Search

The 1:100,000 subsurface geological map of the Torino metropolitan area covers ∼900 km2 in the westernmost Po Plain, an area of great relevance being crossed by the late Neogene to Quaternary ‘Torino Hill Front’ (THF), a tens of kilometers long, NW-verging buried and blind thrust. The map provides an updated representation of the bedrock geology below the late Early Pleistocene-Holocene Alpine-sourced fluvial blanket, relying on novel correlation of shallow water well and borehole logs. The map describes how the syn-depositional thrust-related folding pulses affected the early Piacenzian-early Middle Pleistocene tectono-stratigraphic evolution of this sector. Our results demonstrate that the deposition of the lower Piacenzian shallow marine succession and then of the Piacenzian to Calabrian alluvial record was controlled by the stepwise propagation of the THF, and suggest that this thrust was apparently sealed by the late Early Pleistocene unconformity. Gentle folding characterized the late Early Pleistocene-early Middle Pleistocene time interval.

Objective: This study aims to evaluate the correlation of gestational weight gain (GWG) with pregnancy and perinatal outcomes in a cohort of obese women class I-III receiving standard care (SC) or lifestyle intervention (LI). Methods: This is a prospective cohort study including singleton obese women (body mass index, BMI ≥ 30) who delivered between 2016 and 2020. Women exposed to a LI were referred to an obesity weight management ad hoc clinic. Women followed by family centers or private settings represented the SC group. The LI started between the 9 and 12th week, consisting of a low-calorie diet and physical activity program. Pregnancy and perinatal outcomes were prospectively collected. Women included in the SC group were followed, simply checking their pregnancy and health status, providing general recommendations on a healthy lifestyle in pregnancy. GWG was categorized as insufficient, adequate, or excessive according to the Institute of Medicine (IOM). Results: A total of 1874 obese singleton women delivered in the study period. Among them, 565 (30.1%) were included in the LI while 1309 received SC. Women in SC showed a higher rate of GWG out of the IOM recommendations (excessive/insufficient), while women in the LI group showed higher adequate GWG. The small-for-gestational-age (SGA) rate resulted to be higher in the SC group. Once adjusting for age, BMI, country of origin, provider, and gestational hypertension, the risk for SGA was increased by insufficient GWG (OR = 1.25; 95%CI: 1.03–1.59), while it was reduced by LI (OR = 0.67, 95%CI: 0.42–0.98). Conclusions: In a cohort of obese women, the exposure to an LI was associated with more adequate GWG, reduced insufficient weight gain, and a decreased risk of SGA infants.

In the original publication [...]

Abstract Technical advances in microsurgery have enabled complex oncological reconstructions by performing free tissue transfers, nerve and lymphatic reconstructions. However, the manual abilities required to perform microsurgery can be affected by human fatigue and physiological tremor resulting in tissue damage and compromised outcomes. Robotic assistance has the potential to overcome issues of manual microsurgery by improving clinical value and anastomoses’ outcomes. The Symani Surgical System, a robotic platform designed for microsurgery, was used in this in-vivo preclinical study using a rat animal model. The tests included anastomoses on veins and arteries performed by microsurgeons manually and robotically, with the latter approach using Symani. The anastomoses were assessed for patency, histopathology, and execution time. Patency results confirmed that the robotic and manual techniques for venous and arterial anastomoses were equivalent after anastomosis, however, the time to perform the anastomosis was longer with the use of the robot (p

Ectopic adrenal tissue is rare but is reported in various locations within the urogenital tract and abdominal structures. The vast majority of adrenal rests represent incidental findings in surgical specimens; thus, their incidence is unknown.1 Notwithstanding, the results of reports on their higher frequency in infants than adults and sex distribution are conflicting.1,2 In male subjects, the paratesticular and inguinal regions represent common sites of ectopic adrenal tissue, given the intimate embryologic relationship between the gonad and the adrenal cortex.3 In testis and paratestis, they are also known as Marchand rest and are most commonly found in the spermatic cord,3 followed by testis4 and epididymis.5,6 In these anatomic locations, ectopic adrenals may be associated with undescended testis, inguinal hernia, epididymal abnormality, and spermatic cord torsion, but none represent a predisposing factor. Also, the association with malignant testicular neoplasms merely represents a matter of chance. As a rule, adrenal rests do not show significant clinical implications. However, they may undergo hyperplasia when the function of the main adrenals is deficient or in congenital adrenal hyperplasia (CAH), an autosomal recessive disease with increased ACTH levels.5,6 Also, adrenal rests may be accidentally removed during surgery, leading to adrenal insufficiency. Finally, ectopic adrenal may harbor benign or malignant tumors resulting in clinically evident dysfunctions.3 The adrenal rests comprise nodules ranging between 1 mm and 1 cm, appearing as encapsulated or well-circumscribed round yellowish masses that may be multiple or bilateral. Microscopic appearance reminds normal adrenal cortex, often arranged in different zones, without medullary tissue. Figure 1 refers to a case of a tiny adrenal rest nodule incidentally observed in an orchiectomy specimen obtained from a 40-year-old man affected by a suspect germ cell tumor of the right testis. The surgical specimen´s gross examination depicted a yellowish-brown nodule measuring 2 mm in its longest axis, located under the visceral mesothelium of the tunica vaginalis near the head of the epididymis (Figure 1A). Figure 1A - Gross orchiectomy specimen displaying a tiny nodule yellowish-brown in color (arrowhead) below the visceral layer of the tunica vaginalis and close to the head of the epididymis (scale bar= 3 cm); B - Encapsulated adrenal rest located between epididymis and rete testis; C - Encapsulated adrenal cortical tissue; D - Immunohistochemical positivity for Melan-A.: Microscopical examination diagnosed a pure testicular seminoma infiltrating the albuginea and the visceral part of the tunica vaginalis (pT2). Histology showed a well-encapsulated nodule between the epididymis head and the rete testis (Figure 1B). The nodule was composed of epithelial cells arranged into an organoid pattern consistent with the adrenal cortex (Figure 1C). No adrenal medullary tissue was present. The cells were immunohistochemically positive for Melan-A monoclonal antibody (clone A103) (Figure 1D). No immunostaining was observed for inhibin α (clone R1), calretinin (clone DAK-Calret 1), and BCL2 oncoprotein (clone 124).

Abstract Recently, cancer research protocols have introduced clinical-stage spirooxindole-based MDM2 inhibitors. However, several studies reported tumor resistance to the treatment. This directed efforts to invest in designing various combinatorial libraries of spirooxindoles. Herein, we introduce new series of spirooxindoles via hybridization of the chemically stable core spiro[3H-indole-3,2′-pyrrolidin]-2(1H)-one and the pyrazole motif inspired by lead pyrazole-based p53 activators, the MDM2 inhibitor BI-0252 and promising molecules previously reported by our group. Single crystal X-ray diffraction analysis confirmed the chemical identity of a representative derivative. Fifteen derivatives were screened for cytotoxic activities via MTT assay against a panel of four cancer cell lines expressing wild-type p53 (A2780, A549, HepG2) and mutant p53 (MDA-MB-453). The hits were 8h against A2780 (IC50 = 10.3 µM) and HepG2 (IC50 = 18.6 µM), 8m against A549 (IC50 = 17.7 µM), and 8k against MDA-MB-453 (IC50 = 21.4 µM). Further MTT experiments showed that 8h and 8j potentiated doxorubicin activity and reduced its IC50 by at least 25% in combinations. Western blot analysis demonstrated that 8k and 8m downmodulated MDM2 in A549 cells. Their possible binding mode with MDM2 were simulated by docking analysis.

BACKGROUND: Stillbirth at term has great emotional impact on both parents and professionals. In developed countries, efforts to identify risk factors are mandatory to plan area-specific prevention strategies. OBJECTIVE: The aim of the study was to identify independent risk factors that contribute to stillbirth at 37 weeks’ gestation or later. STUDY DESIGN: This was an area-based, prospective cohort study on pregnancy at term with enrolled from 2014 to 2021 in Emilia-Romagna, a north Italian region. Data were retrieved from both birth certificates and the Stillbirth Surveillance system database. To identify independent risk factors, a multivariate analysis using logistic regression was performed. A descriptive analysis of the causes of stillbirth is also reported. RESULTS: In the observation period, 246,437 babies born at term (including 260 stillbirths, giving a rate of 1.06/1000) were considered. The risk factors independently associated with stillbirth were small for gestational age babies (odds ratio, 2.58; 95% confidence interval, 1.88–3.53), pregnancy achieved though fertility treatments (odds ratio, 2.01; 95% confidence interval, 1.15–3.51), and delayed access to pregnancy services (odds ratio, 1.56; 95% confidence interval, 1.10–2.22). In multipara, the presence of a previous stillbirth (odds ratio, 3.91; 95% confidence interval, 1.98–7.72) was also associated with an increased risk for recurrence. Early- rather than late-term was an additional risk factor. The most frequent causes of death were placental and cord disorders (61/260 and 56/260, respectively). However, 28.1% of cases remain unexplained. CONCLUSION: The risks for stillbirth at term are known early in pregnancy or could be identified through tailored antenatal management, allowing effective preventive strategies to reduce preventable cases.

Introduction. Les personnes en situation d’itinérance qui consomment des substances psychoactives font face à plusieurs barrières à l’accès aux services généraux et ceux qui leur sont dédiés. Cela les mène, entre autres, à interagir fréquemment avec les services d’urgence, que ce soit avec la police, les services paramédicaux et les urgences hospitalières. Pourtant, ces services sont peu adaptés à leurs besoins. Il est donc important d’identifier des pistes de solutions concrètes pour améliorer la réponse d’urgence offerte aux personnes en situation d’itinérance qui consomment des substances psychoactives. Méthodologie. Ce devis évaluatif combine une analyse des besoins avec une évaluation démocratique délibérative. Un processus collaboratif, dont l’utilisation d’une Technique de recherche d’information par l’animation d’un groupe d’experts (TRIAGE) intersectorielle de 32 participants, a été organisé pour prioriser les solutions selon les différentes parties prenantes, soit les prestataires des services d’urgence, les personnes en situation d’itinérance et les autres acteurs qui gravitent autour d’elles (services spécialisés, milieu communautaire, politique et de la recherche). Résultats. Onze solutions ont été priorisées et classées dans quatre catégories : prévention de l’itinérance, approche à bas seuil, continuité des services et gouvernance. Conclusion. Cette étude a permis d’identifier des solutions concrètes et systémiques qui font consensus et qui pourront être implantées dans des contextes similaires au nôtre.

Backgroundwe evaluated the concordance between immunohistochemical p53 staining and TP53 mutations in a series of HGSOC. Moreover, we searched for prognostic differences between p53 overexpression and null expression groups.Methodspatients affected by HGSOC were included. For each case p53 immunohistochemical staining and molecular assay (Sanger sequencing) were performed. Kaplan-Meier survival analyses were undertaken to determine whether the type of TP53 mutation, or p53 staining pattern influenced overall survival (OS) and progression free survival (PFS).Results34 HGSOC were considered. All cases with a null immunohistochemical p53 expression (n=16) showed TP53 mutations (n=9 nonsense, n=4 in-frame deletion, n=2 splice, n=1 in-frame insertion). 16 out of 18 cases with p53 overexpression showed TP53 missense mutation. Follow up data were available for 33 out of 34 cases (median follow up time 15 month). We observed a significant reduction of OS in p53 null group [HR = 3.64, 95% CI 1.01-13.16].Conclusionimmunohistochemical assay is a reliable surrogate for TP53 mutations in most cases. Despite the small cohort and the limited median follow up, we can infer that HGSOC harboring p53 null mutations are a more aggressive subgroup.

The culture confirmation of Mycobacterium tuberculosis (MTB) remains the gold standard for the diagnosis of Tuberculosis (TB) with culture conversion representing proof of cure. However, over 40% of TB samples fail to isolate MTB even though many patients remain infectious due to the presence of viable non-culturable forms. Previously, we have shown that two short cationic peptides, T14D and TB08L, induce a hormetic response at low concentrations, leading to a stimulation of growth in MTB and the related animal pathogen Mycobacterium bovis (bTB). Here, we examine these peptides showing they can influence the mycobacterial membrane integrity and function through membrane potential reduction. We also show this disruption is associated with an abnormal reduction in transcriptomic signalling from specific mycobacterial membrane sensors that normally monitor the immediate cellular environment and maintain the non-growing phenotype. We observe that exposing MTB or bTB to these peptides at optimal concentrations rapidly represses signalling mechanisms maintaining dormancy phenotypes, which leads to the promotion of aerobic metabolism and conversion into a replicative phenotype. We further show a practical application of these peptides as reagents able to enhance conventional routine culture methods by stimulating mycobacterial growth. We evaluated the ability of a peptide-supplemented sample preparation and culture protocol to isolate the MTB against a gold standard routine method tested in parallel on 255 samples from 155 patients with suspected TB. The peptide enhancement increased the sample positivity rate by 46% and decreased the average time to sample positivity of respiratory/faecal sampling by seven days. The most significant improvements in isolation rates were from sputum smear-negative low-load samples and faeces. The peptide enhancement increased sampling test sensitivity by 19%, recovery in samples from patients with a previously culture-confirmed TB by 20%, and those empirically treated for TB by 21%. We conclude that sample decontamination and culture enhancement with D-enantiomer peptides offer good potential for the much-needed improvement of the culture confirmation of TB.

Neuroblastoma (NB) is a paediatric cancer with noteworthy heterogeneity ranging from spontaneous regression to high-risk forms that are characterised by cancer relapse and the acquisition of drug resistance. The most-used anticancer drugs exert their cytotoxic effect by inducing oxidative stress, and long-term therapy has been demonstrated to cause chemoresistance by enhancing the antioxidant response of NB cells. Taking advantage of an in vitro model of multidrug-resistant (MDR) NB cells, characterised by high levels of glutathione (GSH), the overexpression of the oncoprotein BMI-1, and the presence of a mutant P53 protein, we investigated a new potential strategy to fight chemoresistance. Our results show that PTC596, an inhibitor of BMI-1, exerted a high cytotoxic effect on MDR NB cells, while PRIMA-1MET, a compound able to reactivate mutant P53, had no effect on the viability of MDR cells. Furthermore, both PTC596 and PRIMA-1MET markedly reduced the expression of epithelial–mesenchymal transition proteins and limited the clonogenic potential and the cancer stemness of MDR cells. Of particular interest is the observation that PTC596, alone or in combination with PRIMA-1MET and etoposide, significantly reduced GSH levels, increased peroxide production, stimulated lipid peroxidation, and induced ferroptosis. Therefore, these findings suggest that PTC596, by inhibiting BMI-1 and triggering ferroptosis, could be a promising approach to fight chemoresistance.

Abstract Background Multiple gestations represent a considerable proportion of pregnancies delivering in the late preterm (LP) period. Only 30% of LP twins are due to spontaneous preterm labor and 70% are medically indicated; among this literature described that 16–50% of indicated LP twin deliveries are non-evidence based. As non-evidence-based delivery indications account for iatrogenic morbidity that could be prevented, the objective of our observational study is to investigate first neonatal outcomes of LP twin pregnancies according to gestational age at delivery, chorionicity and delivery indication, then non evidence-based delivery indications. Methods Prospective cohort study among twins infants born between 34 + 0 and 36 + 6 weeks, in Emilia Romagna, Italy, during 2013–2015. The primary outcome was a composite of adverse perinatal outcomes. Results Among 346 LP twins, 84 (23.4%) were monochorionic and 262 (75.7%) were dichorionic; spontaneous preterm labor accounted for 85 (24.6%) deliveries, preterm prelabor rupture of membranes for 66 (19.1%), evidence based indicated deliveries were 117 (33.8%), while non-evidence-based indications were 78 (22.5%). When compared to spontaneous preterm labor or preterm prelabor rupture of membranes, pregnancies delivered due to maternal and/or fetal indications were associated with higher maternal age (p

Background Respiratory failure is a severe complication in coronavirus disease 2019 (COVID-19) pneumonia that, in addition to oxygen therapy, may require continuous positive airway pressure (CPAP) support. It has been postulated that COVID-19 lung injury may share some features with those observed in hyperoxic acute lung injury. Thus, a correct target arterial oxygen tension (PaO2) during oxygen supplementation may be crucial to protect the lung from further tissue damage. The aims of this study were: 1) to evaluate the effects of conservative oxygen supplementation during helmet CPAP therapy on mortality and intensive care unit (ICU) admission in patients with COVID-19 and respiratory failure, and 2) to evaluate the effect of conservative oxygen supplementation on new-onset organ failure and secondary pulmonary infections. Methods This was a single-centre, historically controlled study of patients with severe respiratory failure due to COVID-19 pneumonia, receiving either conservative or nonconservative oxygen supplementation during helmet CPAP. A cohort receiving conservative oxygen supplementation was studied prospectively in which oxygen supplementation was administered with a target PaO2

The Symani surgical system undergoes scrutiny in this study as part of a series of preclinical investigations. Previous studies compared the precision of robotic-assisted anastomoses with manual techniques. This study aimed to evaluate the critical, histological, and gross parameters at the site of anastomosis and at distant sites in a rat model to provide insights into the safety and efficacy of robotic-assisted microsurgery to enhance its potential for clinical adoption. Experienced microsurgeons performed arterial and venous anastomoses in 16 Wistar rats, randomized into four treatment groups: robotic artery, robotic vein, manual artery, and manual vein. Various parameters were evaluated at two time points (T0 and T30) on the day of the procedure and at Day 28 (T28d). In the second phase of the study, the animals underwent necropsy, histopathologic analysis, micro-CT scans, and angiography imaging of the anastomosis sites, major organs, and distant target organs by a blinded assessor. Patency rates were 100% at T0 and T30 for all anastomoses and stayed at 100% on T28d for the robotic subgroups; however, it decreased to 87.5% for manual arterial anastomoses owing to a case of obstructive thrombus. No evidence of clot migration was observed. Blood flow parameters and procedure times did not differ significantly. The blinded semiquantitative histological analysis revealed no significant disparities between the robotic and manual anastomoses across various pathological indicators. No gross abnormalities were detected in musculoskeletal examinations. This preclinical study demonstrated the safety of the Symani surgical system. Results suggest equivalence between robotic and manual techniques regarding thrombus formation at the anastomotic site and distal organs. [ABSTRACT FROM AUTHOR]

The current emergency response for substance users experiencing homelessness is not adapted to their needs. This has led to the revolving door phenomenon and to issues of collaboration between involved organizations. This study aims to demonstrate the relevance from the participants' perspective of: 1) the World Café; 2) the deliberative democratic evaluation; and 3) combining these two methods as part of a qualitative study aimed at improving emergency response to substance users experiencing homelessness in Montreal. Thirty-four people participated in an intersectoral World Café guided by the principles of deliberative democratic evaluation. Twenty-three participants responded to a questionnaire regarding their satisfaction, effects of their participation, and adherence to the principles of deliberative democratic evaluation (inclusion, dialogue, and deliberation). We performed descriptive statistics and a thematic content analysis. Ultimately, the respondents were satisfied with the activity and several said they gained new knowledge and improved their network. Roughly half of the participants shared that their participation influenced their representations and their future practices. Our findings suggest that combining deliberative democratic evaluation and World Café is relevant to providing rich qualitative data, gaining systemic insight, and having an impact on our communities (e.g., improving intersectoral collaboration, professional’ attitudes and practices).

Head and neck reconstruction poses unique challenges in rehabilitating surgical defects in terms of integrity, function, and form. The radial forearm free flap (RFFF) has been widely used for defect coverage, especially in the head and neck area, but its versatility allows it to be used for soft-tissue reconstruction in various parts of the body. The vascular features of the flap are quite constant and reliable. Nevertheless, abnormalities of the forearm vascular tree have been described over the decades. We report a case of intraoral reconstruction after verrucous carcinoma recurrence in a 74-year-old woman with an unusual forearm flap, which we called the median forearm free flap, based on a median branch of the radial artery that was preoperatively detected using handheld Doppler ultrasonography. The distally located skin paddle was predominantly supplied by the aberrant median vessel with its perforators. The flap was thus safely harvested with this atypical pedicle. Successful reconstruction of the intraoral defect was achieved, with an uneventful postoperative course.

Abstract Background Large for gestational age infants (LGA) have increased risk of adverse short-term perinatal outcomes. This study aims to develop a multivariable prediction model for the risk of giving birth to a LGA baby, by using biochemical, biophysical, anamnestic, and clinical maternal characteristics available at first trimester. Methods Prospective study that included all singleton pregnancies attending the first trimester aneuploidy screening at the Obstetric Unit of the University Hospital of Modena, in Northern Italy, between June 2018 and December 2019. Results A total of 503 consecutive women were included in the analysis. The final prediction model for LGA, included multiparity (OR = 2.8, 95% CI: 1.6–4.9, p = 0.001), pre-pregnancy BMI (OR = 1.08, 95% CI: 1.03–1.14, p = 0.002) and PAPP-A MoM (OR = 1.43, 95% CI: 1.08–1.90, p = 0.013). The area under the ROC curve was 70.5%, indicating a satisfactory predictive accuracy. The best predictive cut-off for this score was equal to − 1.378, which corresponds to a 20.1% probability of having a LGA infant. By using such a cut-off, the risk of LGA can be predicted in our sample with sensitivity of 55.2% and specificity of 79.0%. Conclusion At first trimester, a model including multiparity, pre-pregnancy BMI and PAPP-A satisfactorily predicted the risk of giving birth to a LGA infant. This promising tool, once applied early in pregnancy, would identify women deserving targeted interventions. Trial registration ClinicalTrials.gov NCT04838431 , 09/04/2021.

Natural Killer (NK) cells are key innate effectors of antiviral immune response, and their activity changes in ageing and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. Here, we investigated the age-related changes of NK cell phenotype and function during SARS-CoV-2 infection, by comparing adult and elderly patients both requiring mechanical ventilation. Adult patients had a reduced number of total NK cells, while elderly showed a peculiar skewing of NK cell subsets towards the CD56lowCD16high and CD56neg phenotypes, expressing activation markers and check-point inhibitory receptors. Although NK cell degranulation ability is significantly compromised in both cohorts, IFN-γ production is impaired only in adult patients in a TGF-β−dependent manner. This inhibitory effect was associated with a shorter hospitalization time of adult patients suggesting a role for TGF-β in preventing an excessive NK cell activation and systemic inflammation. Our data highlight an age-dependent role of NK cells in shaping SARS-CoV-2 infection toward a pathophysiological evolution.

The TP53 tumor suppressor gene is one of the most studied gene in virtue of its ability to prevent cancer development by regulating apoptosis, cell cycle arrest, DNA repair, autophagy and senescence. Furthermore, the modulation of metabolism by P53 is fundamental for tumor suppressor activity. Studies in mouse models showed that mice carrying TP53 mutations affecting the acetylation in the DNA binding domain still retain the ability to transactivate genes involved in metabolism. Noteworthy, mice expressing the triple 3KR or the single K117R mutant do not show early on-set tumor development in contrast to TP53−/− mice. Interestingly, the mouse K117R mutation corresponds to the human tumor-derived K120R modification, which abrogates P53-dependent activation of apoptosis without affecting growth arrest. In this study, we investigated the property of the human P53 K120R mutant in the regulation of metabolism by analyzing the transcriptional specificity in yeast- and mammalian-based reporter assays, the metabolic phenotype associated to its expression in colon cancer HCT116TP53−/− cells and the induction of P53 targets and proteins involved in the antioxidant response. These properties were analyzed in comparison to wild type P53 protein, the human triple mutant corresponding to mouse 3KR and the cancer hot-spot R273H mutant. We confirm the selective functionality of P53 K120R mutant, which shows a transcriptional activity on cell cycle arrest but not on apoptotic targets. Interestingly, this mutant shows a partial transactivation activity on p53 response element belonging to the metabolic target TIGAR. Moreover, we observe a significant uncoupling between oxygen consumption and ATP production associated with higher lipid peroxidation level in all P53 mutants carrying cells with respect to wild type P53 expressing cells. Noteworthy, in the absence of a pro-oxidative challenge, cells expressing K120R mutant retain a partial capacity to modulate glucose metabolism, limiting lipid peroxidation with respect to the other P53 mutants carrying cells. Lastly, especially in presence of human 3KR mutant, a high expression of proteins involved in the antioxidant response is found. However, this response does not avoid the increased lipid peroxidation, confirming that only wild type P53 is able to completely counteract the oxidative stress and relative damages.

Slow-moving landslides are widespread natural hazards that can affect social and economic activities, causing damage to structures and infrastructures. This paper aims at proposing a procedure to analyze road damage induced by slow-moving landslides based on the joint use of landslide susceptibility maps, a road-damage database developed using Google Street View images and ground-displacement measurements derived from the interferometric processing of satellite SAR images. The procedure is applied to the municipalities of Vaglio Basilicata and Trivigno in the Basilicata region (southern Italy) following a matrix-based approach. First, a susceptibility analysis is carried out at the municipal scale, using data from landslide inventories and thematic information available over the entire municipalities. Then, the susceptibility index, the class of movement and the level of damage are calculated for the territorial units corresponding to the road corridors under investigation. Finally, the road networks are divided into stretches, each one characterized by a specific level of risk (or attention required) following the aggregation of the information provided by the performed analyses. The results highlight the importance of integrating all of these different approaches and data for obtaining quantitative information on the spatial and temporal behavior of slow-moving landslides affecting road networks.

In the context of climate change, the correct management of groundwater, which is strategic for meeting water needs, becomes essential. Groundwater modeling is particularly crucial for the sustainable and efficient management of groundwater. This manuscript provides different types of modeling according to data availability and features of three porous aquifer systems in Italy (Empoli, Magra, and Brenta systems). The models calibrated on robust time series enabled the performing of forecast simulations capable of representing the quantitative and qualitative response to expected climate regimes. For the Empoli aquifer, the process-based models highlighted the system’s ability to mitigate the effects of dry climate conditions thanks to its storage capability. The data-driven models concerning the Brenta foothill aquifer pointed out the high sensitivity of the system to climate extremes, thus suggesting the need for specific water management actions. The integrated data-driven/process-based approach developed for the Magra Valley aquifer remarked that the water quantity and quality effects are tied to certain boundary conditions over dry climate periods. This work shows that, for groundwater modeling, the choice of the suitable approach is mandatory, and it mainly depends on the specific aquifer features that result in different ways to be sensitive to climate. This manuscript also provides a novel outcome involving the integrated approach wherein it is a very efficient tool for forecasting modeling when boundary conditions, which significantly affect the behavior of such systems, are subjected to evolve under expected climate scenarios.

The incidence and death rate of pancreatic ductal adenocarcinoma (PDAC) have increased in recent years, therefore the identification of novel targets for treatment is extremely important. Interactions between cancer and stromal cells are critically involved in tumour formation and development of metastasis. Here we report that PDAC cells secrete BAG3, which binds and activates macrophages, inducing their activation and the secretion of PDAC supporting factors. We also identify IFITM-2 as a BAG3 receptor and show that it signals through PI3K and the p38 MAPK pathways. Finally, we show that the use of an anti-BAG3 antibody results in reduced tumour growth and prevents metastasis formation in three different mouse models. In conclusion, we identify a paracrine loop involved in PDAC growth and metastatic spreading, and show that an anti-BAG3 antibody has therapeutic potential.

Objective: The interactions between aortic morphology and hemodynamics play a key role in determining type B aortic dissection (TBAD) progression and remodeling. The study aimed to provide qualitative and quantitative hemodynamic assessment in four different TBAD morphologies based on 4D flow MRI analysis.Materials and Methods: Four patients with different TBAD morphologies underwent CT and 4D flow MRI scans. Qualitative blood flow evaluation was performed by visualizing velocity streamlines and flow directionality near the tears. Quantitative analysis included flow rate, velocity and reverse flow index (RFI) measurements. Statistical analysis was performed to evaluate hemodynamic differences between the true lumen (TL) and false lumen (FL) of patients.Results: Qualitative analysis revealed blood flow splitting near the primary entry tears (PETs), often causing the formation of vortices in the FL. All patients exhibited clear hemodynamic differences between TL and FL, with the TL generally showing higher velocities and flow rates, and lower RFIs. Average velocity magnitude measurements were significantly different for Patient 1 (t = 5.61, p = 0.001), Patient 2 (t = 3.09, p = 0.02) and Patient 4 (t = 2.81, p = 0.03). At follow-up, Patient three suffered from left renal ischemia because of FL collapse. This patient presented a complex morphology with two FLs and marked flow differences between TL and FLs. In Patient 4, left renal artery malperfusion was observed at the 32-months follow-up, due to FL thrombosis growing after PET repair.Conclusion: The study demonstrates the clinical feasibility of using 4D flow MRI in the context of TBAD. Detailed patient-specific hemodynamics assessment before treatment may provide useful insights to better understand this pathology in the future.

This systematic review and meta-analysis aimed to determine if probiotic supplementation in pregnancy reduced maternal Group B streptococcus (GBS) recto-vaginal colonization in pregnant women at 35–37 weeks of gestation. Electronic databases (i.e., PubMed, MEDLINE, ClinicalTrials.gov, ScienceDirect, and the Cochrane Library) were searched from inception up to February 2022. We included RCTs assessing the effects of probiotic supplementation in pregnancy on GBS recto-vaginal colonization. The primary outcome was GBS-positive recto-vaginal cultures performed at 35–37 weeks of gestation. Secondarily, we evaluated obstetric and short-term neonatal outcomes. A total of 132 publications were identified; 9 full-length articles were reviewed to finally include 5 studies. Probiotic supplementation reduced vaginal GBS colonization: the GBS positive culture rate was estimated at 31.9% (96/301) in the intervention group compared to 38.6% (109/282) in the control group (OR = 0.62, 95% CI 0.40–0.94, I2 4.8%, p = 0.38). The treatment started after 30 weeks of gestation and was more effective in reducing GBS colonization (OR 0.41, 95% CI 0.21–0.78, I2 0%, p = 0.55). Probiotic administration during pregnancy, namely in the third trimester, was associated with a reduced GBS recto-vaginal colonization at 35–37 weeks and a safe perinatal profile. Whether this new strategy could reduce the exposition of pregnant women to significant doses of antibiotics in labor needs to be evaluated in other trials.

Introduction: The choice of the mode of delivery, in case of stillbirth (SB) (fetus non-viable >22 weeks’ gestation), should consider maternal preference, gestational age, bishop score, the clinical condition of the woman, and her previous obstetric history. However, despite these clear indications, data on the effective implementation of the latter are lacking. The aim of our study is to evaluate the different modes of delivery in an Italian population of SBs, according to gestational age, parity, causes of death, obstetric history, and maternal characteristics. Material and Methods: This is an area-based, prospective cohort study conducted in Emilia Romagna, Italy between January 2014 to December 2020. Data included all cases of SB (>22 weeks). Results: From 2014 to 2020, 783 SB occurred out of a total of 232.506 births, with a SB rate of 3.3 per 1000. Labor was spontaneous in 85 (11%). Of remnant, 567 (73.6%) were induced and 118 (15.3%) had no labor. The mode of delivery was vaginal in most of the cases (649/770, 84.3%) and by cesarean section in 121/770 (15.7%) of cases. Emergency CS was most frequent and performed in 89/121 (73.5%) of total CS, representing 11.5% of SB deliveries. Mode of induction did not differ in relation to gestational age at stillbirth, while vaginal delivery was significantly higher in women induced with prostaglandins (p = 0.000) respect to other methods. Nulliparous women had a significantly higher need for multiple methods of induction (p = 0.000) respect multiparous and obese women used more frequently prostaglandins (p = 0.03) than other methods. Women with a history of previous CS presented a significantly higher rate of repeated elective CS (p = 0.000). Moreover, emergency CS was performed more frequent in obese (p = 0.02), diabetic (p = 0.04) and hypertensive (p = 0.04) women and in SB caused by placenta disorders, namely in abruptio placentae (p = 0.000). In the case of chorioamnionitis and funisitis women significantly were induced with prostaglandin (p = 0.000) and delivered vaginally (p = 0.000). Conclusions: The method of induction of labor and the mode of delivery in case of SB did not depend on gestational age at the diagnosis of death, while they are related to placenta disorders representing a relevant condition leading to emergency CS also after diagnosis of fetal death. These data could help obstetric providers in managing the deliveries of stillborn infants.

Background: The induction of labor (IOL) is a common obstetric intervention, steadily increasing (one out four pregnancies) in the last years. This procedure should be considered only when there is a medical indication, and when the benefits outweigh the maternal and/or fetal risks of waiting for spontaneous onset of labor. Therefore, this study aims to compare the efficacy of the IOL in terms of induction to delivery time, mode of delivery, and neonatal well-being among different evidence-based and non-evidence-based indications. Methods: This prospective study was conducted at the University Hospital of Modena, between January and December 2020. We included singleton pregnant women undergoing IOL, at the term. Intrauterine deaths, small for gestational age fetuses 41 weeks + 3 days), and non-evidence-based indications (NEBI). The primary outcome is the time occurring between IOL and delivery (TIME), analyzing separately by parity. Moreover, mode of delivery and neonatal well-being were evaluated. Results: A total of 585 women underwent IOL in the study period. Overall, the median TIME between IOL and delivery was 19 hours, and the mean cesarean section CS rate was 15.5% (91/585). Pregnancies induced for postdate and non-evidence-based indications registered respectively a significantly higher mean time (p< 0.001), compared with women induced for PROM. This occurred both in nulliparous and multiparous women. Moreover, at multivariate analysis, the IOL TIME ≥24 hours was significantly influenced by Bishop score (p = 0.000) and NEBI (p = 0.02) in nulliparous and by gestational age (p = 0.000) and NEBI (p = 0.02) in multiparous. Moreover, CS rate was significantly influenced by Bishop score (p = 0.003) in nulliparous and by gestational age (p = 0.01) in multiparous. Finally, neonatal intensive care unit (NICU) admission resulted significantly influenced only by gestational age (p = 0.002) in multiparous. Conclusions: Our study confirms that IOL in non-evidence-based indications, leads to an increase in induction to delivery time comparing with women induced for PROM, both in nulliparous and multiparous women, thus it should be justified and carefully evaluated. Further randomized controlled trials (RCT) conducted in European/Italian settings are needed to determine the perinatal outcomes of IOL in non-evidence-based indications.

Abstract. Background. Mycobacterium avium subsp. hominissuis (MAH) is an important pathogen responsible for most of the human-associated nontuberculous mycobacteria infections. Over the past few decades the incidence of MAH infections is increasing in Italy, as in many countries worldwide. The present study is aimed to elucidate the genetic characteristics of MAH strains isolated from human patients using VNTR typing and to show the genetic relatedness among them. Methods. The genetic diversity of 108 human isolates of MAH was determined by VNTR analysis targeting 8 loci, coded 32, 292, X3, 25, 3, 7, 10 and 47. Results. The VNTR analysis revealed 25 distinct VNTR patterns; of these, 13 patterns were unique, while 12 patterns were shared by 2 or more isolates, thus yielding 12 clusters including a total of 95 isolates. The discriminatory power of our VNTR analysis yielded an HGDI of 0.990, indicating that VNTR typing has an excellent discriminatory power. No association of a particular VNTR pattern with a particular clinical feature, such as the disseminated, pulmonary or extrapulmonary type of infection, was observed. Minimum spanning tree analysis showed that 21 VNTR patterns, occurring either as clustered or unique isolates, differed from the nearest one for one allelic variation. Conclusions. The results obtained through the VNTR analysis showed that most MAH strains displayed a close genetic relationship. This high phylogenetic proximity of the VNTR loci over a long time period supports the concept that the MAH genotype is highly homogeneous in our geographical area, suggesting the hypothesis of the presence of possible sources of infection and transmission pathways at the local level.

Myo-Inositol (myo-Ins), key molecule participating in several intracellular signaling pathways and physiological processes, has been proven to modulate interleukin-6 (IL-6) levels in chronic inflammatory diseases and to possess endothelial protective properties. Moreover, myo-Ins promotes the maturation of pulmonary surfactant phospholipids, with beneficial effects in the treatment of premature infants with respiratory distress syndrome (RDS). On these premises, myo-Ins has a potential application in the treatment of pulmonary diseases, and it could be successfully used to reduce the complications related to the SARS-CoV-2 pandemic event. Though information about the virus is still scarce, it is becoming evident that the Coronavirus infection triggers an interstitial pneumonia that quickly evolves into a severe RDS, associated with a thrombotic and vascular disease targeting endothelial cells throughout the body. These effects are most probably driven by a disastrous overreaction of the immune system, known as “cytokine storm”, which interests not only lungs but also gut, kidneys, heart, and brain, with platelet-endothelial dysfunction and abnormally rapid life-threatening blood clotting. Given the pathophysiology of the SARS-CoV-2 disease (COVID-19), it could be worth investigating whether myo-Ins properties can mitigate the disease-related complications in terms of surfactant production, modulation of inflammatory cytokines and endothelial protection.

The human TP53 locus, located on the short arm of chromosome 17, encodes a tumour suppressor protein which functions as a tetrameric transcription factor capable of regulating the expression of a plethora of target genes involved in cell cycle arrest, apoptosis, DNA repair, autophagy, and metabolism regulation. TP53 is the most commonly mutated gene in human cancer cells and TP53 germ-line mutations are responsible for the cancer-prone Li-Fraumeni syndrome. When mutated, the TP53 gene generally presents missense mutations, which can be distributed throughout the coding sequence, although they are found most frequently in the central DNA binding domain of the protein. TP53 mutations represent an important prognostic and predictive marker in cancer. The presence of a TP53 mutation does not necessarily imply a complete P53 inactivation; in fact, mutant P53 proteins are classified based on the effects on P53 protein function. Different models have been used to explore these never-ending facets of TP53 mutations, generating abundant experimental data on their functional impact. Here, we briefly review the studies analysing the consequences of TP53 mutations on P53 protein function and their possible implications for clinical outcome. The focus shall be on Chronic Lymphocytic Leukemia (CLL), which also has generated considerable discussion on the role of TP53 mutations for therapy decisions.

The Versilia coastal plain hosts an important and strategic aquifer for water supply. Like all coastal aquifers, it is particularly vulnerable to the saltwater intrusion, which can be amplified not only by fresh water over-exploitation, but also by the effects of climate change, including the increase of extreme events. For an optimal management of this precious resource and for its protection both in quantitative and qualitative terms, an adequate knowledge of the aquifer system is necessary through the development of conceptual and mathematical hydrogeological models. The conceptual hydrogeological model was defined on the base of an integrated multidisciplinary approach with the elaboration of stratigraphic, hydrogeological and geochemical-isotopic data. Subsequently, groundwater flow mathematical models were created using the ModFlow code and Groundwater Vistas like graphical interface, subsequently transferred to the Freewat open platform. The models enabled acquiring further knowledge about this aquifer system and to identify and, where possible to quantify, the main processes and groundwater components involved, including the seawater ingression. An important groundwater component, both in terms of water quantity and quality,resulted widespread in the fan of the Versilia River and mainly fed by the river itself in the foothill zone. Although this component seems to be able to guarantee relative protection against marine ingression, in the summer season some piezometric depressions tied to groundwater exploitation tend to expand and move towards the coast, thus favouring the seawater intrusion process. These issues can be amplified by the extreme rainy events that frequently occur in the Apuan Alps region. The huge quantity of water that quickly flows by the river up to the sea during extreme events represents a lack of feeding respect to the aquifer, and consequently the mitigation role of the fan component towards seawater intrusion can be significantly weakened. Thanks to the water budget achieved by numerical model and considering real extreme events recently occurred in the Apuan-Versilian region it was possible to make considerations about possible effects these climate regimes on the aquifer system. As outcomes, we concluded that extreme events as those occurred in the area in the past, and awaited more frequently in the future, represent a concrete threat for the coastal aquifer system that over next decades could suffer more and more seawater intrusion. Given the reliance of local human activities on groundwater, far-sighted actions of water management (e.g. managed aquifer recharge) are recommended for mitigating such as climate effects.

Minimal clinically important difference (MCID) can be defined as the smallest change or difference in an outcome measure that is perceived as beneficial and would lead to a change in the patient's medical management. The aim of the current expert consensus report is to provide a “state-of-the-art” review of the currently available literature evidence about MCID for end-points to monitor asthma control, in order to facilitate optimal disease management and identify unmet needs in the field to guide future research. A series of MCID cut-offs are currently available in literature and validated among populations of asthmatic patients, with most of the evidence focusing on outcomes as patient reported outcomes, lung function and exercise tolerance. On the contrary, only scant and partial data are available for inflammatory biomarkers. These clearly represent the most interesting target for future development in diagnosis and clinical management of asthma, particularly in view of the several biologic drugs in the pipeline, for which regulatory agencies will soon require personalised proof of efficacy and treatment response predictors.