203 incisions and 343 procedures) had one surgical site infection; the no-antibiotic group (48 children with 102 incisions and 177 procedures) had no surgical site infections. CONCLUSION: These results suggest that the use of preoperative antibiotics does not change the rate of postoperative surgical site infections. LEVEL OF EVIDENCE: Level III therapeutic study.

Foot and ankle deformities in children with Down syndrome.

PURPOSE: Foot and ankle deformities are common orthopaedic disorders in children with Down syndrome. However, radiographic measurements of the foot and ankle have not been previously reported. The aim of this study is to describe the foot and ankle deformity in children with Down syndrome. METHODS: Children who had foot and ankle radiographs in the standing weight-bearing position were selected. Three groups of patients were identified. The relationship of radiographic measurements with age, body mass index and pain is discussed. In all, 41 children (79 feet) had foot radiographs and 60 children (117 ankles) had ankle radiographs, with 15 children overlapping between Groups I and II. RESULTS: In Group I, hallux valgus deformity was seen before ten years of age and hallux valgus angle increased afterwards. Metatarsus adductus angle showed a significant increase (p = 0.006) with obesity and was higher in patients who had foot pain (p = 0.05). In Group II, none of the ankle measurements showed a significant difference with age or body mass index percentiles. Tibiotalar angle (TTA) and medial distal tibial angle (MDTA) were higher in patients who had ankle pain. In Group III, correlation analysis was performed between the different measurements with the strongest correlations found between TTA and MDTA. CONCLUSION: In children with Down syndrome, radiographic evaluation of the foot and ankle reveals higher prevalence of deformities than clinical examination. However, foot and ankle radiographs are needed only for symptomatic children with pain and gait changes. LEVEL OF EVIDENCE: Level IV - Prognostic Study.

Useful scars: Physics of the capsids of archaeal viruses.

We propose a physical model for the capsids of tailed archaeal viruses as viscoelastic membranes under tension. The fluidity is generated by thermal motion of scarlike structures that are an intrinsic feature of the ground state of large particle arrays covering surfaces with nonzero Gauss curvature. The tension is generated by a combination of the osmotic pressure of the enclosed genome and an extension force generated by filamentous structure formation that drives the formation of the tails. In continuum theory, the capsid has the shape of a surface of constant mean curvature: an unduloid. Particle arrays covering unduloids are shown to exhibit pronounced subdiffusive and diffusive single-particle transport at temperatures that are well below the melting temperature of defect-free particle arrays on a surface with zero Gauss curvature.

Bilateral Gasser's ganglion sarcoidosis: diagnosis, treatment and unsolved questions.

Magnetic resonance imaging is currently the best means for confirming clinical suspicion of neurosarcoidosis as well as being useful in the follow-up of corticosteroid-treated patients. We report the case of a 34 year old male presenting suspected Heerfordt's syndrome with concentric facial hypesthesia. Mediastinal and parotid sarcoidosis was diagnosed and magnetic resonance imaging showed bilateral sarcoid involvement of Gasser's ganglion cisternae (such involvement was not revealed by computed tomography). The patient received corticosteroid therapy, with a clinical and radiological improvement. Magnetic resonance imaging showed disappearance of Gasser's ganglion lesions despite the persistence of mild facial hypesthesia. This case is noteworthy for its extremely rare lesion site. Post-treatment discrepancy between the clinical picture and imaging results is probably due to low MRI resolution threshold. 18-FDG positron emission tomography imaging might perhaps overcome the limits of magnetic resonance imaging.

Regional segmentation of ventricular models to achieve repolarization dispersion in cardiac electrophysiology modeling.

The electrocardiogram (ECG) is one of the most significant outputs of a computational model of cardiac electrophysiology because it relates the numerical results to clinical data and is a universal tool for diagnosing heart diseases. One key features of the ECG is the T-wave, which is caused by longitudinal and transmural heterogeneity of the action potential duration (APD). Thus, in order to model a correct wave of repolarization, different cell properties resulting in different APDs must be assigned across the ventricular wall and longitudinally from apex to base. To achieve this requirement, a regional parametrization of the heart is necessary. We propose a robust approach to obtain the transmural and longitudinal segmentation in a general heart geometry without relying on ad hoc procedures. Our approach is based on auxiliary harmonic lifting analyses, already used in the literature to generate myocardial fiber orientations. Specifically, the solution of a sequence of Laplace boundary value problems allows parametrically controlled segmentation of both heart ventricles. The flexibility and simplicity of the proposed method is demonstrated through several representative examples, varying the locations and extents of the epicardial, midwall, and endocardial layers. Effects of the control parameters on the T-wave morphology are illustrated via computed ECGs.

Testicular dysfunction in Hodgkin's disease before and after treatment.

Over a 7-year period, semen analysis was performed in 92 male patients with Hodgkin's disease prior to therapy. In 67% of patients semen revealed a decreased chance for fertility (i.e. oligozoospermia, asthenozoospermia and/or teratozoospermia). The mean basal levels of follicle-stimulating hormone (FSH), luteinising hormone, testosterone and prolactin were in the normal range. In 77 patients in complete remission after alternating MOPP/ABVD (mechlorethamine, vincristine, procarbazine, prednisone; doxorubicin, bleomycin, vinblastine, dacarbazine), testicular function was assessed. 87% of patients were azoospermic, 9% had semen abnormalities and only 4% were normospermic. Recovery of spermatogenesis was documented in only 17 of 42 (40%) reassessed patients after a median time of 27 months and was generally not affected by pretreatment sperm quality. After chemotherapy, the mean value of FSH [20.45 (S.E. 1.7) mUI/ml] was significantly superior compared with that of the mean pretreatment values. No difference was documented in the mean testosterone and prolactin values tested before and after treatment. Our findings indicate that, of patients with Hodgkin's disease, about half are affected by hypogonadism before starting chemotherapy. By utilising alternating MOPP/ABVD, persistent testicular dysfunction was documented in half of the patients.

The role of Yp in sex determination: new evidence from X/Y translocations.

A 33-year-old man had azoospermia and tubular atrophy as in the Klinefelter syndrome but short stature. He had a 46,X,t(X/Y) (Xqter lead to p22.3::Yp11 lead to Yqter) translocation and was H-Y antigen-positive. This excludes one of the genes controlling H-Y antigen from the terminal portion of the short arm of the Y chromosome. This case and the two similar ones in the literature indicate that the proximal Yp portion is required for the differentiation of a male gonad. The pattern of X inactivation was random in the patient's fibroblasts, whereas in the lymphocytes the translocated chromosome was preferentially inactivated; comparison with other cases shows that the quantity of Y chromosome material involved in these translocations does not influence the X inactivation patterns. In the three cases with this dicentric translocation the X chromosome centromere is consistently the active one. Our case indicates that the choice of which centromere is inactivated is independent of the replication pattern of the X chromosome. Our patient and a few other relevant cases from the literature confirm that factors controlling height are located on the distal portion of Xp and of Yp.

Diffusion of a single ion in a one-dimensional optical lattice.

We present an experimental study of the spatial diffusion of a single ion in a polarization gradient field. A 24 Mg + ion was radially confined in a two-dimensional radio-frequency (rf) trap, while an optical lattice superimposed to a weak electric potential was applied along the free axis. With the help of a statistical analysis of single ion trajectories, a spatial diffusion constant was obtained as a function of optical potential depth. The results are compared to semiclassical theoretical models for trapped ions and neutral atoms.

Intraperitoneal insemination in the treatment of male and unexplained infertility.

For couples with unexplained or male infertility, intraperitoneal (IP) insemination in induced cycles is a method that increases the chance of fertilization. Seventy-seven couples with male subfertility were subjected to 120 IP insemination cycles and 31 with unexplained sterility to 44 cycles. As a consequence of the treatment, 23 pregnancies were obtained, with pregnancy rates of 23% per cycle and 32% per patient for unexplained infertility and 11% and 17% for male subfertility. Pregnancy loss rate was quite elevated: 9 clinical abortions and 1 ectopic. Intraperitoneal insemination appears to be a relatively noninvasive way to deal with unexplained or male factor infertility, well worth trying before moving on to more invasive and costly approaches, such as gamete intrafallopian transfer or in vitro fertilization.

Effects of physiological concentrations of steroid hormones and interleukin-11 on basal and stimulated production of interleukin-8 by human osteoblast-like cells with different functional profiles.

OBJECTIVE: IL-8 is a CXC chemokine involved in the pathogenesis of articular damage in rheumatoid arthritis. Local hyperproduction of IL-8 has been suggested to play a role in subchondral bone loss, since it suppresses osteoblast activity and promotes osteoclasts recruitment. Osteoblasts are a source of IL-8; its secretion is regulated by a number of hormones and cytokines. The aim of the present study was to evaluate the single and combined effects of physiological concentrations of cortisol, 17 beta-estradiol and IL-11 upon basal and IL-1 beta-inducible production of IL-8 in two human osteoblast-like cell lines, Saos-2 and MG-63. METHODS: Cells were incubated with cortisol (0.01 to 1 microM), 17 beta-estradiol (10 to 1000 pg/ml), IL-11 (1 to 100 ng/ml), in presence or absence of IL-1 beta (10 ng/ml), for 20 h. Combinations of 17 beta-estradiol and cortisol, and of IL-11 and cortisol, were also tested. After incubation, IL-8 levels in supernatants were measured by ELISA. RESULTS: Cortisol dose-dependently inhibited spontaneous IL-8 secretion in both cell lines, although statistical significance was attained in the MG-63 cells only (P < 0.01); no effect of 17 beta-estradiol was apparent. With regard to IL-1 beta-inducible production, cortisol dose-dependently inhibited IL-8 release in both cell lines (P < 0.01); 17 beta-estradiol resulted in only a non-significant decrease in Saos-2, but not in MG-63 cells. 17 beta-estradiol did not alter the effects of cortisol in experiments involving co-incubation. IL-11 did not have any effect on spontaneous IL-8 release, but exerted a significant inhibitory effect on IL-1 beta-inducible release in MG-63 cells (P < 0.05); no additional effect was observed upon the degree of cortisol-dependent inhibition. CONCLUSION: Cortisol is a potent physiological inhibitor of IL-8 production by osteoblast-like cells. The results of the present study support the use of exogenous supplemental glucocorticoids to prevent the deleterious effects of excess IL-8. The estrogenic milieu and local concentrations of IL-11 have little if any effect on the IL-8-dependent mechanisms of disease.

Arthropathies and thyroid diseases.

AIM: Improvement of articular symptoms following thyroidectomy has often been observed in patients with an association of thyroid and joint diseases. An assessment has therefore been made of the types of arthropathy thus benefited and the anatomopathological features of the thyroid in patients with concomitant joint diseases. An account is given of the arthropathies associated with nontoxic nodular goitre (NTG). METHODS: Three cell markers are examined to identify immunocytokine elements differentiating thyroid diseases. RESULTS: Immunohistochemical examination shows extravasal lymphocyte infiltrates; thyrocytes were negative for HLA-Cl II, CD38 and IL-6R, and only dim-positive for HLA-Cl I. Endothelial cells were positive for HLA-Cl I and II and CD38, and negative for IL-6R. The lymphocyte were positive for HLA-Cl I, HLA-Cl II and CD38, but negative for IL-6R. The follow-up of 6 thyroidectomised patients disclosed improvement in joint pain and remission of rheumatoid arthritis and spondylarthritis. Association of nodular goitre with arthro-pathies is demonstrated. CONCLUSION: Arthritis and arthralgia are frequent in patients with thyroid diseases, we particularly found the association with MHNG and Hurthle cell adenoma. Arthritis and arthralgia quickly improve after thyroidectomy. Immunohistochemical NTG thyrocytes are still normal cells (HLA-Cl II negative) by contrast with their HLA-Cl II positivity in autoimmune thyroiditis.

Replication of mitochondrial DNA in the gonadotropin-primed corpus luteum of the rat.

The effect on mitochondria isolated from corpus luteal tissues following priming of immature female rats with pregnant mares serum gonadotropin (PMSG) and human chorionic gonadotropin (hCG) was studied. Ultrastructural studies showed intramitochondrial filamentous nucleic acid networks in situ following intense uranyl acetate staining. The intramitochondrial complexes were sensitive to nuclease treatment. Primed corpora lutea contained a 3.7-fold increase of mitochondrial DNA (mtDNA) per mg of mitochondrial protein when compared to unprimed ovaries. In subsequent experiments female rats were injected with 3H-thymidine 12 h before harvesting gonadotropin-primed corpora lutea from which mitochondria were isolated, purified and lysed. MtDNA was isolated and purified from the lysate by CsCl-ethidium bromide equilibrium buoyant density gradient centrifugation. Both the upper and lower bands of mtDNA as well as the intermediate region of the gradient contained radioactive label. When mtDNA from a fractionated gradient was mounted for electron microscopy and examined, replicative forms of mtDNA were observed. The mechanism of replication appears to be by the displacement-loop model of mtDNA replication. Ultrastructural as well as biochemical evidence indicate that a consequence of corpora lutea formation is the replication of mtDNA.

[Asymptomatic cholelithiasis: indications for cholecystectomy based on the levels of acute phase proteins]. / La litiasi colecistica asintomatica: guida alla colecistectomia dai valori delle proteine della fase acuta.

Prophylactic cholecystectomy for asymptomatic gallstones is still controversial. Aim of the study was to assess whether the determination of serum acute phase proteins (APP) could be utilized as a criterion for cholecystectomy, as they are suggestive of the presence in the blood of cytokines released from the inflamed gallbladder wall, even when clinical signs are missing. In 75 cases of gallstones, free from other coexistent inflammatory processes, red cell sedimentation rate, plasmatic cortisol, immunoglobulin (IgA, IgG, IgM), electrophoresis of the proteins, CPR, fibrinogen, haptoglobin, alfa-1-antitrypsin and bile culture have been detected. The patients have been subdivided into two groups: patients with asymptomatic or mildly symptomatic disease and patients with a clear clinical pattern of acute cholecystitis. In the latter alfa-1-globulin, alfa-2-globulin, ESR, CPR and cortisol turned out to be significantly elevated, while in 20-30% of the former CPR, beta-globulin and cortisol were increased, too. The study demonstrates that among the patients with asymptomatic gallstones there is a population having PFA values higher than normal. This is suggestive of a cytokines activation which, when other inflammatory processes can be excluded, is likely due to gallbladder inflammation and surgery will likely be indicated.