Publications by authors named "Nicola Ferrara"

152 Publications

Aging is associated with cardiac autonomic nerve fiber depletion and reduced cardiac and circulating BDNF levels.

J Geriatr Cardiol 2021 Jul;18(7):549-559

Department of Translational Medical Sciences, Federico II University of Naples Italy.

Background: Aging is a multifactorial process associated with an impairment of autonomic nervous system (ANS) function. Progressive ANS remodeling includes upregulation of expression of circulating catecholamines and depletion of cardiac autonomic nerve fibers, and it is responsible, in part, for the increased susceptibility to cardiac diseases observed in elderly subjects. Neurotrophic factors, such as brain-derived neurotrophic factor (BDNF) and nerve growth factor (NGF), are involved in synaptogenesis and neurite outgrowth processes, supporting neuronal cell differentiation and maturation. However, whether and how these factors and their downstream signaling are involved in cardiac aging remains unclear. Here, we tested whether, in the aged heart, the overall extent of autonomic fibers is reduced, owing to lower production of trophic factors such as BDNF and NGF.

Methods: , we used young (age: 3 months; = 10) and old (age: 24 months; = 11) male Fisher rats, whereas, we used human neuroblastoma (SH-SY5Y) cells .

Results: Compared to the young rats, old rats displayed a marked reduction in the overall ANS fiber density, affecting both sympathetic and cholinergic compartments, as indicated by dopamine β-hydroxylase (dβh) and vesicular acetylcholine transporter (VaChT) immunohistochemical staining. In addition, a marked downregulation of GAP-43 and BDNF protein was observed in the left ventricular lysates of old rats compared to those of young rats. Interestingly, we did not find any significant difference in cardiac NGF levels between the young and old groups. To further explore the impact of aging on ANS fibers, we treated SH-SY5Y cells with serum obtained from young and old rats. Sera from both groups induced a remarkable increase in neuronal sprouting, as evidenced by a crystal violet assay. However, this effect was blunted in cells cultured with old rat serum and was accompanied by a marked reduction in GAP-43 and BDNF protein levels.

Conclusions: Our data indicate that physiological aging is associated with an impairment of ANS structure and function and that reduced BDNF levels are responsible, at least in part, for these phenomena.
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http://dx.doi.org/10.11909/j.issn.1671-5411.2021.07.009DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8352776PMC
July 2021

Infective Endocarditis: A Focus on Oral Microbiota.

Microorganisms 2021 Jun 4;9(6). Epub 2021 Jun 4.

Department of Translational Medical Sciences, Medicine Federico II University of Naples, 80131 Naples, Italy.

Infective endocarditis (IE) is an inflammatory disease usually caused by bacteria entering the bloodstream and settling in the heart lining valves or blood vessels. Despite modern antimicrobial and surgical treatments, IE continues to cause substantial morbidity and mortality. Thus, primary prevention and enhanced diagnosis remain the most important strategies to fight this disease. In this regard, it is worth noting that for over 50 years, oral microbiota has been considered one of the significant risk factors for IE. Indeed, among the disparate recommendations from the American heart association and the European Society of Cardiology, there are good oral hygiene and prophylaxis for high-risk patients undergoing dental procedures. Thus, significant interest has grown in the role of oral microbiota and it continues to be a subject of research interest, especially if we consider that antimicrobial treatments can generate drug-resistant mutant bacteria, becoming a severe social problem. This review will describe the current knowledge about the relationship between oral microbiota, dental procedures, and IE. Further, it will discuss current methods used to prevent IE cases that originate from oral pathogens and how these should be focused on improving oral hygiene, which remains the significant persuasible way to prevent bacteremia and systemic disorders.
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http://dx.doi.org/10.3390/microorganisms9061218DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8227130PMC
June 2021

Targeting GRK5 for Treating Chronic Degenerative Diseases.

Int J Mol Sci 2021 Feb 15;22(4). Epub 2021 Feb 15.

Department of Translational Medical Sciences, University of Naples Federico II, 80131 Naples, Italy.

G protein-coupled receptors (GPCRs) are the largest family of cell-surface receptors and they are responsible for the transduction of extracellular signals, regulating almost all aspects of mammalian physiology. These receptors are specifically regulated by a family of serine/threonine kinases, called GPCR kinases (GRKs). Given the biological role of GPCRs, it is not surprising that GRKs are also involved in several pathophysiological processes. Particular importance is emerging for GRK5, which is a multifunctional protein, expressed in different cell types, and it has been found located in single or multiple subcellular compartments. For instance, when anchored to the plasma membrane, GRK5 exerts its canonical function, regulating GPCRs. However, under certain conditions (e.g., pro-hypertrophic stimuli), GRK5 translocates to the nucleus of cells where it can interact with non-GPCR-related proteins as well as DNA itself to promote "non-canonical" signaling, including gene transcription. Importantly, due to these actions, several studies have demonstrated that GRK5 has a pivotal role in the pathogenesis of chronic-degenerative disorders. This is true in the cardiac cells, tumor cells, and neurons. For this reason, in this review article, we will inform the readers of the most recent evidence that supports the importance of targeting GRK5 to prevent the development or progression of cancer, cardiovascular, and neurological diseases.
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http://dx.doi.org/10.3390/ijms22041920DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7919044PMC
February 2021

Antithrombotic therapy in patients undergoing transcatheter aortic valve replacement: the complexity of the elderly.

Eur J Prev Cardiol 2021 03;28(1):87-97

Department of Translational Medical Sciences, University of Naples "Federico II", Via Sergio Pansini 5, Naples 80131, Italy.

Along with epidemiologic transitions of the global population, the burden of aortic stenosis (AS) is rapidly increasing and transcatheter aortic valve replacement (TAVR) has quickly spread; indeed, it is nowadays also employed in treating patients with AS at intermediate operative risk. Nonetheless, the less invasive interventional strategy still carries relevant issues concerning post-procedural optimal antithrombotic strategy, given the current indications provided by guidelines are not completely supported by evidence-based data. Geriatric patients suffer from high bleeding and thromboembolic risks, whose balance is particularly subtle due to the presence of concomitant conditions, such as atrial fibrillation and chronic kidney disease, that make the post-TAVR antithrombotic management particularly insidious. This scenario is further complicated by the lack of specific evidence regarding the 'real-life' complex conditions typical of the geriatric syndromes, thus, the management of such a heterogeneous population, ranging from healthy ageing to frailty, is far from being defined. The aim of the present review is to summarize the critical points and the most updated evidence regarding the post-TAVR antithrombotic approach in the geriatric population, with a specific focus on the most frequent clinical settings.
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http://dx.doi.org/10.1093/eurjpc/zwaa053DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7665487PMC
March 2021

Impact of the number of comorbidities on cardiac sympathetic derangement in patients with reduced ejection fraction heart failure.

Eur J Intern Med 2021 04 20;86:86-90. Epub 2021 Jan 20.

Department of Translational Medical Sciences, University of Naples "Federico II", Naples, Italy; Istituti Clinici Scientifici Maugeri SpA Società Benefit (ICS Maugeri SpA SB), Telese Terme (BN), Italy. Electronic address:

Introduction: Heart failure (HF) is frequently associated with comorbidities. I-metaiodobenzylguanidine (I-mIBG) imaging constitutes an effective tool to measure cardiac adrenergic innervation and to improve prognostic stratification in HF patients, including the risk of major arrhythmic events. Although comorbidities have been individually associated with reduced cardiac adrenergic innervation, thus suggesting increased arrhythmic risk, very comorbid HF patients seem to be less likely to experience fatal arrhythmias. We evaluated the impact of the number of comorbidities on cardiac adrenergic innervation, assessed through I-mIBG imaging, in patients with systolic HF.

Methods: Patients with systolic HF underwent clinical examination, transthoracic echocardiography and cardiac I-mIBG scintigraphy. The presence of 7 comorbidities/conditions (smoking, chronic obstructive pulmonary disease, diabetes mellitus, peripheral artery disease, atrial fibrillation, chronic ischemic heart disease and chronic kidney disease) was documented in the overall study population.

Results: The study population consisted of 269 HF patients with a mean age of 66±11 years, a left ventricular ejection fraction (LVEF) of 31±7%, and 153 (57%) patients presented ≥3 comorbidities. Highly comorbid patients presented a reduced late heart to mediastinum (H/M) ratio, while no significant differences emerged in terms of early H/M ratio and washout rate. Multiple regression analysis revealed that the number of comorbidities was not associated with mIBG parameters of cardiac denervation, which were correlated with age, body mass index and LVEF.

Conclusion: In systolic HF patients, the number of comorbidities is not associated with alterations in cardiac adrenergic innervation. These results are consistent with the observation that very comorbid HF patients suffer lower risk of sudden cardiac death.
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http://dx.doi.org/10.1016/j.ejim.2021.01.010DOI Listing
April 2021

Sirt1 Activity in PBMCs as a Biomarker of Different Heart Failure Phenotypes.

Biomolecules 2020 11 23;10(11). Epub 2020 Nov 23.

Department of Medicine, Surgery and Dentistry "Scuola Medica Salernitana", University of Salerno, 84081 Baronissi, Italy.

Heart Failure (HF) is a syndrome, which implies the existence of different phenotypes. The new categorization includes patients with preserved ejection fraction (HFpEF), mid-range EF (HFmrEF), and reduced EF (HFrEF) but the molecular mechanisms involved in these HF phenotypes have not yet been exhaustively investigated. Sirt1 plays a crucial role in biological processes strongly related to HF. This study aimed to evaluate whether Sirt1 activity was correlated with EF and other parameters in HFpEF, HFmrEF, and HFrEF. Seventy patients, HFpEF ( = 23), HFmrEF ( = 23) and HFrEF ( = 24), were enrolled at the Cardiology Unit of the University Hospital of Salerno. Sirt1 activity was measured in peripheral blood mononuclear cells (PBMCs). Angiotensin-Converting Enzyme 2 (ACE2) activity, Tumor Necrosis Factor-alpha (TNF-α) and Brain Natriuretic Peptide (BNP) levels were quantified in plasma. HFpEF showed lower Sirt1 and ACE2 activities than both HFmrEF and HFrEF ( < 0.0001), without difference compared to No HF controls. In HFmrEF and HFrEF a very strong correlation was found between Sirt1 activity and EF (r = 0.899 and r = 0.909, respectively), and between ACE2 activity and Sirt1 (r = 0.801 and r = 0.802, respectively). HFrEF showed the highest TNF-α levels without reaching statistical significance. Significant differences in BNP were found among the groups, with the highest levels in the HFrEF. Determining Sirt1 activity in PBMCs is useful to distinguish the HF patients' phenotypes from each other, especially HFmrEF/HFrEF from HFpEF.
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http://dx.doi.org/10.3390/biom10111590DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7700185PMC
November 2020

Potential Bidirectional Relationship Between Periodontitis and Alzheimer's Disease.

Front Physiol 2020 3;11:683. Epub 2020 Jul 3.

Department of Translational Medical Sciences, University of Naples Federico II, Naples, Italy.

Alzheimer's disease (AD) is the most prevalent form of dementia in the elderly population, representing a global public health priority. Despite a large improvement in understanding the pathogenesis of AD, the etiology of this disorder remains still unclear, and no current treatment is able to prevent, slow, or stop its progression. Thus, there is a keen interest in the identification and modification of the risk factors and novel molecular mechanisms associated with the development and progression of AD. In this context, it is worth noting that several findings support the existence of a direct link between neuronal and non-neuronal inflammation/infection and AD progression. Importantly, recent studies are now supporting the existence of a direct relationship between periodontitis, a chronic inflammatory oral disease, and AD. The mechanisms underlying the association remain to be fully elucidated, however, it is generally accepted, although not confirmed, that oral pathogens can penetrate the bloodstream, inducing a low-grade systemic inflammation that negatively affects brain function. Indeed, a recent report demonstrated that oral pathogens and their toxic proteins infect the brain of AD patients. For instance, when AD progresses from the early to the more advanced stages, patients could no longer be able to adequately adhere to proper oral hygiene practices, thus leading to oral dysbiosis that, in turn, fuels infection, such as periodontitis. Therefore, in this review, we will provide an update on the emerging (preclinical and clinical) evidence that supports the relationship existing between periodontitis and AD. More in detail, we will discuss data attesting that periodontitis and AD share common risk factors and a similar hyper-inflammatory phenotype.
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http://dx.doi.org/10.3389/fphys.2020.00683DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7348667PMC
July 2020

Medico-legal assessment of personal damage in older people: report from a multidisciplinary consensus conference.

Int J Legal Med 2020 Nov 17;134(6):2319-2334. Epub 2020 Jul 17.

, Verona, Italy.

Ageing of the global population represents a challenge for national healthcare systems and healthcare professionals, including medico-legal experts, who assess personal damage in an increasing number of older people. Personal damage evaluation in older people is complex, and the scarcity of evidence is hindering the development of formal guidelines on the subject. The main objectives of the first multidisciplinary Consensus Conference on Medico-Legal Assessment of Personal Damage in Older People were to increase knowledge on the subject and establish standard procedures in this field. The conference, organized according to the guidelines issued by the Italian National Institute of Health (ISS), was held in Bologna (Italy) on June 8, 2019 with the support of national scientific societies, professional organizations, and stakeholders. The Scientific Technical Committee prepared 16 questions on 4 thematic areas: (1) differences in injury outcomes in older people compared to younger people and their relevance in personal damage assessment; (2) pre-existing status reconstruction and evaluation; (3) medico-legal examination procedures; (4) multidimensional assessment and scales. The Scientific Secretariat reviewed relevant literature and documents, rated their quality, and summarized evidence. During conference plenary public sessions, 4 pairs of experts reported on each thematic area. After the last session, a multidisciplinary Jury Panel (15 members) drafted the consensus statements. The present report describes Conference methods and results, including a summary of evidence supporting each statement, and areas requiring further investigation. The methodological recommendations issued during the Conference may be useful in several contexts of damage assessment, or to other medico-legal evaluation fields.
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http://dx.doi.org/10.1007/s00414-020-02368-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7578136PMC
November 2020

Angiopoietins, Vascular Endothelial Growth Factors and Secretory Phospholipase A in Ischemic and Non-Ischemic Heart Failure.

J Clin Med 2020 Jun 19;9(6). Epub 2020 Jun 19.

Department of Translational Medical Sciences, University of Naples Federico II, 80100 Naples, Italy.

Heart failure (HF) is a growing public health burden, with high prevalence and mortality rates. In contrast to ischemic heart failure (IHF), the diagnosis of non-ischemic heart failure (NIHF) is established in the absence of coronary artery disease. Angiopoietins (ANGPTs), vascular endothelial growth factors (VEGFs) and secretory phospholipases A (sPLAs) are proinflammatory mediators and key regulators of endothelial cells. In the present manuscript, we analyze the plasma concentrations of angiogenic (ANGPT1, ANGPT2, VEGF-A) and lymphangiogenic (VEGF-C, VEGF-D) factors and the plasma activity of sPLA in patients with IHF and NIHF compared to healthy controls. The concentrations of ANGPT1, ANGPT2 and their ratio significantly differed between HF patients and healthy controls. Similarly, plasma levels of VEGF-D and sPLA activity were higher in HF as compared to controls. Concentrations of ANGPT2 and the ANGPT2/ANGPT1 ratio (an index of vascular permeability) were increased in NIHF patients. VEGF-A and VEGF-C concentrations did not differ among the three examined groups. Interestingly, VEGF-D was selectively increased in IFH patients compared to controls. Plasma activity of sPLA was increased in IHF and NIHF patients compared to controls. Our results indicate that several regulators of vascular permeability and smoldering inflammation are specifically altered in IHF and NIHF patients. Studies involving larger cohorts of these patients will be necessary to demonstrate the clinical implications of our findings.
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http://dx.doi.org/10.3390/jcm9061928DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7356305PMC
June 2020

Atrial fibrillation in the elderly: a risk factor beyond stroke.

Ageing Res Rev 2020 08 29;61:101092. Epub 2020 May 29.

Department of Translational Medical Sciences, University of Naples "Federico II", Italy; Istituti Clinici Scientifici Maugeri SPA, Società Benefit, IRCCS, Istituto Scientifico di Telese Terme, Italy. Electronic address:

Atrial fibrillation (AF) represents the most common arrhythmia worldwide and its prevalence exponentially increases with age. It is related to increased risk of ischemic stroke or systemic embolism, which determines a significant burden of morbidity and mortality, as widely documented in the literature. AF also constitutes a risk factor for other less investigated conditions, such as heart failure, pulmonary embolism, impairment in physical performance, reduced quality of life, development of disability, mood disorders and cognitive impairment up to dementia. In the elderly population, the management of AF and its complications is particularly complex due to the heterogeneity of the ageing process, the lack of specific evidence-based recommendations, as well as the high grade of comorbidity and disability characterizing the over 65 years aged people. In the present review, we aim to summarize the pieces of the most updated evidence on AF complications beyond stoke, mainly focusing on the elderly population.
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http://dx.doi.org/10.1016/j.arr.2020.101092DOI Listing
August 2020

Correction to: Management of chronic ischemic heart disease into internal medicine and geriatric departments in Italy.

Intern Emerg Med 2020 Oct;15(7):1359

Società Italiana dei Geriatri Ospedalieri e del Territorio (SIGOT), Rome, Italy.

In the original publication of the article.
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http://dx.doi.org/10.1007/s11739-020-02298-zDOI Listing
October 2020

Cardioprotective Effects of Dietary Phytochemicals on Oxidative Stress in Heart Failure by a Sex-Gender-Oriented Point of View.

Oxid Med Cell Longev 2020 6;2020:2176728. Epub 2020 Jan 6.

Department of Medicine and Health Sciences, University of Molise, Via Francesco De Sanctis, 1, 86100 Campobasso, Italy.

Dietary phytochemicals are considered an innovative strategy that helps to reduce cardiovascular risk factors. Some phytochemicals have been shown to play a beneficial role in lipid metabolism, to improve endothelial function and to modify oxidative stress pathways in experimental and clinical models of cardiovascular impairment. Importantly, investigation on phytochemical effect on cardiac remodeling appears to be promising. Nowadays, drug therapy and implantation of devices have demonstrated to ameliorate survival. Of interest, sex-gender seems to influence the response to HF canonical therapies. In fact, starting by the evidence of the feminization of world population and the scarce efficacy and safety of the traditional drugs in women, the search of alternative therapeutic tools has become mandatory. The aim of this review is to summarize the possible role of dietary phytochemicals in HF therapy and the evidence of a different sex-gender-oriented response.
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http://dx.doi.org/10.1155/2020/2176728DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6975222PMC
June 2020

Cardiac Rehabilitation Increases SIRT1 Activity and -Hydroxybutyrate Levels and Decreases Oxidative Stress in Patients with HF with Preserved Ejection Fraction.

Oxid Med Cell Longev 2019 27;2019:7049237. Epub 2019 Nov 27.

Department of Medicine, Surgery and Dentistry, University of Salerno, Baronissi, Italy.

Purpose: Exercise training induces beneficial effects also by increasing levels of Sirtuin 1 (Sirt1) and -hydroxybutyrate (OHB). Up to date, no studies investigated the role of exercise training-based cardiac rehabilitation (ET-CR) programs on OHB levels. Therefore, the present study is aimed at investigating whether a supervised 4-week ET-CR program was able to induce changes in Sirt1 activity and OHB levels and to evaluate the possible relationship between such parameters, in Heart Failure with preserved Ejection Fraction (HFpEF) patients.

Methods: A prospective longitudinal observational study was conducted on patients consecutively admitted to the Cardiology and Cardiac Rehabilitation Units of "San Gennaro dei Poveri" Hospital in Naples, Italy. In fifty elderly patients affected by HFpEF, in NYHA II and III class, Sirt1 activity, Trolox Equivalent Antioxidant Capacity (TEAC), OHB, and Oxidized Low-Density Lipoprotein (Ox-LDL) levels were measured before and at the end of the ET-CR program. A control group of 20 HFpEF patients was also recruited, and the same parameters were evaluated 4 weeks after the beginning of the study.

Results: ET-CR induced an increase of Sirt1 activity, OHB levels, and antioxidant capacity. Moreover, it was associated with a rise in NAD and NAD/NADH ratio levels and a reduction in Ox-LDL. No changes affected the controls.

Conclusion: The characterization of the ET-CR effects from a metabolic viewpoint might represent an important step to improve the HFpEF management.
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http://dx.doi.org/10.1155/2019/7049237DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6900956PMC
June 2020

Impact of body mass index on cardiac adrenergic derangement in heart failure patients: a I-mIBG imaging study.

Eur J Nucl Med Mol Imaging 2020 07 24;47(7):1713-1721. Epub 2019 Dec 24.

Department of Translational Medical Sciences, University of Naples "Federico II", Naples, Italy.

Purpose: To assess the impact of body mass index (BMI) on cardiac adrenergic derangement, measured by iodine-123 meta-iodobenzylguanidine (I-mIBG) imaging in heart failure (HF) patients. Overweight and obesity represent relevant health issues, and augmented sympathetic tone has been described in patients with increased BMI. An extensive literature supports that HF-dependent cardiac denervation, measured through mIBG parameters, is an independent predictor of cardiovascular outcomes and mortality. However, the influence of BMI on cardiac mIBG uptake has not been largely investigated.

Methods: We prospectively enrolled patients with systolic HF, collecting demographic, clinical, echocardiographic data, and mIBG imaging parameters. In order to detect the factors associated with mIBG parameters, a model building strategy, based on the Multivariable Fractional Polynomial algorithm, has been employed.

Results: We studied 249 patients with systolic HF, mean age of 66.4 ± 10.6 years, and mean left ventricular ejection fraction (LVEF) of 30.7% ± 6.4, undergoing cardiac I-mIBG imaging to assess HF severity and prognosis. Seventy-eight patients (31.3%) presented a BMI ≥ 30 kg/m and obese patients showed a significant reduction in early heart to mediastinum (H/M) ratio (1.66 ± 0.19 vs. 1.75 ± 0.26; p = 0.008) and a trend to reduction in washout rate (33.6 ± 18.3 vs. 38.1 ± 20.1; p = 0.092) compared with patients with BMI < 30 kg/m. Multiple regression analysis revealed that BMI, age, and LVEF were significantly correlated with early and late H/M ratios.

Conclusions: Results of the present study indicate that BMI, together with LVEF and age, is independently correlated with cardiac mIBG uptake in HF patients.
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http://dx.doi.org/10.1007/s00259-019-04658-0DOI Listing
July 2020

Inter-relationships between Gender, Frailty and 10-Year Survival in Older Italian Adults: an observational longitudinal study.

Sci Rep 2019 12 5;9(1):18416. Epub 2019 Dec 5.

Dept of Translational Medical Sciences, Federico II University of Naples, Naples, Italy.

Aim of the present study was to assess the impact of gender on the relationship between long-term mortality and clinical frailty. In an observational, longitudinal study on 10-year mortality, we examined 1284 subjects. The Frailty Staging System was used to assess frailty. The Cox model was employed to assess variables independently associated with survival using a backward stepwise algorithm. To investigate the possible interactions between gender and the selected variables, an extension of the multivariable fractional polynomial algorithm was adopted. Women were more likely to be older, have a higher disability, present with more comorbidities, consume more drugs, be frail and have a higher rate of survival at the follow-up than were men. At the Cox multivariate analysis only age (HR 2.26), female gender (HR 0.43), and number of drugs (HR 1.57) were significant and independent factors associated with all-cause mortality. In the survival analyses, only frailty (vs no frailty) showed significant interaction with gender (p < 0.001, HR = 1.92). While the presence of frailty reduced the survival rate in women, no effect was observed in men. Importantly, frail women showed higher survival rates than did both frail and no frail men. The main finding of the present study is that gender shapes up the association between frailty and long-term survival rates.
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http://dx.doi.org/10.1038/s41598-019-54897-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6895198PMC
December 2019

Prospective validation of the International Warfarin Pharmacogenetics Consortium algorithm in high-risk elderly people (VIALE study).

Pharmacogenomics J 2020 06 5;20(3):451-461. Epub 2019 Dec 5.

Department of Mental Health and Preventive Medicine, University of Campania Luigi Vanvitelli, Via L. Armanni 5, 80138, Napoli, Italy.

We assessed the predictive accuracy of the Warfarin Pharmacogenetics Consortium (IWPC) algorithm in a prospective cohort of 376 high-risk elderly patients (≥65 years) who required new treatment with warfarin for either medical (non valvular atrial fibrillation) or surgical conditions (heart valve replacement), had ≥1 comorbid conditions, and regularly used ≥2 other drugs. Follow-up visits were performed according to clinical practice and lasted for a maximum of 1 year. Two hundred and eighty-three (75%) patients achieved a stable maintenance dose. Warfarin maintenance doses were low on average (median 20.3 mg/week, interquartile range, 14.1-27.7 mg/week) and were substantially overestimated by the IWPC algorithm. Overall the percentage of patients whose predicted dose of warfarin was within 20% of the actual stable dose was equal to 37.5%, (95% CI 32.0-43.3%). IWPC algorithm explained only 31% of the actual warfarin dose variability. Modifications of the IWPC algorithm are needed in high-risk elderly people.
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http://dx.doi.org/10.1038/s41397-019-0129-6DOI Listing
June 2020

Management of chronic ischemic heart disease into internal medicine and geriatric departments in Italy.

Intern Emerg Med 2020 01 3;15(1):151-154. Epub 2019 Oct 3.

Società Italiana dei Geriatri Ospedalieri e del Territorio (SIGOT), Rome, Italy.

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http://dx.doi.org/10.1007/s11739-019-02197-yDOI Listing
January 2020

Adiponectin Expression and Genotypes in Italian People with Severe Obesity Undergone a Hypocaloric Diet and Physical Exercise Program.

Nutrients 2019 Sep 12;11(9). Epub 2019 Sep 12.

Dipartimento di Scienze e Tecnologie Ambientali, Biologiche, Farmaceutiche, Università della Campania "Luigi Vanvitelli", 81100 Caserta, Italy.

Adiponectin exerts positive effects on metabolic and inflammatory processes. Adiponectin levels and some single-nucleotide polymorphisms (SNPs) seem to be associated with obesity. Here, we investigated the effects of a 4-week Hypocaloric diet and Physical exercise Program (HPP) on 268 young people with severe obesity. We evaluated the relationship between adiponectin levels and anthropometric and biochemical parameters, at baseline and after a 4-week HPP. Finally, we investigated some adiponectin gene variants and their correlation to biochemical parameters. Adiponectin levels were statistically lower in people with severe obesity than in controls. At the end of the HPP, all the people with severe obesity showed a Body Mass Index (BMI) reduction with a statistically significant increase in adiponectin levels. Genotyping, the adiponectin gene demonstrated a significant difference in 3 polymorphisms within the people with severe obesity. Besides, c.11377C>G and c.11391G>A homozygous subjects experienced more advantages by HPP. Furthermore, c.268G>A heterozygous subjects showed an enhancement in lipid profile as well in adiponectin levels. The best predictor of the changes in adiponectin levels was represented by the c.268G>A WT allele. Our study confirmed that a 4-weeks HPP in people with severe obesity results in metabolic amelioration associated with a significant increase of adiponectin levels. Importantly, we found that a specific genetic background in the gene can predispose toward a more significant weight loss.
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http://dx.doi.org/10.3390/nu11092195DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6769478PMC
September 2019

Aldosterone Jeopardizes Myocardial Insulin and β-Adrenergic Receptor Signaling G Protein-Coupled Receptor Kinase 2.

Front Pharmacol 2019 9;10:888. Epub 2019 Aug 9.

Department of Translational Medical Sciences, Federico II University of Naples, Naples, Italy.

Hyperaldosteronism alters cardiac function, inducing adverse left ventricle (LV) remodeling either increased fibrosis deposition, mitochondrial dysfunction, or both. These harmful effects are due, at least in part, to the activation of the G protein-coupled receptor kinase 2 (GRK2). In this context, we have previously reported that this kinase dysregulates both β-adrenergic receptor (βAR) and insulin (Ins) signaling. Yet, whether aldosterone modulates cardiac Ins sensitivity and βAR function remains untested. Nor is it clear whether GRK2 has a role in this modulation, downstream of aldosterone. Here, we show , in 3T3 cells, that aldosterone impaired insulin signaling, increasing the negative phosphorylation of insulin receptor substrate 1 (pIRS1) and reducing the activity of Akt. Similarly, aldosterone prevented the activation of extracellular signal-regulated kinase (ERK) and the production of cyclic adenosine 3',5'-monophosphate (cAMP) in response to the β/βAR agonist, isoproterenol. Of note, all of these effects were sizably reduced in the presence of GRK2-inhibitor CMPD101. Next, in wild-type (WT) mice undergoing chronic infusion of aldosterone, we observed a marked GRK2 upregulation that was paralleled by a substantial β1AR downregulation and augmented pIRS1 levels. Importantly, in keeping with the current data, we found that aldosterone effects were wholly abolished in cardiac-specific GRK2-knockout mice. Finally, in WT mice that underwent 4-week myocardial infarction (MI), we observed a substantial deterioration of cardiac function and increased LV dilation and fibrosis deposition. At the molecular level, these effects were associated with a significant upregulation of cardiac GRK2 protein expression, along with a marked β1AR downregulation and increased pIRS1 levels. Treating MI mice with spironolactone prevented adverse aldosterone effects, blocking GRK2 upregulation, and thus leading to a marked reduction in cardiac pIRS1 levels while rescuing β1AR expression. Our study reveals that GRK2 activity is a critical player downstream of the aldosterone signaling pathway; therefore, inhibiting this kinase is an attractive strategy to prevent the cardiac structural disarray and dysfunction that accompany any clinical condition accompanied by hyperaldosteronism.
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http://dx.doi.org/10.3389/fphar.2019.00888DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6695474PMC
August 2019

Data analysis of atmospheric emission from geothermal power plants in Italy.

Data Brief 2019 Aug 30;25:104339. Epub 2019 Jul 30.

Department of Biotechnology, Chemistry and Pharmacy, University of Siena, Via Aldo Moro 2, 53100, Siena, Italy.

Electric production from geothermal energy is still little exploited compared to its large potential and to the World renewable energy production from other sources. Some countries have exploited this energy source in order to enhance their transition to renewables. Today the largest geothermal energy producers in the world are New Zealand, U.S.A, Mexico, Philippines, Italy, Iceland, and, more recently, Turkey (Geothermal, 2012). Differently from other renewable sources, geothermal energy produces impacts on the environment that are very site-specific because of the nature of the resource and its geological characteristics Bravi et al.,2010; Parisi et al.,2013. In the same way, the atmospheric emissions associated to the activity of geothermal power plants for electric or heat production (mainly CO, HS, NH, Hg, CH) are also site-specific. In fact, due to technological and geographical differences among the geothermal installations operating all over the World, it is quite impossible to identify and attribute typical emission patterns, to perform forecasts valid for multiple sites or to collect universal data. Furthermore, it is virtually impossible the comparison among technologies located in different regions or countries. Definitively, inventories of primary data, as accurate and complete as possible, are essential to correctly evaluate the peculiarities of geo-thermoelectric energy production Parisi et al.,2018. Data reported here try to fill the gap in respect to the Italian situation. To this end, a complete survey of the atmospheric emissions from all the geothermal power plants in operation in the Tuscany Region is performed. In addition to data reporting, also some statistical analysis is performed to process data and to operate a further level of simplification which averages the emissions on the basis of geothermal sub-areas. The data collected is related to the research article "Life cycle assessment of atmospheric emission profiles of the Italian geothermal power plants" Parisi et al.,2019.
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http://dx.doi.org/10.1016/j.dib.2019.104339DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6699452PMC
August 2019

Effectivenesss of ivacaftor in severe cystic fibrosis patients and non-G551D gating mutations.

Pediatr Pulmonol 2019 09 25;54(9):1398-1403. Epub 2019 Jun 25.

Cystic Fibrosis Center, Hospital San Carlo, Potenza, Italy.

Background: Ivacaftor is a significant innovation in the treatment of cystic fibrosis (CF) with gating mutations. A substantial percentage of patients with CF have severe lung involvement, but these patients are usually excluded from phase III clinical trials. Thus, the effectiveness of ivacaftor in this population has not been fully determined.

Methods: Data were collected from Italian CF centers with patients enrolled in an ivacaftor compassionate use programme (percent predicted [pp] forced expiratory volume in 1 second [FEV ] < 40%, or on lung transplant waiting list, or with a fast worsening trend of lung function). Data were collected for 1 year before and 1 year after ivacaftor commencement.

Results: Thirteen patients received ivacaftor for a median of 320 days. Mean (SD) ppFEV increased from 35.1% (14.3%) before treatment to 46.6% (18.8%) after 12 months of treatment (absolute increase 11.5%, relative increase 32.8%). Mean distance of the 6-minute walking test improved significantly, from 535.1 m before to 611.6 m after 12 months of treatment (P = .002). The number of pulmonary exacerbations decreased significantly, from 57 during the year before ivacaftor to 28 in the year following ivacaftor (P = .0048). Five of the 13 patients (38.5%) had no exacerbations during the 12 months after starting ivacaftor. Median weight increased significantly, from 52.7 kg to 55.6 kg (P = .0031). Mean (SD) sweat chloride concentration decreased significantly, from 99.5 (22.8) mmol/L to 39.3 (15.8) mmol/L (P < .0001). No safety concerns were registered.

Conclusions: Ivacaftor was safe and effective in patients with CF with severe lung disease and non-G551D gating mutations.
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http://dx.doi.org/10.1002/ppul.24424DOI Listing
September 2019

Snacking in nutrition and health.

Int J Food Sci Nutr 2019 Dec 10;70(8):909-923. Epub 2019 Apr 10.

Nutrition Foundation of Italy , Milan , Italy.

Many studies suggest that distributing energy and nutrient intake across 4-5 eating occasions/day (rather than across three standard meals) could favourably affect human health. The inclusion of 1-2 snacks in the daily pattern alleviates the potential digestive and metabolic overload caused by fewer heavier meals and might contribute to meet recommendations for food groups (e.g. fruits, dairy) and nutrients like fibre and vitamins. The snack composition should be evaluated taking into account the whole day's diet. In early and late ages, and for specific population groups, snacking may need to follow particular characteristics in order to be optimal, both in terms of composition and timing. This document, which is the result of a collaboration of experts across several fields of research, intends to provide a review of the current scientific literature on meal frequency and health, highlighting the beneficial effects of correct snack consumption across the human lifespan.
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http://dx.doi.org/10.1080/09637486.2019.1595543DOI Listing
December 2019

Timely Detection of Mild Cognitive Impairment in Italy: An Expert Opinion.

J Alzheimers Dis 2019 ;68(4):1401-1414

CNR, Neuroscience Institute, Aging Branch, Padua, Italy.

Mild cognitive impairment (MCI) generally evolves in a gradually progressive decline in memory and non-memory cognitive domains that may eventually decay to dementia. This process might be preventable by improving early detection of the MCI syndrome followed by proper and timely interventions. The aim of this work was providing helpful indications for a standardized early diagnosis of MCI, mainly focusing on the Italian elderly population. We reviewed here MCI epidemiology and classification, as well as the most recent advancements in early detection of the patient with MCI in the Italian scenario. Specialist centers in connection with general practitioners (GPs) have been established across the country and designated as Centers for Cognitive Disorders and Dementia (CDCD). CDCDs are dedicated to the diagnosis and management of patients for all forms of dementia across all the complex staging spectrum. New tools were made available by the advancements of imaging techniques and of the research on biomarkers, leading to novel approaches based on the combination of imaging and biomarker detection, to improve accuracy and effectiveness in the early diagnosis of MCI. Moreover, patient genotyping, alone or in combination with other techniques, was also revealed as a promising method in evaluating and preventing MCI progression. We recommend the introduction of all these novel tools in the diagnostic practice of the specialist centers and that further efforts and resources are spent into the research of the most effective techniques and biomarkers to be introduced as first-level tests into the practice of early diagnosis of MCI.
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http://dx.doi.org/10.3233/JAD-181253DOI Listing
August 2020

Periodontal Disease: A Risk Factor for Diabetes and Cardiovascular Disease.

Int J Mol Sci 2019 Mar 20;20(6). Epub 2019 Mar 20.

Department of Translational Medical Sciences, Federico II University of Naples, 80131 Naples, Italy.

Periodontitis is a chronic inflammatory disease, initiated by the presence of a bacterial biofilm, called dental plaque, which affects both the periodontal ligaments and bone surrounding teeth. In the last decades, several lines of evidence have supported the existence of a relationship between periodontitis and systemic health. For instance, as periodontitis acts within the same chronic inflammatory model seen in cardiovascular disease (CVD), or other disorders, such as diabetes, several studies have suggested the existence of a bi-directional link between periodontal health and these pathologies. For instance, people with diabetes are more susceptible to infections and are more likely to suffer from periodontitis than people without this syndrome. Analogously, it is now evident that cardiac disorders are worsened by periodontitis, both experimentally and in humans. For all these reasons, it is very plausible that preventing periodontitis has an impact on the onset or progression of CVD and diabetes. On these grounds, in this review, we have provided an updated account on the current knowledge concerning periodontal disease and the adverse effects exerted on the cardiovascular system health and diabetes, informing readers on the most recent preclinical studies and epidemiological evidence.
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http://dx.doi.org/10.3390/ijms20061414DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6470716PMC
March 2019

Elder abuse: perception and knowledge of the phenomenon by healthcare workers from two Italian hospitals.

Intern Emerg Med 2019 06 29;14(4):549-555. Epub 2019 Jan 29.

Department of Experimental Medicine, University of Campania "Luigi Vanvitelli", Naples, Italy.

With ageing population the number of elderly vulnerable to abuse is expected to grow. Hospital personnel play a crucial role in identifying mistreatment. The aim of this study was to establish the level of awareness and perception of elder abuse by healthcare workers, and to understand if they are able to recognize and properly report elder abuse, as well as to identify the physical signs of abuse and neglect. A 41-question survey was administered to healthcare professionals, working in the Internal Medicine and Geriatric Wards of two different University Hospitals of Southern Italy, representative of the Italian health public system. The data collection resulted in 98 questionnaires. For the majority, neglect represents a type of abuse, whereas 40% of physicians and 37% of nurses considered this concept false. All the professionals recognized the elder abuse as a violation of the human rights, but 46.94% were not sure about the existence of standard procedures for abuse reporting/treatment. The most of the nurses and the care assistants declared they never had suspected or witnessed abuse, while few physicians stated to have suspected/witnessed abuse 1-3 times in their career. In both the suspected and witnessed cases, the healthcare personnel did not made any action, neither reported them to public authorities nor adult protective service agencies. The level of awareness and perception of elder abuse by healthcare professionals are still poor especially regarding the reporting procedures. There is still strong need for education and specific training programs on elder abuse.
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http://dx.doi.org/10.1007/s11739-019-02038-yDOI Listing
June 2019

Impact of Malnutrition on Long-Term Mortality in Elderly Patients with Acute Myocardial Infarction.

Nutrients 2019 Jan 22;11(2). Epub 2019 Jan 22.

Department of Translational Medical Sciences, University of Naples Federico II, Via Pansini 5, 80131 Naples, Italy.

Background: Malnutrition is a frequent condition in the elderly, and is associated with prolonged hospitalization and increased mortality. However, the impacts of malnutrition among elderly patients with acute myocardial infarction have not been clarified yet.

Methods And Results: We enrolled 174 patients aged 65 years and over, admitted with the diagnosis of acute myocardial infarction (AMI), who underwent evaluation of nutritional status by Mini Nutritional Assessment (MNA) and evaluation of mortality risk by GRACE Score 2.0. All-cause mortality was the outcome considered for this study. Over a mean follow-up of 24.5 ± 18.2 months, 43 deaths have been registered (24.3%). Non-survivors were more likely to be older, with worse glomerular filtration rate, lower systolic blood pressure, lower albumin and MNA score, higher prevalence of Killip classification III-IV grade, and higher Troponin I levels. Multivariate Cox proportional analysis revealed that GRACE Score and MNA showed a significant and independent impact on mortality, (HR = 1.76, 95%, CI = 1.34⁻2.32, and HR = 0.56, 95% CI = 0.42⁻0.73, respectively). Moreover, the clinical decision curve revealed a higher clinical net benefit when the MNA was included, compared to the partial models without MNA.

Conclusion: Nutritional status is an independent predictor of long-term mortality among elderly patients with AMI. MNA score in elderly patients with AMI may help prognostic stratification and identification of patients with, or at risk of, malnutrition in order to apply interventions to improve nutritional status, and maybe survival in this population.
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http://dx.doi.org/10.3390/nu11020224DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6412515PMC
January 2019

Imaging and Molecular Mechanisms of Alzheimer's Disease: A Review.

Int J Mol Sci 2018 Nov 22;19(12). Epub 2018 Nov 22.

Department of Translational Medical Sciences, Federico II University of Naples, 80131 Naples, Italy.

Alzheimer's disease is the most common form of dementia and is a significant burden for affected patients, carers, and health systems. Great advances have been made in understanding its pathophysiology, to a point that we are moving from a purely clinical diagnosis to a biological one based on the use of biomarkers. Among those, imaging biomarkers are invaluable in Alzheimer's, as they provide an in vivo window to the pathological processes occurring in Alzheimer's brain. While some imaging techniques are still under evaluation in the research setting, some have reached widespread clinical use. In this review, we provide an overview of the most commonly used imaging biomarkers in Alzheimer's disease, from molecular PET imaging to structural MRI, emphasising the concept that multimodal imaging would likely prove to be the optimal tool in the future of Alzheimer's research and clinical practice.
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http://dx.doi.org/10.3390/ijms19123702DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6321449PMC
November 2018

Statin therapy modulates thickness and inflammatory profile of human epicardial adipose tissue.

Int J Cardiol 2019 Jan 28;274:326-330. Epub 2018 Jun 28.

Department of Translational Medical Science, University of Naples Federico II, Italy.

Background: Epicardial adipose tissue (EAT) thickness and pro-inflammatory status has been shown to be associated with several cardiac diseases, including aortic stenosis (AS). Thus, cardiac visceral fat could represent a potential new target for drugs. In the present study we evaluate the effect of statin therapy on EAT accumulation and inflammation.

Methods: Echocardiographic EAT thickness was assessed in 193 AS patients taking (n.87) and not taking (n.106) statins, undergoing cardiac surgery. To explore the association between statin therapy and EAT inflammation, EAT biopsies were obtained for cytokines immunoassay determination in EAT secretomes. An in vitro study was also conducted and the modulation of EAT and subcutaneous adipose tissue (SCAT) secretomes by atorvastatin was assessed in paired biopsies.

Results: Statin therapy was significantly associated with lower EAT thickness (p < 0.0001) and with lower levels of EAT-secreted inflammatory mediators (p < 0.0001). Of note, there was a significant correlation between EAT thickness and its pro-inflammatory status. In vitro, atorvastatin showed a direct anti-inflammatory effect on EAT which was significantly higher compared to the SCAT response to statin incubation (p < 0.0001).

Conclusions: The present study indicates a robust association between statin therapy and reduced EAT accumulation in patients with AS. The present data also suggest a direct relationship between EAT thickness and its inflammatory status, both modulated by statin therapy. The in vitro results support the hypothesis of a direct action of statins on EAT secretory profile. Overall our data suggest EAT as a potential new therapeutic target for statin therapy.
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http://dx.doi.org/10.1016/j.ijcard.2018.06.106DOI Listing
January 2019

Aldosterone and Mineralocorticoid Receptor System in Cardiovascular Physiology and Pathophysiology.

Oxid Med Cell Longev 2018 19;2018:1204598. Epub 2018 Sep 19.

Division of Cardiology, Johns Hopkins University, Baltimore, MD, USA.

The mineralocorticoid hormone aldosterone (Aldo) has been intensively studied for its ability to influence both the physiology and pathophysiology of the cardiovascular system. Indeed, although research on Aldo actions for decades has mainly focused on its effects in the kidney, several lines of evidence have now demonstrated that this hormone exerts disparate extrarenal adverse effects, especially in the circulatory system. Accordingly, in the last lusters, a number of studies in preclinical models ( and ) and in humans have established that Aldo, following the interaction with its receptor-the mineralocorticoid receptor (MR)-is able to activate specific intracellular genomic and nongenomic pathways, thus regulating the homeostasis of the cardiovascular system. Importantly, through this mechanism of action, this hormone becomes a crucial regulator of the function and growth of different types of cells, including fibroblasts, cardiomyocytes, and vascular cells. For this main reason, it is plausible that when Aldo is present at high levels in the blood, it profoundly modifies the physiology of these cells, therefore being at the foundation of several cardiovascular disorders, such as heart failure (HF). On these grounds, in this review, we will provide an updated account on the current knowledge concerning Aldo activity in the cardiovascular system and the most recent preclinical studies and clinical trials designed to test better approaches able to counter the hyperactivity of the Aldo/MR signaling pathway in the setting of cardiovascular diseases.
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http://dx.doi.org/10.1155/2018/1204598DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6169243PMC
December 2018

Cow's Milk Consumption and Health: A Health Professional's Guide.

J Am Coll Nutr 2019 Mar-Apr;38(3):197-208. Epub 2018 Sep 24.

ac Interventional Cardiology-CCU Department , G. Rummo Hospital, Benevento and ANMCO-Italian National Association of Hospital Cardiologists , Benevento , Italy.

The most recent scientific evidence supports the consumption of cow's milk and dairy products as part of a balanced diet. However, these days, the public and practicing physicans are exposed to a stream of inconsistent (and often misleading) information regarding the relationship between cow's milk intake and health in the lay press and in the media. The purpose of this article, in this context, is to facilitate doctor-patient communication on this topic, providing physicians with a series of structured answers to frequently asked patient questions. The answers range from milk and milk-derived products' nutritional function across the life span, to their relationship with diseases such as osteoporosis and cancer, to lactose intolerance and milk allergy, and have been prepared by a panel of experts from the Italian medical and nutritional scientific community. When consumed according to appropriate national guidelines, milk and its derivatives contribute essential micro- and macronutrients to the diet, especially in infancy and childhood where bone mass growth is in a critical phase. Furthermore, preliminary evidence suggests potentially protective effects of milk against overweight, obesity, diabetes, and cardiovascular disease, while no clear data suggest a significant association between milk intake and cancer. Overall, current scientific literature suggests that an appropriate consumption of milk and its derivatives, according to available nutritional guidelines, may be beneficial across all age groups, with the exception of specific medical conditions such as lactose intolerance or milk protein allergy. Key teaching points: Milk and its derivatives contribute essential micro and macronutrients to the diet, when consumed according to appropriate national guidelines, especially in infancy and childhood where bone mass growth is in a critical phase. Preliminary evidence suggests potentially protective effects of milk against overweight, obesity, diabetes and cardiovascular disease No clear data are available about the association between milk intake and cancer. Current scientific literature suggests that an appropriate consumption of milk and its derivatives may be beneficial at all ages, with the exception of specific medical conditions such as lactose intolerance or milk protein allergy.
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http://dx.doi.org/10.1080/07315724.2018.1491016DOI Listing
July 2020
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