Clinical presentation and natural history of infantile-onset ascending spastic paralysis from three families with an ALS2 founder variant.

Biallelic mutations of the alsin Rho guanine nucleotide exchange factor (ALS2) gene cause a group of overlapping autosomal recessive neurodegenerative disorders including infantile-onset ascending hereditary spastic paralysis (IAHSP), juvenile primary lateral sclerosis (JPLS), and juvenile amyotrophic lateral sclerosis (JALS/ALS2), caused by retrograde degeneration of the upper motor neurons of the pyramidal tracts. Here, we describe 11 individuals with IAHSP, aged 2-48 years, with IAHSP from three unrelated consanguineous Iranian families carrying the homozygous c.1640+1G>A founder mutation in ALS2. Three affected siblings from one family exhibit generalized dystonia which has not been previously described in families with IAHSP and has only been reported in three unrelated consanguineous families with JALS/ALS2. We report the oldest individuals with IAHSP to date and provide evidence that these patients survive well into their late 40s with preserved cognition and normal eye movements. Our study delineates the phenotypic spectrum of IAHSP and ALS2-related disorders and provides valuable insights into the natural disease course

Structural and electronic properties of chain-like structures formed by mixed PbAl dimers on Si(001) - computational DFT study

The energetics as well as structural and electronic properties of one-dimensional chains composed of mixed PbAl ad-dimers on the Si(001) surface are investigated using density functional theory. It is shown that the mixed PbAl ad-dimer chains are always energetically more stable than the corresponding homogenous Pb or Al chain configurations. This agrees with available experimental data but contradicts earlier theoretical results. It is also demonstrated that while the isolated mixed dimers and trimers are metallic, the longer chains tend to form semiconducting structures

Novel SPAST deletion and reduced DPY30 expression in a Spastic Paraplegia type 4 kindred

Background: The hereditary spastic paraplegias (HSPs) are pleiomorphic disorders of motor pathway and a large number of affected genes have been discovered. Yet, mutations in SPG4/SPAST represent the most frequent molecular etiology in autosomal dominant (AD) patients and sporadic cases. We describe a large, AD-HSP Sardinian family where 5 out of several living members harbored a novel deletion affecting also the 5′UTR of SPAST and resulting in reduced expression of DPY30, the gene located upstream SPAST in a head-to-head manner. Case presentation: A 54-year-old woman manifested leg stiffness at age 39 and required a cane to walk at age 50. Neurological examination disclosed mild spasticity and weakness in the legs, hyperreflexia in all limbs, and bilateral Babinski sign. She also complained of urinary urgency, but no additional neurological symptoms or signs were detected at examination. The clinical examination of 24 additional relatives disclosed three further affected individuals, two men and one woman. In the four symptomatic patients the initial manifestations were walking abnormalities and leg stiffness with a mean age at onset (SD) of 46.75 (5.44) years (range 39-51). The mean disease duration was 13.2 (13.4) years (range 6-35), and it correlated well with clinical severity (SPRS score) (r = 0.975, p = 0.005). One patient was confined to bed and displayed knee and ankle contractures, another case needed a cane to walk, and two individuals were able to walk without aids. Interestingly, a patient had also had a miscarriage during her first pregnancy.Gene testing revealed an heterozygous deletion spanning from the 5′-UTR to intron 4 of SPAST in the affected individuals and in one clinically unaffected woman. In three affected patients, the deletion also determined low mRNA levels of SPAST and DPY30, a component of the Set1-like multiprotein histone methyltransferase complex located upstream, head-to-head with SPAST.Conclusion: Together with data described in a Japanese family, our findings seem to suggest that genes close to spastin might be candidates in modulating the clinical phenotype. This report endorses future research on the role of neighboring genes as potential players in SPG4 disease variability

Theoretical study of the initial stages of Ba growth on Si(100) substrate

We present theoretical study based on DFT calculations of the initial stages of Ba growth on Si(100) substrate. The obtained results indicate the possibility of coexistence of the inter-row and intra-row Ba monomers, as predicted by reported earlier STM measurements – the inter-row configuration has only 0.15 eV lower energy than the intra-row system. The detailed analysis of the atomic and electronic structures of both monomers have been performed. It was found that in all cases Ba adatom tends to interact with silicon surface atoms with higher vertical position. Presented study shows that the presence of both types of Ba monomer increases the local chemical reactivity of silicon surface, however this effect is stronger for the inter-row configuration. It was shown that such modification of substrate reactivity influences the form of the further aggregation of Ba adatoms. The obtained results indicate the tendency to formation by adatoms of linear-zigzag chains across the surface dimer rows, which seems to be in the agreement with reported earlier STM data

Self-organisation of inorganic elements on Si(001) mediated by pre-adsorbed organic molecules

A combined theoretical and experimental study on the adsorption of an isolated benzonitrile molecule on the Si(001) surface, followed by the adsorption of Al (group III), Pb (carbon group) and Ag (transition metal) is presented.</p

P11 QUICK PREVENTION OF THE POTENTIALLY SERIOUS CONSEQUENCES OF ELECTROMAGNETIC INTERFERENCE ON A ICD PATIENT THANKS TO THE REMOTE MONITORING SYSTEM OF THE DEVICE

Abstract Clinical Case We report the case of a 84–year–old female patient suffering from post–infarct heart disease with severe systolic dysfunction, wearing a dual–chamber defibrillator in secondary prevention because she had previously presented an episode of monomorphic ventricular tachycardia. After the implant, the patient was enrolled in the remote monitoring service of the device and constantly followed by our team. After a few months, at the remote control we found repeated episodes of very short duration of an alarm recognized by the device as ventricular arrhythmia in the VF window. Contrary to the arrhythmic interpretation of the device, the analysis of the EGM by the medical and nursing staff highlighted an electromagnetic interference defined by the type of signal, the presence of the same in all channels and by the lack of correlation with the underlying heart rhythm. The sensing of the ventricular lead was 5–6 mV, at the lower limits but stable over time, the other parameters were optimal. The patient was promptly contacted and questioned about the circumstances and symptoms: she was asymptomatic and we found that the interference came in conjunction with the use of a cordless telephone. The alarm was related to the electromagnetic field generated by the phone and the woman was asked to stop using the device with subsequent absence of device alarms. Electromagnetic interference in defibrillators can be a cause of potentially serious inappropriate therapies (ATP, pacing and shock), the analysis and correct interpretation of the EGM by the clinician is essential for the prevention of the same. Thanks to the efficiency of the remote monitoring service, the risk of serious consequences for our patient was avoided. Subsequently the lead was repositioned due to a worsening of the sensing, but even before the re–intervention there was no longer any false alarm thanks to the absence of the environmental source of interference. The remote monitoring service applied to implantable defibrillation systems is a valuable tool for identifying lead problems or, as in this case, environmental problems, and toprevent, thanks to rapid intervention, further potentially serious complications. </jats:sec