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Maria Stella Graziani

Deputy Director
Martina Zaninotto

Associate Editors
Ferruccio Ceriotti
Davide Giavarina
Bruna Lo Sasso
Giampaolo Merlini
Martina Montagnana
Andrea Mosca
Paola Pezzati
Rossella Tomaiuolo
Matteo Vidali

EIC Assistant
Francesco Busardò

International Advisory Board Khosrow Adeli Canada
Sergio Bernardini Italy
Marcello Ciaccio Italy
Eleftherios Diamandis Canada
Philippe Gillery France
Kjell Grankvist Sweden
Hans Jacobs The Netherlands
Eric Kilpatrick UK
Magdalena Krintus Poland
Giuseppe Lippi Italy
Mario Plebani Italy
Sverre Sandberg Norway
Ana-Maria Simundic Croatia
Tommaso Trenti Italy
Cas Weykamp The Netherlands
Maria Willrich USA
Paul Yip Canada

Biomedia srl
Via L. Temolo 4, 20126 Milano

Responsible Editor
Giuseppe Agosta

Editorial Secretary
Chiara Riva
Biomedia srl
Via L. Temolo 4, 20126 Milano
Tel. 0245498282


ISSN print: 0393 – 0564
ISSN digital: 0392- 7091

BC: Articoli scritti da R. Tomaiuolo

La diagnostica molecolare in epoca prenatale: evoluzione tecnologica ed implicazioni etiche in medicina della riproduzione
Molecular diagnostics in the prenatal age: technological evolution and ethical implications in reproductive medicine
<p>Congenital anomalies have a birth rate of 3-5% in the general population. The ability to identify genetic alterations in the prenatal age is noticeably increased with the advancement of molecular diagnostic techniques, which are included today in clinical practice. Nowadays, we have several non-invasive and invasive testing options and it is relevant to consider that some of them have a screening value while others have a proper diagnostic role. Based on that, when we are approaching prenatal molecular tests, it is crucial to weigh the multiple ethical implications, related to specific single testing or shared by more of them. Indeed, the interpretation of the testing results may be straightforward especially when the test aims to assess a known familial alteration, while it is more challenging when a genetic variation of unknown significance has to be reported. Thus, prenatal genetic counselling, pre and post-test, is essential to drive the couples to balance the desire to acquire as much information as possible and the real clinical utility of prenatal genetic investigations.&nbsp;</p>
Biochimica Clinica ; 46(3) S089-S094
Rassegne - Reviews
Comunicare nell’infosfera: sfide e opportunità per la Medicina di Laboratorio
Communicating in the infosphere: challenges and opportunities for Laboratory Medicine
<p>Communication is becoming more important than ever for health care and health care professionals, as the recent COVID-19 pandemic has dramatically highlighted. The fast evolution of the mass and social media and the continuous development of new health-related platforms and applications are imposing new challenges that involve also laboratory medicine and that need to be carefully considered. In fact, these novel, fast and effective strategies of communication are inherently prone to the risk of publishing misleading, incorrect or fake information which can spread uncontrollably and diffuse all over the world in a very short time. However, social media are undoubtedly a great opportunity to communicate, in a responsible and credible way, health-related data and scientific updates and discoveries. As for the therapeutic alliance, it is now required to establish an &ldquo;information alliance&rdquo; between different healthcare professionals which, based on a trustworthy relationship, will allow the correct diffusion of health-related information and will contribute to citizens&rsquo; education.</p>
Biochimica Clinica ; 45(3) 290-298
Opinioni - Opinions
Il microbiota umano: il buono, il brutto e il cattivo
Human microbiota: the good, the bad and the ugly
<p>In recent years, the development and the huge diffusion of Next Generation Sequencing (NGS)-based techniques has allowed the study of microbial communities at a previously unimaginable resolution level. Consequently, the knowledge of the role and functions of the human microbiota in various body sites has increased, identifying several fundamental roles for the microbiota in the development and maintenance of body homeostasis, also in relation to various ages of life. On the other hand, a number of microbiota qualitative and/or quantitative alterations have been associated with several diseases, and the trend is increasing. Since targeted interventions can modify the microbiota, the definition of its composition in physiological and pathological conditions acquires crucial importance for the development of new diagnostic tools and/or therapeutic approaches aimed at manipulating the microbiota.<br />In this context, the definition of standardized protocols and common guidelines to study the microbiota, and therefore the role of Laboratory Medicine, appears to be fundamental for the diffusion of metagenomic analyses in diagnostic contexts and will acquire greater relevance in the near future.</p>
Biochimica Clinica ; 45(2) 109-122
Rassegne - Reviews
Glossario di biologia molecolare e biologia molecolare clinica Parte III: diagnostica molecolare
Glossary of molecular biology and clinical molecular biology. Part III: molecular diagnostics
<p>This document is the third and last section of a glossary on molecular biology. In particular, the main categories of the currently available molecular diagnostic procedures, and the related terminology, will be described herein. Based on the availability of more and more sensitive and standardized technologies for the study of DNA/RNA alterations, molecular diagnostic tests are now widely diffused in clinical laboratories, and commonly offered to patients and their families.<br />Aiming to support less experienced readers, the terms related to the main molecular diagnostic procedures and tests are included in this third part of the glossary. For each term the corresponding English version is reported (see also the complete list, both in Italian and in English alphabetical order, reported in the Appendix). In addition, for some of the terms, a link to articles already published in Biochimica Clinica, where they have been used, is reported.</p>
Biochimica Clinica ; 44(2) 174-179
Documenti - Documents
La valutazione della frammentazione del DNA spermatico nei soggetti infertili
The laboratory assessment of sperm DNA fragmentation in infertile patients
<p>Over 15% of couples worldwide suffer from infertility and in 50% of cases a male factor is found. According to the World Health Organization, sperm analysis is the most appropriate test to assess male infertility. Since quite often, the conventional semen parameters are related to sperm DNA damage, the integration of this evaluation with sperm DNA fragmentation (SDF) could independently predict the sperm reproductive potential. Unfortunately, this analysis has not entered into routine clinical practice. The aim of this review is to discuss the importance of the SDF analysis and its clinical implication and to evaluate the extrinsic and intrinsic factors that affect the DNA fragmentation. In addition, principles and protocols of different methods used to evaluate and quantify the SDF are reviewed; advantages and disadvantages of different methods are reported.</p>
Biochimica Clinica ; 44(1) 013-020
Rassegne - Reviews
Glossario di biologia molecolare e biologia molecolare clinica. Parte II: metodologie di biologia molecolare
Glossary of molecular biology and clinical molecular biology. Part II: laboratory methodologies
<p>This document represents the second part of a glossary on molecular biology. In particular, the main laboratory techniques for molecular biology are be described. Indeed, recent technological advances made available a number of technologies featured by higher accuracy and sensitivity that are becoming commonly used in routine molecular diagnostics. Aiming to support less experienced readers, the terms related to the main molecular biology techniques are listed herein. For each term the corresponding English version is reported (see also the complete list, both in Italian and in English alphabetical order, reported in the Appendix). In addition, for some of the terms, a link to articles published in Biochimica Clinica, where they have been used, is reported.</p>
Biochimica Clinica ; 43(4) 435-448
Documenti - Documents
Glossario di biologia molecolare e biologia molecolare clinica. Parte I: termini generali
Glossary of molecular biology and clinical molecular biology. Part I: general terms.
<p>This glossary has beenconceived to help readers, who are less experienced with molecular biology, to approach this field of laboratorymedicine, which is gaining increasing importance in the analytical and diagnostic processes. The glossary isorganized into two separate sections: general terms of molecular biology and clinical molecular biology (molecularbiology techniques, and molecular diagnostic testing). For some of the terms, a link to articles published in BiochimicaClinica, where these terms are employed is included. For each term the corresponding English version is reported;in addition, all the entries of the glossary are listed in the Appendix both in Italian and in English alphabetical order.</p>
Biochimica Clinica ; 43(1) 090-105
Documenti - Documents
Il laboratorio nella medicina della riproduzione
Laboratory and Reproductive Medicine
Biochimica Clinica ; 41(4) 292-293
Editoriale - Editorial
Indicazioni e limiti della diagnosi genetica preimpianto
Indications and limitations for preimplantation genetic diagnosis
<p>The preimplantation genetic diagnosis allows to identify genetic disease and chromosomal alterations in early stages of embryonic development, giving the opportunity to overcome the risk of transmitting an inherited disease and to improve the efficiency of in vitro fertilization techniques. In this paper, we provide an overview of indications and of the advantages and limits of techniques used to perform the preimplantation genetic diagnosis. We describe the multiplex-polymerase chain reaction (PCR) and the karyomapping for the genetic diagnosis of inherited disease as well as the comparative genomic hybridization array, the qualitative real-time PCR and the next generation sequencing for the screening of chromosomal aneuploidy.</p>
Biochimica Clinica ; 41(4) 314-321
Rassegne - Reviews
Oncofertilità: dove siamo?
An update about oncofertility
<p>Over the last years we are experiencing an increased incidence of cancer in young population. Chemotherapy and radiotherapy often result in reduced fertility in these patients. With increasing survival rates, fertility is becoming an important quality-of-life concern for young cancer patients. They may be interested in parenthood, but the number of patients who access fertility preservation techniques before treatment is low. There is a need for improvements in clinical care to ensure patients about infertility risks and fertility preservation options and to support them in their reproductive decision-making before cancer treatment. Nowadays, many opportunities exist for fertility preservation. Sperm cryopreservation is a well-established method in male. In female, there are several strategies such as ovarian suppression with gonadotropin-releasing hormone analogues, ovarian tissue cryopreservation, <em>in vitro</em> maturation or<em> in vitro</em> fertilization after ovulation induction. Recently, developed ovarian stimulation protocols using tamoxifen and letrozole have been applied to increase the margin of safety in breast cancer patients. This review is focused on the effect of cancer treatments on fertility and on the assisted-reproduction innovations devoted to the cancer survivors.</p>
Biochimica Clinica ; 41(4) 322-334
Rassegne - Reviews
La “whole genome amplification” su singola cellula
Whole genome amplification on single cell
<p>The whole genome amplification (WGA) is a method for an entire genome amplification, starting with low amounts of DNA. Particularly, it allows downstream analysis, such as genomic screening [i.e., comparative genomic hybridization (CGH) array, next generation sequencing] and single gene mutation detection in single cells. Because WGA could introduce few bias, dependent on different methods, their selection should be related to the application. The first WGA method was based on amplification reaction and differently from a regular polymerase chain reaction (PCR), in which a single genetic locus is amplified, different locus were amplified simultaneously. Nowadays, several methods have been developed for WGA: degenerate oligonucleotide PCR and primer extension preamplification based on PCR, and multiple displacement amplification achieved with isothermal reaction setup. Each WGA approach has limitations, such as the genome coverage, chimeric DNA molecules, preferential allele amplification or allele drop-out and the guanine-cytosine (GC) richness (GC%). In this review, we detailed different WGA methods for single cell and their most important applications, such as cancer diagnosis and reproductive medicine.</p>
Biochimica Clinica ; 40(4) 293-301
Rassegne - Reviews
Armonizzazione in Medicina di Laboratorio
Harmonization in Laboratory Medicine
F. Ceriotti  |  M. Panteghini  |  A. Tosetto  |  V. Valentini  |  L. Politi  |  R. Rolla  |  T. Guastafierro  |  T. Köken  |  E. Capoluongo  |  C. Mazzaccara  |  V. D'Argenio  |  V. D'Argenio  |  G. Lippi  |  M. Plebani  |  D. Giavarina  |  M. Berardi  |   A survey on sample matrix and preanalytical management in clinical laboratories  |  D. Bozzato  |  G. Messeri  |  M. Zaninotto  |  M. Vidali  |  A. Padoan  |  G. Parigi  |  A. Clerico  |  L. Sciacovelli  |  M. Ciaccio  |  G.L. Salvagno  |  G. Barberio  |  G. Barberio  |  G.L. Salvagno  |  M. Pepe  |  M. Panteghini  |  F. Braga  |  G. Gessoni  |  M. Montagnana  |  N. Doğan  |  M. Barberis  |  M. Barberis  |  A. Marchetti  |  F. Borrillo  |  L. Bonfanti  |  P.M. Ness  |  G. Messeri  |  S. Nannini  |  J. Queraltò  |  M. Zaninotto  |  A. Mosca  |  BM. Henry  |  G. Santini  |  A. Coglianese  |  V. D'Argenio  |  E. Fiorio  |  L. Crinò  |  M. A. V. Willrich  |  A. Modenese  |  M. Berardi  |  G. Nordera  |  M. Girelli  |  R. Tomaiuolo  |  D. Giavarina  |  R. Dittadi  |  L. Pighi  |  V. Guaraldo  |  G. Bambagiotti  |  R. Danesi  |  M. Locatelli  |  F. Balboni  |  D. Cosseddu  |  M. Savoia  |  S. Bernardini  |  C. Domenichini  |  M. Lamonaca  |  M. Perrone  |  M. Perrone  |   per il Gruppo di Studio Intersocietario SIBioC-SIPMeL Diabete Mellito  |  P. Pradella  |  A. Padoan  |  M.T. Sandri  |  L. Belloni  |  A. D'Avolio  |  T. Trenti  |  A. Fortunato  |  T. Trenti  | 
Biochimica Clinica ; 39(6) 546-547
Editoriale - Editorial
Suicidio tra umanesimo e scienza
Suicide between humanism and science
<p>Suicide is among the first 10 causes of death in industrialized countries,&nbsp;even if its incidence is declining. Familiarity frequently occurs in suicide and a myriad of polymorphisms in candidate&nbsp;genes has been studied as risk factors. Among these, genes encoding enzymes, transporters or receptors of the&nbsp;serotoninergic and dopaminergic systems have been widely studied with conflicting results. Also the metabolism of&nbsp;cholesterol (and serum cholesterol concentrations) seems to have a role in the pathogenesis of suicide. In the last&nbsp;years, our group contributed to study brain derived neurotrophic factor (BDNF) and its TrkB receptor genes in the&nbsp;DNA from Wernicke area from a large cohort of suicide subjects and controls. In particular, we excluded that the<br />expression of BDNF and its receptor may be modulated by gene mutations. However, the levels of BDNF gene<br />expression were significantly lower in the brain tissue from suicide subjects. We demonstrated that the altered BDNF&nbsp;expression was due to the enhanced methylation of BDNF promoter. These studies first revealed the association&nbsp;between epigenetics and suicide suggesting a novel model of interaction between environment and genes in the&nbsp;pathogenesis of suicide.</p>
Biochimica Clinica ; 38(2) 121-128
Opinioni - Opinions
Emofilia, come si concluderà la storia?
Hemophilia, how will end the story?
<p>Hemophilia A (HA) and B (HB) are the most frequent inherited bleeding&nbsp;disorders caused by defects in the F8C and F9 genes that encode coagulation factor VIII and factor IX, respectively.&nbsp;Both HA and HB are X-linked recessive diseases and have an incidence of 1:5000 and 1:30,000 males, respectively.&nbsp;The diagnosis is based on normal prothrombin time, altered activated partial thromboplastin time and reduced activity<br />of factor VIII or factor IX in plasma. Furthermore, laboratory contributes to identify the inhibitor (an immunoglobulin&nbsp;against the factor that some hemophilic patients develop during therapy) and to reveal acquired hemophilia. Carrier&nbsp;females of HA and HB are tipically asymptomatic and can be identified only by molecular analysis; their evaluation is&nbsp;important, as one third of cases of hemophilia is due to novel mutations and in these cases the mother (and&nbsp;consanguineous females) of the proband have no risk to be carrier. Both diseases are due to a myriad of different&nbsp;mutations (mostly private), so that the molecular diagnosis is based on scanning techniques or gene sequencing.&nbsp;Given the number of hemophilic patients that experience severe perinatal complications, high-risk couples usually&nbsp;require prenatal diagnosis. We revise here our experience on 50 prenatal diagnoses of hemophilia. The clinical&nbsp;heterogeneity of hemophilic patients prompted many groups to study prothrombotic gene variants in these subjects&nbsp;to investigate whether such variants modify the clinical expression of disease. Finally, therapy (using recombinant&nbsp;factors) and, in a near future, gene therapy will change the natural history of hemophilic patients.</p>
Biochimica Clinica ; 37(6) 454-460
Rassegne - Reviews
Identificazione e caratterizzazione di mutazioni in regioni regolatorie del gene malattia della fibrosi cistica
Identification and characterization of mutations in regulatory regions of cystic fibrosis disease gene
<p>Mutation&nbsp;epidemiology is crucial for cystic fibrosis (CF) diagnosis and counselling. ~6%-7% of alleles from CF patients do not bear&nbsp;mutations in the coding regions of the Cystic Fibrosis Transmembrane Regulator (CFTR) disease gene. In these&nbsp;patients, mutations may be present in non-coding, regulatory regions of the gene as i) intronic regions (particularly in&nbsp;high conserved sequences), ii) the promoter region or iii) the area at the 3&rsquo; of the gene, which is the target of microRNA&nbsp;regulation. We studied these regions by gene sequencing in a group of CF patients with one or both unidentified&nbsp;mutations after the analysis of CFTR coding regions, and in a group of CF patients with a different clinical expression of&nbsp;disease to evaluate if mutations in such regions may have a role in modulating CF clinical expression. Our analysis&nbsp;revealed: i) a dozen of mutations (most novel) in the large promoter area of 6000 bp at the 5&rsquo; of the gene; expression&nbsp;studies in four cell lines demonstrated that a half of such mutations may have a pathogenic effect; ii) a series of mutations&nbsp;in 52 conserved sequence tags (CSTs), i.e. intronic regions with a high homology between humans and mouse;&nbsp;expression studies revealed the pathogenic effect of one of these mutations; iii) finally, three mutations in the 1500 bp&nbsp;region at the 3&rsquo; of the gene; one of this has a pathogenic role, enhancing the interaction of CFTR with two inhibitory&nbsp;microRNAs. To the best of our knowledge, this is the first example of such pathogenic mechanism in a monogenic&nbsp;disorder. On the contrary, no mutations were identified in patients with different clinical expression in any of the three<br />non-coding regions. To conclude, the sequencing of non coding regions may improve the detection rate of molecular&nbsp;analysis in CF, but functional studies are required to define the pathogenic effect of novel mutations.</p>
Biochimica Clinica ; 37(6) 465-469
Contributi scientifici - Scientific papers
Polimorfismo I/D del gene per l’enzima di conversione dell’angiotensina (ACE): gene della longevità o fattore di rischio nella patologia ipertensiva?
Polymorphism of the angiotensin converting enzyme gene: longevity gene or risk factor in hypertensive disease?
<p>In recent decades, the increase in life expectancy stimulated the study of aging processes and the search for&nbsp;candidate genes involved in longevity. The angiotensin converting enzyme (ACE), present in all endothelial cells, plays&nbsp;an essential role in maintaining the homeostasis of blood flow by regulating the production of the vasoconstrictor&nbsp;angiotensin II and inactivating the bradykinin. Some studies reported a possible association between the polymorphism&nbsp;I/D of ACE gene and either hypertension and longevity. The present study was aimed to confirm these data. We studied&nbsp;two large cohorts of nonagenarians and centenarians. One was from Sardinia (200 subjects, 88 males, mean age: 96&nbsp;years) and their data were compared to a group of 222 subjects (106 males, mean age: 44 years) from the general&nbsp;population of the same geographic area. The latter group of longeve subjects (161 subjects, 71 males, mean age: 97&nbsp;years) was from Southern Italy. Furthermore, we studied 146 hypertensive patients (98 males, mean age: 51 years) and&nbsp;172 normotensive subjects (86 males, mean age: 33 years) from Southern Italy. The ACE I/D polymorphism was typed&nbsp;by polymerase chain reaction; the amplified 490 bp (allele I) and 190 bp (allele D) were visualized on 2% agarose gel.&nbsp;Hypertensive subjects had a significantly different distribution of ACE genotypes as compared to normotensive ones&nbsp;(P=0.001) and a higher frequency of the D/D genotype. Long-lived subjects from Sardinia showed a significantly different&nbsp;distribution of ACE genotypes as compared to subjects from the general population of the same geographic area (P&nbsp;&lt;0.001), to long-lived subjects from Southern Italy (P &lt;0.001), to hypertensive patients (P=0.011) and to normotensive&nbsp;subjects from Southern Italy (P &lt;0.001). Surprisingly, they had the highest frequency of the D/D genotype among the&nbsp;compared groups. Our study indicates that: i) centenarians of different ethnic origin have a different genetic background,&nbsp;ii) there is a possible association between longevity and allelic variants of ACE, even if only in specific ethnic groups (i.e.,&nbsp;Sardinian) and iii) ACE polymorphisms are a predisposing factor to hypertension.</p>
Biochimica Clinica ; 37(6) 461-464
Contributi scientifici - Scientific papers