Biochemical data from the characterization of a new pathogenic mutation of human pyridoxine-5'-phosphate oxidase (PNPO)

PNPO deficiency is responsible of severe neonatal encephalopathy, responsive to pyridoxal-5’-phosphate (PLP) or pyridoxine. Recent studies widened the phenotype of this condition and detected new genetic variants on PNPO gene, whose pathogenetic role and clinical expression remain to be established. One of these mutations, Arg116Gln, is of particular interest because of its later onset of symptoms (beyond the first months of life) and its peculiar epileptic manifestations in patients. This protein variant was expressed as recombinant protein in E coli, purified to homogeneity, and characterized with respect to structural and kinetic properties, stability, binding constants of cofactor flavin mononucleotide (FMN) and product (PLP) in order to define the molecular and structural bases of its pathogenicity. For interpretation and discussion of reported data, together with the description of clinical studies, refer to the article [7][1] (doi: 10.1016/j.ymgme.2017.08.003)

Observation of replica symmetry breaking in disordered nonlinear wave propagation

A landmark of statistical mechanics, spin-glass theory describes critical phenomena in disordered systems that range from condensed matter to biophysics and social dynamics. The most fascinating concept is the breaking of replica symmetry: identical copies of the randomly interacting system that manifest completely different dynamics. Replica symmetry breaking has been predicted in nonlinear wave propagation, including Bose-Einstein condensates and optics, but it has never been observed. Here, we report the experimental evidence of replica symmetry breaking in optical wave propagation, a phenomenon that emerges from the interplay of disorder and nonlinearity. When mode interaction dominates light dynamics in a disordered optical waveguide, different experimental realizations are found to have an anomalous overlap intensity distribution that signals a transition to an optical glassy phase. The findings demonstrate that nonlinear propagation can manifest features typical of spin-glasses and provide a novel platform for testing so-far unexplored fundamental physical theories for complex systems

Anti-diffracting beams through the diffusive optical nonlinearity

Anti-diffraction is a theoretically predicted nonlinear optical phenomenon that occurs when a light beam spontaneously focalizes independently of its intensity. We observe anti-diffracting beams supported by the peak-intensity-independent diffusive nonlinearity that are able to shrink below their diffraction-limited size in photorefractive lithium-enriched potassium-tantalate-niobate (KTN:Li)

Aging solitons in photorefractive dipolar glasses

We study experimentally the aging of optical spatial solitons in a dipolar glass hosted by a nanodisordered sample of photorefractive potassium-sodium-tantalate-niobate (KNTN). As the system ages, the waves erratically explore varying strengths of the nonlinear response, causing them to break up and scatter. We show that this process can still lead to solitons, but in a generalized form for which the changing response is compensated by changing the normalized wave size and intensity so as to maintain fixed the optical waveform

Photorefractive light needles in glassy nanodisordered KNTN

We study the formation of 2D self-trapped beams in nanodisordered potassium-sodium-tantalate-niobate (KNTN) cooled below the dynamic glass transition. Supercooling is shown to accelerate the photorefractive response and enhance steady-state anisotropy. Effects in the excited state are attributed to the anomalous slim-loop polarization curve typical of relaxors dominated by non-interacting polar-nano-regions

Observation of an intrinsic nonlinearity in the electro-optic response of freezing relaxors ferroelectrics

We demonstrate an electro-optic response that is linear in the amplitude but independent of the sign of the applied electric field. The symmetry-preserving linear electro-optic effect emerges at low applied electric fields in freezing nanodisordered KNTN above the dielectric peak temperature, deep into the nominal paraelectric phase. Strong temperature dependence allows us to attribute the phenomenon to an anomalously reduced thermal agitation in the reorientational response of the underlying polar-nanoregions

Remote multiparametric monitoring and management of heart failure patients through cardiac implantable electronic devices

In this review we focus on heart failure (HF) which, as known, is associated with a substantial risk of hospitalizations and adverse cardiovascular outcomes, including death. In recent years, systems to monitor cardiac function and patient parameters have been developed with the aim to detect subclinical pathophysiological changes that precede worsening HF. Several patient-specific parameters can be remotely monitored through cardiac implantable electronic devices (CIED) and can be combined in multiparametric scores predicting patients' risk of worsening HF with good sensitivity and moderate specificity. Early patient management at the time of pre-clinical alerts remotely transmitted by CIEDs to physicians might prevent hospitalizations. However, it is not clear yet which is the best diagnostic pathway for HF patients after a CIED alert, which kind of medications should be changed or escalated, and in which case in-hospital visits or in-hospital admissions are required. Finally, the specific role of healthcare professionals involved in HF patient management under remote monitoring is still matter of definition. We analyzed recent data on multiparametric monitoring of patients with HF through CIEDs. We provided practical insights on how to timely manage CIED alarms with the aim to prevent worsening HF. We also discussed the role of biomarkers and thoracic echo in this context, and potential organizational models including multidisciplinary teams for remote care of HF patients with CIEDs

Super-crystals in composite ferroelectrics

As atoms and molecules condense to form solids, a crystalline state can emerge with its highly ordered geometry and subnanometric lattice constant. In some physical systems, such as ferroelectric perovskites, a perfect crystalline structure forms even when the condensing substances are non-stoichiometric. The resulting solids have compositional disorder and complex macroscopic properties, such as giant susceptibilities and non-ergodicity. Here, we observe the spontaneous formation of a cubic structure in composite ferroelectric potassium– lithium–tantalate–niobate with micrometric lattice constant, 104 times larger than that of the underlying perovskite lattice. The 3D effect is observed in specifically designed samples in which the substitutional mixture varies periodically along one specific crystal axis. Laser propagation indicates a coherent polarization super-crystal that produces an optical X-ray diffractometry, an ordered mesoscopic state of matter with important implications for critical phenomena and applications in miniaturized 3D optical technologies

Bilateral temporal lobe dysplasia and seizure onset associated with biallelic CNTNAP2 variants

Biallelic CNTNAP2 variants have been associated with Pitt-Hopkins like syndrome. We describe six novel and one previously reported patients from six independent families and review the literature including 64 patients carrying biallelic CNTNAP2 variants. Initial reports highlighted intractable focal seizures and the failure of epilepsy surgery in children, but subsequent reports did not expand on this aspect. In all our patients (n=7), brain MRI showed bilateral temporal grey/white matter blurring with white matter high signal intensity, more obvious in the T2-FLAIR sequences, consistent with bilateral temporal lobe dysplasia. All patients had focal seizures with temporal lobe onset and semiology, which were recorded in five, showing bilateral independent temporal onset in four. Epilepsy was responsive to anti-seizure medications in two patients (2/7, 28.5%), and pharmaco-resistant in five (5/7, 71.5%). Splice-site variants identified in five patients (5/7, 71.5%) were the most common mutational finding. Our observation expands the phenotypic and genetic spectrum of biallelic CNTNAP2 alterations focusing on the neuroimaging features and provides evidence for an elective bilateral anatomoelectroclinical involvement of the temporal lobes in the associated epilepsy with relevant implications on clinical management