Clinical and biochemical response to neridronate treatment in a patient with osteoporosis-pseudoglioma syndrome (OPPG)

Osteoporosis-pseudoglioma syndrome (OPPG) is a rare autosomal recessive syndrome characterized by juvenile-onset osteoporosis and ocular abnormalities due to a low-density lipoprotein receptor-related protein 5 (LRP5) gene mutation. Treatment with bisphosphonates, particularly with pamidronate and risedronate, has been reported to be of some efficacy in this condition. We report on a patient with OPPG due to an LRP5 gene mutation, who showed an encouraging response after a 36-month period of neridronate therapy. We report a case of a patient treated with bisphosphonates. Bisphosphonates should be administered in OPPG patients as a first-line therapy during early childhood

Serum creatine kinase isoenzymes in children with osteogenesis imperfecta

This study evaluates serum creatine kinase isoenzyme activity in children with osteogenesis imperfecta to determine its usefulness as a biochemical marker during treatment with bisphosphonate. The changes of creatine kinase (CK) isoenzyme activity during and after discontinuation therapy were observed. These results could be useful in addressing over-treatment risk prevention. Introduction The brain isoenzyme of creatine kinase (CKbb) is highly expressed in mature osteoclasts during osteoclastogenesis, thus plays an important role in bone resorption. We previously identified high serum CKbb levels in 18 children with osteogenesis imperfect (OI) type 1 treated for 1 year with bisphosphonate (neridronate). In the present study, serum CK isoenzymes were evaluated in the same children with continuous versus discontinued neridronate treatment over a further 2-year follow-up period. Methods This study included 18 children with OI type 1, 12 with continued (group A) and 6 with ceased (group B) neridronate treatment. Auxological data, serum biochemical markers of bone metabolism, bone mineral density z-score, and serum total CK and isoenzyme activities were determined in both groups. Results Serum CKbb was progressively and significantly increased in group A (p < 0.004) but rapidly decreased to undetectable levels in group B. In both groups, the cardiac muscle creatine kinase isoenzyme (CKmb) showed a marked decrease, while serum C-terminal telopeptide (CTx) levels were almost unchanged. Conclusions This study provides evidence of the cumulative effect of neridronate administration in increasing serum CKbb levels and the reversible effect after its discontinuation. This approach could be employed for verifying the usefulness of serum CKbb as a biochemical marker in patients receiving prolonged bisphosphonate treatment. Moreover, the decreased serum CKmb levels suggest a systemic effect of these drugs

A Complex Mantle Plume Head Below East Africa-Arabia Shaped by the Lithosphere-Asthenosphere Boundary Topography

Hot plumes rising from Earth's deep mantle are thought to cause uplift, rifting and large igneous province (LIP) emplacement. LIP volcanism in continents often spans tens of Ma and scatters unevenly over broad areas. This has been attributed to lateral flow of hot plume material, but observational evidence on such flow is scarce. New waveform tomography with massive data sets reveals detailed seismic velocity structure beneath the East Africa-Arabia region, where these processes occur at present. It shows interconnected sub-lithospheric corridors of hot, partially molten rock, fed by three mantle upwellings beneath Kenya, Afar, and Levant. The spatio-temporal distribution of the volcanism suggests that we are witnessing an integral plume head, which morphed into a three-pointed star by ponding and channeling within thin-lithosphere corridors. Plate reconstructions indicate that it spread south-to-north since ∼45 Ma. These results suggest that complex-shape plume heads can explain the enigmatic, scattered LIP volcanism and are, probably, an inherent feature of plume-continent interaction

Revisiting the geodynamics of the Middle East region from an integrated geophysical perspective

A long-standing question in geodynamics is whether mantle flow is driven by the plate motion alone, or mantle upwelling makes a significant contribution to it. Subducting slabs and lateral variations of the continental lithosphere can further influence the asthenospheric flow and control its direction. The Middle East region (MER) is a complex continental setting where different processes such as rifting, break-up, plate collision, and tectonic escape kinematically interact with each other. In this context, the role that lithospheric structure, mantle flow, and active upwellings may play is debated. Tomographic images provide a snapshot of the current thermal conditions of a region and seismic anisotropy can also help resolve mantle convection. Here, we synthesize shear-wave splitting observations together with up-to-date tomography models of the mantle structure beneath the MER and other geophysical data. Low-velocity anomalies are seen at asthenospheric depths beneath W Arabia, NW Iran, and Anatolia, suggesting a spreading zone of warm mantle. Two deep low-velocity bodies in Afar and Levant –interpreted as hot mantle plumes– are the sources of this shallower mantle flow. Where low velocities are imaged, we observe predominantly NE–SW oriented anisotropy, anomalously high topography, and abundant basaltic volcanism. The integrated analysis suggests that a horizontal component associated with active upwelling is present in the upper-mantle flow field. The large-scale circulation flow fed by the Afar and Levant Plumes, aided by the subduction-induced forces, facilitates the lateral motion of the Anatolian microplate and affects the dynamic evolution of the Zagros orogen. The proposed scenario demonstrates that the interplay between plate-tectonic events and mantle dynamics controls the kinematics of the region and can explain the general patterns of deformation observed at the surface

Evolution of Conversations in the Age of Email Overload

Email is a ubiquitous communications tool in the workplace and plays an important role in social interactions. Previous studies of email were largely based on surveys and limited to relatively small populations of email users within organizations. In this paper, we report results of a large-scale study of more than 2 million users exchanging 16 billion emails over several months. We quantitatively characterize the replying behavior in conversations within pairs of users. In particular, we study the time it takes the user to reply to a received message and the length of the reply sent. We consider a variety of factors that affect the reply time and length, such as the stage of the conversation, user demographics, and use of portable devices. In addition, we study how increasing load affects emailing behavior. We find that as users receive more email messages in a day, they reply to a smaller fraction of them, using shorter replies. However, their responsiveness remains intact, and they may even reply to emails faster. Finally, we predict the time to reply, length of reply, and whether the reply ends a conversation. We demonstrate considerable improvement over the baseline in all three prediction tasks, showing the significant role that the factors that we uncover play, in determining replying behavior. We rank these factors based on their predictive power. Our findings have important implications for understanding human behavior and designing better email management applications for tasks like ranking unread emails.Comment: 11 page, 24th International World Wide Web Conferenc

Bio-based furan-polyesters/graphene nanocomposites prepared by in situ polymerization

In situ intercalative polymerization has been investigated as a strategic way to obtain poly(propylene 2,5-furandicarboxylate) (PPF) and poly(hexamethylene 2,5-furandicarboxylate) (PHF) nanocomposites with different graphene types and amounts. Graphene (G) has been dispersed in surfactant stabilized water suspensions. The loading range in composites was 0.25–0.75 wt %. For the highest composition, a different type of graphene (XT500) dispersed in 1,3 propanediol, containing a 6% of oxidized graphene and without surfactant has been also tested. The results showed that the amorphous PPF is able to crystallize during heating scan in DSC and graphene seems to affect such capability: G hinders the polymer chains in reaching an ordered state, showing even more depressed cold crystallization and melting. On the contrary, such hindering effect is absent with XT500, which rather induces the opposite. Concerning the thermal stability, no improvement has been induced by graphene, even if the onset degradation temperatures remain high for all the materials. A moderate enhancement in mechanical properties is observed in PPF composite with XT500, and especially in PHF composite, where a significative increase of 10–20% in storage modulus E’ is maintained in almost all the temperature range. Such an increase is also reflected in a slightly higher heat distortion temperature. These preliminary results can be useful in order to further address the field of application of furan-based polyesters; in particular, they could be promising as packaging materials

Autophagy as a gateway for the effects of methamphetamine: From neurotransmitter release and synaptic plasticity to psychiatric and neurodegenerative disorders.

As a major eukaryotic cell clearing machinery, autophagy grants cell proteostasis, which is key for neurotransmitter release, synaptic plasticity, and neuronal survival. In line with this, besides neuropathological events, autophagy dysfunctions are bound to synaptic alterations that occur in mental disorders, and early on, in neurodegenerative diseases. This is also the case of methamphetamine (METH) abuse, which leads to psychiatric disturbances and neurotoxicity. While consistently altering the autophagy machinery, METH produces behavioral and neurotoxic effects through molecular and biochemical events that can be recapitulated by autophagy blockade. These consist of altered physiological dopamine (DA) release, abnormal stimulation of DA and glutamate receptors, as well as oxidative, excitotoxic, and neuroinflammatory events. Recent molecular insights suggest that METH early impairs the autophagy machinery, though its functional significance remains to be investigated. Here we discuss evidence suggesting that alterations of DA transmission and autophagy are intermingled within a chain of events underlying behavioral alterations and neurodegenerative phenomena produced by METH. Understanding how METH alters the autophagy machinery is expected to provide novel insights into the neurobiology of METH addiction sharing some features with psychiatric disorders and parkinsonism

Experimental Evidence of Amplitude-Dependent Surface Wave Dispersion via Nonlinear Contact Resonances

In this letter, we provide an experimental demonstration of amplitude-dependent dispersion tuning of surface acoustic waves interacting with nonlinear resonators. Leveraging the similarity between the dispersion properties of plate edge waves and surface waves propagating in a semi-infinite medium, we use a setup consisting of a plate with a periodic arrangement of bead-magnet resonators along one of its edges. Nonlinear contact between the ferromagnetic beads and magnets is exploited to realize nonlinear local resonance effects. First, we experimentally demonstrate the nonlinear softening nature and amplitude-dependent dynamics of a single bead-magnet resonator on both rigid and compliant substrates. Next, the dispersion properties of the system in the linear regime are investigated. Finally, we demonstrate how the interplay of nonlinear local resonances with plate edge waves gives rise to amplitude-dependent dispersion properties. The findings will inform the design of more versatile surface acoustic wave devices that can passively adapt to loading conditions.Comment: 6 pages, 5 figures, 2 table

Wavepacket instability in a rectangular porous channel uniformly heated from below

This paper is aimed to investigate the transition to absolute instability in a porous layer with horizontal throughflow. The importance of this analysis is due to the possible experimental failure to detect growing perturbations which are localised in space and which may be convected away by the throughflow. The instability of the uniform flow in a horizontal rectangular channel subject to uniform heating from below and cooled from above is studied. While the lower wall is modelled as an impermeable isoflux plane, the upper wall is assumed to be impermeable and imperfectly conducting, so that a Robin temperature condition with a given Biot number is prescribed. The sidewalls are assumed to be adiabatic and impermeable. The basic state considered here is a stationary parallel flow with a vertical uniform temperature gradient, namely the typical configuration describing the Darcy–Bénard instability with throughflow. The linear instability of localised wavepackets is analysed, thus detecting the parametric conditions for the transition to absolute instability. The absolute instability is formulated through an eigenvalue problem based on an eighth–order system of ordinary differential equations. The solution is sought numerically by utilising the shooting method. The threshold to absolute instability is detected versus the Péclet number associated with the basic flow rate along the channel