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Abstract B cells are known to contribute to the anti-tumor immune response, especially in immunogenic tumors such as melanoma, yet humoral immunity has not been characterized in these cancers to detail. Here we show comprehensive phenotyping in samples of circulating and tumor-resident B cells as well as serum antibodies in melanoma patients. Memory B cells are enriched in tumors compared to blood in paired samples and feature distinct antibody repertoires, linked to specific isotypes. Tumor-associated B cells undergo clonal expansion, class switch recombination, somatic hypermutation and receptor revision. Compared with blood, tumor-associated B cells produce antibodies with proportionally higher levels of unproductive sequences and distinct complementarity determining region 3 properties. The observed features are signs of affinity maturation and polyreactivity and suggest an active and aberrant autoimmune-like reaction in the tumor microenvironment. Consistent with this, tumor-derived antibodies are polyreactive and characterized by autoantigen recognition. Serum antibodies show reactivity to antigens attributed to autoimmune diseases and cancer, and their levels are higher in patients with active disease compared to post-resection state. Our findings thus reveal B cell lineage dysregulation with distinct antibody repertoire and specificity, alongside clonally-expanded tumor-infiltrating B cells with autoimmune-like features, shaping the humoral immune response in melanoma.

IntroductionChildhood cancer is rare, but it is the most frequent serious event with a high risk of traumatization for children, adolescents, parents and siblings. EMDR is widely studied as clinical intervention that addressed cancer-related stressors among cancer adult population, but to our knowledge, no researches have been conducted among children and adolescent with cancer.MethodsThe purpose of this case study is to describe for the first time the application of the EMDR protocol in a pediatric hospital setting with a 17-years-old Italian adolescent who received a diagnosis of leukemia. He accessed the psychological support service complaining of feelings of anxiety and general discomfort. EMDR protocol started after the diagnosis and ended after the usual eight phases. The Impact of Event Scale—Revised (IES-R) was used to assess stress disorders symptoms as outcome at the baseline (before the First Phase) and at the end of the EMDR protocol (after the Eight Phase).ResultsBy using EMDR protocol the patient reported a decrease of emotional activation after a few EMDR sessions.ConclusionEMDR protocol may be effective for pediatric cancer patients in treating stress disorders symptoms and it can be proposed immediately after diagnosis as a standard care also in pediatric hospital setting.

In children with acute myeloid leukemia (AML) who lack an HLA identical sibling, the donor can be replaced with an HLA matched unrelated donor (MUD) or a haploidentical donor (haplo). We compared outcomes of patients

Summary: Background: Infections are the main reason for mortality during acute leukaemia treatment and invasive aspergillosis (IA) is a major concern. Allogeneic stem cell transplantation (alloSCT) is a standard therapy and often is the only live-saving procedure in leukaemia patients. The profound immunodeficiency occurring after alloSCT led to high IA-associated mortality in the past. Therefore, patients with IA were historically considered transplant-ineligible. Recently, there has been improvement of anti-fungal management including novel anti-fungal agents. As a result, more leukaemia patients with IA are undergoing alloSCT. Outcome has not been prospectively assessed. Methods: We performed a prospective study in acute leukaemia patients undergoing alloSCT to analyse the impact of a prior history of probable or proven IA (pre-SCT IA). The primary endpoint was 1-year non-relapse mortality (NRM). Relapse free survival and overall survival were analysed as secondary endpoints. Findings: 1439 patients were included between 2016 and 2021. The incidence of probable or proven pre-SCT IA was 6.0% (n = 87). The cumulative incidence of 1-year NRM was 17.3% (95% CI 10.2–26.0) and 11.2% (9.6–13.0) for patients with and without pre-SCT IA. In multivariate analyses the hazard ratio (HR) for 1-year NRM was 2.1 (1.2–3.6; p = 0.009) for patients with pre-SCT IA. One-year relapse-free survival was inferior in patients with pre-SCT IA (59.4% [48.3–68.9] vs. 70.4 [67.9–72.8]; multivariate HR 1.5 [1.1–2.1]; p = 0.02). Consequently, 1-year overall survival was lower in patients with pre-SCT IA: (68.8% [57.8–77.4] vs. 79.0% [76.7–81.1]; multivariate HR 1.7 [1.1–2.5]; p = 0.01). Interpretation: Pre-SCT IA remains to be significantly associated with impaired alloSCT outcome. On the other hand, more than two thirds of patients with pre-SCT IA were alive at one year after alloSCT. IA is not anymore an absolute contraindication for alloSCT because the majority of patients with IA who undergo alloSCT benefit from this procedure. Funding: There was no external funding source for this study.

Objective To investigate safety and effectiveness of NOMAC-E2 and levonorgestrel-containing COCs (COCLNG) in users over 40.Methods In this large, observational study, new users1 of NOMAC-E2 and COCLNG were recruited in Europe, Australia, and Latin America and followed-up via questionnaires. Incidence of venous thromboembolism (VTE) was expressed as incidence rate (IR; events/104 women-years [WY]). Unintended pregnancy was expressed by the Pearl Index (PI; contraceptive failures/100 WY). Mood and weight changes were defined as mean changes in mood score and percentage of body weight.Results Overall, 7,762 NOMAC-E2 and 6,059 COCLNG users over 40 were followed-up. NOMAC-E2 showed no increased VTE risk compared to COCLNG; confirmed events: 5 NOMAC-E2 (IR 5.9; 95% CI, 1.9–13.7) vs 4 COCLNG (IR 5.9; 95% CI, 1.6–15.1). Unintended pregnancy did not differ substantially between cohorts; confirmed events: 4 NOMAC-E2 (PI 0.05; 95% CI, 0.01–0.13) vs 5 COCLNG (PI 0.08; 95% CI, 0.03–0.18). No differential effect on mood and weight was observed between cohorts.Conclusions NOMAC-E2 can be considered a valid alternative to COCLNG in perimenopausal women.

Objective: To investigate unintended pregnancy and changes in mood, acne, and weight in NOMAC-E2 vs levonorgestrel-containing COC (COCLNG) users under 25 years.Methods: In this large, observational study, new users (first-ever users of an eligible COC or restarting with the same or a new eligible COC after a break of at least 2 months) of NOMAC-E2 and COCLNG were recruited in 12 countries in Europe, Australia, and Latin America and followed up via questionnaires for up to 2 years. Unintended pregnancy was expressed by the Pearl Index (PI; contraceptive failures/100 women-years). Crude (HRcrude) and adjusted hazard ratios (HRadj) were calculated. Mood and acne changes were defined as change of score from baseline. Weight change was defined as percent change of body weight.Results: Overall, 12,829 NOMAC-E2 users and 17,095 COCLNG users under 25 were followed-up. The risk of unintended pregnancy was statistically significantly lower in the NOMAC-E2 cohort; confirmed events: 30 NOMAC-E2 (PI 0.24; 95% CI, 0.16–0.35) vs 94 COCLNG (PI 0.51; 95% CI, 0.41–0.62). The HRcrude for unintended pregnancy comparing NOMAC-E2 to COCLNG was 0.47 (95% CI, 0.31–0.71) and the HRadj was 0.52 (95% CI, 0.34–0.78). No differential effect on acne, mood, and weight was observed between cohorts.Conclusions: NOMAC-E2 shows a significantly better contraceptive effectiveness in young women and has no differential effect on acne, mood, and weight compared to COCLNG.

Introduction: Describe how physical late effects, and particularly fertility, impact on the psycho-social well-being (anxiety, depression and perception of HRQoL) in a cohort of childhood cancer survivors (CCS). Methods: Eligibility criteria: a) cancer diagnosis at age 5 years; c) age at the time of the study > 18 years and

BackgroundInfant leukemia is a rare form of acute leukemia diagnosed prior to the age of 1 and is characterized by an extremely poor prognosis due to its dismal response to current therapeutic approaches. It comprises about 4% of all childhood cases of acute lymphoblastic leukemia (ALL). Isolated initial cutaneous involvement in ALL is uncommon, and even more so in infant ALL.Case presentationHere, we present the case of a 2-month-old healthy-appearing infant, initially presenting with a single scalp nodule and subsequently diagnosed with an infant ALL. The leukemia was characterized by the most immature B-lineage immunophenotype [pro-B ALL/B-I, according to the European Group for the Immunological Characterization of Leukaemias (EGIL) classification] and chromosomal translocation t(9;11)(p22;q23), resulting in fusion gene KMTLA2::MLLT3, which is considered a negative prognostic factor. The patient underwent hematopoietic stem cell transplantation and is still in remission.ConclusionsThis case is peculiar because of the rare occurrence of isolated initial cutaneous involvement in ALL. Despite the healthy appearance of the patient, every suspicious symptom suggestive of malignancies should be further investigated to anticipate the diagnosis and start treatment early.

Background: In adult oncology, the practice of tracking symptoms and toxicities using patient-reported outcomes (PROs) has increased and correlates with increased survival. In contrast, symptom monitoring using PROs is not common in pediatric oncology. Only in the last couple of years attention has also been paid to the patient’s perception in pediatrics and listening to the voice of children and to making them participate in the treatment. Methods: A comprehensive literature search was conducted in MEDLINE/PubMed and PsycINFO to identify relevant articles published through December 2022. Results: From 58 non-duplicate articles, 33 met our eligibility criteria. Of these, 17 were used in clinical trials. Conclusions: The dissemination and use of these tools will therefore have surprising repercussions on the control of pain and physical symptoms of small patients as well as on physical and psychological aspects. The administration and use of the PROs ensures optimal use of the drugs currently present in clinical trials by researcher and nurse and aims at a safer and more controlled approval of new drugs.

Background: The pandemic of coronavirus disease 2019 (COVID-19) was undoubtedly a stressful experience for everyone. General opinion believed that children with acute or chronic illness could experience additional burden, but this is not confirmed. The aim of this study is to understand how children and adolescents already suffering from acute or chronic illness (e.g., cancer, cystic fibrosis, neuropsychiatric disorders) feel about the COVID-19 pandemic, and if the experience is significantly different between these children and children without illness. Methods: Children and adolescents affected by acute or chronic illness (named the “fragile group”) treated at the Regina Margherita Children Hospital in Italy, were enrolled in the study by filling a questionnaire about their pandemic experiences. Also, a group of children and adolescents without acute or chronic illness (named the “low-risk group”) recruited in the emergency department of the hospital, participated in the study in order to compare experiences. Results: The study group was composed of 166 children and adolescents (Median age = 12 yrs; 78% fragile group, 22% low-risk group). Participants experienced a general state of fear of the virus and of a potential infection for both themselves and their families, while feelings and thoughts that interfere with daily functioning were less frequent. The fragile group seems to be more resilient towards the pandemic situation than low-risk group and some differences on the basis of the type of illness were found in the fragile group. Conclusions: Dedicated psychosocial intervention must be proposed in order to support fragile children and adolescents’ well-being during the pandemic, also on the basis of their clinical and mental history.

Abstract Background Rice is one of the most salt sensitive crops at seedling, early vegetative and reproductive stages. Varieties with salinity tolerance at seedling stage promote an efficient growth at early stages in salt affected soils, leading to healthy vegetative growth that protects crop yield. Saltol major QTL confers capacity to young rice plants growing under salt condition by maintaining a low Na+/K+ molar ratio in the shoots. Results Marker-assisted backcross (MABC) procedure was adopted to transfer Saltol locus conferring salt tolerance at seedling stage from donor indica IR64-Saltol to two temperate japonica varieties, Vialone Nano and Onice. Forward and background selections were accomplished using polymorphic KASP markers and a final evaluation of genetic background recovery of the selected lines was conducted using 15,580 SNP markers obtained from Genotyping by Sequencing. Three MABC generations followed by two selfing, allowed the identification of introgression lines achieving a recovery of the recurrent parent (RP) genome up to 100% (based on KASP markers) or 98.97% (based on GBS). Lines with highest RP genome recovery (RPGR) were evaluated for agronomical-phenological traits in field under non-salinized conditions. VN1, VN4, O1 lines were selected considering the agronomic evaluations and the RPGR% results as the most interesting for commercial exploitation. A physiological characterization was conducted by evaluating salt tolerance under hydroponic conditions. The selected lines showed lower standard evaluation system (SES) scores: 62% of VN4, and 57% of O1 plants reaching SES 3 or SES 5 respectively, while only 40% of Vialone Nano and 25% of Onice plants recorded scores from 3 to 5, respectively. VN1, VN4 and O1 showed a reduced electrolyte leakage values, and limited negative effects on relative water content and shoot/root fresh weight ratio. Conclusion The Saltol locus was successfully transferred to two elite varieties by MABC in a time frame of three years. The application of background selection until BC3F3 allowed the selection of lines with a RPGR up to 98.97%. Physiological evaluations for the selected lines indicate an improved salinity tolerance at seedling stage. The results supported the effectiveness of the Saltol locus in temperate japonica and of the MABC procedure for recovering of the RP favorable traits.

Abstract Background Tumor progression is based on a close interaction between cancer cells and Tumor MicroEnvironment (TME). Here, we focus on the role that Cancer Associated Fibroblasts (CAFs), Mesenchymal Stem Cells (MSCs) and microRNAs (miRs) play in breast cancer and melanoma malignancy. Methods We used public databases to investigate miR-214 expression in the stroma compartment of primary human samples and evaluated tumor formation and dissemination following tumor cell injections in miR-214 overexpressing (miR-214over) and knock out (miR-214ko) mice. In addition, we dissected the impact of Conditioned Medium (CM) or Extracellular Vesicles (EVs) derived from miR-214-rich or depleted stroma cells on cell metastatic traits. Results We evidence that the expression of miR-214 in human cancer or metastasis samples mostly correlates with stroma components and, in particular, with CAFs and MSCs. We present data revealing that the injection of tumor cells in miR-214over mice leads to increased extravasation and metastasis formation. In line, treatment of cancer cells with CM or EVs derived from miR-214-enriched stroma cells potentiate cancer cell migration/invasion in vitro. Conversely, dissemination from tumors grown in miR-214ko mice is impaired and metastatic traits significantly decreased when CM or EVs from miR-214-depleted stroma cells are used to treat cells in culture. Instead, extravasation and metastasis formation are fully re-established when miR-214ko mice are pretreated with miR-214-rich EVs of stroma origin. Mechanistically, we also show that tumor cells are able to induce miR-214 production in stroma cells, following the activation of IL-6/STAT3 signaling, which is then released via EVs subsequently up-taken by cancer cells. Here, a miR-214-dependent pro-metastatic program becomes activated. Conclusions Our findings highlight the relevance of stroma-derived miR-214 and its release in EVs for tumor dissemination, which paves the way for miR-214-based therapeutic interventions targeting not only tumor cells but also the TME.

Abstract Multidomain proteins composed of individual domains connected by flexible linkers pose a challenge for structural studies due to their intrinsic conformational dynamics. Integrated modelling approaches provide a means to characterise protein flexibility by combining experimental measurements with molecular simulations. In this study, we characterise the conformational dynamics of the catalytic RBR domain of the E3 ubiquitin ligase HOIP, which regulates immune and inflammatory signalling pathways. Specifically, we combine small angle X-ray scattering experiments and molecular dynamics simulations to generate weighted conformational ensembles of the HOIP RBR domain using two different approaches based on maximum parsimony and maximum entropy principles. Both methods provide optimised ensembles that are instrumental in rationalising observed differences between SAXS-based solution studies and available crystal structures and highlight the importance of interdomain linker flexibility.

Abstract Post-COVID condition is a new and highly debated entity that is still to be outlined in its complexity, especially in the pediatric population. In response to the article by Trapani and colleagues, we report the results of a long-term follow-up conducted in the outpatient clinic of the Pediatric Infectious Diseases Unit on children admitted to our hospital with SARS-CoV-2 infection.

On the 8th and 9th of May 2021, an online conference was organized to connect Italian physicians, dentists and oral care specialists, students, nurses, psychologists, dental hygiene experts, and other professionals to discuss controversial issues about Medication-Related Osteonecrosis of Jaw (MRONJ). The first section evaluated differences between Italian recommendations, released on 2020 by Italian Societies of Oral Pathology and Medicine (SIPMO) and Maxillofacial Surgery (SICMF), and other international practice guidelines or documents. A first round table gathered expert opinions about MRONJ definitions and staging systems. Another round table was dedicated to opinion of drug prescribers (oncologists, hematologists, rheumatologists, and other physicians treating osteoporosis). Educational sessions illustrated the main differences between previous (2013) and more recent (2020) Italian recommendations. A large space was dedicated to the presentation of scientific contributions from centers in Italy, divided in specific sessions (epidemiology; case series; special case reports; prevention experiences; MRONJ treatment). Conclusions: in an innovative web conference, talks and scientific reports underlined importance of adequate imaging study of bone in definition and staging of MRONJ cases, the role of surgery in treatment of the disease, and the value of oral hygiene in the prevention.

Intestinal graft-versus-host disease (I-GvHD) represents a life-threatening complication in allogeneic stem cell transplantation (SCT). Unfortunately, non-invasive validated diagnostic tools to diagnose I-GvHD, evaluate treatment response, and guide the duration of immunosuppression are still lacking. We employed standard ultrasound and power Doppler to diagnose and follow up on pediatric intestinal GvHD. We herein report on three patients, prospectively evaluated among 24 pediatric patients referred to our center for allogeneic SCT. These three patients presented abdominal pain and diarrhea within the first 200 days after transplantation. In the reported cases, we performed small- and large-intestine ultrasound (US) at clinical onset of lower-intestinal symptoms and, when intestinal GvHD was confirmed, at GvHD flares, if any, and at follow-up. US constantly (3/3 patients) revealed increased bowel wall thickening (BWT) with different bowel segments’ involvement from patient to patient. Further, a moderate or strong increased Doppler signaling was seen in 2 out of 3 patients, according to clinical GVHD staging (e.g., the more the increase, the more the staging). Standard sonography corroborated GvHD diagnosis in all patients considered and was able to detect GvHD progression or complete normalization of findings, thus simplifying ensuing clinical decisions. Our report highlights the need to design clinical trials for the validation of non-invasive radiologic tools for diagnosis and follow-up of GvHD, especially in pediatric patients.

The primary aim of this systematic analysis is to highlight opportunities to improve the environmental impact of advanced therapy medicinal products (ATMP) manufacturing. We have compared the Greenhouse Gas (GHG) emissions expressed in CO2eq of a classic clean room open system (AinB) Cell Factory versus a comparable closed system equipped with isolators (AinD). We have therefore outlined a theoretical situation to simulate the use of a closed system with an equivalent production output to that obtained in the Cell Factory (CF) of the Regina Margherita Children’s Hospital. Open and closed systems for ATMPs have been compared as regards energy requirements, ecological footprints, and costs by analyzing a hypothetic cell production cycle of 21 days. The results demonstrate energy saving and a reduction of 52% in GHG emissions using closed systems per process cycle. Moreover, a reduction in production costs in an isolator setting is also evident. This study shows that the closed system solution has evident advantages compared with the open one.

Background: Osteosarcoma (OS) represents a rare cancer with an unfavorable prognosis that needs innovative treatment. The aim was to isolate a secretome from mesenchymal stem cells (MSCs) that are treated with paclitaxel (PTX)-containing microvesicles as a drug delivery system and analyze its cytotoxic effects on OS cell lines (SJSA, MG63, and HOS). Methods: Three batches of secretome (SECR-1, SECR-2, and SECR-3) were produced from three bone marrow (BM) MSCs samples treated for 24 h with 15 µg/mL of PTX or with a standard medium. The viability of the OS cell lines after 5 days of exposure to SECR-1-2-3 (pure and diluted to 1:2 and 1:4) was analyzed with an MTT assay. The same SECR batches were analyzed with high-performance liquid chromatography (HPLC) and with a nanoparticle tracking assay (NTA). Results: A statistically significant decrease in the viability of all OS cell lines was observed after treatment with SECR-PTX 1-2-3 in a dose–response manner. The NTA analyses showed the presence of nanoparticles (NPs) with a mean size comparable to that of extracellular vesicles (EVs). The HPLC analyses detected the presence of PTX in minimal doses in all SECR batches. Conclusions: This proof-of-concept study showed that the conditioned medium isolated from MSCs loaded with PTX had a strong cytotoxic effect on OS cell lines, due to the presence of EV and PTX.

HSCT from an unrelated HLA-mismatched donor (MMUD) is one of the alternatives where an HLA-matched donor is not found. The aim of this study was to compare GvHD prophylaxis with anti-thymocyte globulin (ATG) vs. post-transplant cyclophosphamide (PT-Cy). Thirty-nine adult patients were uniformly treated with rabbit ATG-Cy-A-MTX and peripheral blood stem cell (PBSC) and 40 adult patients with PT-Cy-MMF-tacrolimus and PBSC. This retrospective study was registered at ClinicalTrials.gov NCT04598789. Three-year overall survival was 42% vs. 64% for ATG and PT-Cy (p < 0.0005), three-year treatment-related mortality (TRM) was 36% vs. 8% (p = 0.0033) and the three-year relapse incidence (RI) was 15% vs. 28% (p = NS), respectively. The incidences of day-100 GvHD graded II–IV and III–IV were 39% vs. 7% (p = 0.0006) and 11% vs. 0% (p = 0.04), respectively, whereas the three-year cGvHD incidences were 48% vs. 13% (p = 0.0005), respectively. We were able to show how PT-Cy can reduce the incidence of GvHDs and TRM in adults, but relapse remains an issue.

Coronavirus disease 2019 (COVID-19) caused by SARS-CoV-2 is an ongoing pandemic that causes significant health/socioeconomic burden. Variants of concern (VOCs) have emerged affecting transmissibility, disease severity and re-infection risk. Studies suggest that the - N-terminal domain (NTD) of the spike protein may have a role in facilitating virus entry via sialic-acid receptor binding. Furthermore, most VOCs include novel NTD variants. Despite global sequence and structure similarity, most sialic-acid binding pockets in NTD vary across coronaviruses. Our work suggests ongoing evolutionary tuning of the sugar-binding pockets and recent analyses have shown that NTD insertions in VOCs tend to lie close to loops.We extended the structural characterisation of these sugar-binding pockets and explored whether variants could enhance sialic acid-binding. We found that recent NTD insertions in VOCs (i.e., Gamma, Delta and Omicron variants) and emerging variants of interest (VOIs) (i.e., Iota, Lambda and Theta variants) frequently lie close to sugar-binding pockets. For some variants, including the recent Omicron VOC, we find increases in predicted sialic acid-binding energy, compared to the original SARS-CoV-2, which may contribute to increased transmission. These binding observations are supported by molecular dynamics simulations (MD).We examined the similarity of NTD across Betacoronaviruses to determine whether the sugar-binding pockets are sufficiently similar to be exploited in drug design. Whilst most pockets are too structurally variable, we detected a previously unknown highly structurally conserved pocket which can be investigated in pursuit of a generic pan-Betacoronavirus drug. Our structure-based analyses help rationalise the effects of VOCs and provide hypotheses for experiments. Our findings suggest a strong need for experimental monitoring of changes in NTD of VOCs.

The 2021 World Health Organization Classification of Tumors of the Central Nervous System, Fifth Edition (WHO-CNS5), has strengthened the concept of tumor grade as a combination of histologic features and molecular alterations. The WHO-CNS5 tumor type “Diffuse midline glioma, H3K27-altered,” classified within the family of “Pediatric-type diffuse high-grade gliomas,” incarnates an ideally perfect integrated diagnosis in which location, histology, and genetics clearly define a specific tumor entity. It tries to evenly characterize a group of neoplasms that occur primarily in children and midline structures and that have a dismal prognosis. Such a well-defined pathological categorization has strongly influenced the pediatric oncology community, leading to the uniform treatment of most cases of H3K27-altered diffuse midline gliomas (DMG), based on the simplification that the mutation overrides the histological, radiological, and clinical characteristics of such tumors. Indeed, multiple studies have described pediatric H3K27-altered DMG as incurable tumors. However, in biology and clinical practice, exceptions are frequent and complexity is the rule. First of all, H3K27 mutations have also been found in non-diffuse gliomas. On the other hand, a minority of DMGs are H3K27 wild-type but have a similarly poor prognosis. Furthermore, adult-type tumors may rarely occur in children, and differences in prognosis have emerged between adult and pediatric H3K27-altered DMGs. As well, tumor location can determine differences in the outcome: patients with thalamic and spinal DMG have significantly better survival. Finally, other concomitant molecular alterations in H3K27 gliomas have been shown to influence prognosis. So, when such additional mutations are found, which one should we focus on in order to make the correct clinical decision? Our review of the current literature on pediatric diffuse midline H3K27-altered DMG tries to address such questions. Indeed, H3K27 status has become a fundamental supplement to the histological grading of pediatric gliomas; however, it might not be sufficient alone to exhaustively define the complex biological behavior of DMG in children and might not represent an indication for a unique treatment strategy across all patients, irrespective of age, additional molecular alterations, and tumor location.

In this contribution, new data concerning the distribution of native vascular flora in Italy are presented. It includes new records, confirmations, exclusions, and status changes to the Italian administrative regions. Nomenclatural and distribution updates, published elsewhere, and corrigenda are provided as Suppl. material 1.

Objectives: To investigate whether saliva formulations with reduced calcium (Ca) and inorganic phosphorous (Pi) concentration would affect dental erosion caused by hydrochloric acid (HCl). Methods: Enamel and root dentine bovine slabs were embedded, polished, and measured for surface Knoop microhardness (SMH). After reference areas were created, specimens were exposed to HCl solution (0.01 M; pH 2; 120 s) and immersed in artificial salivas (6 hr) containing three different Ca/Pi concentrations (n = 15), which simulate serum conditions of normo‐, mild, or severe hypocalcemia. The control group was immersed in Ca/Pi‐free saliva. The study protocol was carried out 2×/day for 5 days. Surface loss of enamel and root dentine was assessed using an optical profilometer, and SMH was remeasured for enamel. Results: One‐way analysis of variance (p < .001) and Tukey’s test showed that enamel loss in groups subjected to artificial salivas that simulated mild or severe hypocalcemia did not differ from that resembling normocalcemia. %SMH was lower when saliva was mildly and normally concentrated in Ca/Pi (p < .001). Root dentine loss was higher in saliva simulating severe hypocalcemia than in those referring to mild, hypo‐, and normocalcemia. Conclusions: Depending on the dental substrate, salivary formulations resembling serum hypocalcemia affected surface loss due to erosion and rehardening thereof. [ABSTRACT FROM AUTHOR]