Gambling and internet addiction: a pilot study among a Population of Italian Healthcare : Gambling and Internet Addition in a Healthcare Group.

AIM: Measuring the phenomenon of gambling and Internet addiction, with analysis of attitudes and psychophysical consequences among nurses working in different care settings. METHODS: An observational, cross sectional, multicenter study was conducted from April to September 2020. Participants' socio-demographic information, the "Internet Addiction Test" (IAT) scale, and the "South Oaks Gambling Screen" (SOGS) were collected in order to assess the overuse of and whether an individual has a problematic relationship with gambling, respectively. RESULTS: 502 nurses were enrolled in the study. Significant correlations were found (p < .001) between the IAT score and gender, number of years of work experience, job role, educational qualification; and between the SOGS and gender, number of years of work experience, job role and regions of Italy. CONCLUSIONS: The study highlighted an emerging social problem, and the results may be just the tip of the iceberg. Given the lack of knowledge of these phenomena and a high percentage of people who suffer from them but are afraid to admit it and get help, this study could also be useful in expanding knowledge and allow more professionals to get help and learn about possible treatments and cures for the resolution of these addictions.

Light-Induced Quantum Droplet Phases of Lattice Bosons in Multimode Cavities.

Multimode optical cavities can be used to implement interatomic interactions which are highly tunable in strength and range. For bosonic atoms trapped in an optical lattice we show that, for any finite range of the cavity-mediated interaction, quantum self-bound droplets dominate the ground state phase diagram. Their size and in turn density is not externally fixed but rather emerges from the competition between local repulsion and finite-range cavity-mediated attraction. We identify two different regimes of the phase diagram. In the strongly glued regime, the interaction range exceeds the droplet size and the physics resembles the one of the standard Bose-Hubbard model in a (self-consistent) external potential, where in the phase diagram two incompressible droplet phases with different filling are separated by one with a superfluid core. In the opposite weakly glued regime, we find instead direct first order transitions between the two incompressible phases, as well as pronounced metastability. The cavity field leaking out of the mirrors can be measured to distinguish between the various types of droplets.

Ossicular chain reconstruction using costal cartilage in malleoincudal osteoma.

OBJECTIVES: To report an extremely rare case of malleoincudal osteoma that led to conductive hearing loss despite an unusually normal otomicroscopic appearance, and to highlight the usefulness of costal cartilage for ossicular chain reconstruction after tumour removal. CASE REPORT: A 37-year-old woman presented with a 2-year history of progressive, right-sided hearing loss. Physical examination revealed a normal tympanic membrane. Pure tone audiometry showed a right-sided conductive hearing loss. High-resolution computed tomography revealed a right-sided epitympanic mass arising from the malleus head and contiguous with the incus. The patient underwent a closed mastoido-epitympanectomy. The malleus head and the incus with associated malleoincudal osteoma were removed. Ossicular chain reconstruction using costal cartilage was performed at the time of tumour removal. CONCLUSION: The possibility of a middle-ear osteoma must be considered in cases of unilateral and progressive conductive hearing loss with a normal otomicroscopic appearance in patients with no history of ear infection, trauma or prior surgery, and with no family history of hearing loss. Surgical treatment is indicated in cases of significant conductive hearing loss. To our knowledge, this is the first case report of malleoincudal osteoma in which the ossicular chain was reconstructed using costal cartilage.

A challenging diagnosis of reversible "vascular" dementia: Cerebral amyloid angiopathy-related inflammation.

Cerebral amyloid angiopathy-related inflammation (CAA-ri) is a rare and treatable variant of CAA likely due to an autoimmune response directed toward beta-amyloid deposits. Cognitive and behavioral manifestations are the most common symptoms, followed by focal neurological signs, headache and seizures, associated with characteristics neuroradiological features on brain magnetic resonance imaging (MRI). We describe the clinical course, radiological features and therapeutic approach of two patients with probable CAA-ri with the aim of emphasizing the importance of an early diagnosis of this potentially reversible disease in different neurological settings, such as memory clinics and stroke units.

Comparison between thrombotic risk scores in essential thrombocythemia and survival implications.

The conventional thrombotic risk stratification in essential thrombocythemia (ET) distinguishes patients in two risk groups based on previous thrombosis and age (< or >60). The IPSET-thrombosis takes into account four risk factors: age greater than 60 years and the presence of CV risk factors, thrombosis history and JAK2 V617F presence. The revised IPSET-thrombosis uses three adverse variables to delineate four risk categories: age greater than 60, thrombosis history, and JAK2 V617F presence. We compared different risk models in the estimation of thrombotic risk in 191 patients with ET and the role of specific driver mutations affecting overall survival, according to thrombotic risk. We also evaluated the mutational status of patients showing history of thrombosis or cardiovascular events versus patients who did not. Finally, we verified whether the thrombotic risk had a significant impact on survival in our ET patients. The data analysis has been performed through the conventional statistics and overall survival estimated by using the Kaplan-Meyer method. Interestingly, either using the traditional system for thrombotic risk or the IPSET-t prognostic score or the current stratification for the thrombotic risk, high-risk patients are always highly represented. This evidence is of note, being the high-risk category indicated for cytoreduction, affecting quality of life, despite the good overall prognosis of patients with ET diagnosis in general. The analysis of overall survival in our patients, according to different models for thrombotic risk, highlighted the poor prognosis of high-risk patients compared with those with a lower thrombotic risk, in particular when using traditional stratification and current stratification. In conclusion, the occurrence of thrombotic or cardiovascular events represents one of the most severe complications at diagnosis or during follow-up of ET despite current recommendations, having a significant impact on morbidity and survival.

Point-particle method to compute diffusion-limited cellular uptake.

We present an efficient point-particle approach to simulate reaction-diffusion processes of spherical absorbing particles in the diffusion-limited regime, as simple models of cellular uptake. The exact solution for a single absorber is used to calibrate the method, linking the numerical parameters to the physical particle radius and uptake rate. We study the configurations of multiple absorbers of increasing complexity to examine the performance of the method by comparing our simulations with available exact analytical or numerical results. We demonstrate the potential of the method to resolve the complex diffusive interactions, here quantified by the Sherwood number, measuring the uptake rate in terms of that of isolated absorbers. We implement the method in a pseudospectral solver that can be generalized to include fluid motion and fluid-particle interactions. As a test case of the presence of a flow, we consider the uptake rate by a particle in a linear shear flow. Overall, our method represents a powerful and flexible computational tool that can be employed to investigate many complex situations in biology, chemistry, and related sciences.

Protein kinase CK2 regulates AKT, NF-κB and STAT3 activation, stem cell viability and proliferation in acute myeloid leukemia.

Protein kinase CK2 sustains acute myeloid leukemia cell growth, but its role in leukemia stem cells is largely unknown. Here, we discovered that the CK2 catalytic α and regulatory ß subunits are consistently expressed in leukemia stem cells isolated from acute myeloid leukemia patients and cell lines. CK2 inactivation with the selective inhibitor CX-4945 or RNA interference induced an accumulation of leukemia stem cells in the late S-G2-M phases of the cell cycle and triggered late-onset apoptosis. As a result, leukemia stem cells displayed an increased sensitivity to the chemotherapeutic agent doxorubicin. From a molecular standpoint, CK2 blockade was associated with a downmodulation of the stem cell-regulating protein BMI-1 and a marked impairment of AKT, nuclear factor-κB (NF-κB) and signal transducer and activator of transcription 3 (STAT3) activation, whereas FOXO3a nuclear activity was induced. Notably, combined CK2 and either NF-κB or STAT3 inhibition resulted in a superior cytotoxic effect on leukemia stem cells. This study suggests that CK2 blockade could be a rational approach to minimize the persistence of residual leukemia cells.

Targeting CK2-driven non-oncogene addiction in B-cell tumors.

Genetic mutations of oncogenes often underlie deranged cell growth and altered differentiation pathways leading to malignant transformation of B-lymphocytes. However, addiction to oncogenes is not the only drive to lymphoid tumor pathogenesis. Dependence on non-oncogenes, which act by propelling basic mechanisms of cell proliferation and survival, has also been recognized in the pathobiology of lymphoid leukemias, lymphomas and multiple myeloma. Among the growing number of molecules that may uphold non-oncogene addiction, a key place is increasingly being recognized to the serine-threonine kinase CK2. This enzyme is overexpressed and overactive in B-acute lymphoblastic leukemia, multiple myeloma, chronic lymphocytic leukemia and non-Hodgkin lymphomas, such as mantle cell, follicular, Burkitt's and diffuse large B-cell lymphomas. In these tumors, CK2 may serve the activity of oncogenes, similar to BCR-ABL and c-MYC, control the activation of critical signaling cascades, such as NF-κB (nuclear factor-κB), STAT3 (signal transducer and activator of transcription 3) and PTEN/PI3K/AKT (phosphatase and tensin homolog protein/phosphoinositide 3-kinase/AKR thymoma), and sustain multiple cellular stress-elicited pathways, such as the proteotoxic stress, unfolded protein and DNA-damage responses. CK2 has also been shown to have an essential role in tuning signals derived from the stromal tumor microenvironment. Not surprisingly, targeting CK2 in lymphoid tumor cell lines or mouse xenograft models can boost the cytotoxic effects of both conventional chemotherapeutics and novel agents, similar to heat-shock protein 90, proteasome and tyrosine kinases inhibitors. In this review, we summarize the evidence indicating how CK2 embodies most of the features of a cancer growth-promoting non-oncogene, focusing on lymphoid tumors. We further discuss the preclinical data of the use of small ATP-competitive CK2 inhibitors, which hold the promise to be additional options in novel drug combinations for the therapy of lymphoid and plasmacellular malignancies.

Instability of the Superfluid Flow as Black-Hole Lasing Effect.

We show that the critical velocity of a superfluid flow through a penetrable barrier coincides with the onset of the analog black-hole lasing effect. This dynamical instability is triggered by modes resonating in an effective cavity formed by two horizons enclosing the barrier. The location of the horizons is set by v(x)=c(x), with v(x),c(x) being the local fluid velocity and sound speed, respectively. We compute the critical velocity analytically and show that it is univocally determined by the configuration of the horizons. In the limit of broad barriers, the continuous spectrum at the origin of the Hawking-like radiation and of the Landau energetic instability is recovered.

Haploidentical, G-CSF-primed, unmanipulated bone marrow transplantation for patients with high-risk hematological malignancies: an update.

Ninety-seven patients affected by high-risk hematological malignancies underwent G-CSF primed, unmanipulated bone marrow (BM) transplantation from a related, haploidentical donor. All patients were prepared with an identical conditioning regimen including Thiotepa, Busilvex, Fludarabine (TBF) and antithymocyte globulin given at myeloablative (MAC = 68) or reduced (reduced intensity conditioning (RIC) = 29) dose intensity and received the same GvHD prophylaxis consisting of the combination of methotrexate, cyclosporine, mycofenolate-mofetil and basiliximab. Patients were transplanted in 1st or 2nd CR (early phase: n = 60) or in > 2nd CR or active disease (advanced phase: n = 37). With a median time of 21 days (range 12-38 days), the cumulative incidence (CI) of neutrophil engraftment was 94 ± 3%. The 100-day CI of III-IV grade acute GvHD and the 2-year CI of extensive chronic GvHD were 9 ± 3% and 12 ± 4%, respectively. Overall, at a median follow-up of 2.2 years (range 0.3-5.6), 44 out of 97 (45%) patients are alive in CR. The 5-year probability of overall survival (OS) and disease-free survival (DFS) for patients in early and advanced phase was 53 ± 7 vs 24 ± 8% (P = 0.006) and 48 ± 7 vs 22 ± 8% (P = 0.01), respectively. By comparing MAC with RIC patient groups, the transplant-related mortality was equivalent (36 ± 6 vs 28 ± 9%) while the relapse risk was lower for the MAC patients (22 ± 6 vs 45 ± 11%), who showed higher OS (48 ± 7 vs 29 ± 10%) and DFS (43 ± 7 vs 26 ± 10%). However, all these differences did not reach a statistical significance. In multivariate analysis, diagnosis and recipient age were significant factors for OS and DFS. In conclusion, this analysis confirms, on a longer follow-up and higher number of patients, our previous encouraging results obtained by using MAC and RIC TBF regimen as conditioning for G-CSF primed, unmanipulated BM transplantation from related, haploidentical donor in patients with high-risk hematological malignancies, lacking an HLA-identical sibling or unrelated donor and in need to be urgently transplanted.

Which cephalometric analysis for maxillo-mandibular surgery in patients with obstructive sleep apnoea syndrome?

Maxillo-mandibular advancement MMA is considered an efficacious treatment for patients affected by severe obstructive sleep apnoea syndrome (OSAS). Even though OSAS improvement is the main goal of MMA, excessive maxillo-mandibular protrusion should be avoided to guarantee pleasant postoperative facial aesthetics. In order to attain such a result, the amount of MMA should be planned preoperatively by both aesthetic and cephalometric analyses. Steiner and Delaire cephalometric analyses are commonly used in the preoperative planning of orthognatic surgery for dentofacial deformities, however controversies still exist about the basis and postoperative aesthetic results of such cephalometric analyses in OSAS patients candidate for MMA. Forty-eight patients affected by severe OSAS were submitted to MMA. Pre- and post-operative Steiner and Delaire cephalometric tracings were assessed in each subject. For Steiner analysis, the variation in the SNA and SNB angles was measured, while for Delaire tracings the variation in the C3/FM-CPA and C3/FM-Me angles was assessed. Mean MMA was 6.9 + 3.8 mm for the maxilla and 13.6 + 5 mm for the mandible. After surgery, an improvement of the apnoea-hypopnoea index was recorded (40.47 + 7.64 preoperative vs. 12.56 + 5.78 postoperative). In all patients, both cephalometric analyses showed presurgical bimaxillary retrusion. After surgery, the mean value of Steiner's SNA angle increased from 78.18° to 85.58° (p < 0.001), while mean Delaire's C3/FM-CPA angle increased from 81.19° to 89.71° (p < 0.001). The mean value of Steiner's SNB angle increased from 74.33° to 80.73° (p < 0.001), while Delaire's C3/FM-Me angle increased from 80.10° to 87.29° (p < 0.001). Postoperatively, both the maxilla and mandible were in a more protrusive position (p < 0.001) according to Steiner analysis compared with Delaire tracing. Basing MMA on Delaire cephalometric analysis leads to an increased advancement of the maxillo-mandibular complex than Steiner tracing. The consequences of this aspect on facial aesthetics should be considered during surgical planning and preoperative informed consent in OSAS patients candidate for MMA.

Diffusion-limited reactions in crowded environments: a local density approximation.

In the real world, diffusion-limited reactions in chemistry and biology mostly occur in crowded environments, such as macromolecular complex formation in the cell. Despite the paramount importance of such phenomena, theoretical approaches still mainly rely on the Smoluchowski theory, only valid in the infinite dilution limit. In this paper we introduce a novel theoretical framework to describe the encounter rate and the stationary density profiles for encounters between an immobilized target and a fluid of interacting spherical particles, valid in the local density approximation. A comparison with numerical simulations performed for a fluid of hard spheres and square well attractive hard spheres confirms the accuracy of our treatment.

Macromolecular crowding: chemistry and physics meet biology (Ascona, Switzerland, 10-14 June 2012).

More than 60 years of biochemical and biophysical studies have accustomed us to think of proteins as highly purified entities that act in isolation, more or less freely diffusing until they find their cognate partner to bind to. While in vitro experiments that reproduce these conditions largely remain the only way to investigate the intrinsic properties of molecules, this approach ignores an important factor: in their natural milieu , proteins are surrounded by several other molecules of different chemical nature, and this crowded environment can considerably modify their behaviour. About 40% of the cellular volume on average is occupied by all sorts of molecules. Furthermore, biological macromolecules live and operate in an extremely structured and complex environment within the cell (endoplasmic reticulum, Golgi apparatus, cytoskeletal structures, etc). Hence, to further complicate the picture, the interior of the cell is by no means a simply crowded medium, rather, a most crowded and confining one. In recent times, several approaches have been developed in the attempt to take into account important factors such as the ones mentioned above, at both theoretical and experimental levels, so that this field of research is now emerging as one of the most thriving in molecular and cell biology (see figure 1). [Formula: see text] Figure 1. Left: number of articles containing the word 'crowding' as a keyword limited to the biological and chemical science domains (source: ISI Web of Science). The arrow flags the 2003 'EMBO Workshop on Biological Implications of Macromolecular Crowding' (Embo, 2012). Right: number of citations to articles containing the word 'crowding' limited to the same domains (bars) and an exponential regression curve (source: Elsevier Scopus). To promote the importance of molecular crowding and confinement and provide researchers active in this field an interdisciplinary forum for meeting and exchanging ideas, we recently organized an international conference held in Ascona from 10 to 14 June 2012. In the unique scenario of the Maggiore lake and absorbed in the magic atmosphere of the Centro Stefano Franscini (CSF) at Monte Verità, we enjoyed three-and-a-half days of intense and inspiring activity, where not only many of the most prominent scientists working on macromolecular crowding, but also experts in closely related fields such as colloids and soft matter presented their work. The meeting was intended and has been organized to bring theoreticians and experimentalists together in the attempt to promote an active dialogue. Moreover, we wanted different disciplines to be represented, notably physics and chemistry, besides biology, as cross-fertilization is proving an increasingly fundamental source of inspiration and advancement. This issue of Physical Biology (PB) features a selection of the oral contributions presented at the conference, expanded in the form of research or review articles. PB, one of the scientific journals of the Institute of Physics (IOP), is one of the most dynamic and lively forums active at the interface between biology on one side, and physics and mathematics on the other. As its mission is stated by IOP, PB 'focuses on research in which physics-based approaches lead to new insights into biological systems at all scales of space and time, and all levels of complexity'. For these reasons, and also in view of its high reputation and broad readership, PB appears to be the ideal place for disseminating the thriving pieces of research presented at the conference. We are extremely grateful to PB and its kind and efficient editorial staff who helped make this issue a great scientific follow-up to the conference. The opening lecture of the conference, the first of four day-opening keynote lectures, was given by Allen P Minton from NIH (USA), possibly the most influential among the pioneers in the field. He provided a lucid and well-thought-out overview of the concept of macromolecular crowding through an exhaustive chronological account of the major milestones. It is clear that the concept of excluded volume as a key factor remains central to the concept of molecular crowding. As a consequence, simple descriptive paradigms borrowed essentially from colloid physics may still provide useful tools to understand the subtle effects of crowding and confinement in living matter. The contiguity between crowding, colloids and soft matter further emerged as an important concept in the course of the conference in several theoretical lectures and a few experimental ones. Dave Thirumalai, from the University of Maryland (USA), one of the most active theoreticians in the field of theoretical biophysics, outlined scaling theories, concepts from colloid literature and different simulation techniques to describe scenarios for crowding-induced changes in the structure and dynamics of proteins and RNA. In particular, he showed the importance of the shape of crowding particles in affecting folding oligomerization of amyloidogenic peptides. Johannes Schöneberg, from IMPRS, Mathematics Institute (Germany), illustrated ReaDDy , a newly developed particle-based simulation software tool for reaction-diffusion dynamics, developed in the group of Frank Noe at EMPRS. He showed that ReaDDy makes it possible to bridge the gap between soft matter and molecular dynamics (MD) simulations on the one hand and particle-based stochastic reaction-diffusion simulations on the other. We asked Johannes to organize a tutorial session to lead interested participants into the package and 'get their hands wet' under the guidance of the developers. The tutorial session was indeed successful and the broad possibilities offered by the simulation toolkit appeared to be clear to the participants. Paolo De Los Rios, from the Ecole Polytechnique Fédérale de Lausanne (EPFL, Switzerland), examined the complexity of the effects caused by crowding conditions from the point of view of statistical physics. Starting from a modification of the well-known Smoluchowski approach to calculate the encounter rate of diffusion-limited reactions, he showed how more realistic situations accounting for crowding effects could be treated equally well on the same theoretical grounds. This talk marked an important point in the conference as it reinforced the idea that simple models of theoretical physics still have the power to provide inspiring results in spite of the intrinsic simplifications of such theoretical approaches. Along the same lines, Nicolas Dorsaz, from the University of Cambridge (UK), proposed an extension of the Smoluchowski framework that incorporates repulsive and attracting interactions between the reactants. This approach was illustrated by reaction rates obtained from event-driven Brownian dynamics and dynamical Monte Carlo simulations. Another striking example of the physical subtleties associated with modelling crowding effects was provided by Jeffrey Skolnick, from the Georgia Institute of Technology (USA). He examined the role of hydrodynamic interactions in the self-organization of biological assemblies in the presence of crowding. His results strongly suggest that hydrodynamic interactions greatly affect the kinetics of self-assembly reactions, so that including them in the picture appears crucial for understanding the dynamics of biological systems in vivo . Margareth Cheung, from the University of Houston (USA), emphasized that how the crowded environment inside a cell affects the structural conformation of a protein with a spherical shape is a vital question because the geometry of proteins and protein-protein complexes are far from globules in vivo . Her work demonstrates the malleability of 'native' proteins and implies that crowding-induced shape changes may be important for protein function and malfunction in vivo . Huan-Xiang Zhou, from the Florida State University (USA), focused on atomistic simulations of protein folding and binding under crowding conditions. His lab has developed a post-processing method that allows the atomistic representation of proteins in folding and binding processes under crowding. A comparison with experimental results was also presented. Other lecturers pointed out that there are still aspects not entirely explored in the effects of both crowding and confinement. As suggested in the talk by Gary Pielak, from the University of North Carolina (USA), the currently used synthetic crowding agents are far from being satisfactory in replicating naturally occurring effects associated with crowded environments. For example, non-specific binding seems to play a subtle role in the cell, as natural macromolecules can induce both stabilization and destabilization when used as crowders. It is indeed possible to fine-tune the effect of proteins, as crowders, on the stability of other proteins. Another aspect that became clear is that new, more powerful methods need to be developed to study the effect of crowding, but even more to compare crowding and confinement. Indeed, it appeared clear from the lecture by Pierandrea Temussi, from the University of Naples (Italy), that a reliable comparison of the effects of crowding and confinement on the stability of proteins can only be based on the measurement of the whole stability curve of the same protein. Controversial aspects do not pertain only to the influence of crowding on protein stability, but also to aggregation phenomena in natural fluids. Domenico Sanfelice, from NIMR (London, UK), reported an interesting case of the apparent influence of crowding on aggregation. Hen egg white, a possible natural medium to study macromolecules in crowded conditions can dramatically increase the aggregation kinetics of proteins with an inbuilt tendency to associate. By carefully dissecting the phenomenology, it was shown that only part of this effect is due to crowding, while another factor playing an important role is the interaction withproteins from the milieu . In other words, high-molecular-weight glycoproteins can act as efficient molecular seeds for aggregation. A special topic of great relevance in the conference appeared to be the direct study of crowding in living systems. Alan Verkman, from the University of California, San Francisco (USA), one of the world's leading scientific personalities in the field of experimental investigation of crowding and confinement, was invited to give the second plenary lecture devoted to the experimental study of crowding effects in vivo . In his keynote lecture, Dr Verkman led us on a wide and compelling tour, exploring the main experimental approaches to study molecular crowding in and around cells. After a thorough examination of methods such as fluorescence recovery after photo-bleaching, fluorescence correlation spectroscopy, photo-activation localization microscopy and stochastic reconstruction microscopy, he concluded that the general consensus emerging from experimental studies is that the notion of universally anomalous diffusion in and around cells as a consequence of molecular crowding may not be correct, and that the slowing of diffusion in cells is less marked than has been widely assumed and can be simply described through a five- to sixfold reduction of the normal diffusion coefficient. A Soranno, from the University of Zürich (Switzerland), described how, by employing FRET measurements, it is possible to quantify the effect of molecular crowding on the dimensions of the highly charged, intrinsically disordered protein human prothymosin alpha. For a large variety of polymeric crowders (PEG, PVP, Ficoll, Dextran, PVA, PAA), a collapse of the polypeptide chain is observed with increasing polymer size and polymer concentration. The largest extent of collapse is observed for polymer radii comparable to the dimensions of the protein, in agreement with theoretical considerations. For his contribution, A Soranno was awarded the CSF Award for the best contributed talk. In his most inspiring talk, Clifford Brangwynne, from Princeton University (USA), drew attention to very important objects, namely Ribonucleoprotein (RNP) bodies. These are non-membrane-bound macromolecular assemblies that form from the dynamic interactions of RNA and proteins. The assembly of RNP bodies may sensitively depend on the biophysical features of the surrounding cytoplasm, including the degree of crowding, transport coefficients and mechanical properties. This dependency may have important implications for the RNA processing reactions involved in fundamental biological processes such as developmental cell growth. Remarkably, Brangwynne showed how RNPs behave in the cell as liquid droplets, pointing to a possible entirely new means that the cell could use to control and fine-tune its internal processes, in fact, more than that, a completely unexplored, new state of organization of living matter, and a functional one. Giuseppe Zaccai, from Institut Laue Langevin, Grenoble (France), showed that protein dynamics is more sensitive than structure to environmental factors such as crowding, solvent, temperature or pressure. Furthermore, he convincingly explained how neutron scattering provides unique experimental data to underpin MD calculations in this context. Following up on environment-induced modulations of protein functional dynamics, Ruth Nussinov, from Tel Aviv University (Israel), addressed the important problem of whether cellular signals can travel long distances in a crowded environment. She proposed a model based on the evolution of at least three properties: a modular functional organization of the cellular network, sequences in some key regions of proteins, such as linkers or loops, and compact interactions between proteins, possibly favoured by a crowded environment. The workshop ended on a keynote lecture by Jean-Marie Lehn, from the Université de Strasbourg (France). Lehn, 1987 Nobel Laureate in chemistry, offered a 'supramolecular view' of the field of molecular interactions. Supramolecular chemistry explores the design of systems undergoing self-organization , i.e. systems capable of generating well-defined functional supramolecular architectures by self-assembling from their components, thus behaving as programmed chemical systems . Chemistry may therefore be considered an information science , the science of informed matter. Supramolecular chemistry is intrinsically a dynamic chemistry in view of the ability of the interactions connecting the molecular components of a supramolecular entity and the resulting ability of supramolecular species to exchange their constituents. The same holds for molecular chemistry when the molecular entity contains covalent bonds that may form and break reversibly, so as to allow a continuous change in constitution by the reorganization and exchange of building blocks. These features define a constitutional dynamic chemistry (CDC) on both the molecular and supramolecular levels. CDC takes advantage of dynamic constitutional diversity to allow variation and selection in response to either internal or external factors to achieve adaptation . The merging of the features-information and programmability, dynamics and reversibility, constitution and structural diversity-points towards the emergence of adaptive and evolutive chemistry . The whole workshop could have not taken place without the help of the Centro Stefano Franscini. The CSF is the congress centre of the Swiss Federal Institute of Technology of Zurich (ETH Zurich) and has been situated at Monte Verità since 1989. It is an ideal meeting point for all members of the international scientific community who wish to discuss the state-of-the-art and new challenges of any field of research. The CSF supports 20-25 international conferences every year and, since 2010, up to ten winter doctoral schools1. The competence and professionalism of the staff were at the same level of beauty and inspiring character as that of Monte Verità. A meeting of this sort, if successful, leaves the audience with more open questions than settled answers, and this was definitely the case for Crowding 2012. Excluded volume is clearly a fundamental concept that has allowed crowding, a very familiar concept in soft matter, to enter into the domain of biological sciences. However, the complexity of the biological milieu calls for more refined descriptions. What is the role of electrostatic and electrodynamic interactions? What is the role of hydrodynamics interactions? To what extent does the strong spatial inhomogeneity (clustering of molecules, cellular compartmentalization, etc) have to be taken into account? Or, more generally, what are the minimal elements that prove crucial to describe reactions within a cell? How does the diffusion proceed (diffusion, slow diffusion, sub-diffusion) given that the experimental evidences are still controversial? In conclusion, we knew that allowing scientists with very different backgrounds and ideas to mingle was a hazardous attempt. Despite that, the workshop turned out to be a very successful experiment, which was highly enjoyed both by the participants and the organizers. Discussions sparked regularly among ever-changing groups, comprising senior scientists and students, despite the rather tight schedule, adding to the sense of fulfilment ignited by the outstanding level of the presentations. Given the success of the meeting Crowding 2012, a new event has been organized and will take place on the same themes during fall 2013, this time in the beautiful scenery of the Loire valley in France. The workshop 'Macromolecular crowding effects in cell biology: models and experiments' will be held on the CNRS campus in Orléans, France, on 24-25 October 2013. More information can be found on the workshop website: http://dirac.cnrs-orleans.fr/∼piazza/. 1Source: www.csf.ethz.ch/

Unilateral hemiplegia: a unique complication of septoplasty.

BACKGROUND: Septoplasty is one of the most common otolaryngological operations. It is often dismissed as a simple procedure, despite the wide range of potential complications. We describe the first reported case of unilateral hemiplegia as a complication of septoplasty. METHODS AND RESULTS: A 51-year-old man presented with right hemiplegia following a septoplasty and turbinoplasty procedure carried out elsewhere. Cranial imaging showed a breakthrough fracture of the left sphenoid sinus anterior wall and clivus, with a haemorrhagic area in the left paramedian pons, which was responsible for the patient's right hemiplegia. Despite neurological and physiotherapeutic rehabilitation, the patient gained only partial recovery from his right hemiplegia. CONCLUSION: Good intra-operative visualisation and appropriate surgical technique are essential to prevent complications and achieve a functional nasal airway. The importance of the presented case to the pre-operative informed consent process is underlined.

A study on occupational exposure of Sicilian farmers to Giardia and Cryptosporidium.

INTRODUCTION: A cross-sectional study was undertaken to determine the prevalence of Giardia and Cryptosporidium in calves of Palermo area (Sicily) and to evaluate the occupational risk associated with occurrence of zoonotic genotypes. METHODS: A total of 217 faecal samples, from 149 calves (between 2 and 240 days of age) and 68 farmers, were collected in 19 cattle-farms of Palermo area. A questionnaire regarding demographic characteristics and personal hygienic measures was submitted to all farmers. All faecal samples were analyzed by Immunofluorescence assay and Polimerase Chain Reaction (PCR); genotypes were determined by DNA sequencing of Triose Phosphate Isomerase gene for Giardia and Small Subunit Ribosomal RNA gene for Cryptosporidium. RESULTS: None farmer tested was positive for Giardia and Cryptosporidium, whereas these protozoa were respectively detected in 53 (including 5 with zoonotic G. duodenalis genotype A) and 17 (of which 1 with zoonotic C. ubiquitum) of the examined calves. DISCUSSION: The results indicate that the risk of transmitting both protozoa to farmers in Palermo area is negligible although it cannot be considered null because of identification of human genotypes/species in calves.

A congenital tympanic membrane cholesteatoma (CTMC) in the adult: a case report.

OBJECTIVE: We present an additional very rare case of a congenital tympanic membrane cholesteatoma (CTMC) in the adult. METHOD: Case report and literature review of CTMC. CASE REPORT: A 54-year old man was referred to us by his primary care physician who noted a white mass on the right tympanic membrane without prior history of otorrhea, tympanic perforations or previous otologic procedures. The pearl was about 5 mm diameter, centered on the umbo of a normal tympanic membrane (TM). The audiogram and the tympanogram was absolutely normal. CT confirmed a soft round shape tissue mass, located in the centre of the TM near umbo. The mass protruded both in the auditory canal and in the middle ear space, touching the malleus extremity, without any relationship with medial wall of the cavum tympani. A surgical excision was performed using a "minimal" retroauricolar transcanalar approach: the CTMC was located into the thickness of the TM, between epidermic and mucous layers. The ossicular chain was preserved intact. A partial myringoplasty (underlay technique) using a temporalis fascia graft was necessary. Histopathology confirmed a cystic cholesteatoma. After two months and one year follow-up, otoendoscopy showed a well-healed TM with a preserved normal audiogram and tympanogram. DISCUSSION: This exceptional (probably the first reported) case showed the possible localization of the CC in the TM, also in the adult. Criteria for classification of a TM cholesteatoma as congenital and possible pathogenetic mechanisms are discussed.