An Unclassified Deletion Involving the Proximal Short Arm of Chromosome 10: A New Syndrome?

To date, only 13 studies have described patients with large overlapping deletions of 10p11.2-p12. These individuals shared a common phenotype characterized by intellectual disability, developmental delay, distinct facial dysmorphic features, abnormal behaviour, visual impairment, cardiac malformation, and cryptorchidism in males. Molecular cytogenetic analysis revealed that the deletion in this chromosomal region shares a common smallest region of overlap (SRO) of 80 kb, which contains only the WAC gene (WW-domain-containing adaptor with coiled coil). In this clinical case report, we report a 5-year-old girl, born from non-consanguineous parents, with a 10p11.22p11.21 microdeletion. She presents clinical features that overlap with other patients described in the literature, such as dysmorphic traits, speech delay, and behavioural abnormalities (hyperactivity), even though the WAC gene is not involved in the microdeletion. Our results are the first to highlight that the deletion described here represents a contiguous gene syndrome that is enough to explain the distinct phenotype but partially overlaps with the previous cases reported in the literature, even though the same genes are not involved. In particular, in this study, we speculate about the role of the WAC gene that seems to be associated with normal motor development. In fact, we found that our patient is the only one described in the literature with a large deletion in the 10p11.22p11.21 region without the involvement of the WAC gene deletion, and, interestingly, the patient did not have motor delay.

Comparison between Two Methods of Skeletal Growth Evaluation: Cervical Vertebrae Maturations and Middle Phalanx Maturation.

Aim: Growth measurement has always been essential to identify the best time to employ orthopedic or orthodontic appliances. Optimal timing for orthodontic treatment is strictly linked to the identification of periods of craniofacial growth when treatment is more effective.The aim of this study was to compare two different methods, middle phalanx maturation (MPM) and cervical vertebrae maturation (CVM), used to evaluate the stage of facial growth. Materials and methods: The research data was collected from July 2018 to April 2019 at the Dental Clinic of the San Gerardo Hospital in Monza. The study included a sample of 98 patients-46 males and 52 females. For each patient, a latero-lateral teleradiography of the skull and an X-ray on the middle finger of the right hand were obtained.The statistical analysis of the comparison of the stages of skeletal maturation obtained by the MPM and CVM methods was performed using the correlation coefficient for ranks of Spearman. Results: A descriptive statistical analysis of the entire sample of 98 patients was performed (mean age of 12.2 years and median of 12.2 years). The average age of females in every single stage of MPM was significantly lower than the average age of males. Of the total sample, 87 patients (88.8%) showed complete agreement between the two methods. Conclusion: The results obtained from the statistical analysis of this study allowed us to confirm a satisfactory agreement between the two methods.The intermediate phalanx method is a valid and alternative indicator to CVM for the identification of the puberty growth peak. We can, therefore, consider the MPM method a valid indicator of skeletal maturity. How to cite this article: Mirabelli L, Bianco E, Pigato G, et al. Comparison between Two Methods of Skeletal Growth Evaluation: Cervical Vertebrae Maturations and Middle Phalanx Maturation. Int J Clin Pediatr Dent 2023;16(2):327-332.

Controllable structural and optical properties of NaYF4:Tm, Yb microparticles by Yb3+ doping for anti-counterfeiting.

Hexagonal NaYF4:Tm, Yb upconversion (UC) phosphors with excellent UC luminescence quantum efficiency and chemical stability meet demands for applications in bioimaging and anti-counterfeiting printing. In this work, a series of NaYF4:Tm, Yb upconversion microparticles (UCMPs) with different concentrations of Yb were synthesized by a hydrothermal method. Then, the UCMPs become hydrophilic through surface oxidation of the oleic acid (C-18) ligand to azelaic acid (C-9) using the Lemieux-von Rodloff reagent. The structure and morphology of UCMPs were investigated by X-ray diffraction and scanning electron microscopy. The optical properties were studied using diffusion reflectance spectroscopy and photoluminescent spectroscopy under 980 nm laser irradiation. The emission peaks of the Tm3+ ions are 450, 474, 650, 690, and 800 nm, attributed to the transitions from the excited state to ground state 3H6. These emissions are the results of two or three photon absorption through multi-step resonance energy transfer from excited Yb3+, confirmed via a power-dependent luminescence study. The results show that the crystal phases and luminescence properties of the NaYF4:Tm, Yb UCMPs are controlled by changing the Yb doping concentration. The printed patterns are readable under the excitation of a 980 nm LED. Moreover, the zeta potential analysis shows that the UCMPs after surface oxidation are water dispersible. In particular, the naked eye can observe the enormous upconversion emissions in UCMPs. These findings indicated that this fluorescent material is an ideal candidate for anti-counterfeiting and biological applications.

Toolkit for emerging technologies in laboratory medicine.

An emerging technology (ET) for laboratory medicine can be defined as an analytical method (including biomarkers) or device (software, applications, and algorithms) that by its stage of development, translation into broad routine clinical practice, or geographical adoption and implementation has the potential to add value to clinical diagnostics. Considering the laboratory medicine-specific definition, this document examines eight key tools, encompassing clinical, analytical, operational, and financial aspects, used throughout the life cycle of ET implementation. The tools provide a systematic approach starting with identifying the unmet need or identifying opportunities for improvement (Tool 1), forecasting (Tool 2), technology readiness assessment (Tool 3), health technology assessment (Tool 4), organizational impact map (Tool 5), change management (Tool 6), total pathway to method evaluation checklist (Tool 7), and green procurement (Tool 8). Whilst there are differences in clinical priorities between different settings, the use of this set of tools will help support the overall quality and sustainability of the emerging technology implementation.

Sol-Gel Photonic Glasses: From Material to Application.

In this review, we present a short overview of the development of sol-gel glasses for application in the field of photonics, with a focus on some of the most interesting results obtained by our group and collaborators in that area. Our main attention is devoted to silicate glasses of different compositions, which are characterized by specific optical and spectroscopic properties for various applications, ranging from luminescent systems to light-confining structures and memristors. In particular, the roles of rare-earth doping, matrix composition, the densification process and the fabrication protocol on the structural, optical and spectroscopic properties of the developed photonic systems are discussed through appropriate examples. Some achievements in the fabrication of oxide sol-gel optical waveguides and of micro- and nanostructures for the confinement of light are also briefly discussed.

Emerging technology: a definition for laboratory medicine.

The term "emerging technology" (ET) is used extensively, and there are numerous definitions offered, but to our knowledge, none specifically encompass the field of laboratory medicine. An ET definition that incorporates the overarching IFCC aim of "Advancing excellence in laboratory medicine to support healthcare worldwide" would clarify discussions. We discuss key aspects of the term "emerging technology(ies)" as it applies to laboratory medicine with a view to laying the foundations for a practical definition for the profession and propose the definition of an ET as "An analytical method or device that by virtue of its stage of development, translation into broad routine clinical practice, or geographical adoption and implementation has the potential to add value to clinical diagnostics".

Genotype-phenotype correlation in the spectrum of frontotemporal dementia-parkinsonian syndromes and advanced diagnostic approaches.

The term frontotemporal dementia (FTD) refers to a group of progressive neurodegenerative disorders characterized mainly by atrophy of the frontal and anterior temporal lobes. Based on clinical presentation, three main clinical syndromes have traditionally been described: behavioral variant frontotemporal dementia (bvFTD), non-fluent/agrammatic primary progressive aphasia (nfPPA), and semantic variant PPA (svPPA). However, over the last 20 years, it has been recognized that cognitive phenotypes often overlap with motor phenotypes, either motor neuron diseases or parkinsonian signs and/or syndromes like progressive supranuclear palsy (PSP) and cortico-basal syndrome (CBS). Furthermore, FTD-related genes are characterized by genetic pleiotropy and can cause, even in the same family, pure motor phenotypes, findings that underlie the clinical continuum of the spectrum, which has pure cognitive and pure motor phenotypes as the extremes. The genotype-phenotype correlation of the spectrum, FTD-motor neuron disease, has been well defined and extensively investigated, while the continuum, FTD-parkinsonism, lacks a comprehensive review. In this narrative review, we describe the current knowledge about the genotype-phenotype correlation of the spectrum, FTD-parkinsonism, focusing on the phenotypes that are less frequent than bvFTD, namely nfPPA, svPPA, PSP, CBS, and cognitive-motor overlapping phenotypes (i.e. PPA + PSP). From a pathological point of view, they are characterized mainly by the presence of phosphorylated-tau inclusions, either 4 R or 3 R. The genetic correlate of the spectrum can be heterogeneous, although some variants seem to lead preferentially to specific clinical syndromes. Furthermore, we critically review the contribution of genome-wide association studies (GWAS) and next-generation sequencing (NGS) in disentangling the complex heritability of the FTD-parkinsonism spectrum and in defining the genotype-phenotype correlation of the entire clinical scenario, owing to the ability of these techniques to test multiple genes, and so to allow detailed investigations of the overlapping phenotypes. Finally, we conclude with the importance of a detailed genetic characterization and we offer to patients and families the chance to be included in future randomized clinical trials focused on autosomal dominant forms of FTLD.

A Whole-Genome Sequencing Study Implicates GRAMD1B in Multiple Sclerosis Susceptibility.

While the role of common genetic variants in multiple sclerosis (MS) has been elucidated in large genome-wide association studies, the contribution of rare variants to the disease remains unclear. Herein, a whole-genome sequencing study in four affected and four healthy relatives of a consanguineous Italian family identified a novel missense c.1801T > C (p.S601P) variant in the GRAMD1B gene that is shared within MS cases and resides under a linkage peak (LOD: 2.194). Sequencing GRAMD1B in 91 familial MS cases revealed two additional rare missense and two splice-site variants, two of which (rs755488531 and rs769527838) were not found in 1000 Italian healthy controls. Functional studies demonstrated that GRAMD1B, a gene with unknown function in the central nervous system (CNS), is expressed by several cell types, including astrocytes, microglia and neurons as well as by peripheral monocytes and macrophages. Notably, GRAMD1B was downregulated in vessel-associated astrocytes of active MS lesions in autopsied brains and by inflammatory stimuli in peripheral monocytes, suggesting a possible role in the modulation of inflammatory response and disease pathophysiology.

Urinary miRNAs as a Diagnostic Tool for Bladder Cancer: A Systematic Review.

Bladder cancer is the 10th most common cancer type worldwide. Cystoscopy represents the gold standard for bladder cancer diagnosis, but this procedure is invasive and painful, hence the need to identify new biomarkers through noninvasive procedures. microRNAs (miRNAs) are considered to be promising diagnostic molecules, because they are very stable in biological fluids (including urine) and easily detectable. This systematic review analyses the power of urine miRNAs as bladder cancer diagnostic markers. We conducted this systematic review according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement. A total of 293 records related to miRNAs and their diagnostic significance in BC were retrieved from the PubMed and Embase databases. A systematic search of the literature was performed, and a total of 25 articles (N = 4054 participants) were identified and reviewed. Although many of the selected studies were of high scientific quality, the results proved to be quite heterogeneous, because we did not identify a univocal consensus for a specific miRNA signature but only isolated the signatures. We did not identify a univocal consensus for a specific diagnostic miRNA signature but only isolated the signatures, some of them with better diagnostic power compared to the others.

The need to perform α-thalassemia genetic testing in Italian patients with ß-thalassemia trait: A case report.

Here, we describe a case report of a Sardinian woman diagnosed as pure beta-thalassemia carrier for her anemia who underwent to alpha-thalassemia genetic testing that revealed she was heterozygous for both thalssemias. This allowed to reach a conclusive diagnosis useful for family counseling and for assess the reproductive risk.

Rapid, scalable assessment of SARS-CoV-2 cellular immunity by whole-blood PCR.

Fast, high-throughput methods for measuring the level and duration of protective immune responses to SARS-CoV-2 are needed to anticipate the risk of breakthrough infections. Here we report the development of two quantitative PCR assays for SARS-CoV-2-specific T cell activation. The assays are rapid, internally normalized and probe-based: qTACT requires RNA extraction and dqTACT avoids sample preparation steps. Both assays rely on the quantification of CXCL10 messenger RNA, a chemokine whose expression is strongly correlated with activation of antigen-specific T cells. On restimulation of whole-blood cells with SARS-CoV-2 viral antigens, viral-specific T cells secrete IFN-γ, which stimulates monocytes to produce CXCL10. CXCL10 mRNA can thus serve as a proxy to quantify cellular immunity. Our assays may allow large-scale monitoring of the magnitude and duration of functional T cell immunity to SARS-CoV-2, thus helping to prioritize revaccination strategies in vulnerable populations.

Eu3+ as a Powerful Structural and Spectroscopic Tool for Glass Photonics.

The unique properties of the Eu3+ ion make it a powerful spectroscopic tool to investigate structure or follow processes and mechanisms in several high-tech application areas such as biology and health, structural engineering, environment monitoring systems and quantum technology, mainly concerning photonics. The traditional method is to exploit the unique photoluminescent properties of Eu3+ ions to understand complex dynamical processes and obtain information useful to develop materials with specific characteristics. The objective of this review is to focus on the use of Eu3+ optical spectroscopy in some condensed matter issues. After a short presentation of the more significant properties of the Eu3+ ion, some examples regarding its use as a probe of the local structure in sol-gel systems are presented. Another section is devoted to dynamical processes such as the important technological role of nanocrystals as rare-earth sensitizers. The appealing effect of the site-selection memory, observed when exciting different sites into the 5D1 state, which the 5D0 → 7F0 emission band reflects following the sites' distribution, is also mentioned. Finally, a section is devoted to the use of Eu3+ in the development of a rare-earth-based platform for quantum technologies.

Abnormal Circulating Maternal miRNA Expression Is Associated with a Low (<4%) Cell-Free DNA Fetal Fraction.

The present pilot study investigates whether an abnormal miRNA profile in NIPT plasma samples can explain the finding of a low cell-free DNA (cfDNA) fetal fraction (cfDNAff) in euploid fetuses and non-obese women. Twelve women who underwent neoBona® NIPT with a normal fetal karyotype were studied. Six with a cfDNAff < 4% were matched with a control group with normal levels of cfDNAff > 4%. Samples were processed using the nanostring nCounter® platform with a panel of 800 miRNAs. Four of the maternal miRNAs, miR-579, miR-612, miR-3144 and miR-6721, had a significant abnormal expression in patients. A data filtering analysis showed that miR-579, miR-612, miR-3144 and miR-6721 targeted 169, 1, 48 and 136 placenta-specific genes, respectively. miR-579, miR-3144 and miR-6721 shared placenta-specific targeted genes involved in trophoblast invasion and migration pathways (IGF2R, PTCD2, SATB2, PLAC8). Moreover, the miRNA target genes encoded proteins localized in the placenta and involved in the pathogenesis of pre-eclampsia, including chorion-specific transcription factor GCMa, PRG2, Lin-28 Homolog B and IGFBP1. In conclusion, aberrant maternal miRNA expression in circulating plasma could be a source of dysregulating trophoblast invasion and migration and could represent a novel cause of a low cfDNAff in the sera of pregnant women at the time of NIPT analysis.

SETBP1 accumulation induces P53 inhibition and genotoxic stress in neural progenitors underlying neurodegeneration in Schinzel-Giedion syndrome.

The investigation of genetic forms of juvenile neurodegeneration could shed light on the causative mechanisms of neuronal loss. Schinzel-Giedion syndrome (SGS) is a fatal developmental syndrome caused by mutations in the SETBP1 gene, inducing the accumulation of its protein product. SGS features multi-organ involvement with severe intellectual and physical deficits due, at least in part, to early neurodegeneration. Here we introduce a human SGS model that displays disease-relevant phenotypes. We show that SGS neural progenitors exhibit aberrant proliferation, deregulation of oncogenes and suppressors, unresolved DNA damage, and resistance to apoptosis. Mechanistically, we demonstrate that high SETBP1 levels inhibit P53 function through the stabilization of SET, which in turn hinders P53 acetylation. We find that the inheritance of unresolved DNA damage in SGS neurons triggers the neurodegenerative process that can be alleviated either by PARP-1 inhibition or by NAD + supplementation. These results implicate that neuronal death in SGS originates from developmental alterations mainly in safeguarding cell identity and homeostasis.

Towards population-based genetic screenings for breast and ovarian cancer: A comprehensive review from economic evaluations to patient perspectives.

Genetic testing for hereditary breast and ovarian cancer following genetic counseling is based on guidelines that take into account particular features of the personal and family history, and clinical criteria conferring a probability of having a BRCA mutation greater than 10% as a threshold for accessing the test. However, besides reducing mortality and social impact, the extension of screening programs also for healthy family members would allow a huge saving of the rising costs associated with these pathologies, supporting the choice of the "Test" strategy versus a "No Test" one. Analyses of different health care systems show that by applying the "Test" strategy on patients and their families, a decrease in breast and ovarian cancer cases is achieved, as well as a substantial decrease in costs of economic resources, including the costs of the clinical management of early detected tumors. In this review, we analyzed the most recent papers published on this topic and we summarized the findings on the economic evaluations related to breast and ovarian cancer population screenings. These results proved and validated that the population-wide testing approach is a more accurate screening and preventive intervention than traditional guidelines based on personal/family history and clinical criteria to reduce breast and ovarian cancer risk.

Fluoroindate Glass Co-Doped with Yb3+/Ho3+ as a 2.85 µm Luminescent Source for MID-IR Sensing.

This work reports on the fabrication and analysis of near-infrared and mid-infrared luminescence spectra and their decays in fluoroindate glasses co-doped with Yb3+/Ho3+. The attention has been paid to the analysis of the Yb3+→ Ho3+ energy transfer processed ions in fluoroindate glasses pumped by 976 nm laser diode. The most effective sensitization for 2 µm luminescence has been obtained in glass co-doped with 0.8YbF3/1.6HoF3. Further study in the mid-infrared spectral range (2.85 µm) showed that the maximum emission intensity has been obtained in fluoroindate glass co-doped with 0.1YbF3/1.4HoF3. The obtained efficiency of Yb3+→ Ho3+ energy transfer was calculated to be up to 61% (0.8YbF3/1.6HoF3), which confirms the possibility of obtaining an efficient glass or glass fiber infrared source for a MID-infrared (MID-IR) sensing application.

Luminescent Ink Based on Upconversion of NaYF4:Er,Yb@MA Nanoparticles: Environmental Friendly Synthesis and Structural and Spectroscopic Assessment.

NaYF4:Er,Yb upconversion luminescent nanoparticles (UCNPs) were prepared by hydrothermal methods at 180 °C for 24 h. The X-ray diffraction (XRD) and TEM (transmission electron microscopy) images show that the resulting 60 nm UCNPs possess a hexagonal structure. In this work, maleic anhydride (MA) was grafted on the surface of UCNPs to induce hydrophilic properties. The photoluminescence spectra (PL) show upconversion emissions centered around 545 nm and 660 nm under excitation at 980 nm. The luminescent inks, including UCNPs@MA, polyvinyl alcohol (PVA), deionized water (DI), and ethylene glycol (EG), exhibit suitable properties for screen printing, such as high stability, emission intensity, and tunable dynamic viscosity. The printed patterns with a height of 5 mm and a width of 1.5 mm were clearly observed under the irradiation of a 980 nm laser. Our strategy provides a new route for the controlled synthesis of hydrophilic UCNPs, and shows that the UCNPs@MAs have great potential in applications of anti-counterfeiting packing.

Upconversion Luminescence of Silica-Calcia Nanoparticles Co-doped with Tm3+ and Yb3+ Ions.

Looking for upconverting biocompatible nanoparticles, we have prepared by the sol-gel method, silica-calcia glass nanopowders doped with different concentration of Tm3+ and Yb3+ ions (Tm3+ from 0.15 mol% up to 0.5 mol% and Yb3+ from 1 mol% up to 4 mol%) and characterized their structure, morphology, and optical properties. X-ray diffraction patterns indicated an amorphous phase of the silica-based glass with partial crystallization of samples with a higher content of lanthanides ions. Transmission electron microscopy images showed that the average size of particles decreased with increasing lanthanides content. The upconversion (UC) emission spectra and fluorescence lifetimes were registered under near infrared excitation (980 nm) at room temperature to study the energy transfer between Yb3+ and Tm3+ at various active ions concentrations. Characteristic emission bands of Tm3+ ions in the range of 350 nm to 850 nm were observed. To understand the mechanism of Yb3+-Tm3+ UC energy transfer in the SiO2-CaO powders, the kinetics of luminescence decays were studied.

Generation of ß Cells from iPSC of a MODY8 Patient with a Novel Mutation in the Carboxyl Ester Lipase (CEL) Gene.

CONTEXT: Maturity-onset diabetes of the young (MODY) 8 is a rare form of monogenic diabetes characterized by a mutation in CEL (carboxyl ester lipase) gene, which leads to exocrine pancreas dysfunction, followed by ß cell failure. Induced pluripotent stem cells can differentiate into functional ß cells. Thus, ß cells from MODY8 patients can be generated in vitro and used for disease modelling and cell replacement therapy. METHODS: A genetic study was performed in a patient suspected of monogenic diabetes. RESULTS: A novel heterozygous pathogenic variant in CEL (c.1818delC) was identified in the proband, allowing diagnosis of MODY8. Three MODY8-iPSC (induced pluripotent stem cell) clones were reprogrammed from skin fibroblasts of the patient, and their pluripotency and genomic stability confirmed. All 3 MODY8-iPSC differentiated into ß cells following developmental stages. MODY8-iPSC-derived ß cells were able to secrete insulin upon glucose dynamic perifusion. The CEL gene was not expressed in iPSCs nor during any steps of endocrine differentiation. CONCLUSION: iPSC lines from a MODY8 patient with a novel pathogenic variant in the CEL gene were generated; they are capable of differentiation into endocrine cells, and ß cell function is preserved in mutated cells. These results set the basis for in vitro modelling of the disease and potentially for autologous ß cell replacement.

Current scenario of the genetic testing for rare neurological disorders exploiting next generation sequencing.

Next generation sequencing is currently a cornerstone of genetic testing in routine diagnostics, allowing for the detection of sequence variants with so far unprecedented large scale, mainly in genetically heterogenous diseases, such as neurological disorders. It is a fast-moving field, where new wet enrichment protocols and bioinformatics tools are constantly being developed to overcome initial limitations. Despite the as yet undiscussed advantages, however, there are still some challenges in data analysis and the interpretation of variants. In this review, we address the current state of next generation sequencing diagnostic testing for inherited human disorders, particularly giving an overview of the available high-throughput sequencing approaches; including targeted, whole-exome and whole-genome sequencing; and discussing the main critical aspects of the bioinformatic process, from raw data analysis to molecular diagnosis.