Challenges in anti-aging medicine-trends in biomarker discovery and therapeutic interventions for a healthy lifespan.

We are facing a growing aging population, along with increasing pressure on health systems, caused by the impact of chronic co-morbidities (i.e. cancer, cardiovascular and neurodegenerative diseases) and functional disabilities as people age. Relatively simple preventive lifestyle interventions, such as dietary restriction and physical exercise, are important contributors to active and healthy aging in the general population. However, as shown in model organisms or in 'in vitro' conditions, lifestyle-independent interventions may have additional health benefits and can even be conceived as possible reversers of the aging process. Thus, pharmaceutical laboratories, research institutes, and universities are putting more and more effort into finding new molecular pathways and druggable targets to develop gerotherapeutics. One approach is to target the driving mechanisms of aging, some of which, like cellular senescence and impaired autophagy, we discussed in an update on the biology of aging at AgingFit 2023 in Lille, France. We underline the importance of carefully and extensively testing senotherapeutics, given the pleiotropism and heterogeneity of targeted senescent cells within different organs, at different time frames. Other druggable targets emerging from new putative mechanisms, like those based on transcriptome imbalance, nucleophagy, protein phosphatase depletion, glutamine metabolism, or seno-antigenicity, have been evidenced by recent preclinical studies in classical models of aging but need to be validated in humans. Finally, we highlight several approaches in the discovery of biomarkers of healthy aging, as well as for the prediction of neurodegenerative diseases and the evaluation of rejuvenation strategies.

Development and validation of combined symptom-medication scores for allergic rhinitis.

BACKGROUND: Validated combined symptom-medication scores (CSMSs) are needed to investigate the effects of allergic rhinitis treatments. This study aimed to use real-life data from the MASK-air® app to generate and validate hypothesis- and data-driven CSMSs. METHODS: We used MASK-air® data to assess the concurrent validity, test-retest reliability and responsiveness of one hypothesis-driven CSMS (modified CSMS: mCSMS), one mixed hypothesis- and data-driven score (mixed score), and several data-driven CSMSs. The latter were generated with MASK-air® data following cluster analysis and regression models or factor analysis. These CSMSs were compared with scales measuring (i) the impact of rhinitis on work productivity (visual analogue scale [VAS] of work of MASK-air® , and Work Productivity and Activity Impairment: Allergy Specific [WPAI-AS]), (ii) quality-of-life (EQ-5D VAS) and (iii) control of allergic diseases (Control of Allergic Rhinitis and Asthma Test [CARAT]). RESULTS: We assessed 317,176 days of MASK-air® use from 17,780 users aged 16-90 years, in 25 countries. The mCSMS and the factor analyses-based CSMSs displayed poorer validity and responsiveness compared to the remaining CSMSs. The latter displayed moderate-to-strong correlations with the tested comparators, high test-retest reliability and moderate-to-large responsiveness. Among data-driven CSMSs, a better performance was observed for cluster analyses-based CSMSs. High accuracy (capacity of discriminating different levels of rhinitis control) was observed for the latter (AUC-ROC = 0.904) and for the mixed CSMS (AUC-ROC = 0.820). CONCLUSION: The mixed CSMS and the cluster-based CSMSs presented medium-high validity, reliability and accuracy, rendering them as candidates for primary endpoints in future rhinitis trials.

ARIA digital anamorphosis: Digital transformation of health and care in airway diseases from research to practice.

Digital anamorphosis is used to define a distorted image of health and care that may be viewed correctly using digital tools and strategies. MASK digital anamorphosis represents the process used by MASK to develop the digital transformation of health and care in rhinitis. It strengthens the ARIA change management strategy in the prevention and management of airway disease. The MASK strategy is based on validated digital tools. Using the MASK digital tool and the CARAT online enhanced clinical framework, solutions for practical steps of digital enhancement of care are proposed.

Position Paper on Young Vascular Surgeons Training of the Mediterranean Federation for the Advancing of Vascular Surgery (MeFAVS): State of the Art and Perspectives.

The Mediterranean Federation for the Advancing of Vascular Surgery (MeFAVS) was founded in 2018, with the aim to promote cooperation among vascular professionals within Mediterranean countries. Due to its prominent social and economic impact on national health systems, diabetic peripheral artery was selected as the very first topic to be investigated by the federation. In this second paper, different experiences from delegates of participating countries were shared to define common strategies to harmonize, standardize, and optimize education and training in the Vascular Surgery specialty.

The role of health determinants in the influenza vaccination uptake among older adults (65+): a scope review.

BACKGROUND: Although the burden of influenza infection is the highest in older adults, vaccination coverage remains low, despite this age group being more vulnerable than others. AIMS: Given the current pandemic of SARS-CoV-2, it was the aim of this scope review to update knowledge on factors affecting seasonal influenza vaccine uptake among older adults to strengthen prevention approaches in the context of an overall burden of infectious diseases. METHODS: We searched bibliographic databases from 2012 to 2019. All studies reviewed one or more social determinant of health listed by WHO, or factors affecting the decision-making process whether to accept influenza vaccine or not. RESULTS: Overall, 44 studies were included, 41 determinants were extracted and summarized into six categories. Older age and constitutional factors including multiple chronic diseases as well as preventive lifestyle and frequent routine healthcare utilization positively affected vaccination uptake (VU). Living and working conditions are also researched determinants of influenza vaccine uptake. A small number of studies explored the role of social inclusion and system-based interventions. DISCUSSION AND CONCLUSIONS: This scope review provides a comprehensive overview on factors affecting seasonal influenza vaccination uptake among older citizens. The review also clearly shows gaps for evidence on system-based level or political strategies to improve vaccination uptake.

Mini-Mental State Examination: new normative values on subjects in Southern Italy.

OBJECTIVE: The aims of the present study were: (a) to obtain new normative data of the Italian version of the Mini-Mental Examination State (MMSE) (Measso et al. in Dev Neuropsychol 9:77-85, 1993) by administering the tool to a sample of normal Italian individuals more representative of the current Italian population; (b) to compare the sensitivity of this tool in detecting patients suffering from Alzheimer's disease (AD according to NIA-AA), as compared to the those reported in previous normative Italian studies. METHODS: MMSE was administered to 314 normal subjects recruited among individuals (and/or their relatives) attending the Offices of General Practitioners (GP) or Memory Clinics in Campania (Italy) by convenience sampling. A group of 47 patients with AD were included into the study. The effect of demographic variables on the raw MMSE scores of normal subjects was checked by multiple linear regression assuming MMSE scores as dependent variable and age, gender and education as the independent one(s). Therefore, a simultaneous regression model was constructed to correct the raw scores according the sensitive variables. Correction grid and equivalent scores were devised to classify subject's performance. RESULTS: The mean raw MMSE score was 27.78 (SD = 1.80) (range 22-30/30). There was no significant difference between scores achieved by men or women (p = 0.688). Multiple linear regression analysis showed a significant effect of age and years of school attendance on the MMSE raw score, whereas gender did not show any significant effect. The cutoff score, distinguishing between pathological and normal performances, was fixed at the fifth centile corresponding to 24.9/30, higher than the current score of 23.8/30. The new cutoff value was able to identify 44/47 patients with AD, in contrast to 38/47 subjects detected by currently used norms. CONCLUSIONS: (1) A more updated and representative population sample; (2) a new cutoff threshold able to distinguish between normal and pathological performances; (3) a correction grid that reduces the risk of false-positive and false-negative values due to the influence of the main demographic factors; (4) greater sensitivity, compared to previous Italian normative studies in identifying people with dementia.

Monitoring Biochemical and Structural Changes in Human Periodontal Ligaments during Orthodontic Treatment by Means of Micro-Raman Spectroscopy.

The aim of the study was to examine the biochemical and structural changes occurring in the periodontal ligament (PDL) during orthodontic-force application using micro-Raman spectroscopy ( µ -RS). Adolescent and young patients who needed orthodontic treatment with first premolar extractions were recruited. Before extractions, orthodontic forces were applied using a closed-coil spring that was positioned between the molar and premolar. Patients were randomly divided into three groups, whose extractions were performed after 2, 7, and 14 days of force application. From the extracted premolars, PDL samples were obtained, and a fixation procedure with paraformaldehyde was adopted. Raman spectra were acquired for each PDL sample in the range of 1000-3200 cm - 1 and the more relevant vibrational modes of proteins (Amide I and Amide III bands) and CH 2 and CH 3 modes were shown. Analysis indicated that the protein structure in the PDL samples after different time points of orthodontic-force application was modified. In addition, changes were observed in the CH 2 and CH 3 high wavenumber region due to local hypoxia and mechanical force transduction. The reported results indicated that µ -RS provides a valuable tool for investigating molecular interchain interactions and conformational modifications in periodontal fibers after orthodontic tooth movement, providing quantitative insight of time occurring for PDL molecular readjustment.

Allergic Rhinitis and its Impact on Asthma (ARIA) Phase 4 (2018): Change management in allergic rhinitis and asthma multimorbidity using mobile technology.

Allergic Rhinitis and its Impact on Asthma (ARIA) has evolved from a guideline by using the best approach to integrated care pathways using mobile technology in patients with allergic rhinitis (AR) and asthma multimorbidity. The proposed next phase of ARIA is change management, with the aim of providing an active and healthy life to patients with rhinitis and to those with asthma multimorbidity across the lifecycle irrespective of their sex or socioeconomic status to reduce health and social inequities incurred by the disease. ARIA has followed the 8-step model of Kotter to assess and implement the effect of rhinitis on asthma multimorbidity and to propose multimorbid guidelines. A second change management strategy is proposed by ARIA Phase 4 to increase self-medication and shared decision making in rhinitis and asthma multimorbidity. An innovation of ARIA has been the development and validation of information technology evidence-based tools (Mobile Airways Sentinel Network [MASK]) that can inform patient decisions on the basis of a self-care plan proposed by the health care professional.

ARIA pharmacy 2018 "Allergic rhinitis care pathways for community pharmacy": AIRWAYS ICPs initiative (European Innovation Partnership on Active and Healthy Ageing, DG CONNECT and DG Santé) POLLAR (Impact of Air POLLution on Asthma and Rhinitis) GARD Demonstration project.

Pharmacists are trusted health care professionals. Many patients use over-the-counter (OTC) medications and are seen by pharmacists who are the initial point of contact for allergic rhinitis management in most countries. The role of pharmacists in integrated care pathways (ICPs) for allergic diseases is important. This paper builds on existing studies and provides tools intended to help pharmacists provide optimal advice/interventions/strategies to patients with rhinitis. The Allergic Rhinitis and its Impact on Asthma (ARIA)-pharmacy ICP includes a diagnostic questionnaire specifically focusing attention on key symptoms and markers of the disease, a systematic Diagnosis Guide (including differential diagnoses), and a simple flowchart with proposed treatment for rhinitis and asthma multimorbidity. Key prompts for referral within the ICP are included. The use of technology is critical to enhance the management of allergic rhinitis. However, the ARIA-pharmacy ICP should be adapted to local healthcare environments/situations as regional (national) differences exist in pharmacy care.

The Italian version of the quick mild cognitive impairment (Qmci-I) screen: normative study on 307 healthy subjects.

OBJECTIVE: To devise an Italian version of the quick mild cognitive impairment screen (Qmci) and to obtain normative data. METHODS: An Italian version of the Qmci screen (Qmci-I) was administered to 307 subjects free from cognitive impairment. The normative sample was divided into three age levels (50-59; 60-69 and 70-80 years) and four education levels (3-5; 6-8; 9-13; >13 years of school attendance). Multiple regression analyses were used to evaluate the effect of age, sex and schooling on Qmci-I scores (overall and by domains) and to calculate cut-off values, with reference to the confidence interval on the fifth centile. RESULTS: The mean Qmci-I score was 64/100 (SD = 11). The age variable showed a significant negative effect on the overall Qmci-I score, with older people performing worse than younger ones. Conversely, education was associated with higher scores. Significant effects of age and education affected logical memory alone. For the other domains, the following effects were found: (1) higher age associated with lower scores on delayed recall; (2) higher education levels associated with higher scores on immediate recall, clock drawing and word fluency. The adjusted cut-off score for the Qmci-I screen in this sample was 49.4. Qmci-I scores were weakly correlated with those of MMSE (rho = 0.20). CONCLUSIONS: The Qmci-I is a rapid and multi-domain short cognitive screening instrument useful for evaluating cognitive functions. However, like other screening tools, it is significantly influenced by age and education, requiring normative data and correction of values when used in the clinical practice.

Animal-Assisted Therapy in Elderly Patients: Evidence and Controversies in Dementia and Psychiatric Disorders and Future Perspectives in Other Neurological Diseases.

Animal-assisted therapy (AAT) includes a set of nonpharmacological interventions aimed at improving human health through the use of trained or untrained animals. In recent decades, AAT has been trialed for different neurological and psychiatric disorders. In patients with dementia, interaction with animals seems to have a positive influence on aggressiveness and anxiety and to ameliorate quality of life and relationship skills. In psychiatric patients, AAT seems to increase motivation and self-esteem, improve prosocial conduct, and decrease behavioral problems. The aim of this study is to review the literature on AAT for elderly people with dementia and psychiatric disorders. Other fields of possible application for AAT are suggested.

Educational strategies to train health care professionals across the education continuum on the process of frailty prevention and frailty management: a systematic review.

BACKGROUND: In addition to the normal process of ageing, frailty, defined as a geriatric syndrome, is becoming more prevalent. Around 10% of people over 65 years and 25-50% of those aged over 85 years are frail. Frail elderly are more vulnerable to external stressors and have an increased risk of adverse health outcomes. To tackle these challenges, European Union (EU) member states need to develop a health work force capable of the right skills mix. A goal-centred education and training of professionals is crucial for effective and efficient health care delivery for Europe's greying population. AIMS: The aim of this study was to systematically collect, review and critically appraise studies carried out to investigate the efficacy and effectiveness of comprehensive educational programmes for health professionals related to frailty prevention and/or frailty management. METHODS: A systematic review was carried out searching the databases PubMed, CINAHL, Cochrane CENTRAL, Medline, Up to date and Embase. Additionally, a manual search of the reference lists and searches via Google Scholar and greylit.org was done. RESULTS: No relevant publications addressing the evidence and sustainability of educational/training programmes for frailty prevention and/or frailty management were identified. DISCUSSION: The result of an empty review is surprising because several educational programmes in different countries are currently run. CONCLUSIONS: A significant knowledge gap exists in the scientific literature regarding education and training of health care workers regarding prevention and management of frailty. Further research is needed to identify effective educational strategies for health professionals to prevent and manage frailty.

The Amino-Terminal Domain of GRK5 Inhibits Cardiac Hypertrophy through the Regulation of Calcium-Calmodulin Dependent Transcription Factors.

We have recently demonstrated that the amino-terminal domain of G protein coupled receptor kinase (GRK) type 5, (GRK5-NT) inhibits NFκB activity in cardiac cells leading to a significant amelioration of LVH. Since GRK5-NT is known to bind calmodulin, this study aimed to evaluate the functional role of GRK5-NT in the regulation of calcium-calmodulin-dependent transcription factors. We found that the overexpression of GRK5-NT in cardiomyoblasts significantly reduced the activation and the nuclear translocation of NFAT and its cofactor GATA-4 in response to phenylephrine (PE). These results were confirmed in vivo in spontaneously hypertensive rats (SHR), in which intramyocardial adenovirus-mediated gene transfer of GRK5-NT reduced both wall thickness and ventricular mass by modulating NFAT and GATA-4 activity. To further verify in vitro the contribution of calmodulin in linking GRK5-NT to the NFAT/GATA-4 pathway, we examined the effects of a mutant of GRK5 (GRK5-NTPB), which is not able to bind calmodulin. When compared to GRK5-NT, GRK5-NTPB did not modify PE-induced NFAT and GATA-4 activation. In conclusion, this study identifies a double effect of GRK5-NT in the inhibition of LVH that is based on the regulation of multiple transcription factors through means of different mechanisms and proposes the amino-terminal sequence of GRK5 as a useful prototype for therapeutic purposes.

Rates and reasons for lack of persistence with anti-osteoporotic drugs: analysis of the Campania region database.

Subjects with chronic diseases are more likely to be nonpersistent to pharmacological treatment. Lack of persistence is common among subjects using oral anti-osteoporotic drugs, and leads to increased risk of fragility fracture. The aim of our retrospective study is to analyze the rates and reasons for discontinuation of anti-osteoporotic drugs in the Campania Region. Subjects aged over 40 years were included if they had received at least one prescription for any anti-osteoporotic drugs. Data were obtained from an administrative database of regional data on outpatient drug prescriptions reimbursed by the National Health Service. Patients were followed until the discontinuation of anti-osteoporotic therapy or until the end of the observation period. A total of 30,048 were incident users of anti-osteoporotic drugs: 28,317 (94.2%) females. The mean age of the cohort was 69.0±10.0 years. Weekly bis-phosphonates (51.1%) were the most commonly prescribed drugs. In the overall population, persistence rates were 34.8% after 6 months and 13.4% at one year. A multivariate Cox proportional hazard analysis showed that daily regimen (HR 1.9) treatments remained at higher risk of early discontinuation compared to weekly regimen therapies. Our data showed that the persistence to osteoporosis therapy is significantly worse than reported in literature.

Polypharmacy Management in Chronic Conditions: A Systematic Literature Review of Italian Interventions.

Background: Potentially inappropriate polypharmacy (PIP) is among the major factors leading to adverse drug reactions, increased healthcare costs, reduced medication adherence, and worsened patient conditions. This study aims to identify existing interventions implemented to monitor and manage polypharmacy in the Italian setting. Methods: A systematic literature review (PROSPERO: CRD42023457049) was carried out according to the PRISMA statement guidelines. PubMed, Embase, ProQuest, and Web of Science were queried without temporal constraints, encompassing all published papers until October 2023. Inclusion criteria followed the PICO model: patients with polypharmacy; interventions to monitor/manage polypharmacy regimen versus no/any intervention; outcomes in terms of intervention effectiveness and cost variation. Results: After duplicate deletion, 153 potentially relevant publications were extracted. Following abstract and full-text screenings, nine articles met the inclusion criteria. Overall, 78% (n = 7) were observational studies, 11% (n = 1) were experimental studies, and 11% (n = 1) were two-phase studies. A total of 44% (n = 4) of the studies involved patients aged ≥ 65 years, while 56% (n = 5) were disease-specific. Monitoring was the most prevalent choice of intervention (67%; n = 6). Outcomes were mainly related to levels of polypharmacy (29%; n = 6) and comorbidities (29%; n = 6), effectiveness rates (14%; n = 3), and avoidable costs (9%; n = 2). Conclusions: This review outlines that Italy is still lacking in interventions to monitor/manage PIP, addressing an unmet need in developing patient-tailored strategies for reducing health-system burden.

Development and implementation of multicomponent homecare interventions for multimorbid and frail older people based on Information and Communication Technologies: The MULTIPLAT_AGE project.

The prevention and treatment of frailty condition among multimorbid older adults, in community and hospital settings, is becoming a healthcare priority. Growing evidence suggests that a multidimensional approach could help not only in the early identification of older patients' needs but also in designing personalized preventive interventions. However, in clinical practice, the effectiveness of such interventions is limited by a lack of continuity of care and poor compliance of patients. The widespread diffusion of the information and communication technology (ICT) could offer an excellent way to implement and monitor multidimensional and personalized interventions for multimorbid older adults. In this scenario, the MULTIPLAT_AGE, is a network project involving five research centers with the main objective to supply multidimensional interventions targeted to cognitive, motor, pharmacological, and functional domains including ICT-based: i) transitional care model from the hospital to a protected home area; ii) automatic home-care system to improve activities of daily living; iii) program to improve appropriate drug prescription in nursing-home residents; iv) tele-rehabilitation program to reduce the risk of falls and v) cognitive stimulation delivered by remote in older adults with neurological disorders. Each project is linked to the others by employing a shared online platform, in a perspective of technological-supplied multicomponent interventions according to the concept of "aging in place" as the best solution for the treatment and healthcare of older people. Here we describe the general framework of the MULTIPLAT_AGE, and we examine every single project, pointing out innovative aspects, and discussing the expected results.

N-(Phenoxyalkyl)amides as MT(1) and MT(2) ligands: antioxidant properties and inhibition of Ca(2+)/CaM-dependent kinase II.

Recently a series of chiral N-(phenoxyalkyl)amides have been reported as potent MT(1) and MT(2) melatonergic ligands. Some of these compounds were selected and tested for their antioxidant properties by measuring their reducing effect against oxidation of 2',7'-dichlorodihydrofluorescein (DCFH) in the DCFH-diacetate (DCFH-DA) assay. Among the tested compounds, N-[2-(3-methoxyphenoxy)propyl]butanamide displayed potent antioxidant activity that was stereoselective, the (R)-enantiomer performing as the eutomer. This compound displayed strong cytoprotective activity against H(2)O(2)-induced cytotoxicity resulting slightly more active than melatonin, and performed as Ca(2+)/calmodulin-dependent kinase II (CaMKII) inhibitor, too.

Gastrointestinal bezoars: Review of the literature and report of a rare case of pumpkin seed rectal impaction.

In science, bezoar is a mass of hair or undigested vegetable matter, found in a human or animal's intestines, similar to a hairball. Usually, it is found trapped in every part of the gastrointestinal system and must be distinguished by pseudobezoar which is an indigestive object voluntarily introduced into the digestive tract. The term Bezoar is from Arabic bazahr, "bezoar" or ultimately from Middle Persian p'tzhl padzahr, "antidote, bezoar"ægagropile o egagropile It should be a universal antidote that works against any poison, and could neutralize any poison. Otherwise, the name could derive from a kind of Turkish goat whose name is just bezoar. Authors report a case of fecal impaction by pumpkin seeds bezoar with abdominal pain: a difficulty to void with subsequent rectal inflammation and hemorrhoid enlargement was observed. The patient underwent a successful manual disimpaction. Guidelines do not require IRB approval Authors examined the literature about occlusion from bezoar The most common causes of occlusion from bezoar are: a previous gastric surgery such as a gastric band (for weight loss) or gastric bypass, a reduced stomach acid (hypochlorhydria) or decreased stomach size, a delayed gastric emptying, typically due to diabetes, autoimmune disorders, or mixed connective tissue disease. Seed bezoars are usually found in the rectum of patients without predisposing factors, causing constipation and pain. Rectal impaction is common after ingestion of seeds while a true occlusion is rare. Although several cases of phytobezoars composed of various types of seeds are reported in literature, bezoars of pumpkin seeds have rarely been reported.

Exploratory Factor Analysis (EFA) of the Short Functional Geriatric Evaluation (SFGE) to Assess the Multidimensionality of Frailty in Community-Dwelling Older Adults.

The Short Functional Geriatric Evaluation (SFGE) is a multidimensional and short questionnaire to assess biopsychosocial frailty in older adults. This paper aims to clarify the latent factors of SFGE. Data were collected from January 2016 to December 2020 from 8800 community-dwelling older adults participating in the "Long Live the Elderly!" program. Social operators administered the questionnaire through phone calls. Exploratory factor analysis (EFA) was carried out to identify the quality of the structure of the SFGE. Principal component analysis was also performed. According to the SFGE score, 37.7% of our sample comprised robust, 24.0% prefrail, 29.3% frail, and 9.0% very frail individuals. Using the EFA, we identified three main factors: psychophysical frailty, the need for social and economic support, and the lack of social relationships. The Kaiser-Meyer-Olkin measure of sampling adequacy was 0.792, and Bartlett's test of sphericity had a statistically significant result (p-value < 0.001). The three constructs that emerged explain the multidimensionality of biopsychosocial frailty. The SFGE score, 40% of which is social questions, underlines the crucial relevance of the social domain in determining the risk of adverse health outcomes in community-dwelling older adults.