Managing carious lesions:consensus recommendations on carious tissue removal

The International Caries Consensus Collaboration undertook a consensus process and here presents clinical recommendations for carious tissue removal and managing cavitated carious lesions, including restoration, based on texture of demineralized dentine. Dentists should manage the disease dental caries and control activity of existing cavitated lesions to preserve hard tissues and retain teeth long-term. Entering the restorative cycle should be avoided as far as possible. Controlling the disease in cavitated carious lesions should be attempted using methods which are aimed at biofilm removal or control first. Only when cavitated carious lesions either are noncleansable or can no longer be sealed are restorative interventions indicated. When a restoration is indicated, the priorities are as follows: preserving healthy and remineralizable tissue, achieving a restorative seal, maintaining pulpal health, and maximizing restoration success. Carious tissue is removed purely to create conditions for long-lasting restorations. Bacterially contaminated or demineralized tissues close to the pulp do not need to be removed. In deeper lesions in teeth with sensible (vital) pulps, preserving pulpal health should be prioritized, while in shallow or moderately deep lesions, restoration longevity becomes more important. For teeth with shallow or moderately deep cavitated lesions, carious tissue removal is performed according toselective removal to firm dentine.In deep cavitated lesions in primary or permanent teeth,selective removal to soft dentineshould be performed, although in permanent teeth,stepwise removalis an option. The evidence and, therefore, these recommendations support less invasive carious lesion management, delaying entry to, and slowing down, the restorative cycle by preserving tooth tissue and retaining teeth long-term.status: publishe

CariesCare International adapted for the pandemic in children: Caries OUT multicentre single-group interventional study protocol

Background Comprehensive caries care has shown effectiveness in controlling caries progression and improving health outcomes by controlling caries risk, preventing initial-caries lesions progression, and patient satisfaction. To date, the caries-progression control effectiveness of the patient-centred risk-based CariesCare International (CCI) system, derived from ICCMS™ for the practice (2019), remains unproven. With the onset of the COVID-19 pandemic a previously planned multi-centre RCT shifted to this “Caries OUT” study, aiming to assess in a single-intervention group in children, the caries-control effectiveness of CCI adapted for the pandemic with non-aerosols generating procedures (non-AGP) and reducing in-office time. Methods In this 1-year multi-centre single-group interventional trial the adapted-CCI effectiveness will be assessed in one single group in terms of tooth-surface level caries progression control, and secondarily, individual-level caries progression control, children’s oral-health behaviour change, parents’ and dentists’ process acceptability, and costs exploration. A sample size of 258 3–5 and 6–8 years old patients was calculated after removing half from the previous RCT, allowing for a 25% dropout, including generally health children (27 per centre). The single-group intervention will be the adapted-CCI 4D-cycle caries care, with non-AGP and reduced in-office appointments’ time. A trained examiner per centre will conduct examinations at baseline, at 5–5.5 months (3 months after basic management), 8.5 and 12 months, assessing the child’s CCI caries risk and oral-health behaviour, visually staging and assessing caries-lesions severity and activity without air-drying (ICDAS-merged Epi); fillings/sealants; missing/dental-sepsis teeth, and tooth symptoms, synthetizing together with parent and external-trained dental practitioner (DP) the patient- and tooth-surface level diagnoses and personalised care plan. DP will deliver the adapted-CCI caries care. Parents’ and dentists’ process acceptability will be assessed via Treatment-Evaluation-Inventory questionnaires, and costs in terms of number of appointments and activities. Twenty-one centres in 13 countries will participate. Discussion The results of Caries OUT adapted for the pandemic will provide clinical data that could help support shifting the caries care in children towards individualised oral-health behaviour improvement and tooth-preserving care, improving health outcomes, and explore if the caries progression can be controlled during the pandemic by conducting non-AGP and reducing in-office time. Trial registration: Retrospectively-registered-ClinicalTrials.gov-NCT04666597-07/12/2020: https://register.clinicaltrials.gov/prs/app/action/SelectProtocol?sid=S000AGM4&selectaction=Edit&uid=U00019IE&ts=2&cx=uwje3h. Protocol-version 2: 27/01/2021

Using fish to understand how cities affect sexual selection before and after mating

Urbanization transforms natural and agricultural areas into built landscapes. Such profound habitat alteration imposes strong pressure on phenotypic trait changes through processes related to natural and/or sexual selection. Evidence of how natural selection drives changes to traits in urban biota is increasing, but little is known about the role of sexual selection. In this study, we assessed the effect of urbanization on the expression and interaction of males' pre-mating traits (body size and color) and a post-mating trait (sperm load). We used a widespread invasive species, the guppy (Poecilia reticulata), which is a wellknown model for studying sexual selection, but have never been studied in urban systems for this purpose. We found that urbanization did not affect mean body size or condition, but it resulted in size-dependent reductions in the expression of orange and iridescent colors, as well as sperm load. The orange color was reduced in small urban guppies, while the iridescent colors were reduced in large urban guppies compared to non-urban guppies. The difference in sperm load was only found in large males, with lower sperm load in urban guppies. The relationship between orange color and sperm load was positive in urban guppies but negative in non-urban guppies, while the association between iridescent color and sperm load followed the opposite pattern. Our findings suggest that sexual selection on pre- and post-mating traits is weaker in urban than in non-urban systems and that interactions between such traits are context dependent. These responses can be related to the pollution and altered visual environment of urban systems and provide an opportunity to advance our understanding of the mechanisms determining adaptation in cities

Serum tissue factor as a biomarker for renal clear cell carcinoma

ABSTRACT Purpose to determine the usefulness of serum TF as a potential marker for patients with clear cell RCC. Materials and Methods prospective study of 30 patients with clear cell RCC submitted to nephrectomy and 16 controls without clear cell RCC treated surgically for other conditions. TF is a endothelium marker that was correlated with worse prognosis in a variety of solid tumors including RCC. Serum TF was collected before surgery at the operating room and in the postoperative setting after at least four weeks. Serum samples were analyzed with a commercial ELISA kit for human TF (R&D Systems®). Results Mean preoperative serum TF levels in clear cell RCC patients and in controls were 66.8 pg/dL and 28.4 pg/dL, respectively (p<0.001). Mean postoperative serum TF levels in clear cell RCC patients were 26.3 pg/dL. In all patients with clear cell RCC postoperative serum levels of TF were lower, with a mean reduction of 41.6 pg/dL in the postoperative setting (p<0.001). Linear regression revealed that tumor size was correlated with the postoperative reduction of serum TF levels (p=0.037). Conclusions We have shown a 3-fold reduction in the median preoperative serum levels of TF in patients with clear cell RCC after surgery. We have also shown a difference of the same magnitude in the serum levels of TF compared with those of a control group of patients with benign diseases. TF appears to be a useful serum marker for the presence of clear cell RCC. Further studies are needed to validate these findings

Detection of cmv-related gastrointestinal tract infections in a series of 49 xenotransplanted primates

Background: Generalized CMV infections have been observed in immunosuppressed cynomolgus monkeys. Therefore, in this study we have investigated, using different approaches, the presence of CMV infection in a series of 49 primate recipients of porcine renal xenografts. Methods: Fifty-two Macaca fascicularis were used: 49 were recipients of kidney xenografts and 3 were part of a pharmacokinetic trial. All primates were housed in the same facility and treated with immunosuppressive drugs. As a high level of homology between Rhesus and Macaca fascicularis CMV has previously been reported, primates were tested serologically by ELISA for rhCMV upon arrival at the facility and, in some cases, also at the time of transplantation. Three-hundred and twenty formalin-fixed paraffin-embedded sections of gastrointestinal (GI) tract were analysed by light microscopy. All sections were also studied by immunohistochemistry (IHC) for expression of RhCMV IE1 antigen. A consensus-PCR with specificity for the herpesviral DNA-directed DNA polymerase gene (DPOL) was performed on a cryopreserved lung tissue of an IHC strongly positive primate. Results: Upon arrival at the facility, 22 primates were serologically positive for CMV, 20 were negative and 10 were equivocal. The serological test repeated on the negative and doubtful animals at the time of transplantation showed that all primates had serum-converted. GI-tract sections of 5 of the 52 primates analysed showed lesions associated with CMV infection. However, 8 primates were IHC positive for CMV although 3 did not show any histological evidences of CMV infection. Antigen IE1 was detected in epithelial cells in 6 out of 8 primates. The molecular analysis by PCR revealed a 99% identity of the DPOL gene between Rhesus and Macaca fascicularis CMV (100% identity at amino acid level). Conclusions: IHC is more sensitive and specific in the detection of CMV infection in immunosuppressed, xenotransplanted primates than classical histology. Our data suggest that all the animals serum-converted for CMV whilst waiting for xenotransplantation. In the light of the frequent observation of CMV-related lesions in xenotransplanted animals, an effective anti-CMV prophylaxis appears to be indispensable in such model

Linee-guida per la progettazione

Rapporto conclusivo del Progetto di ricerca finalizzata sugli ospedali ad alta tecnologia ed assistenza (ex art.12, Dlgs 502/92) Agenzia per i Servizi Sanitari Regionali, Rom

Predicting functional impairment trajectories in amyotrophic lateral sclerosis: a probabilistic, multifactorial model of disease progression

Objective: To employ Artificial Intelligence to model, predict and simulate the amyotrophic lateral sclerosis (ALS) progression over time in terms of variable interactions, functional impairments, and survival. Methods: We employed demographic and clinical variables, including functional scores and the utilisation of support interventions, of 3940 ALS patients from four Italian and two Israeli registers to develop a new approach based on Dynamic Bayesian Networks (DBNs) that models the ALS evolution over time, in two distinct scenarios of variable availability. The method allows to simulate patients’ disease trajectories and predict the probability of functional impairment and survival at different time points. Results: DBNs explicitly represent the relationships between the variables and the pathways along which they influence the disease progression. Several notable inter-dependencies were identified and validated by comparison with literature. Moreover, the implemented tool allows the assessment of the effect of different markers on the disease course, reproducing the probabilistically expected clinical progressions. The tool shows high concordance in terms of predicted and real prognosis, assessed as time to functional impairments and survival (integral of the AU-ROC in the first 36 months between 0.80–0.93 and 0.84–0.89 for the two scenarios, respectively). Conclusions: Provided only with measurements commonly collected during the first visit, our models can predict time to the loss of independence in walking, breathing, swallowing, communicating, and survival and it can be used to generate in silico patient cohorts with specific characteristics. Our tool provides a comprehensive framework to support physicians in treatment planning and clinical decision-making