Clinical comparison of 10q26 overlapping deletions: delineating the critical region for urogenital anomalies.

The 10q26 deletion syndrome is a clinically heterogeneous disorder. The most common phenotypic characteristics include pre- and/or postnatal growth retardation, microcephaly, developmental delay/intellectual disability and a facial appearance consisting of a broad nasal bridge with a prominent nose, low-set malformed ears, strabismus, and a thin vermilion of the upper lip. In addition, limb and cardiac anomalies as well as urogenital anomalies are occasionally observed. In this report, we describe three unrelated females with 10q26 terminal deletions who shared clinical features of the syndrome, including urogenital defects. Cytogenetic studies showed an apparently de novo isolated deletion of the long arm of chromosome 10, with breakpoints in 10q26.1, and subsequent oligo array-CGH analysis confirmed the terminal location and defined the size of the overlapping deletions as ∼ 13.46, ∼ 9.31 and ∼ 9.17 Mb. We compared the phenotypic characteristics of the present patients with others reported to have isolated deletions and we suggest that small 10q26.2 terminal deletions may be associated with growth retardation, developmental delay/intellectual disability, craniofacial features and external genital anomalies whereas longer terminal deletions affecting the 10q26.12 and/or 10q26.13 regions may be responsible for renal/urinary tract anomalies. We propose that the haploinsufficiency of one or several genes located in the 10q26.12-q26.13 region may contribute to the renal or urinary tract pathogenesis and we highlight the importance of FGFR2 and probably of CTBP2 as candidate genes.

STEM-EELS analysis reveals stable high-density He in nanopores of amorphous silicon coatings deposited by magnetron sputtering.

A broad interest has been showed recently on the study of nanostructuring of thin films and surfaces obtained by low-energy He plasma treatments and He incorporation via magnetron sputtering. In this paper spatially resolved electron energy-loss spectroscopy in a scanning transmission electron microscope is used to locate and characterize the He state in nanoporous amorphous silicon coatings deposited by magnetron sputtering. A dedicated MATLAB program was developed to quantify the helium density inside individual pores based on the energy position shift or peak intensity of the He K-edge. A good agreement was observed between the high density (∼35-60 at nm(-3)) and pressure (0.3-1.0 GPa) values obtained in nanoscale analysis and the values derived from macroscopic measurements (the composition obtained by proton backscattering spectroscopy coupled to the macroscopic porosity estimated from ellipsometry). This work provides new insights into these novel porous coatings, providing evidence of high-density He located inside the pores and validating the methodology applied here to characterize the formation of pores filled with the helium process gas during deposition. A similar stabilization of condensed He bubbles has been previously demonstrated by high-energy He ion implantation in metals and is newly demonstrated here using a widely employed methodology, magnetron sputtering, for achieving coatings with a high density of homogeneously distributed pores and He storage capacities as high as 21 at%.

Array CGH detection of a novel cryptic deletion at 3q13 in a complex chromosome rearrangement.

Complex chromosome rearrangements (CCRs) are extremely rare in humans. About 20% of the apparently balanced CCRs have an abnormal phenotype and the degree of severity correlates with a higher number of breakpoints. Several studies using FISH and microarray technologies have shown that deletions in the breakpoints are common although duplications, insertions and inversions have also been detected. We report a patient with two simultaneous reciprocal translocations, t(3;4) and t(2;14;18), involving five chromosomes and six breakpoints. He showed dysmorphic features, preaxial polydactyly in the left hand, brachydactyly, postnatal growth retardation and developmental delay. The rearrangement was characterized by FISH analysis which detected an interstitial segment from chromosome 14 inserted in the derivative chromosome 2, and by whole genome array which revealed an interstitial deletion of approximately 4.5 Mb at the breakpoint site on chromosome 3. To our knowledge this microdeletion has not been previously reported and includes ~12 genes. The haploinsufficiency of one or several of these genes is likely to have contributed to the clinical phenotype of the patient.

Intrachromosomal 3p insertion as a cause of reciprocal pure interstitial deletion and duplication in two siblings: further delineation of the emerging proximal 3p deletion syndrome.

Very few cases of constitutional interstitial deletions of the proximal short arm of chromosome 3 have been reported; however, the proximal 3p deletion is emerging as a clinically recognizable syndrome. We present an intrachromosomal insertion of 3p12.3p14.1 in a phenotypic normal man (46,XY,ins(3)(p25p12.3p14.1)) which is responsible for the unbalanced karyotype in 2 affected offspring, one with a 3p12.3p14.1 interstitial deletion and the other with a reciprocal duplication. The exceptionality of these 2 reciprocal recombinants contributes to a better definition of the proximal 3p deletion syndrome and its duplication counterpart.

A nanoscale characterization with electron microscopy of multilayered CrAlYN coatings: a singular functional nanostructure.

A combination of transmission electron microscopy techniques and spatially resolved microanalysis is used to investigate the nanostructure, constituting phases, and chemical elemental distribution in CrAlYN multilayered coatings. The location of the metallic elements and their chemical state are needed to understand their functional properties. Samples were prepared with variable Al (4-12 at%) and Y (2-5 at%) contents by direct current reactive magnetron sputtering on silicon substrates using metallic targets and Ar/N2 mixtures under different deposition parameters (power applied to the target and rotation speed of the sample holder). The changes produced in the nanostructure and chemical distribution were investigated. Nanoscale resolution electron microscopy analysis has shown that these coatings present a singular nanostructure formed by multilayers containing at a certain periodicity nanovoids filled with molecular nitrogen. Spatially resolved energy dispersive spectroscopy and electron energy loss elemental mappings and profiles showed that the chromium, aluminum, and yttrium atoms are distributed in a sequential way following the position of the targets inside the deposition chamber. Analysis of the different atomic distribution and phases formed at the nanoscale is discussed depending on the deposition parameters.

Tomographic heating holder for in situ TEM: study of Pt/C and PtPd/Al2O3 catalysts as a function of temperature.

A tomographic heating holder for transmission electron microscopy that can be used to study supported catalysts at temperatures of up to ~1,500°C is described. The specimen is placed in direct thermal contact with a tungsten filament that is oriented perpendicular to the axis of the holder without using a support film, allowing tomographic image acquisition at high specimen tilt angles with minimum optical shadowing. We use the holder to illustrate the evolution of the active phases of Pt nanoparticles on carbon black and PtPd nanoparticles on γ-alumina with temperature. Particle size distributions and changes in active surface area are quantified from tilt series of images acquired after subjecting the specimens to increasing temperatures. The porosity of the alumina support and the sintering mechanisms of the catalysts are shown to depend on distance from the heating filament.

Synergistic Effect of He for the Fabrication of Ne and Ar Gas-Charged Silicon Thin Films as Solid Targets for Spectroscopic Studies.

Sputtering of silicon in a He magnetron discharge (MS) has been reported as a bottom-up procedure to obtain He-charged silicon films (i.e., He nanobubbles encapsulated in a silicon matrix). The incorporation of heavier noble gases is demonstrated in this work with a synergistic effect, producing increased Ne and Ar incorporations when using He-Ne and He-Ar gas mixtures in the MS process. Microstructural and chemical characterizations are reported using ion beam analysis (IBA) and scanning and transmission electron microscopies (SEM and TEM). In addition to gas incorporation, He promotes the formation of larger nanobubbles. In the case of Ne, high-resolution X-ray photoelectron and absorption spectroscopies (XPS and XAS) are reported, with remarkable dependence of the Ne 1s photoemission and the Ne K-edge absorption on the nanobubble's size and composition. The gas (He, Ne and Ar)-charged thin films are proposed as "solid" targets for the characterization of spectroscopic properties of noble gases in a confined state without the need for cryogenics or high-pressure anvils devices. Also, their use as targets for nuclear reaction studies is foreseen.

Digital PCR Improves Sensitivity and Quantification in Monitoring CAR-T Cells in B Cell Lymphoma Patients.

Chimeric antigen receptor T cells (CAR-T) has emerged as a promising therapy, over 60% of patients fail to sustain a long-term response. The underlying factors that leads to the effectiveness of this therapy are not completely understood, CAR-T cell persistence and monitoring seems to be pivotal for ensuring a successful response. Various monitoring methods such as multiparametric flow cytometry (MFC) or quantitative PCR (qPCR) have been applied. Our objective is to develop digital PCR (dPCR) assays for detection and quantification of CAR-T cells, comparing them with MFC and qPCR. Samples taken at different follow-up times from 45 patients treated with CAR-T therapy were analyzed to assess the correlation between the different methodologies. dPCR presented a high correlation with MFC and qPCR (r = 0.97 and r = 0.87, respectively), while offering a higher sensitivity (0.01%) compared to MFC (0.1%) and qPCR (1%). dPCR emerged as an alternative and highly sensitivity method for monitoring CAR-T cell dynamics. This technique is well-suited for implementation in clinical practice as a complementary technique to MFC.

Trisomy 18p caused by a supernumerary marker with a chromosome 13/21 centromere: a possible recurrent chromosome aberration.

We present a clinical and molecular cytogenetic characterization of two new patients with a complex supernumerary marker consisting of the entire short arm of chromosome 18 with a chromosome 13/21 centromere. One patient is a girl with a nonsyndromic intellectual disability and the second is a prenatally diagnosed fetus. To our knowledge, these are the fourth and fifth such cases to be described in the literature, suggesting the existence of a possible recurring constitutional structural chromosome abnormality.

Pre- and postnatal findings in a patient with a novel rec(8)dup(8q)inv(8)(p23.2q22.3) associated with San Luis Valley syndrome.

San Luis Valley syndrome, which is due to a recombinant chromosome 8 (SLV Rec8) found in Hispanic individuals from Southwestern United States, is a well-established syndrome associated with intellectual disabilities and, frequently, severe cardiac anomalies. We report for the first time on a Moroccan girl with a recombinant chromosome 8 prenatally diagnosed as SLV Rec8 by conventional cytogenetic studies. At birth, an oligo array-CGH (105 K) defined the breakpoints and the size of the imbalanced segments, with a deletion of ≈ 2.27 Mb (8p23.2-pter) and a duplication of ≈ 41.93 Mb (8q22.3-qter); thus this recombinant chromosome 8 differed from that previously reported in SLV Rec8 syndrome. The phenotypic characteristics associated with this SLV Rec8 genotype overlap those commonly found in patients with 8q duplication reported in the literature. We review SLV Rec8 and other chromosome 8 aberrations and suggest that the overexpression of cardiogenic genes located at 8q may be the cause of the cardiac defects in this patient.

Multiple interatrial electrical connection after heart transplantation.

A 62-year-old woman who underwent heart transplantation 6 years later presented a regular atrial tachycardia. Electrophysiologic evaluation showed an atrial arrhythmia in the recipient atrium with 2:1 conduction to the donor atrium, with a confusing electroanatomical map. With the suspect of alternant conduction through two different breakthroughs, the map was split in two concordant maps, corresponding to two connections that were successfully ablated. Later on, a third connection was detected and therefore ablated.

Microstructural and chemical characterization of nanostructured TiAlSiN coatings with nanoscale resolution.

Nanoscale resolution electron microscopy analysis combined with ion beam assisted techniques are presented here, to give answers to full characterization of morphology, growth mode, phase formation, and compositional distribution in nanocomposite TiAlSiN coatings deposited under different energetic conditions. Samples were prepared by magnetron sputtering, and the effects of substrate temperature and bias were investigated. The nanocomposite microstructure was demonstrated by the formation of a face-centered cubic (Ti,Al)N phase, obtained by substitution of Al in the cubic titanium nitride (c-TiN) phase, and an amorphous matrix at the column boundary regions mainly composed of Si, N (and O for the samples with higher oxygen contents). Oxygen impurities, predicted as the principal responsible for the degradation of properties, were identified, particularly in nonbiased samples and confirmed to occupy preferentially nitrogen positions at the column boundaries, being mainly associated to silicon forming oxynitride phases. It has been found that the columnar growth mode is not the most adequate to improve mechanical properties. Only the combination of moderate bias and additional substrate heating was able to reduce the oxygen content and eliminate the columnar microstructure leading to the nanocomposite structure with higher hardness (>30 GPa).

Pd-C Catalytic Thin Films Prepared by Magnetron Sputtering for the Decomposition of Formic Acid.

Formic acid is an advantageous liquid organic hydrogen carrier. It is relatively nontoxic and can be synthesized by the reaction of CO2 with sustainable hydrogen or by biomass decomposition. As an alternative to more widely studied powdery catalysts, supported Pd-C catalytic thin films with controlled nanostructure and compositions were newly prepared in this work by magnetron sputtering on structured supports and tested for the formic acid decomposition reaction. A two-magnetron configuration (carbon and tailored Pd-C targets) was used to achieve a reduction in Pd consumption and high catalyst surface roughness and dispersion by increasing the carbon content. Activity and durability tests were carried out for the gas phase formic acid decomposition reaction on SiC foam monoliths coated with the Pd-C films and the effects of column width, surface roughness and thermal pre-reduction time were investigated. Activity of 5.04 molH2·gPd-1·h-1 and 92% selectivity to the dehydrogenation reaction were achieved at 300 °C for the catalyst with a lower column width and higher carbon content and surface roughness. It was also found that deactivation occurs when Pd is sintered due to the elimination of carbon and/or the segregation and agglomeration of Pd upon cycling. Magnetron sputtering deposition appears as a promising and scalable route for the one-step preparation of Pd-C catalytic films by overcoming the different deposition characteristics of Pd and C with an appropriate experimental design.

Molecular characterization of a new patient with a non-recurrent inv dup del 2q and review of the mechanisms for this rearrangement.

We report on newborn baby with microcephaly, facial anomalies, congenital heart defects, hypotonia, wrist contractures, long fingers, adducted thumbs, and club feet. Cytogenetic studies revealed an inverted duplication with terminal deletion (inv dup del) of 2q in the patient and a paternal 2qter deletion polymorphism. Microsatellite markers demonstrated that the inv dup del was maternal in origin and intrachromosomal. Intra or interchromosomal rearrangements may cause this aberration either by a U-type exchange (end-to-end fusion), an unequal crossover between inverted repeats (non-allelic homologous recombination: NAHR), or through breakage-fusion-bridge (BFB) cycles leading to a sister chromatid fusion by non-homologous end joining (NHEJ). A high-resolution oligo array-CGH (244 K) defined the breakpoints and did not detect a single copy region with a size exceeding 12.93 Kb in the fusion site. The size of the duplicated segment was 38.75 Mb, extending from 2q33.1 to 2q37.3 and the size of the terminal deletion was 2.85 Mb in 2q37.3. Our results indicate that the inv dup del (2q) is likely a non-recurrent chromosomal rearrangement generated by a NHEJ mechanism. The major clinical characteristics associated with this 2q rearrangement overlap with those commonly found in patients with 2q duplication reported in the literature.

Characterization of a de novo complex chromosomal rearrangement in a patient with cri-du-chat and trisomy 5p syndromes.

Two syndromes with abnormalities of the short arm of chromosome 5 have been described: cri-du-chat (resulting from 5p deletion) and trisomy 5p. We report for the first time a patient with both syndromes, resulting from a complex chromosomal rearrangement with an inverted duplication of 5p13.1-p14.2, a deletion of 5p14.2-pter, and a duplication of 5p12, characterized by array-CGH and BAC clones. The patient showed phenotypic characteristics of both syndromes and died at 3 months of age as a result of cardiorespiratory failure, probably associated with the clinical severity of the trisomy 5p syndrome. We propose a potential causative mechanism for this rearrangement.

[Conjunctivodacryocystorhinostomy with the assistance of diode laser. Endoscopic placement of Jones lacrimal tubes]. / Conjuntivodacriocistorrinostomía con láser diodo. Inserción endoscópica de tubos de Jones.

OBJECTIVE: To describe and assess a surgical technique for cases of complete bicanalicular lachrymal destruction by means of the endoscopic insertion use of the Jones tube with a diode laser to study functionality and complications. PATIENTS AND METHOD: A descriptive study of a case series with 24 consecutive patients with complete bicanalicular obstruction who underwent conjunctivodacryocystorhinostomy with diode laser. The surgery time, intra-operative and post-operative complications, long-term patency, and need for secondary revision were evaluated. RESULTS: Twenty-four consecutive patients were included in the study. All surgical procedures were successfully performed without significant complications. Average operating time was 15 minutes. The length of the tubes used ranged from 17 to 26 mm. Patients were evaluated at 24 hours, 3 weeks, 3 months, and 6 months and then every 6 months. The most frequent post-surgical complication was the downward migration of the tube towards the nasal fossa (37.5%). Secondary intervention was performed in 6 patients. Success was demonstrated using the fluoresceinic staining test under endoscopic monitoring and represented 37.5% after the initial surgery and 50% including revision surgery. CONCLUSIONS: Laser-guided endoscopic intubation is a speedy and accurate surgical procedure that is well-tolerated during the operation and leaves no scar on the skin surface. However, it is associated with a considerable number of post-surgical complications.

[Comparative study between auditory steady-state responses, auditory brain-stem responses and liminar tonal audiometry]. / Estudio comparativo entre potenciales evocados auditivos de estado estable, potenciales evocados auditivos de tronco cerebral y audiometría tonal liminar.

OBJECTIVES: Auditory steady-state responses (ASSR) using frequencies of modulation between 70-110 Hz are a new auditive exploration technique. The aim of the study was to evaluate the contribution of the ASSR to diagnostic of the audition. MATERIAL AND METHOD: Different aportations of auditory steady-states responses (ASSR) and auditory brain-stem responses (ABR) to diagnostic of threshold of audition were studied Differences between these thresholds and thresholds obtained by liminar tonal audiometry (LTA) were studied too. Correlations between thresholds obtained by ASSR and LTA were studied. RESULTS: ASSR detected rest of audition that transients ABR did not detect. Differences about -13.750 dB HL (-5.209 to -22.291) and -13.250 dB HL (-7.337 to -19.163) were found between registered values for carriers of 500 and 1000 Hz and the thresholds by LTA for these carriers. Differences about 1.625 dB HL (-6.967 to 10.217) and -2.875 dB HL (-7.446 to 1.696) were found between estimations for the carries of 500 and 1000 Hz and thresholds by TLA. Statistically very significant (P=.01) coefficients of correlation were found between registered and estimated thresholds by ASSR for carrier of 500 and 1000 Hz and threshold by TLA for these frequencies. CONCLUSIONS: Auditory steady-state responses (ASSR) using frequencies of modulation between 70-110 Hz are a new auditive technique of exploration. This stimulus is more frequency-specific than clicks for auditory brain-stem responses (ABR). Response is not modificated by steady of consciousness. The technique is doublely objective. Thresholds obtained by ASSR permits to estimation of the audition threshold.

Nb2O5 "pathway effect" on hydrogen sorption in Mg.

In the present work we investigate the hydrogen sorption mechanism in a MgH(2)/Nb(2)O(5) composite and analyze why Nb(2)O(5) could strongly improve hydrogen sorption kinetics in magnesium. Hereby we make use of the fact that Nb(2)O(5) nanoparticles are able to reduce the milling time significantly with the achievement of excellent sorption kinetics, and can so exclude effects occurring at long-term milling that make difficult the study of the mechanism. On the basis of extensive chemical, crystalline, and microstructural characterization of the MgH(2)/Nb(2)O(5) nanopowder system, a "pathway model" is proposed, which explains the kinetic hydrogen sorption improvement by a formation of pathways of niobium oxide species with lower oxidation state that facilitate the hydrogen transport into the sample. This mechanism is shown to be supported by additional oxidation experiments, which indicate increased oxygen diffusion through these pathways.

Gold and gold-iron oxide magnetic glyconanoparticles: synthesis, characterization and magnetic properties.

The preparation, characterization and the magnetic properties of gold and gold-iron oxide glyconanoparticles (GNPs) are described. Glyconanoparticles were prepared in a single step procedure in the presence of aqueous solution of thiol functionalized neoglycoconjugates and either gold salts or both gold and iron salts. Neoglycoconjugates of lactose and maltose disaccharides with different linkers were used. Iron-free gold or gold-iron oxide GNPs with controlled gold-iron ratios were obtained. The average core-size diameters are in the range of 1.5-2.5 nm. The GNPs are fully characterized by (1)H NMR spectrometry, transmission electron microscopy (TEM), and UV-vis and X-ray absorption (XAS) spectroscopies. Inductive plasma-atomic emission spectrometry (ICP) and elemental analysis gave the average number of neoglycoconjugates per cluster. The magnetic properties were measured in a SQUID magnetometer. The most remarkable results was the observation of a permanent magnetism up to room temperature in the iron-free gold GNPs, that was not present in the corresponding gold-iron oxide GNPs.

Structural characterization and oxidative dehydrogenation activity of V2O5/Ce(x)Zr(1-x)O2/SiO2 catalysts.

The thermal stability of a nanosized Ce(x)Zr(1-x)O2 solid solution on a silica surface and the dispersion behavior of V2O5 over Ce(x)Zr(1-x)O2/SiO2 have been investigated using XRD, Raman spectroscopy, XPS, HREM, and BET surface area techniques. Oxidative dehydrogenation of ethylbenzene to styrene was performed as a test reaction to assess the usefulness of the VOx/Ce(x)Zr(1-x)O2/SiO2 catalyst. Ce(x)Zr(1-x)O2/SiO2 (1:1:2 mol ratio based on oxides) was synthesized through a soft-chemical route from ultrahigh dilute solutions by adopting a deposition coprecipitation technique. A theoretical monolayer equivalent to 10 wt % V2O5 was impregnated over the calcined Ce(x)Zr(1-x)O2/SiO2 sample (773 K) by an aqueous wet impregnation technique. The prepared V2O5/Ce(x)Zr(1-x)O2/SiO2 sample was subjected to thermal treatments from 773 to 1073 K. The XRD measurements indicate the presence of cubic Ce0.75Zr0.25O2 in the case of Ce(x)Zr(1-x)O2/SiO2, while cubic Ce0.5Zr0.5O2 and tetragonal Ce0.16Zr0.84O2 in the case of V2O5/Ce(x)Zr(1-x)O2/SiO2 when calcined at various temperatures. Dispersed vanadium oxide induces more incorporation of zirconium into the ceria lattice, thereby decreasing its lattice size and also accelerating the crystallization of Ce-Zr-O solid solutions at higher calcination temperatures. Further, it interacts selectively with the ceria portion of the composite oxide to form CeVO4. The RS measurements provide good evidence about the dispersed form of vanadium oxide and the CeVO4 compound. The HREM studies show the presence of small Ce-Zr-oxide particles of approximately 5 nm size over the surface of amorphous silica and corroborate with the results obtained from other techniques. The catalytic activity studies reveal the ability of vanadium oxide supported on Ce(x)Zr(1-x)O2/SiO2 to efficiently catalyze the ODH of ethylbenzene at normal atmospheric pressure. The remarkable ability of Ce(x)Zr(1-x)O2 to prevent the deactivation of supported vanadium oxide leading to stable activity in the time-on-stream experiments and high selectivity to styrene are other important observations.