In vitro profiling of endothelial volatile organic compounds under resting and pro-inflammatory conditions.

INTRODUCTION: The evaluation of volatile organic compounds(VOCs) emitted by human body offers a unique tool to set up new non-invasive devices for early diagnosis and long-lasting monitoring of most human diseases. However, their cellular origin and metabolic fate have not been completely elucidated yet, thus limiting their clinical application. Endothelium acts as an interface between blood and surrounding tissues. As such, it adapts its physiology in response to different environmental modifications thus playing a role in the pathogenesis of many metabolic and inflammatory diseases. OBJECTIVES: Since endothelium specifically reshapes its physiologic functions upon environmental changes the objective of this study was to evaluate if and how pro-inflammatory stimuli affect VOC metabolism in endothelial cell in culture. METHODS: Gas chromatography with mass spectrometric detection was applied to profile VOCs in the headspace of cultured endothelial cells (EC) in the absence or presence of the pro-inflammatory stimulus lipopolysaccharide (LPS). RESULTS: We observed that, under resting conditions, EC affected the amount of 58 VOCs belonging to aldehyde, alkane and ketone families. Among these, LPS significantly altered the amount of 15 VOCs. ROC curves show a perfect performance (AUC = 1) for 10 metabolites including 1-butanol, 3-methyl-1-butanol and 2-ethyl-1-hexanol. DISCUSSION: The emission and uptake of the aforementioned VOCs disclose potential unexplored metabolic pathways for EC that deserve to be investigated. Overall, we identified new candidate VOC potentially exploitable, upon experimental confirm in in vivo model of disease, as potential biomarkers of sepsis and pro-inflammatory clinical settings.

Therapeutic approach for metabolic disorders and infertility in women with PCOS.

Polycystic ovary syndrome (PCOS) is a complex endocrine disorder affecting 5-10% of women of reproductive age. It generally shows with oligo/amenorrhea, anovulatory cycles, clinical o biochemical hirsutism, polycystic ovaries and, in a significant percentage of cases, insulin resistance. PCOS is defined as a multifactorial pathology, determined by the association of many factors: genetic, endocrine and environmental. The first and most effective treatment of PCOS is to change life-style and lose weight. The use of oral contraceptives has been shown effective in reducing acne and hirsutism and regulates the menstrual cycle. For women with severe hirsutism, the addition of antiandrogens to estrogen-progestin therapy has significantly improved the results. In cases of anovulatory infertility, the drug of first choice is clomiphene citrate, followed by low-dose gonadotropins. Recently, insulin-sensitizing drugs have been widely prescribed for PCOS patients. They are particularly effective in reducing insulin resistance and improving ovulatory performance. Besides insulin-sensitizing drugs, natural substances, such as inositol, seems to have good efficacy, similar to metformin with fewer side effects. New substances that could be used include statins and natural statins, such as monakolin, alone or combined with myo-inositol. These substances do not have side effects and greatly reduce the hyperandrogenic component in these patients.

Genetic, hormonal and metabolic aspects of PCOS: an update.

Polycystic ovary syndrome (PCOS) is a complex endocrine disorder affecting 5-10 % of women of reproductive age. It generally manifests with oligo/anovulatory cycles, hirsutism and polycystic ovaries, together with a considerable prevalence of insulin resistance. Although the aetiology of the syndrome is not completely understood yet, PCOS is considered a multifactorial disorder with various genetic, endocrine and environmental abnormalities. Moreover, PCOS patients have a higher risk of metabolic and cardiovascular diseases and their related morbidity, if compared to the general population.

Paediatricians' attitudes toward pain in children with severe cognitive impairment. A regional survey.

INTRODUCTION: pain is a frequent and relevant problem in children with severe cognitive impairments. Assessing pain in these patients can be difficult. Specific observational tools such as the Collignon Giusiano Questionnaire or the Non-communicating Children's Pain Checklist ( NCCPC) are available, but their use is not widespread. Children with severe cognitive impairment are frequently in need of painful procedures but data about availability of procedural sedation in this setting are limited. OBJECTIVE OF THE STUDY: to evaluate paediatricians' attitudes toward pain in children with severe cognitive impairment by measuring the use of specific pain scales and the use of analgesia or procedural sedation in course of a frequent procedure such as botulinum toxin injection. METHODS: phone interview with the doctor on duty of 56 paediatric wards in 3 regions of the North East of Italy, addressing the routine use of pain scales, and the use of specific observational tools for non communicating children. A phone interview was also conducted in 4 centers routinely practicing botulinum toxin injection about the use of analgesia or procedural sedation. RESULTS: 1 centre out of 55 reported to use specific scales for children with cognitive impairment, specifically the Collignon Giusiano Questionnaire. No centre used procedural sedation for botulinum toxin injection. CONCLUSION: in the investigated area there is a lack of attention to pain in children with severe cognitive impairment. Specific educational efforts should be done to improve the quality of care in this setting.

Physical activity habits prevent psychological distress in female academic students: The multiple mediating role of physical and psychosocial parameters.

Background: Psychological distress is recognised as the most common mental health difficulty in emerging adult (18-to-24-year-old) female academic students. This study aimed to test a novel model positing physical activity habits as a protective factor for psychological distress through the mediating role of physical and psychological parameters. Adherence to the Mediterranean diet and self-reported physical health status were included as physical parameters. Self-reported psychological health status and time spent on leisure activities were the psychological parameters considered. Method: Data were collected between April and May 2021. Correlation analyses and a multiple mediation model were computed on 411 online questionnaires filled out by 18-to-24-year-old female students from the University of blind (Italy). Results: The multiple indirect effects were significant (ß = -0.088; p < 0.001). This means that physical activity habits reduce psychological distress through high adherence to the Mediterranean diet, a good self-assessment of one's physical and psychological health status, and more time spent on leisure activities outdoors, with friends, and with family members. Conclusions: Results show that academic policies should be adopted so as to design physical activity programmes that may improve the students' healthy behaviours and social interactions, which, in turn, mitigate the detrimental effects of psychological distress.

Definitive results of a prospective non-randomized phase 2 study on stereotactic body radiation therapy (sbrt) for medically inoperable lung and liver oligometastases from breast cancer.

BACKGROUND AND PURPOSE: To report mature results for local control and survival in oligometastatic (OM) breast cancer patients treated with stereotactic body radiotherapy (SBRT) on lung and/or liver lesions in a phase II trial. METHODS: This is a prospective non-randomized phase II trial (NCT02581670) which enrolled patients from 2015 to 2021. Eligibility criteria included: age > 18 years, ECOG 0-2, diagnosis of breast cancer, maximum of 4 lung/liver lesions (with a maximum diameter < 5 cm), metastatic disease confined to the lungs and liver or extrapulmonary or extrahepatic disease stable or responding to systemic therapy. The primary end-points were local control (LC) and treatment-related toxicities. The secondary end-points included overall survival (OS), distant metastasis-free survival (DMFS), time to next systemic therapy (TTNS), poly-progression free survival (PPFS). RESULTS: The study included 64 patients with a total of 90 lesions treated with SBRT. LC at 1 and 2 years was 94.9 %, 91 % at 3 years. Median local control was not reached. Median OS was 16.5 months, OS at 1, 2 and 3 years was 87.5 %, 60.9 % and 51.9 %, respectively. Median DMFS was 8.3 months, DMFS at 1, 2 and 3 years was 38.1 %, 20.6 % and 16 % respectively. At univariate analysis, local response to SBRT was found to be statistically linked with better OS, DMFS and STFS. CONCLUSION: SBRT is a safe and valid option in oligometastatic breast cancer patients, with very high rates of local control. An optimal selection of patients is likely needed to improve survival outcomes and reduce the rate of distant progression.

Agenesis of the fetal corpus callosum: sonographic signs change with advancing gestational age.

OBJECTIVES: To assess the presence and degree of indirect signs of agenesis of the corpus callosum (ACC) according to gestational age and determine the percentage of cases in which each sign is present by 24 gestational weeks. METHODS: We analyzed retrospectively 54 cases of ACC which underwent three-dimensional neurosonography at our unit between January 2005 and December 2012. A single examination was available in 48 cases and six cases were followed up longitudinally, giving a total of 69 examinations. The following variables were assessed: indication for referral, karyotype, width of the atrium and presence/absence of colpocephaly, the cavum septi pellucidi, dorsal cyst and additional central nervous system (CNS) and non-CNS anomalies. RESULTS: Overall, there were 31 cases of complete ACC (cACC, 42 examinations) and 23 cases of partial ACC (pACC, 27 examinations). The mean gestational age was lower in the cases referred because of anomalies other than ACC than it was in those referred because of ventriculomegaly and/or suspicion of ACC (P < 0.05). Atrial width showed a positive linear correlation with advancing gestational age (P < 0.0001); it was < 10.0 mm in 25/34 (73.5%) examinations < 24 gestational weeks and in 9/35 (25.7%) ≥ 24 weeks (P < 0.001). Colpocephaly was present in 20.6% (7/34) of examinations < 24 weeks and in 68.6% (24/35) of those after 23 weeks (P < 0.05). The cavum septi pellucidi was present and visible at least in part in 17 (63%) of the 27 pACC examinations. In nine of the 27 (33.3%) pACC examinations, there was neither ventriculomegaly nor absence of the cavum septi pellucidi. Associated anomalies were present in 25/54 (46.3%) cases, and in 11 these included or consisted of CNS abnormalities. Karyotype was abnormal in seven of the 40 (17.5%) cases in which it was available. CONCLUSIONS: In a significant proportion of cases, most of the indirect signs of ACC are either absent or barely visible at the time of the midtrimester screening ultrasound examination. Therefore, ACC may escape diagnosis at midtrimester screening ultrasound. In particular, a third of examinations in fetuses with pACC may not show any abnormality in the transventricular screening view < 24 weeks. The medicolegal implications of such findings are important and should be considered.

Pain in cognitively impaired children: a focus for general pediatricians.

UNLABELLED: Pain in children with cognitive impairment and cerebral palsy is a particularly relevant issue due to its high prevalence and impact on quality of life. We review available evidence about prevalence of pain, causes and specific treatment, recognition and use of specific pain scales, physiology, and consequences of pain in this subset of patients. CONCLUSIONS: Pain is very common and is a critical determinant of quality of life in children with cognitive impairment and cerebral palsy. The diseases and associated complications that frequently expose these patients to pain can be treated and pain prevented. For patients with communication difficulties, appropriate, effective, validated tools are available and should be used to diagnose pain in itself, to >choose analgesic treatment and to determine effectiveness of these therapies. The level of awareness of pediatricians towards this issue seems to be quite low.

Role of nutrients in modulating microbiota and immunity in COVID-19 disease.

COVID-19 is a novel disease with a broad range of clinical patterns. Several patients show dysbiosis in the intestinal tract, with evidence of reduced beneficial bacteria, such as Bifidobacteria and Lactobacilli. It is well established that human gut microbiota dysbiosis is associated with several clinical conditions, including respiratory tract diseases due to the gut-lung axis. This narrative review discusses the role of nutrients in the relationship between the gut microbiota and the immune response in SARS-CoV-2 infection. In particular, we will focus on the benefits offered by vitamins and micronutrients on different aspects of COVID-19 disease while also discussing which diets seem to provide the most advantages.

Arterial involvement in Fabry disease: state of the art and future diagnostic purposes.

Anderson-Fabry disease (FD) is a rare genetic, progressive, and multi-systemic condition, with X-linked inheritance. This is caused by pathogenic variants in the GLA gene, coding for the lysosomal enzyme called alpha-galactosidase A (aGLA), responsible for the cleavage of globotriaosylceramide (Gb3). The reduced or absent activity of aGLA causes the intracellular accumulation of Gb3, particularly in smooth and endothelial muscle cells, which causes cellular dysfunction. The main organs involved are the central nervous system, heart, and kidneys. However, being a ubiquitous enzyme, FD disease must be considered a systemic disease involving the peripheral nervous system, ocular and audio-vestibular systems. Also, the vascular district is damaged but the pathophysiology of vasculopathy in FD is not yet entirely understood. In literature, many vascular diagnostic tests were used to evaluate this specific involvement in FD, i.e., carotid intima media thickness (cIMT), arterial stiffness (AS), flow-mediated dilation (FMD) and atherosclerotic plaques; evaluation of vascular calcifications in FD patients is not presently available. In this review, we examined the current available literature on vascular aspects in FD. Moreover, we presented our global vascular evaluation, based on Radio Frequency Duplex Ultrasound (RF-DU), plaques, and vascular calcifications, to apply to FD patients.

Omega-3 fatty acids, inflammation and angiogenesis: basic mechanisms behind the cardioprotective effects of fish and fish oils.

Atherosclerosis is now widely accepted to be an inflammatory disease, characterized by degenerative as well as proliferative changes and extracellular accumulation of lipid and cholesterol, in which an ongoing inflammatory reaction plays an important role both in initiation and progression/destabilization, converting a chronic process into an acute disorder. Neovascularization has also been recognized as an important process for the progression/destabilization of atherosclerotic plaques. In fact, vulnerable atherosclerotic plaques prone to rupture are characterized by an enlarged necrotic core, containing an increased number of vasa vasorum, apoptotic macrophages, and more frequent intraplaque haemorrhage. Various functional roles have been assigned to intimal microvessels, however the relationship between the process of angiogenesis and its causal association with the progression and complications of atherosclerosis are still challenging and controversial. In the past 30 years, the dietary intake of omega-3 (n-3) polyunsaturated fatty acids--mainly derived from fish--has emerged as an important way to modify cardiovascular risk through beneficial effects on all stages of atherosclerosis, including plaque angiogenesis. This review specifically focuses on the modulating effects of n-3 fatty acids on molecular events involved in early and late atherogenesis, including effects on endothelial expression of adhesion molecules, as well as pro-inflammatory and pro-angiogenic enzymes. By accumulating in endothelial membrane phospholipids, omega-3 fatty acids have been shown to decrease the transcriptional activation of several genes through an attenuation of activation of the nuclear factor-kappaB system of transcription factors. This occurs secondary to decreased generation of intracellular reactive oxygen species. This series of investigations configures a clear example of nutrigenomics--i.e., how nutrients may affect gene expression, ultimately affecting a wide spectrum of human diseases.

Therapeutic management of idiopathic recurrent serositis: a retrospective study.

OBJECTIVE: Idiopathic recurrent serositis (IRS) is the most frequent serositis encountered in real-life medical sceneries, and its management represents a therapeutic challenge. There are few epidemiologic data related to IRS, though most studies have focused on recurrent pericarditis, revealing that 70% of all forms of pericarditis are idiopathic and caused by innate immunity abnormalities. The aim of this study was to evaluate outcome and recurrence rates of patients with IRS, assessing management modalities used in our Periodic Fever Centre of the Gemelli Hospital, Rome, Italy, in comparison with previous treatments in other centres. PATIENTS AND METHODS: Retrospectively, we analyzed the medical charts of 57 unselected patients with history of IRS managed during the period 1998-2017. RESULTS: A strong heterogeneity emerged by evaluating treatments of this cohort. In particular, in our Centre there was a larger use of combined therapies: 14 patients out of 27 (52%) were treated with nonsteroidal anti-inflammatory drugs (NSAIDs) and colchicine, compared to only 2 patients (7.4%) previously treated with combined treatments. We used corticosteroid monotherapy only in 1 case, against 7 from other centres. The mean duration of NSAID treatment in other hospitals was 43.8 days (SD ±27.40) and 191.25 days (SD ±42.23) in our Centre; the mean duration of corticosteroid treatment in other hospitals was 101.5 days (SD ±56.40) and 180.7 days (SD ±84.87) in our Centre. Colchicine was administered in other hospitals for the same duration of NSAIDs, and corticosteroids with an average duration of 111 days (SD ±30); conversely, we administered colchicine for an average duration of 250.12 days (SD ±80.7). Relapses of IRS were reported in 1/3 of cases who had discontinued therapies. CONCLUSIONS: The overall duration of treatments to manage IRS has a weight in terms of patients' outcome. A reduced duration of therapy with corticosteroids and a longer duration of therapy with NSAIDs determine a longer disease-free interval. A significant discriminating effect in terms of risk of IRS recurrence relies in an earlier combination therapy with colchicine independently from the start with either NSAIDs or corticosteroids. Finally, the evaluation of genes causing autoinflammatory diseases has not revealed any pathogenetic variants in a subcohort of 20/57 patients with IRS.

Local and metastatic curative radiotherapy in patients with de novo oligometastatic prostate cancer.

The aim of this observational study is to investigate whether local consolidative treatment delivered to the primary site and metastatic tumour burden may add survival benefit to de novo oligometastatic prostate cancer (Oligo-PCa) patients. We retrospectively reviewed all Oligo-PCa patients treated with radiotherapy to the primary tumor sites and metastatic tumor burden at our institution between March 2010 and June 2019. All patients having ≤ 5 metastases involving nodes and/or bones, loco-regional and/or extra-pelvic sites, were included. Most of the patients had started androgen deprivation therapy with or without docetaxel as standard of care before radiotherapy. The Kaplan Meier analysis was performed to estimate survival outcomes. The univariate analysis tested possible prognostic factors increasing the rate of biochemical relapse. We analysed 37 Oligo-PCa patients. Twenty-eight (75.7%) had loco-regional metastases, in 9 patients (24.3%) the metastatic tumour burden was extra-pelvic. Nineteen (51.4%) had bone metastases, 21 (56.8%) nodal involvement and 7 (18.9%) both. Twenty (54.1%) had a single metastasis. The median follow-up was 55.5 months. The median overall survival (OS) was 68.8 months, the 2- and 5-year OS rates were 96.9% and 65.4%. The median biochemical relapse free survival (b-RFS) was 58 months and the 2- and 5-year b-RFS rates were 73.3% and 39.3%. The 2- and 5-year local relapse free survival rates were 93.9% and 83.7%. On the univariate analysis post-treatment PSA level ≤ 1 ng/ml was significantly related with the b-RFS (p = 0.004). Curative approach in Oligo-PCa patients involving both the primary tumor and metastatic sites may be feasible and well tolerate. Many patients presented longer survival and PSA at first follow-up was the most important prognostic factor. Further trials are needed to confirm our results and to evaluate if patients with PSA at first follow-up > 1 ng/ml may benefit from further treatments.

Metformin doses and body mass index: clinical outcomes in insulin resistant polycystic ovary syndrome women.

OBJECTIVE: PCOS is the most common endocrinopathy among reproductive age women. Approximately 60% of PCOS women have insulin resistance. While the efficacy of metformin in reducing insulin resistance and decreasing androgen level has been widely validated, there is no agreement on the dose of metformin to be used. PATIENTS AND METHODS: Prospective non-randomized cohort study of 108 insulin resistant, overweight and obese PCOS women, aged between 22 and 35 years. All patients received 1500 mg of metformin (500 mg x 3 times/day) for the first 6 months. At the end of this period, the patients' HOMA index was evaluated. In subjects, who did not demonstrate normalization of the HOMA index, the dose was increased to 2500 mg/day (500 mg at breakfast and 1000 mg at lunch and dinner) for additional 6 months. The hormonal blood profile, fasting insulin and fasting glucose levels, HOMA index, anthropometric assessment, pelvic ultrasound, FAI index and cholesterol were evaluated. RESULTS: Overall results showed a good response to metformin therapy in insulin-resistant PCOS patients with BMI >25, while in patients with higher BMI (31.15 ± 0.40), no normalization of HOMA was found. At the higher dose of metformin, obese patients achieved a good response to therapy, with improvement in BMI, menstrual pattern, cholesterol levels and hyperandrogenism. CONCLUSIONS: Our results demonstrate a correlation between the required dose of metformin, BMI and hyperandrogenism. The dose of metformin should be adjusted to patients' BMI in order to obtain significant results in terms of clinical, metabolic and hormonal responses.

Virulence traits in Escherichia coli strains isolated from outpatients with urinary tract infections.

This study aims to characterize phenotypic and genotypic virulence traits in Escherichia coli strains, isolated from outpatients with urinary tract infections, comparing with those obtained from inpatients. Information on the pathogenic behavior of the uropathogenic strains was obtained by monitoring different biological properties, such as autoagglutination, hemagglutination, adhesiveness to and invasion of human bladder (HT1376) cells, biofilm formation, phylogenetic grouping, and virulence-related genes. The results show similar behavior in the two groups concerning autoagglutination, hemagglutination, and biofilm formation. None of the strains examined was invasive. However, in strains from outpatients there was an increased adhesion to HT1376 cells compared with clinical strains, a significant higher presence of genes codifying for adhesins and cell protection factors, and a lower proportion of strains belonging to B1 group. These findings add further information on the pathogenic traits of community E. coli, since strains isolated from the outpatients' group were differently "armed" in comparison with those of clinical cases, and more suitable to infect healthy individuals.

Native reptiles alter their foraging in the presence of the olfactory cues of invasive mammalian predators.

Invasive mammalian predators are linked to terrestrial vertebrate extinctions worldwide. Prey naïveté may explain the large impact invasive predators have on native prey; prey may fail to detect and react appropriately to the cues of novel predators, which results in high levels of depredation. In Australia, the feral cat (Felis catus) and the red fox (Vulpes vulpes) are implicated in more than 30 animal extinctions and the naïveté of native prey is often used to explain this high extinction rate. Reptiles are one group of animals that are heavily preyed upon by F. catus and V. vulpes. However, very few studies have examined whether reptiles are naive to their cues. In this study, we examine the ability of two native reptile species (Morethia boulengeri and Christinus marmoratus) to detect and distinguish between the chemical cues of two invasive predators (V. vulpes and F. catus) and three native predators (spotted-tailed quoll, Dasyurus maculatus; dingo, Canis lupus dingo; eastern brown snake, Pseudonaja textilis), as well as two non-predator controls (eastern grey kangaroo, Macropus giganteus and water). We conducted experiments to quantify the effects of predator scents on lizard foraging (the amount of food eaten) during 1 h trials within Y-maze arenas. We found both study species reduced the amount they consumed when exposed to predator scents-both native and invasive-indicating that these species are not naive to invasive predators. An evolved generalized predator-recognition system, rapid evolution or learned behaviour could each explain the lack of naïveté in some native Australian reptiles towards invasive predators.

The prominent role of p38 mitogen-activated protein kinase in insulin-mediated enhancement of VCAM-1 expression in endothelial cells.

Insulin levels are a marker for cardiovascular events, but the link between hyperinsulinemia and atherosclerosis is poorly understood. We previously showed that insulin increases monocyte-endothelial interactions and the endothelial expression of the pro-atherogenic vascular cell adhesion molecule-1 (VCAM-1). The aim of this study is to examine molecular mechanisms involved in the effect of insulin on VCAM-1 expression. Human umbilical vein endothelial cells (HUVEC) were incubated with insulin (0-24 h)+/- inhibitors of signaling pathways potentially involved. At pathophysiological concentrations (10(-9)-10(-7) M), insulin selectively induced VCAM-1 expression. The p38 mitogen activated protein(MAP) kinase inhibitors SB203580 and SB202190, and partially the c-Jun NH2-terminal kinase (JNK) inhibitor SP600127, decreased insulin effect on VCAM-1. Gene silencing by small interfering RNA significantly reduced the expression of p38MAP kinase, and this was accompanied by suppression of insulin-stimulated VCAM-1 expression. Treatment with insulin also led to the activation of NF-KB and induction of IKB-alpha phosphorylation, thus accounting for NF-KB translocation into the nucleus. Co-treatment of HUVEC with insulin and SB202190 strongly reverted the stimulatory effect of insulin on NF-KB activation, thus establishing a link between NF-KB activation and p38MAPkinase-mediated induction of VCAM-1 by insulin. In conclusion, pathophysiological insulin concentrations increase VCAM-1 expression and activate NF-KB. This mostly occurs through stimulation of p38MAP kinase.

Covalently modified halloysite clay nanotubes: synthesis, properties, biological and medical applications.

Halloysite (HNT) is a promising natural nanosized tubular clay mineral that has many important uses in different industrial fields. It is naturally occurring, biocompatible, and available in thousands of tons at low cost. As a consequence of a hollow cavity, HNT is mainly used as nanocontainer for the controlled release of several chemicals. Chemical modification of both surfaces (inner lumen and outer surface) is a strategy to tune the nanotube's properties. Specifically, chemical modification of HNT surfaces generates a nanoarchitecture with targeted affinity through outer surface functionalization and drug transport ability from functionalization of the nanotube lumen. The primary focus of this review is the research of modified halloysite nanotubes and their applications in biological and medical fields.

Correction: Covalently modified halloysite clay nanotubes: synthesis, properties, biological and medical applications.

Correction for 'Covalently modified halloysite clay nanotubes: synthesis, properties, biological and medical applications' by M. Massaro et al., J. Mater. Chem. B, 2017, 5, 2867-2882.

Validation of the Italian version of the Non-Communicating Children's Pain Checklist-Postoperative Version.

BACKGROUND: This study evaluated the validity and reliability of the Italian version of the Non-Communicating Children's Pain Checklist-Postoperative version (I-NCCPC-PV). METHODS: The original NCCPC-PV version was translated into Italian following the guidelines for "the translation, adaptation, and validation of instruments or scales for cross-cultural healthcare research". We tested the Italian NCCPC-PV version (I-NCCPC-PV) in 40 children (3-18 years of age) with severe to profound Intellectual Disability and no verbal communication. Each child's behavior was observed by a parent or caregiver and by an external observer in a quiet situation and a painful one. They independently assessed the child's level of pain using the translated Italian version of the NCCPCPV (I-NCCPC-PV). RESULTS: The results from 80 assessments showed that children's behavioral signs differed significantly between painful and calm situations (p < 0.001). The inter-rater reliability was poor in a quiet condition (ICC 0.62) and fair in a painful situation (ICC 0.77). The inter-rater agreement was good in both calm and painful conditions (72.50% and 77.50% respectively). CONCLUSION: The Italian version of the NCCPC-PV (I-NCCPC-PV) can be used for pain assessment in children with Intellectual Disability who lack verbal communication.