Reply to Ranucci

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The dental management of patients at risk of medication-related osteonecrosis of the jaw: New paradigm of primary prevention

Medication-related osteonecrosis of the jaw (MRONJ) is a serious adverse reaction of antiresorptive and antiangiogenic agents; it is a potentially painful and debilitating condition that can considerably affect the quality of life of patients. Furthermore, even if its epidemiology and pathogenesis have still not been fully clarified, several risk factors related to MRONJ have been recognized in prevention protocols. Three main risk factors are as follows: (i) the type of ONJ-related medications: antiresorptive (e.g., Bisphosphonates, Denosumab) and antiangiogenic drugs (e.g., Bevacizumab, Sunitinib); (ii) the category of patient at MRONJ risk: cancer versus non-cancer patient; (iii) the typologies and timing of dental treatments (e.g., before, during, or after the drug administration). The aim of this paper is to describe the new paradigm by the Italian Society of Oral Pathology and Medicine (SIPMO) on preventive dental management in patients at risk of MRONJ, prior to and during/after the administration of the aforementioned ONJ-related drugs. In reducing the risk of MRONJ, dentists and oral hygienists are key figures in applying a correct protocol of primary prevention for pre-treatment and in-treatment patients. However, the necessity of a multidisciplinary standardized approach, with a sustained dialogue among specialists involved, should be always adopted in order to improve the efficacy of preventive strategies and to ameliorate the patient\u2019s quality of life

Simplifying the dental/periodontal management of patients with metabolic bone fragility receiving treatment with denosumab

Denosumab (DNB) is a bone-targeted medication used to preserve structural integrity and minimise the risk of fragility fractures in metastatic cancer and metabolic bone disorders. DNB targets and binds RANK Ligand, inhibiting osteoclast maturation, function, and survival. In contrast with nitrogen-containing bisphosphonates (N-BPs), DNB does not bind to hydroxyapatite and incorporate into bone; thus, bone cellular remodelling recovers rapidly after drug suspension. Denosumab has benn linked to the occurrence of osteonecrosis of the jaw (MRONJ), a uncommon but severe oral side effect with a higher prevalence in metastatic cancer patients than in patients with metabolic bone fragility. Although several oral triggers can initiate MRONJ, invasive oral treatments and tooth extraction still remain the most common precipitating event. In general, tooth extraction and oral surgery should be avoided in patients at increased risk of MRONJ, while extraction of unsalvageable teeth should be performed based on specific risk reduction protocols to eliminate dental/periodontal infections, still protectig from MRONJ onset. Based on the different pharmacological properties of DNB and N-BPs, it is likely that the MRONJ risk profile of patients with metabolic bone fragility receiving receiving different ARs could somewhat vary. We hypothesize the chance to maximize the pharmacokinetic of Prolia\uae and identify a time interval in which invasive oral treatments can ideally take place without restrictions in patients with metabolic bone fragility, provided that careful case selection, adequate communication among specialists, planning of a delayed dosing window and rigorous postoperative follow-up are granted

A Network of X-Band Meteorological Radars to Support the Motorway System (Campania Region Meteorological Radar Network Project)

he transport sector and road infrastructures are very sensitive to the issues connected to the atmospheric conditions. The latter constitute a source of relevant risk, especially for roads running in mountainous areas, where a wide spectrum of meteorological phenomena, such as rain showers, snow, hail, wind gusts and ice, threatens drivers’ safety. In such contexts, to face out critical situations it is essential to develop a monitoring system that is able to capillary surveil specific sectors or very small basins, providing real time information that may be crucial to preserve lives and assets. In this work, we present the results of the “Campania Region Meteorological Radar Network”, which is focused on the development of X-band radar-based meteorological products that can support highway traffic management and maintenance. The X-band measurements provided by two single-polarization systems, properly integrated with the observations supplied by disdrometers and conventional automatic weather stations, were involved in the following main tasks: (i) the development of a radar composite product; (ii) the devise of a probability of hail index; (iii) the real time discrimination of precipitation type (rain, mixed and snow); (iv) the development of a snowfall rate estimator. The performance of these products was assessed for two case studies, related to a relevant summer hailstorm (which occurred on 1 August 2020) and to a winter precipitation event (which occurred on 13 February 2021). In both cases, the X-band radar-based tools proved to be useful for the stakeholders involved in the management of highway traffic, providing a reliable characterization of precipitation events and of the fast-changing vertical structure of convective cells

ANDIL experience for building process optimization through an efficient data management / L’esperienza di ANDIL per l’ottimizzazione del processo edilizio attraverso una gestione efficiente delle informazioni

A building process optimization needs a systemic approach in order to correctly manage its complexity. Despite many important contributions have been provided in the last few years, both from a procedural point of view and from a normative one, building process management is often fragmented. This may cause repercussions on building quality and inefficiency in cost and time management. That is why, the research project INNOVance has developed an unambiguous classification system for every object and informative attribute for construction, creating a unique database to smartly store and share information. This through a proper definition of the content of data sheets which can be collected and easily shared together with their complementary attributes by different stakeholders. Unambiguous language and standardized information, in and of themselves, increase building process efficiency. If we then consider that data exchange is possible through the exploitation of a user friendly web portal and some interoperable web services, efficiency and economic savings in the entire construction chain could be extremely relevant. The present paper describes the results achieved during the last year of the research project, in terms of information standardization and data collection

Beta-Defensin-2 and Beta-Defensin-3 Reduce Intestinal Damage Caused by Salmonella typhimurium

The intestinal microbiota is a major factor in human health and disease. This microbial community includes autochthonous (permanent inhabitants) and allochthonous (transient inhabitants) microorganisms that contribute to maintaining the integrity of the intestinal wall, modulating responses to pathogenic noxae and representing a key factor in the maturation of the immune system. If this healthy microbiota is disrupted by antibiotics, chemotherapy, or a change in diet, intestinal colonization by pathogenic bacteria or viruses may occur, leading to disease. To manage substantial microbial exposure, epithelial surfaces of the intestinal tract produce a diverse arsenal of antimicrobial peptides (AMPs), including, of considerable importance, the β-defensins, which directly kill or inhibit the growth of microorganisms. Based on the literature data, the purpose of this work was to create a line of intestinal epithelial cells able to stably express gene encoding human β-defensin-2 (hBD-2) and human β-defensin-3 (hBD-3), in order to test their role in S. typhimurium infections and their interaction with the bacteria of the gut microbiota

Submodular Maximization subject to a Knapsack Constraint: Combinatorial Algorithms with Near-optimal Adaptive Complexity *

International audienceThe growing need to deal with massive instances motivates the design of algorithms balancing the quality of the solution with applicability. For the latter, an important measure is the adaptive complexity, capturing the number of sequential rounds of parallel computation needed. In this work we obtain the first constant factor approximation algorithm for non-monotone submodular maximization subject to a knapsack constraint with near-optimal O(log n) adaptive complexity. Low adaptivity by itself, however, is not enough: one needs to account for the total number of function evaluations (or value queries) as well. Our algorithm asksÕ(n 2) value queries, but can be modified to run with onlyÕ(n) instead, while retaining a low adaptive complexity of O(log 2 n). Besides the above improvement in adaptivity, this is also the first combinatorial approach with sublinear adaptive complexity for the problem and yields algorithms comparable to the state-of-the-art even for the special cases of cardinality constraints or monotone objectives. Finally, we showcase our algorithms' applicability on real-world datasets

The role of HMGA1 protein in gastroenteropancreatic neuroendocrine tumors

Neuroendocrine tumors (NETs) are neoplasms derived from neuroendocrine cells. One of their main features is to often remain asymptomatic and clinically undetectable. High Mobility Group A (HMGA) proteins belong to a family of non-histone chromatinic proteins able to modulate gene expression through the interaction with DNA and transcription factors. They are overexpressed in most of the human malignancies, playing a critical role in carcinogenesis. However, their expression levels and their role in neuroendocrine carcinogenesis has not been exhaustively evaluated until now. Therefore, in this study, we have addressed the validity of using the expression of HMGA1 as a diagnostic marker and have investigated its role in NET carcinogenesis. The expression of HMGA1 has been evaluated by qRT-PCR and immunohistochemistry, using NET tissue microarrays, in a cohort of gastroenteropancreatic (GEP)-NET samples. The expression levels of HMGA1 have been then correlated with the main clinical features of NET samples. Finally, the contribution of HMGA1 overexpression to NET development has been addressed as far as the modulation of proliferation and migration abilities of NET cells is concerned. Here, we report that HMGA1 is overexpressed in GEP-NET samples, at both mRNA and protein levels, and that the silencing of HMGA1 protein expression interferes with the ability of NET cells to proliferate and migrate through the downregulation of Cyclin E, Cyclin B1 and EZH2. These results propose the HMGA proteins as new diagnostic and prognostic markers