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

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

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

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

Valorization of Ferulic Acid from Agro-Industrial by-Products for Application in Agriculture

The use of bioplastic mulch in agriculture has increased dramatically in the last years throughout the world. Nowadays, biodegradable materials for mulching films strive to constitute a reliable and more sustainable alternative to classical materials such as polyethylene (PE). The main challenge is to improve their durability in the soil to meet the required service length for crop farming by using benign and sustainable antioxidant systems. Here, we report the design and fabrication of biodegradable materials based on polybutylene (succinate adipate) (PBSA) for mulching applications, incorporating a fully biobased polymeric antioxidant deriving from ferulic acid, which can be extracted from an industrial by-product. Poly-dihydro (ethylene ferulate) (PHEF) from ferulic acid was synthesized by a two-step polymerization process. It is characterized by improved thermal stability in comparison with ferulic acid monomer and therefore suitable for common industrial processing conditions. Different blends of PBSA and PHEF obtained by melt mixing or by reactive extrusion were prepared and analyzed to understand the effect of the presence of PHEF. The results demonstrate that PHEF, when processed by reactive extrusion, presents a remarkable antioxidant effect, even in comparison with commercial additives, preserving a high level of the mechanical properties of the PBSA matrix without affecting the biodegradable character of the blend

Onset of Darcy-B\ue9nard convection under throughflow of a shear-thinning fluid

We present an investigation on the onset of Darcy-B\ue9nard instability in a two-dimensional porous medium saturated with a non-Newtonian fluid and heated from below in the presence of a uniform horizontal pressure gradient. The fluid is taken to be of power-law nature with constant rheological index and temperature-dependent consistency index. A two-dimensional linear stability analysis in the vertical plane yields the critical wavenumber and the generalised critical Rayleigh number as functions of dimensionless problem parameters, with a non-monotonic dependence from and with maxima/minima at given values of , a parameter representing the effects of consistency index variations due to temperature. A series of experiments are conducted in a Hele-Shaw cell of aspect ratio to provide a verification of the theory. Xanthan Gum mixtures (nominal concentration from 0.10 % to 0.20 %) are employed as working fluids with a parameter range and. The experimental critical wavenumber corresponding to incipient instability of the convective cells is derived via image analysis for different values of the imposed horizontal velocity. Theoretical results for critical wavenumber favourably compare with experiments, systematically underestimating their experimental counterparts by 10 % at most. The discrepancy between experiments and theory is more relevant for the critical Rayleigh number, with theory overestimating the experiments by a maximum factor less than two. Discrepancies are attributable to a combination of factors: nonlinear phenomena, possible subcritical bifurcations, and unaccounted-for disturbing effects such as approximations in the rheological model, wall slip, ageing and degradation of the fluid properties