Publications by authors named "Giovanni Neri"

216 Publications

Co-Occurrence of Fragile X Syndrome with a Second Genetic Condition: Three Independent Cases of Double Diagnosis.

Genes (Basel) 2021 11 27;12(12). Epub 2021 Nov 27.

Sezione di Medicina Genomica, Dipartimento Universitario Scienze della Vita e Sanità Pubblica, Università Cattolica del Sacro Cuore, Fondazione Policlinico Universitario A. Gemelli IRCCS, 00168 Rome, Italy.

Fragile X syndrome (FXS) is the most common form of inherited intellectual disability and autism caused by the instability of a CGG trinucleotide repeat in exon 1 of the gene. The co-occurrence of FXS with other genetic disorders has only been occasionally reported. Here, we describe three independent cases of FXS co-segregation with three different genetic conditions, consisting of Duchenne muscular dystrophy (DMD), --related neurodevelopmental disorder, and 2p25.3 deletion. The co-occurrence of DMD and FXS has been reported only once in a young boy, while in an independent family two affected boys were described, the elder diagnosed with FXS and the younger with DMD. This represents the second case in which both conditions coexist in a 5-year-old boy, inherited from his heterozygous mother. The next double diagnosis had never been reported before: through exome sequencing, a girl with FXS who was of 7 years of age with macrocephaly and severe psychomotor delay was found to carry a variant in the gene. Finally, a maternally inherited 2p25.3 deletion associated with a decreased level of the transcript, only in the patient, was observed in a 33-year-old FXS male with severe seizures compared to his mother and two sex- and age-matched controls. All of these patients represent very rare instances of genetic conditions with clinical features that can be modified by FXS and .
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http://dx.doi.org/10.3390/genes12121909DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8701878PMC
November 2021

Electrochemical Amino Acid Sensing: A Review on Challenges and Achievements.

Biosensors (Basel) 2021 Dec 7;11(12). Epub 2021 Dec 7.

Department of Engineering, University of Messina, C.Da Di Dio, I-98166 Messina, Italy.

The rapid growth of research in electrochemistry in the last decade has resulted in a significant advancement in exploiting electrochemical strategies for assessing biological substances. Among these, amino acids are of utmost interest due to their key role in human health. Indeed, an unbalanced amino acid level is the origin of several metabolic and genetic diseases, which has led to a great need for effective and reliable evaluation methods. This review is an effort to summarize and present both challenges and achievements in electrochemical amino acid sensing from the last decade (from 2010 onwards) to show where limitations and advantages stem from. In this review, we place special emphasis on five well-known electroactive amino acids, namely cysteine, tyrosine, tryptophan, methionine and histidine. The recent research and achievements in this area and significant performance metrics of the proposed electrochemical sensors, including the limit of detection, sensitivity, stability, linear dynamic range(s) and applicability in real sample analysis, are summarized and presented in separate sections. More than 400 recent scientific studies were included in this review to portray a rich set of ideas and exemplify the capabilities of the electrochemical strategies to detect these essential biomolecules at trace and even ultra-trace levels. Finally, we discuss, in the last section, the remaining issues and the opportunities to push the boundaries of our knowledge in amino acid electrochemistry even further.
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http://dx.doi.org/10.3390/bios11120502DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8699811PMC
December 2021

Electrochemical and Fluorescent Properties of Crown Ether Functionalized Graphene Quantum Dots for Potassium and Sodium Ions Detection.

Nanomaterials (Basel) 2021 Oct 29;11(11). Epub 2021 Oct 29.

Department of Engineering, University of Messina, Contrada Di Dio, I-98166 Messina, Italy.

The concentration of sodium and potassium ions in biological fluids, such as blood, urine and sweat, is indicative of several basic body function conditions. Therefore, the development of simple methods able to detect these alkaline ions is of outmost importance. In this study, we explored the electrochemical and optical properties of graphene quantum dots (GQDs) combined with the selective chelating ability of the crown ethers 15-crown-5 and 18-crown-6, with the final aim to propose novel composites for the effective detection of these ions. The results obtained comparing the performances of the single GQDs and crown ethers with those of the GQDs-15-crown-5 and GQDs-18-crown-6 composites, have demonstrated the superior properties of these latter. Electrochemical investigation showed that the GQDs based composites can be exploited for the potentiometric detection of Na and K ions, but selectivity still remains a concern. The nanocomposites showed the characteristic fluorescence emissions of GQDs and crown ethers. The GQDs-18-crown-6 composite exhibited ratiometric fluorescence emission behavior with the variation of K concentration, demonstrating its promising properties for the development of a selective fluorescent method for potassium determination.
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http://dx.doi.org/10.3390/nano11112897DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8625964PMC
October 2021

GD2 CAR T cells against human glioblastoma.

NPJ Precis Oncol 2021 Oct 27;5(1):93. Epub 2021 Oct 27.

Laboratory of Cellular Therapy, Division of Oncology, Department of Medical and Surgical Sciences for Children & Adults, University of Modena and Reggio Emilia, Modena, Italy.

Glioblastoma is the most malignant primary brain tumor and is still in need of effective medical treatment. We isolated patient-derived glioblastoma cells showing high GD2 antigen expression representing a potential target for CAR T strategy. Data highlighted a robust GD2 CAR antitumor potential in 2D and 3D glioblastoma models associated with a significant and CAR T-restricted increase of selected cytokines. Interestingly, immunosuppressant TGF β1, expressed in all co-cultures, did not influence antitumor activity. The orthotopic NOD/SCID models using primary glioblastoma cells reproduced human histopathological features. Considering still-conflicting data on the delivery route for targeting brain tumors, we compared intracerebral versus intravenous CAR T injections. We report that the intracerebral route significantly increased the length of survival time in a dose-dependent manner, without any side effects. Collectively, the proposed anti-GD2 CAR can counteract human glioblastoma potentially opening a new therapeutic option for a still incurable cancer.
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http://dx.doi.org/10.1038/s41698-021-00233-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8551169PMC
October 2021

Electrochemical Detection of Dopamine and Riboflavine on a Screen-Printed Carbon Electrode Modified by AuNPs Derived from Plant Extract.

ACS Omega 2021 Sep 9;6(37):23666-23675. Epub 2021 Sep 9.

Department of Engineering, University of Messina, C.Da Di Dio, I-98166 Messina, Italy.

A AuNP-modified screen-printed carbon electrode (AuNP/SPCE) for monitoring important biomolecules, such as dopamine (DA) and riboflavin (RF), having a high potential for personalized medicine and for continuous monitoring of human health is here proposed. AuNPs were synthesized using the extract of as a reducing medium and were characterized by UV-vis spectroscopy, dynamic light scattering (DLS), and scanning and transmission electron microscopy (SEM and TEM). The synthesized AuNPs appear spherical and present a bimodal size distribution with a maximum centered at around 30-50 nm. Cyclic voltammetry (CV) experiments demonstrated that the modified AuNP/SPCE sensor exhibits superior electrochemical performances to the bare SPCE. Low limits of detection (LODs) of 0.2 and 0.07 μM at S/N = 3 and sensitivities of 550.4  and 2399 μA mM cm were registered for DA and RF detection, respectively. Results demonstrate the promising electrochemical characteristics of the synthesized AuNPs and developed AuNP/SPCE electrochemical sensor for the determination of these important biomolecules.
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http://dx.doi.org/10.1021/acsomega.1c00793DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8459371PMC
September 2021

LRG1 Expression Is Elevated in the Eyes of Patients with Neovascular Age-Related Macular Degeneration.

Int J Mol Sci 2021 Aug 18;22(16). Epub 2021 Aug 18.

Department of Biotechnology, Chemistry and Pharmacy, University of Siena, Via A. Moro, 2, 53100 Siena, Italy.

Leucine-rich a-2-glycoprotein 1 (LRG1) is a candidate therapeutic target for treating the neovascular form of age-related macular degeneration (nvAMD). In this study we examined the expression of LRG1 in eyes of nvAMD patients. Choroidal neovascular membranes (CNVMs) from patients who underwent submacular surgery for retinal pigment epithelium-choroid graft transplantation were collected from 5 nvAMD patients without any prior intravitreal anti-VEGF injection, and from six patients who received intravitreal anti-VEGF injections before surgery. As controls free of nvAMD, retina sections were obtained from the eyes resected from a patient with lacrimal sac tumor and from a patient with neuroblastoma. CNVMs were immunostained for CD34, LRG1, and α-smooth muscle actin (α-SMA). Aqueous humor samples were collected from 58 untreated-naïve nvAMD patients prior to the intravitreal injection of anti-VEGF and 51 age-matched cataract control patients, and LRG1 concentration was measured by ELISA. The level of LRG1 immunostaining is frequently high in both the endothelial cells of the blood vessels, and myofibroblasts in the surrounding tissue of CNVMs of treatment-naïve nvAMD patients. Furthermore, the average concentration of LRG1 was significantly higher in the aqueous humor of nvAMD patients than in controls. These observations provide a strong experimental basis and scientific rationale for the progression of a therapeutic anti-LRG1 monoclonal antibody into clinical trials with patients with nvAMD.
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http://dx.doi.org/10.3390/ijms22168879DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8396268PMC
August 2021

Ultrathin Silicon Nanowires for Optical and Electrical Nitrogen Dioxide Detection.

Nanomaterials (Basel) 2021 Jul 7;11(7). Epub 2021 Jul 7.

CNR-IPCF, Istituto per i Processi Chimico-Fisici, Viale F. Stagno D'Alcontres 37, 98158 Messina, Italy.

The ever-stronger attention paid to enhancing safety in the workplace has led to novel sensor development and improvement. Despite the technological progress, nanostructured sensors are not being commercially transferred due to expensive and non-microelectronic compatible materials and processing approaches. In this paper, the realization of a cost-effective sensor based on ultrathin silicon nanowires (Si NWs) for the detection of nitrogen dioxide (NO) is reported. A modification of the metal-assisted chemical etching method allows light-emitting silicon nanowires to be obtained through a fast, low-cost, and industrially compatible approach. NO is a well-known dangerous gas that, even with a small concentration of 3 ppm, represents a serious hazard for human health. We exploit the particular optical and electrical properties of these Si NWs to reveal low NO concentrations through their photoluminescence (PL) and resistance variations reaching 2 ppm of NO. Indeed, these Si NWs offer a fast response and reversibility with both electrical and optical transductions. Despite the macro contacts affecting the electrical transduction, the sensing performances are of high interest for further developments. These promising performances coupled with the scalable Si NW synthesis could unfold opportunities for smaller sized and better performing sensors reaching the market for environmental monitoring.
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http://dx.doi.org/10.3390/nano11071767DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8308154PMC
July 2021

Smart Biosensors for Cancer Diagnosis Based on Graphene Quantum Dots.

Cancers (Basel) 2021 Jun 26;13(13). Epub 2021 Jun 26.

Department of Engineering, University of Messina, Contrada Di Dio, 98166 Messina, Italy.

The timely diagnosis of cancer represents the best chance to increase treatment success and to reduce cancer deaths. Nanomaterials-based biosensors containing graphene quantum dots (GQDs) as a sensing platform show great promise in the early and sensitive detection of cancer biomarkers, due to their unique chemical and physical properties, large surface area and ease of functionalization with different biomolecules able to recognize relevant cancer biomarkers. In this review, we report different advanced strategies for the synthesis and functionalization of GQDs with different agents able to selectively recognize and convert into a signal specific cancer biomarkers such as antigens, enzymes, hormones, proteins, cancer related byproducts, biomolecules exposed on the surface of cancer cells and changes in pH. The developed optical, electrochemical and chemiluminescent biosensors based on GQDs have been shown to ensure the effective diagnosis of several cancer diseases as well as the possibility to evaluate the effectiveness of anticancer therapy. The wide linear range of detection and low detection limits recorded for most of the reported biosensors highlight their great potential in clinics for the diagnosis and management of cancer.
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http://dx.doi.org/10.3390/cancers13133194DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8269110PMC
June 2021

CNT/AlO core-shell nanostructures for the electrochemical detection of dihydroxybenzene isomers.

Phys Chem Chem Phys 2021 Jun;23(25):14064-14074

Department of Engineering, University of Messina, C.Da Di Dio, I-98166 Messina, Italy.

We report CNT/Al2O3 core-shell nanostructures for the electrochemical detection of dihydroxybenzene (DHB) isomers. Amorphous films of Al2O3 (1.2-15.4 nm in thickness) are uniformly deposited onto the inner and outer walls of CNTs by atomic layer deposition. The effect of the Al2O3 shell thickness on the electrochemical detection of dihydroxybenzene isomers was explored using cyclic and square-wave voltammetry. The best sensing properties are found at a shell thickness of approx. 2.4 nm (CNT/Al2O3(9) sensor), where the oxidation peak currents (sensor-signal) increased ca. 10 times as compared to a sensor fabricated with non-coated CNTs. All of the three DHB isomers (hydroquinone, catechol and resorcinol) are independently detected in the concentration ranges of 2-1000 μmol L-1, 0.5-700 μmol L-1 and 3.5-500 μmol L-1, respectively. The sensors show reliable repeatability, reproducibility, long-term stability, and applicability in the analysis of real samples. Based on these findings, a plausible mechanism is proposed highlighting the role of the Al2O3-shell.
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http://dx.doi.org/10.1039/d1cp00315aDOI Listing
June 2021

Syndromes and birth defects in art and antiquities: New perspectives on a familiar theme.

Am J Med Genet C Semin Med Genet 2021 06 29;187(2):107-110. Epub 2021 May 29.

Institute of Genomic Medicine, Catholic University School of Medicine, Rome, Italy.

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http://dx.doi.org/10.1002/ajmg.c.31913DOI Listing
June 2021

Overgrowth in myth and art.

Am J Med Genet C Semin Med Genet 2021 06 13;187(2):176-181. Epub 2021 May 13.

JC Self Research Institute, Greenwood Genetic Center, Greenwood, South Carolina, USA.

Individuals with overgrowth have been the subjects of numerous myths and art pieces in various cultures, often depicted as deities or creatures of divine origin, such as giants or titans. In more recent times, however, subjects with signs of generalized or segmental overgrowth have been considered as "freaks of nature," in the disparaging language of the time, and represented in artworks as elements of entertainment or amusement. The different meanings assigned to overgrowth in myth and art through time provide an interesting perspective of the sociocultural approach to dysmorphic traits and genetic disorders.
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http://dx.doi.org/10.1002/ajmg.c.31910DOI Listing
June 2021

The earliest depictions of a PIK3CA-Related Overgrowth Spectrum disorder: 17th-18th century prints of women with severe limb overgrowth.

Am J Med Genet C Semin Med Genet 2021 06 13;187(2):168-172. Epub 2021 May 13.

Genetics Unit, MassGeneral Hospital for Children, Boston, Massachusetts, USA.

We report two prints (a woodcut from the 17th century and an engraving from the 18th century) that likely show individuals with PIK3CA-Related Overgrowth Spectrum (PROS). These prints are likely the earliest known depictions of this complex condition.
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http://dx.doi.org/10.1002/ajmg.c.31892DOI Listing
June 2021

Metal-Oxide Based Nanomaterials: Synthesis, Characterization and Their Applications in Electrical and Electrochemical Sensors.

Sensors (Basel) 2021 Apr 3;21(7). Epub 2021 Apr 3.

Department of Engineering, Messina University, I-98166 Messina, Italy.

Pure, mixed and doped metal oxides (MOX) have attracted great interest for the development of electrical and electrochemical sensors since they are cheaper, faster, easier to operate and capable of online analysis and real-time identification. This review focuses on highly sensitive chemoresistive type sensors based on doped-SnO, RhO, ZnO-Ca, Sm-CoFeO semiconductors used to detect toxic gases (H, CO, NO) and volatile organic compounds (VOCs) (e.g., acetone, ethanol) in monitoring of gaseous markers in the breath of patients with specific pathologies and for environmental pollution control. Interesting results about the monitoring of biochemical substances as dopamine, epinephrine, serotonin and glucose have been also reported using electrochemical sensors based on hybrid MOX nanocomposite modified glassy carbon and screen-printed carbon electrodes. The fundamental sensing mechanisms and commercial limitations of the MOX-based electrical and electrochemical sensors are discussed providing research directions to bridge the existing gap between new sensing concepts and real-world analytical applications.
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http://dx.doi.org/10.3390/s21072494DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8038368PMC
April 2021

Synthesis of Silver and Gold Nanoparticles from Plant Extract and Their Application in Electrochemical Sensors.

Nanomaterials (Basel) 2021 Mar 15;11(3). Epub 2021 Mar 15.

Department of Engineering, University of Messina, C.da Di Dio, I-98166 Messina, Italy.

The room-temperature synthesis of silver (AgNPs) and gold (AuNPs) nanoparticles from aqueous solution of AgNO and HAuCl respectively, using (RR) plant extract as a reducing agent, is reported here for the first time. The nanoparticles obtained were characterized by UV-Vis spectroscopy, transmission electron microscopy (TEM) and dynamic light scattering (DLS). The formation of nanoparticles with spherical-shaped morphology was verified by TEM and confirmed by UV-Vis spectroscopy through the analysis of Ag and Au plasmon resonance peak and DLS measurements. New electrochemical sensors have been developed by employing the synthesized Ag and Au nanoparticles as modifiers of glassy carbon electrode (GCE) and screen-printed carbon electrode (SPCE), respectively. The AgNPs-modified GCE was investigated for the electrochemical determination of hydrogen peroxide (HO). Further enhancement of electrochemical performances was obtained using a nanocomposite made of AgNPs and reduced graphene oxide (rGO)-modified GCE. The AuNPs-SPCE sensor was instead tested in the electrochemical sensing of riboflavin (RF). To our knowledge, this is the first paper reporting plant extract as a source for the synthesis of metal nanoparticles and their use for developing simple, sensitive and reliable electrochemical sensors for HO and RF.
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http://dx.doi.org/10.3390/nano11030739DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8000144PMC
March 2021

DNA Methylation, Mechanisms of Inactivation and Therapeutic Perspectives for Fragile X Syndrome.

Biomolecules 2021 02 16;11(2). Epub 2021 Feb 16.

Sezione di Medicina Genomica, Dipartimento Scienze della Vita e Sanità Pubblica, Fondazione Policlinico Universitario A. Gemelli IRCCS, Università Cattolica del Sacro Cuore, 00168 Rome, Italy.

Among the inherited causes of intellectual disability and autism, Fragile X syndrome (FXS) is the most frequent form, for which there is currently no cure. In most FXS patients, the gene is epigenetically inactivated following the expansion over 200 triplets of a CGG repeat (FM: full mutation). encodes the Fragile X Mental Retardation Protein (FMRP), which binds several mRNAs, mainly in the brain. When the FM becomes methylated at 10-12 weeks of gestation, the gene is transcriptionally silent. The molecular mechanisms involved in the epigenetic silencing are not fully elucidated. Among FXS families, there is a rare occurrence of males carrying a FM, which remains active because it is not methylated, thus ensuring enough FMRPs to allow for an intellectual development within normal range. Which mechanisms are responsible for sparing these individuals from being affected by FXS? In order to answer this critical question, which may have possible implications for FXS therapy, several potential epigenetic mechanisms have been described. Here, we focus on current knowledge about the role of DNA methylation and other epigenetic modifications in gene silencing.
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http://dx.doi.org/10.3390/biom11020296DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7920310PMC
February 2021

Fabrication of a Novel Electrochemical Sensor Based on Carbon Cloth Matrix Functionalized with MoO and 2D-MoS Layers for Riboflavin Determination.

Sensors (Basel) 2021 Feb 16;21(4). Epub 2021 Feb 16.

Department of Engineering, University of Messina, C.da Di Dio, I-98166 Messina, Italy.

The preparation and characterization of a hybrid composite, based on carbon cloth (CC) matrix functionalized with two-dimensional (2D) MoS flakes and MoO, and its use for developing an electrochemical sensor for the determination of riboflavin (RF) is here reported. The 2D-MoS-MoOCC composite was prepared by depositing 2D-MoS nanosheets, obtained by liquid phase exfoliation (LPE), on the surface of a carbon cloth fiber network, previously functionalized with a layer of molybdenum oxide (α-MoO) by radio-frequency magnetron reactive sputtering technique. The 2D-MoS-MoOCC composite was characterized by scanning electron microscopy and energy dispersive X-ray analysis (SEM-EDX), and Raman spectroscopy. An electrochemical sensor has been then fabricated by fixing a slice of the 2D-MoS-MoOCC composite on the working electrode of a screen-printed carbon electrode (SPCE). The 2D-MoS-MoO-CC/SPCE sensor display good electrochemical characteristics which have been exploited, for the first time, in the electroanalytical determination of riboflavin (RF). The sensitivity to RF, equal to 0.67 µA mM in the linear range from 2 to 40 µM, and a limit of detection (LOD) of 1.5 µM at S/N = 3, demonstrate the promising characteristics of the proposed 2D-MoS-MoO-CC/SPCE electrochemical sensor for the determination of riboflavin.
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http://dx.doi.org/10.3390/s21041371DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7919667PMC
February 2021

Factors associated with the transition of adolescent inpatients from an intensive residential ward to adult mental health services.

Eur Child Adolesc Psychiatry 2021 Jan 24. Epub 2021 Jan 24.

Department of Biomedical, Metabolic and Neural Sciences, University of Modena and Reggio Emilia, 41125, Modena, Italy.

Transition of young people from Child and Adolescent Mental Health Services (CAMHS) to Adult Mental Health Services (AMHS) is a complex process. Transition rates are heterogeneously reported, with wide definitions and ranges. Few data are available regarding predictive factors of a successful transition. We explored factors associated with transition in a cohort of former inpatients of a Children and Adolescents Intensive Treatment Ward (CAITW). Socio-demographic and clinical features of patients previously admitted to CAITW were matched to AMHS data for those patients having reached age requirements. We built multiple logistic regression models to identify factors associated with transfer to AMHS (either inpatient or outpatient) and with successful retention in treatment (RIT) at six (short RIT), 12 (intermediate RIT) and 24 months after transfer (long RIT). From a cohort of 322 inpatients, 126 reached the age threshold for transfer to AMHS in the study period. The transfer rate was 50%. Two years after transition-age boundary, CAMHS-AMHS continuity of care was found in 40% and disengagement in 6% of cases. Longer and multiple hospitalizations, atypical antipsychotics prescription and a diagnosis of psychotic disorders were factors associated with short and intermediate RIT. A positive psychiatric family history was negatively associated with successful short and intermediate RIT. Diagnosis of psychosis and learning-supported school attendance were associated with long RIT. Young adults with a history of psychiatric inpatient admission as children or adolescents have a relatively high rate of transition to AMHS. A diagnosis of psychosis seems to be the strongest predictor for transition in these patients. Further research should focus on patients' schooling needs and on children of parents with mental health problems to enhance family and educational system engagement.
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http://dx.doi.org/10.1007/s00787-020-01717-yDOI Listing
January 2021

Chromosome 14 deletions, rings, and epilepsy genes: A riddle wrapped in a mystery inside an enigma.

Epilepsia 2021 01 17;62(1):25-40. Epub 2020 Nov 17.

Institute of Genomic Medicine, Catholic University School of Medicine, Rome, Italy.

The ring 14 syndrome is a rare condition caused by the rearrangement of one chromosome 14 into a ring-like structure. The formation of the ring requires two breakpoints and loss of material from the short and long arms of the chromosome. Like many other chromosome syndromes, it is characterized by multiple congenital anomalies and developmental delays. Typical of the condition are retinal anomalies and drug-resistant epilepsy. These latter manifestations are not found in individuals who are carriers of comparable 14q deletions without formation of a ring (linear deletions). To find an explanation for this apparent discrepancy and gain insight into the mechanisms leading to seizures, we reviewed and compared literature cases of both ring and linear deletion syndrome with respect to both their clinical manifestations and the role and function of potentially epileptogenic genes. Knowledge of the epilepsy-related genes in chromosome 14 is an important premise for the search of new and effective drugs to combat seizures. Current clinical and molecular evidence is not sufficient to explain the known discrepancies between ring and linear deletions.
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http://dx.doi.org/10.1111/epi.16754DOI Listing
January 2021

Limited Vitrectomy versus Complete Vitrectomy for Epiretinal Membranes: A Comparative Multicenter Trial.

J Ophthalmol 2020 20;2020:6871207. Epub 2020 Oct 20.

Clinic of Ophthalmology, Department of Biomedical Sciences, University of Messina, Messina, Italy.

Purpose: To evaluate whether limited vitrectomy is as effective as complete vitrectomy in eyes with epiretinal membrane (ERM) and to compare the surgical times and rates of complications.

Methods: In this multicentre European study, data of eyes with ERM that underwent vitrectomy from January 2017 to July 2018 were analyzed retrospectively. In the limited vitrectomy group, a posterior vitreous detachment (PVD) was induced up till the equator as opposed to complete PVD induction till the vitreous base in the comparison group. Incidence of iatrogenic retinal breaks, retinal detachment, surgical time, and visual outcomes were compared between groups.

Results: We included 139 eyes in the analysis with a mean age being 72.2 ± 6.9 years. In this, sixty-five eyes (47%) underwent limited vitrectomy and 74 eyes (53%) underwent complete vitrectomy. Iatrogenic retinal tears were seen in both groups (5% in limited vitrectomy versus 7% in complete vitrectomy, =0.49). Retinal detachment occurred in 2 eyes in the limited vitrectomy group (3%) compared to none in the complete vitrectomy group (=0.22). Best-corrected visual acuity (BCVA) and central macular thickness improved significantly with no intergroup differences (=0.18). Surgical time was significantly shorter in the limited vitrectomy group with 91% surgeries taking less than 1 hour compared to 71% in the complete vitrectomy group ( < 0.001).

Conclusion: A limited vitrectomy is a time-efficient and effective surgical procedure for removal of epiretinal membrane with no additional complications.
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http://dx.doi.org/10.1155/2020/6871207DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7603613PMC
October 2020

Preparation of parenteral nanocrystal suspensions of etoposide from the excipient free dry state of the drug to enhance in vivo antitumoral properties.

Sci Rep 2020 10 22;10(1):18059. Epub 2020 Oct 22.

Université de Paris, CNRS, Inserm, UTCBS, Chemical and Biological Technologies for Health Group (utcbs.cnrs.fr), Faculté de Pharmacie, 4 Avenue de l'Observatoire, 75006, Paris, France.

Nanoparticle technology in cancer chemotherapy is a promising approach to enhance active ingredient pharmacology and pharmacodynamics. Indeed, drug nanoparticles display various assets such as extended blood lifespan, high drug loading and reduced cytotoxicity leading to better drug compliance. In this context, organic nanocrystal suspensions for pharmaceutical use have been developed in the past ten years. Nanocrystals offer new possibilities by combining the nanoformulation features with the properties of solid dispersed therapeutic ingredients including (i) high loading of the active ingredient, (ii) its bioavailability improvement, and (iii) reduced drug systemic cytotoxicity. However, surprisingly, no antitumoral drug has been marketed as a nanocrystal suspension until now. Etoposide, which is largely used as an anti-cancerous agent against testicular, ovarian, small cell lung, colon and breast cancer in its liquid dosage form, has been selected to develop injectable nanocrystal suspensions designed to be transferred to the clinic. The aim of the present work is to provide optimized formulations for nanostructured etoposide solutions and validate by means of in vitro and in vivo evaluations the efficiency of this multiphase system. Indeed, the etoposide formulated as a nanosuspension by a bottom-up approach showed higher blood life span, reduced tumor growth and higher tolerance in a murine carcinoma cancer model. The results obtained are promising for future clinical evaluation of these etoposide nanosuspensions.
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http://dx.doi.org/10.1038/s41598-020-74809-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7581827PMC
October 2020

MicroRNA Expression in the Aqueous Humor of Patients with Diabetic Macular Edema.

Int J Mol Sci 2020 Oct 3;21(19). Epub 2020 Oct 3.

Ophthalmology Unit of the Department of Medicine, Surgery and Neuroscience, University of Siena, 53100 Siena, Italy.

We identified and compared secreted microRNA (miRNA) expression in aqueous humor (AH) and plasma samples among patients with: type 2 diabetes mellitus (T2D) complicated by non-proliferative diabetic retinopathy (DR) associated with diabetic macular edema (DME) (DME group: 12 patients); T2D patients without DR (D group: 8 patients); and non-diabetic patients (CTR group: 10 patients). Individual patient AH samples from five subjects in each group were profiled on TaqMan Low Density MicroRNA Array Cards. Differentially expressed miRNAs identified from profiling were then validated in single assay for all subjects. The miRNAs validated in AH were then evaluated in single assay in plasma. Gene Ontology (GO) analysis was conducted. From AH profiling, 119 mature miRNAs were detected: 86 in the DME group, 113 in the D group and 107 in the CTR group. miRNA underexpression in the DME group was confirmed in single assay for let-7c-5p, miR-200b-3p, miR-199a-3p and miR-365-3p. Of these four, miR-199a-3p and miR-365-3p were downregulated also in the plasma of the DME group. GO highlighted 54 validated target genes of miR-199a-3p, miR-200b-3p and miR-365-3p potentially implied in DME pathogenesis. Although more studies are needed, miR-200b-3p, let-7c-5p, miR-365-3p and miR-199a-3p represent interesting molecules in the study of DME pathogenesis.
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http://dx.doi.org/10.3390/ijms21197328DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7582592PMC
October 2020

Mo-Based Layered Nanostructures for the Electrochemical Sensing of Biomolecules.

Sensors (Basel) 2020 Sep 21;20(18). Epub 2020 Sep 21.

Department of Engineering, University of Messina, C.da Di Dio, I-98166 Messina, Italy.

Mo-based layered nanostructures are two-dimensional (2D) nanomaterials with outstanding characteristics and very promising electrochemical properties. These materials comprise nanosheets of molybdenum (Mo) oxides (MoO and MoO), dichalcogenides (MoS, MoSe, MoTe), and carbides (MoC), which find application in electrochemical devices for energy storage and generation. In this feature paper, we present the most relevant characteristics of such Mo-based layered compounds and their use as electrode materials in electrochemical sensors. In particular, the aspects related to synthesis methods, structural and electronic characteristics, and the relevant electrochemical properties, together with applications in the specific field of electrochemical biomolecule sensing, are reviewed. The main features, along with the current status, trends, and potentialities for biomedical sensing applications, are described, highlighting the peculiar properties of Mo-based 2D-nanomaterials in this field.
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http://dx.doi.org/10.3390/s20185404DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7571038PMC
September 2020

The Binding of CD93 to Multimerin-2 Promotes Choroidal Neovascularization.

Invest Ophthalmol Vis Sci 2020 07;61(8):30

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Purpose: The purpose of this study was to investigate the involvement of CD93 and Multimerin-2 in three choroidal neovascularization (CNV) models and to evaluate their contribution in the neovascular progression of age-related macular degeneration (AMD).

Methods: Choroidal neovascular membranes collected during surgery from AMD patients were analyzed by microscopy methods. Laser-induced CNV mouse models and choroid sprouting assays (CSAs) were carried out using the CD93 knockout mouse model. An original ex vivo CSA of vascular angiogenesis, employing choroid tissues isolated from human donors, was developed.

Results: In contrast to healthy choroid endothelium, hyperproliferative choroidal endothelial cells (ECs) of AMD patients expressed high levels of CD93, and Multimerin-2 was abundantly deposited along the choroidal neovasculature. CD93 knockout mice showed a significant reduced neovascularization after laser photocoagulation, and their choroidal ECs displayed a decreased ability to produce sprouts in ex vivo angiogenesis assays. Moreover, the presence of an antibody able to hamper the CD93/Multimerin-2 interaction reduced vascular sprouting in the human CSA.

Conclusions: Our results demonstrate that CD93 and its interaction with Multimerin-2 play an important role in pathological vascularization of the choroid, disclosing new possibilities for therapeutic intervention to neovascular AMD.
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http://dx.doi.org/10.1167/iovs.61.8.30DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7425738PMC
July 2020

Nanostructured Metal Oxide-Based Acetone Gas Sensors: A Review.

Sensors (Basel) 2020 May 30;20(11). Epub 2020 May 30.

Department of Math., Stat. and Physics, Qatar University, Doha, P.O.Box 2713, Qatar.

Acetone is a well-known volatile organic compound that is widely used in different industrial and domestic areas. However, it can have dangerous effects on human life and health. Thus, the realization of sensitive and selective sensors for recognition of acetone is highly important. Among different gas sensors, resistive gas sensors based on nanostructured metal oxide with high surface area, have been widely reported for successful detection of acetone gas, owing to their high sensitivity, fast dynamics, high stability, and low price. Herein, we discuss different aspects of metal oxide-based acetone gas sensors in pristine, composite, doped, and noble metal functionalized forms. Gas sensing mechanisms are also discussed. This review is an informative document for those who are working in the field of gas sensors.
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http://dx.doi.org/10.3390/s20113096DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7308862PMC
May 2020

Electrochemical Sensing of Serotonin by a Modified MnO-Graphene Electrode.

Biosensors (Basel) 2020 Apr 2;10(4). Epub 2020 Apr 2.

Department of Engineering, University of Messina, 98166 Messina, Italy.

The development of MnO-graphene (MnOGR) composite by microwave irradiation method and its application as an electrode material for the selective determination of serotonin (SE), popularly known as "happy chemical", is reported. Anchoring MnO nanoparticles on graphene, yielded MnO-GR composite with a large surface area, improved electron transport, high conductivity and numerous channels for rapid diffusion of electrolyte ions. The composite was characterized by X-ray photoelectron spectroscopy (XPS), Raman spectroscopy and scanning electron microscopy (SEM) for assessing the actual composition, structure and morphology. The MnO-GR composite modified glassy carbon electrode (GCE) exhibited an excellent electrochemical activity towards the detection of SE in phosphate buffer saline (PBS) at physiological pH of 7.0. Under optimum conditions, the modified electrode could be applied to the quantification of serotonin by square wave voltammetry over a wide linear range of 0.1 to 800 µM with the lowest detection limit of 10 nM (S/N = 3). The newly fabricated sensor also exhibited attractive features such as good anti-interference ability, high reproducibility and long-term stability.
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http://dx.doi.org/10.3390/bios10040033DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7235847PMC
April 2020

DNA Methylation in the Diagnosis of Monogenic Diseases.

Genes (Basel) 2020 03 26;11(4). Epub 2020 Mar 26.

Dipartimento di Scienze e Tecnologie Ambientali Biologiche e Farmaceutiche, Università degli Studi della Campania "Luigi Vanvitelli", 81100 Caserta, Italy.

DNA methylation in the human genome is largely programmed and shaped by transcription factor binding and interaction between DNA methyltransferases and histone marks during gamete and embryo development. Normal methylation profiles can be modified at single or multiple loci, more frequently as consequences of genetic variants acting in cis or in trans, or in some cases stochastically or through interaction with environmental factors. For many developmental disorders, specific methylation patterns or signatures can be detected in blood DNA. The recent use of high-throughput assays investigating the whole genome has largely increased the number of diseases for which DNA methylation analysis provides information for their diagnosis. Here, we review the methylation abnormalities that have been associated with mono/oligogenic diseases, their relationship with genotype and phenotype and relevance for diagnosis, as well as the limitations in their use and interpretation of results.
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http://dx.doi.org/10.3390/genes11040355DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7231024PMC
March 2020

Baseline SD-OCT characteristics of diabetic macular oedema patterns can predict morphological features and timing of recurrence in patients treated with dexamethasone intravitreal implants.

Acta Diabetol 2020 Jul 29;57(7):867-874. Epub 2020 Feb 29.

IRCCS - Fondazione Bietti, Rome, Italy.

Aims: To evaluate the timing and spectral-domain optical coherence tomography (SD-OCT) features of diabetic macular oedema (DME) recurrence according to baseline OCT patterns in patients treated with dexamethasone implant (DEX-I).

Methods: This is a retrospective observational study (72 eyes/65 patients). Best-corrected visual acuity, timing of DME recurrence, and SD-OCT pattern [intraretinal cysts (IRC), IRC plus subretinal fluid (mixed), external limiting membrane (ELM), ellipsoid (IS/OS) layer integrity] were assessed at baseline and monthly until first DME recurrence.

Results: Forty-two (58.3%) and 30 (41.6%) DME eyes had an IRC and mixed DME pattern at baseline, respectively. Twenty-four out of thirty mixed eyes (80%) relapsed without subretinal fluid. At baseline, mixed eyes showed similar changes in ELM and IS/OS (60 and 76.6% of eyes, respectively) versus IRC eyes (42.8 and 80.9% of eyes). After DME recurrence, more mixed eyes at baseline showed ELM and IS/OS changes (63.3 and 86.6%) than IRC eyes (50 and 76.2%). 33.3% of mixed eyes had DME recurrence at ≥ 6 months from first DEX-I implant versus 19% of IRC eyes.

Conclusions: Mixed DME eyes were treated with DEX-I relapse later and more frequently without subretinal fluid than IRC eyes. SD-OCT characteristics of different DME patterns at baseline can predict morphological features and timing of DME recurrence.
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http://dx.doi.org/10.1007/s00592-020-01504-wDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7311372PMC
July 2020

Reversion to Normal of Expanded Alleles: A Rare Event in Two Independent Fragile X Syndrome Families.

Genes (Basel) 2020 02 26;11(3). Epub 2020 Feb 26.

Fondazione Policlinico Universitario "A. Gemelli" IRCCS, Istituto di Medicina Genomica, Università Cattolica del Sacro Cuore, 00168 Roma, Italia.

Fragile X syndrome (FXS) is mostly due to the expansion and subsequent methylation of a polymorphic CGG repeat in the 5' UTR of the gene. Full mutation alleles (FM) have more than 200 repeats and result in gene silencing and FXS. FMs arise from maternal premutations (PM) that have 56-200 CGGs; contractions of a maternal PM or FM are rare. Here, we describe two unaffected boys in two independent FXS families who inherited a non-mosaic allele in the normal and intermediate range, respectively, from their mothers who are carriers of an expanded CGG allele. The first boy inherited a 51 CGG allele (without AGG interruptions) from his mother, who carries a PM allele with 72 CGGs. The other boy inherited from his FM mother an unusual allele with 19 CGGs resulting from a deletion, removing 85 bp upstream of the CGG repeat. Given that transcription of the deleted allele was found to be preserved, we assume that the binding sites for transcription factors are excluded from the deletion. Such unusual cases resulting in non-mosaic reduction of maternal CGG expansions may help to clarify the molecular mechanisms underlying the instability of the gene.
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http://dx.doi.org/10.3390/genes11030248DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7140891PMC
February 2020

Altered mitochondrial function in cells carrying a premutation or unmethylated full mutation of the FMR1 gene.

Hum Genet 2020 Feb 9;139(2):227-245. Epub 2020 Jan 9.

Istituto di Medicina Genomica, Università Cattolica del Sacro Cuore, Fondazione Policlinico Universitario A. Gemelli IRCCS, Largo F. Vito 1, 00168, Roma, Italy.

Fragile X-related disorders are due to a dynamic mutation of the CGG repeat at the 5' UTR of the FMR1 gene, coding for the RNA-binding protein FMRP. As the CGG sequence expands from premutation (PM, 56-200 CGGs) to full mutation (> 200 CGGs), FMRP synthesis decreases until it is practically abolished in fragile X syndrome (FXS) patients, mainly due to FMR1 methylation. Cells from rare individuals with no intellectual disability and carriers of an unmethylated full mutation (UFM) produce slightly elevated levels of FMR1-mRNA and relatively low levels of FMRP, like in PM carriers. With the aim of clarifying how UFM cells differ from CTRL and FXS cells, a comparative proteomic approach was undertaken, from which emerged an overexpression of SOD2 in UFM cells, also confirmed in PM but not in FXS. The SOD2-mRNA bound to FMRP in UFM more than in the other cell types. The high SOD2 levels in UFM and PM cells correlated with lower levels of superoxide and reactive oxygen species (ROS), and with morphological anomalies and depolarization of the mitochondrial membrane detected through confocal microscopy. The same effect was observed in CTRL and FXS after treatment with MC2791, causing SOD2 overexpression. These mitochondrial phenotypes reverted after knock-down with siRNA against SOD2-mRNA and FMR1-mRNA in UFM and PM. Overall, these data suggest that in PM and UFM carriers, which have high levels of FMR1 transcription and may develop FXTAS, SOD2 overexpression helps to maintain low levels of both superoxide and ROS with signs of mitochondrial degradation.
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http://dx.doi.org/10.1007/s00439-019-02104-7DOI Listing
February 2020

The Peculiar Pattern of Type IV Collagen Deposition in Epiretinal Membranes.

J Histochem Cytochem 2020 02 20;68(2):149-162. Epub 2019 Dec 20.

Department of Molecular and Developmental Medicine, University of Siena, Siena, Italy.

Idiopathic epiretinal membranes are sheets of tissue that develop in the vitreoretinal interface. They are formed by cells and extracellular matrix, and they are considered the expression of a fibrotic disorder of the eye. Confocal and immunoelectron microscopy of the extracellular matrix of excised membranes, revealed high contents of type IV collagen. It was distributed within epiretinal membranes in basement membrane-like structures associated with cells and in interstitial deposits. In both cases, type IV collagen was always associated with type I collagen. Col IV was also coupled with Col VI and laminin. At high magnification, type IV collagen immunolabelling was associated with interstitial deposits and showed a reticular appearance due to the intersection of beaded microfilaments. The microfilaments are about 12 nm in diameter with interbead distance of 30-40 nm. Cells of the epiretinal membranes showed intracellular lysosome-like bodies heavily labeled for type IV collagen suggesting an active role in membrane remodeling. Hence, type IV collagen is not necessarily always associated with basement membranes; the molecular interactions that it may develop when not incorporated in basement membranes are still unknown. It is conceivable, however, that they might have implications in the progression of epiretinal membranes and other fibrotic disorders.
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http://dx.doi.org/10.1369/0022155419897258DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7003493PMC
February 2020
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