Sirt3 and metabolic reprogramming mediate the antiproliferative effects of whey in human colon cancer cells

Emerging strategies to improve healthy aging include dietary interventions as a tool to promote health benefits and reduce the incidence of aging-related comorbidities. The health benefits of milk are also linked to its richness in betaines and short-chain acylcarnitines, which act synergisti-cally in conferring anticancer, anti-inflammatory, and antioxidant properties. Whey, despite being a dairy by-product, still has a considerable content of bioactive betaines and acylcarnitines. Here, we investigated the anticancer properties of whey from Mediterranean water buffalo (Bubalus bubalis) milk by testing its antiproliferative effects in colorectal cancer (CRC) cells HT-29, HCT 116, LoVo and SW480. Results indicated that treatment with whey for 72 h inhibited cell proliferation (p < 0.001), induced cell cycle arrest, and apoptosis via caspase-3 activation, and modulated cell metabolism by limiting glucose uptake and interfering with mitochondrial energy metabolism with the highest effects observed in HT-29 and HCT 116 cells. At molecular level, these effects were accompanied by upregulation of sirtuin 3 (SIRT3) (p < 0.01) and peroxisome proliferator-activated receptor (PPAR)-γ expression (p < 0.001), and downregulation of lactate dehydrogenase A (LDHA) (p < 0.01), sterol regulatory-element binding protein 1 (SREBP1) (p < 0.05), and PPAR-α (p < 0.01). Transient SIRT3 gene silencing blocked the effects of whey on the LDHA, PPAR-γ, and PPAR-α protein expressions (p < 0.01) suggesting that the whey capacity of perturbating the metabolic homeostasis in CRC cell lines is mediated by SIRT3

Association between benzodiazepine prescriptions and potential risk factors of adverse drug reactions among elderly and very elderly: Findings from Friuli Venezia Giulia region, Italy

4noBackground: benzodiazepines (BDZs) highly increase the risk of adverse drug reactions (ADRs), especially in the elderly with certain medical conditions. Methods: point-prevalence study in December 2017; 2,456 patients ≥65 years were included from 14 regional public and private hospitals, 24 long-term chronic care facilities (LTCCFs) and 20 nursing homes (NHs). Data regarded BDZ prescriptions and comorbidities, co-prescriptions, or concurrent diseases, which could increase the risk of ADRs in BDZ users. Univariate and multivariate logistic regression analyses were used to assess associations between ADRs in BDZ users vs. non-users, as well as within users. Results: 671 patients were prescribed BDZ, whose half were in NHs. Being prescribed 10 or more drugs was twice more common among BDZ users compared to non-users. BDZs were prescribed for long-term to 80% of patients in NHs, while proportions were halved in hospitals and LTCCFs. In the analyses within BDZ users, patients in NHs and LTCCFs were at higher risk of dementia and concurrent use of opioid analgesic and antipsychotics compared to hospitalized patients. Conclusions: the use of BDZs in older patients is common in FVG. A great extent of comorbidities and concurrent medications at higher risk of ADRs was found. Analyses in different healthcare settings can allow to drive evidence-based interventions in order to discourage the use of BDZs and monitor the raise of ADRs.nonenoneCastelpietra G.; Balestrieri M.; Brusaferro S.; Arnoldo L.Castelpietra, G.; Balestrieri, M.; Brusaferro, S.; Arnoldo, L

SIRT3 Modulates Endothelial Mitochondrial Redox State during Insulin Resistance

Emerging evidence indicates that defects in sirtuin signaling contribute to impaired glucose and lipid metabolism, resulting in insulin resistance (IR) and endothelial dysfunction. Here, we examined the effects of palmitic acid (PA) treatment on mitochondrial sirtuins (SIRT2, SIRT3, SIRT4, and SIRT5) and oxidative homeostasis in human endothelial cells (TeloHAEC). Results showed that treatment for 48 h with PA (0.5 mM) impaired cell viability, induced loss of insulin signaling, imbalanced the oxidative status (p &lt; 0.001), and caused negative modulation of sirtuin protein and mRNA expression, with a predominant effect on SIRT3 (p &lt; 0.001). Restoration of SIRT3 levels by mimic transfection (SIRT3+) suppressed the PA-induced autophagy (mimic NC+PA) (p &lt; 0.01), inflammation, and pyroptosis (p &lt; 0.01) mediated by the NLRP3/caspase-1 axis. Moreover, the unbalanced endothelial redox state induced by PA was counteracted by the antioxidant δ-valerobetaine (δVB), which was able to upregulate protein and mRNA expression of sirtuins, reduce reactive oxygen species (ROS) accumulation, and decrease cell death. Overall, results support the central role of SIRT3 in maintaining the endothelial redox homeostasis under IR and unveil the potential of the antioxidant δVB in enhancing the defense against IR-related injuries

Validation of the Italian version of the Revised Prenatal Coping Inventory (NuPCI) and its correlations with pregnancy-specific stress

Background: Pregnancy is a period of happiness but also of physical and psychological changes that can lead to distress. Functional coping strategies can reduce the pregnancy specific-stress. This study aimed to assess the psychometric properties of the Revised Prenatal Coping Inventory (NuPCI) in an Italian sample and to investigate how coping strategies were associated with pregnancy-specific stress. Methods: In this cross-sectional study, low-risk pregnant women (N = 211) were assessed with NuPCI, NuPDQ (Revised-Prenatal Distress Questionnaire), Brief-COPE (Coping Orientation to the Problems Experienced), and STAI (State-Trait Anxiety Inventory). The reliability of NuPCI was evaluated by assessing its internal consistency and factor structure (with a Confirmatory Factor Analysis, CFA). The concurrent validity between NuPCI and Brief-COPE and NuPDQ and STAI was investigated. Lastly, the relationship between NuPCI and NuPDQ was analyzed, as well as the ability of these scales to predict Apgar score at birth. Results: Internal consistency of NuPCI scales was good for Planning-Preparation (\u251C=0.84) and Spiritual-Positive Coping (\u251C=0.81) scales, acceptable for Avoidance (\u251C=0.76) scale. Moreover, the original three-factor structure was confirmed using a CFA with 29 of the 32 items (\u3c72374 = 618.06; RMSEA = 0.056, 95% confidence interval: [0.048, 0.063]); CFI = 0.920; and TLI = 0.913). Statistically significant correlations between NuPCI scales and Brief-COPE subscales ranged between r = + 0.217 and r = + 0.624; also, NuPDQ score was positively correlated with STAI scales (State scale: r = + 0.539; Trait scale: r = + 0.462). Concurrent validity was confirmed reporting that NuPDQ score was predicted by NuPCI scores (R2 = 0.423, p < 0.001), positively by Avoidance (\u3b2=+0.572) and Planning-Preparation (\u3b2=+0.215) and negatively by Spiritual-Positive Coping (\u3b2=-0.132). Finally, considering the stress, the effect of the Avoidance and Spiritual-Positive Coping scores respectively in decreasing (+ 155%) and increasing (+ 16%) the Apgar score became stronger. Conclusions: Italian NuPCI has sound psychometric properties and it is a useful coping measure. NuPDQ showed also a good validity. Our results may suggest a significant role for coping strategies, particularly in modulating the condition of the newborn at birth

New perspectives on an “old” technique: Lipari obsidian and Neolithic communities investigated by Fission Track Dating

“Lipari obsidian and Neolithic human communities in the Aeolian islands” is a project aimed at studying the connection between obsidian flows on the island of Lipari and Neolithic populations on the Aeolian archipelago, in Italy. As it is well known, obsidian is of particular interest to trace prehistorical trading patterns; indeed, Lipari obsidian has the widest distribution and has been found in southern France, Dalmazia, Sicily and mainland Italy. The project outputs will give a general vision of both archaeological and volcanological aspects through thestratigraphic and radiometric dating of eruptions which produced obsidian, in relationship with the first phases of the human settlements and row material exploitation. To reach this goal, we are considering both raw materials (geological samples) from different flows and artifacts from Neolithic settlements (archaeological samples) on the Aeolian islands, and performing fission track dating to get the age of obsidian sources and artefacts. Obtained results are expected to shed some new light on the raw material procurement and on the ability of the Neolithic populations to move from their locations, with particular attention to the consequences of environmental features on the first human settlements on the Aeolian islands

Psychometric properties and diagnostic accuracy of the short form of the geriatric anxiety scale (GAS-10)

Background: Anxious symptoms have a negative impact on different aspects of the elderly\u2019s quality of life, ranging from the adoption of unhealthy lifestyle behaviours to an increased functional impairment and a greater physical disability. Different brief assessment instruments have been developed as efficacy measures of geriatric anxiety in order to overcome psychometric weaknesses of its long form. Among these, the 10-item Geriatric Anxiety Scale (GAS-10) showed strong psychometric properties in community-dwelling samples. However, its diagnostic accuracy is still unexplored, as well as its discriminative power in clinical samples. Methods: In the present study, we explored the psychometric performance of the GAS-10 in the elderly through Item Response Theory in a sample of 1200 Italian community-dwelling middle-aged and elderly adults (53.8% males, mean age = 65.21 \ub1 9.19 years). Concurrent validity, as well as diagnostic accuracy, was examined in a non-clinical sample (N = 229; 46.72% males) and clinical sample composed of 35 elderly outpatients (74.28% females) with Generalized Anxiety Disorder (GAD). Results: The GAS-10 displayed good internal construct validity, with unidimensional structure and no local dependency, good accuracy, and no signs of Differential Item Functioning (DIF) or measurement bias due to gender, but negligible due to the age. Differences in concurrent validity and diagnostic accuracy among the long form version of the GAS and the GAS-10 were not found significant. The GAS-10 may be more useful than the longer versions in many clinical and research applications, when time constraints or fatigue are issues. Conclusion: Using the ROC curve, the GAS-10 showed good discriminant validity in categorizing outpatients with GAD disorder, and high anxiety symptoms as measured by the GAS-SF cut-off. The stable cut-off point provided could enhance the clinical usefulness of the GAS-10, which seems to be a promising valid and reliable tool for maximize diagnostic accuracy of geriatric anxiety symptoms

Erdheim-Chester disease presenting with cough, abdominal pain, and headache

Erdheim-Chester disease (ECD) is a rare non-Langerhans cell histiocytic disorder. The diagnosis was based on the relationship between radiologic findings, clinical manifestations, and pathologic features of the bone biopsy. We report a case of ECD with unusual presenting symptoms: a 56 year-old man presented with cough, abdominal pain, and recurrent episodes of headache associated without any seizures. Peculiar computer tomography (CT) findings were key for the diagnostic suspicion. Bone biopsy and other radiological investigations confirmed the diagnosis. CT findings can help raise the suspicion of ECD. CT is easy to perform and widely available in comparison with kinetic cardiac magnetic resonance imaging and nuclear imaging. Therefore, CT findings of ECD can reduce the therapeutic delay between diagnosis and therapy prescription

Multicentre narrative research on major depression to integrate the experiences of patients, their caregivers and healthcare providers in Italy

OBJECTIVE: This research aimed to investigate the experience of major depression by integrating the perspectives of patients, caregivers and healthcare providers through narrative-based medicine (NBM) to provide new insights to improve care relationships. DESIGN AND SETTING: The research was conducted in 2019 and involved five Italian psychiatric centres and targeted adult patients, their caregivers and healthcare providers to address data source triangulation. A sociodemographic survey and a narrative plot, based on Natural Semantic Metalanguage were collected. Narratives were analysed through NBM classifications, NVivo software and interpretative coding. PARTICIPANTS: Thirty-six patients with a diagnosis of major depression, 27 caregivers and 33 healthcare providers participated in the research. RESULTS: Among the 96 collected narratives, 'lonely' was the word patients used most frequently, while 'sad' and 'lifeless' were used most respectively by caregivers and healthcare providers. A positive care relationship was crucial for 84% of patients in relation to their care pathway, and nature (36%) and the arts (28%) were the most frequent resources. Caregivers expressed feelings of powerlessness and inadequacy, and 21% of them reported a declining social life while providing care to a loved one with depression. Thirty-one percent of mental health professionals experienced difficulties in their first encounter with patients; however, their emotions progressively moved towards trust and satisfaction. Furthermore, 89% of patients and healthcare providers and 58% of caregivers evaluated writing the narrative to be a positive experience. CONCLUSION: Findings suggested the possible role for language in understanding major depression, thereby improving care relationships between patients and physicians. Care pathways might also be more attentive to caregivers, to reduce their risk of burnout. Finally, narrative medicine could be integrated with the care pathway as an additional space of expression, dialogue, reflection and development of empathy

Cardiac computed tomography radiomics: an emerging tool for the non-invasive assessment of coronary atherosclerosis

In the last decades, significant advances have been made in the preventive approaches to cardiovascular disease. Even so, coronary artery disease remains one of the main causes of morbidity and mortality worldwide. Invasive imaging modalities, such as intravascular ultrasound or optical coherence tomography, have played a key role in the comprehension of the pathological processes underlying myocardial infarction and cerebrovascular disease. These imaging techniques have contributed greatly to the identification and phenotyping of the culprit lesion, the so-called vulnerable plaque. Coronary computed tomographic angiography (CCTA) has emerged in more recent years as the non-invasive modality of choice in the study of coronary atherosclerosis, showing in many studies a diagnostic yield comparable to invasive approaches. Moreover, being able to describe extra-luminal characteristics of the affected vessel, CCTA has greatly contributed towards shifting the attention of researchers from the mere quantification of luminal stenosis to the identification of adverse plaque features, which appear to have a stronger prognostic value. However, the identification of some of the hallmarks of vulnerable plaques is qualitative in nature and, therefore, subject to some degree of inter-reader variability. Moreover, CCTA is still unable to identify some fine markers of plaque vulnerability which can be detected by invasive techniques, such as neovascularization and plaque erosion, among others. Nonetheless, radiological images can be viewed as vast 3-D datasets which, via the use of recent technology, allow for the extraction of numerous quantitative features that may be used to accurately phenotype a given lesion. Radiomics is the process of extrapolating innumerable parameters from a given region of interest, with the goal of establishing correlations between quantitative variables and clinical data. These datasets can then be manipulated to create predictive models via the use of automated algorithms in a process called machine learning. As a result of these approaches, radiological images may offer information regarding the characterization of a plaque which can go much beyond the boundaries of what can be qualitatively asserted by the human eye, contributing to expanding the knowledge of the disease and ultimately assist clinical decisions. Thus far, radiomics has found its more consistent area of application in the field of oncology; to present date, the amount of clinical data regarding coronary artery disease is still relatively small, partly due to the technical difficulties associated with the implementation of such techniques to the study of a small and geometrically complex lesion such as the coronary plaque. The present review, after a summary of the imaging modalities most commonly used nowadays in the study of coronary plaques, will provide a perspective on the application of radiomic analysis to coronary artery disease