THE MILAN GERIATRICS 75+ COHORT STUDY: UNRAVELLING THE DETERMINANTS OF HEALTHY AGEING AND LONGEVITY

Current evidence on older adults is derived from population-based cohort studies and randomized controlled trials, which may not include frail individuals. Data are lacking on older outpatients, a potentially diverse population. Therefore, we initiated the Milan Geriatrics 75+ Cohort Study, a prospective hospital-based outpatient cohort study. Chapter 1 of this thesis provides a background on the controversies regarding the homeostasis of older adults. Chapter 2, 3 and 4 report findings from the Milan Geriatrics 75+ Cohort Study. Chapter 2 explores the association between blood pressure and cognition, and whether it varies according to age and functional status. Chapter 3 examines the relationship between blood pressure and mortality risk, and whether it varies according to functional and cognitive status. Chapter 4 investigates the association between thyroid status and mortality risk in euthyroid older adults, and whether it differs by sex and age. Chapter 5 and 6 report findings from the PROSPER cohort, which includes older adults at high cardiovascular risk. Chapter 5 presents new evidence on the association of heart rate and heart rate variability with functional decline. Chapter 6 analyses the relationship between blood pressure variability and functional decline. Chapter 7 summarises and discusses the main findings of this thesis

Electric Vehicles Charging Sessions Classification Technique for Optimized Battery Charge Based on Machine Learning

The fast increase in electric vehicle (EV) usage in the last 10 years has raised the need to properly forecast their energy consumption during charge. Lithium-ion batteries have become the major storage component for electric vehicles, avoiding their overcharge can preserve their health and prolong their lifetime. This paper proposes a Machine Learning model based on the K-Nearest Neighbors classification algorithm for EV charging session duration forecast. The model forecasts the duration of the charge by assigning the event to its correct class. Each class contains the charging events whose duration is comprised of a certain interval. The only information used by the algorithm is the one available at the beginning of the charging event (arrival time, starting SOC, calendar data). The model is validated on a real-world dataset containing records of charging sessions from more than 100 users, a sensitivity analysis is performed to assess the impact of different information given as input. The effectiveness of the model with respect to the benchmark models is demonstrated with an increase in performance

Valutazione multidimensionale di ultralongevi a Milano

Scopo: caratterizzare i soggetti ultralongevi reclutati dal punto di visto clinico e funzionale (sia fisico sia cognitivo) e in seguito analizzare il loro fenotipo immunologico, infiammatorio, coagulativo e metabolico. Materiali e metodi: sono stati reclutati nell\u2019ambito dello studio PRIN \u201cLa longevit\ue0 dei genitori influenza lo stato di salute dei figli?\u201d fino ad oggi 45 centenari o ultracentenari (16 nati nel 1908, 13 nati nel 1907, 6 nati nel 1906, 7 nati nel 1905, 1 nato nel 1904, 1 nato nel 1902, 1 nato nel 1901; 11 M e 34 F) residenti in Milano citt\ue0, e intervistati al loro domicilio o in ospedale. Il reclutamento \ue8 avvenuto mediante posta, chiamata telefonica, annunci su quotidiani nazionali e locali, e con contatti con medici di base. I centenari sono stati sottoposti ad un prelievo di sangue venoso e hanno raccolto un campione di urine e un campione di feci per lo studio delle popolazioni batteriche. \uc8 stata somministrata un\u2019intervista come da protocollo del progetto, raccogliendo l\u2019anamnesi fisiologica, familiare, patologica e farmacologica. \uc8 stato esaminato lo stato cognitivo mediante MMSE, il tono dell\u2019umore mediante short GDS test, il grado di autonomia mediante le scale di valutazione ADL e IADL, la funzionalit\ue0 fisica mediante hand-grip test e chair standing test. Abbiamo classificato i centenari in tre gruppi secondo lo stato di salute 1: A (molto buono), B (intermedio), C (presenza di uno dei seguenti: MMSE <12, grave disabilit\ue0, presenza di tumore in atto o di altre patologie invalidanti). Risultati: i dati preliminari ci hanno permesso di classificare 6 centenari come A, 8 centenari B, 31 centenari C. Alcuni centenari mostravano un ottimo stato cognitivo secondo il mmse, ma dovettero essere classificati come B o C per mancanza di autonomia o presenza di tumore. Circa il 24% dei centenari presentavano grave demenza, definita come MMSE 19, ed in particolare 6 (13,3%) ottennero MMSE >26. Il livello di istruzione era nel complesso elevato: 14 centenari (31,1%) erano diplomati o laureati. Circa met\ue0 degli intervistati presentava sintomi di depressione (short GDS >5). Nel complesso, un terzo dei centenari definiva il proprio stato di salute come \u201cbuono\u201d o \u201cmolto buono\u201d, un terzo \u201cnormale\u201d, un terzo \u201cscarso\u201d o \u201cmolto scarso\u201d. Stato funzionale: 14 centenari erano istituzionalizzati, gli altri 31 vivevano nell\u2019abitazione propria o di figli o nipoti; 4 vivevano da soli ed in quasi totale autonomia. Circa la met\ue0 dei centenari presentava totale dipendenza nelle attivit\ue0 strumentali della vita quotidiana (IADL =0). Il numero di farmaci assunti cronicamente dai centenari varia da 0 a 14. Non vi \ue8 correlazione tra il numero di farmaci assunti e lo stato di salute complessivo. Abbiamo frequentemente osservato scarsa compliance alle prescrizioni mediche, autoprescrizione di farmaci ed uso empirico di farmaci o parafarmaci. Abbiamo inoltre cercato di classificare i centenari in tre gruppi in base all\u2019et\ue0 d\u2019insorgenza di alcune patologie et\ue0 correlate2 (BPCO, demenza, diabete, cardiopatie, ictus, Parkinson e tumore): \u201csurvivors\u201d (et\ue0 85) e \u201cescapers\u201d. La maggior parte dei centenari erano \u201cdelayers\u201d. Solo 4 erano sopravvissuti: un uomo ad IMA all\u2019et\ue0 di 55 anni, una donna a carcinoma mammario all\u2019et\ue0 di 72 anni, trattato mediante sola mastectomia, un uomo al cancro del colon retto trattato solo chirurgicamente, una donna a NIDDM insorto a 66 anni d\u2019et\ue0. Conclusione: \ue8 interessante notare che talvolta vi \ue8 discrepanza tra un punteggio alla GDS indicativo di sintomatologia depressiva e un autovalutazione positiva del proprio stato di salute. Dal punto di vista socio-relazionale, abbiamo osservato che molte donne centenarie avevano vissuto sole per numerosi anni, in quanto nubili o vedove, mentre i centenari maschi sembravano beneficiare di un maggiore supporto familiare, in quanto sposati una o due volte o accuditi dai figli. Bibliografia: 1.Franceschi C., Motta L., Valensin S.,Rapisarda R.,Frantone A., Berardelli M. et al Aging Clin. Exp. Res. 2000;12: 77-84. 2. Perls T Am J Clin Nutr 2006;83(suppl):484S-7

Doxorubicin and congo red effectiveness on prion infectivity in golden Syrian hamster

The effect of doxorubicin and Congo Red on prion protein (PrP) infectivity in experimental scrapie was studied to better understand the effect of these compounds in prion diseases and to establish whether a dose-response correlation exists for Congo Red. This was performed in order to test the effectiveness of compounds that may easily be used in human prion diseases. Brain homogenate containing membrane bound PrPSc monomers was used as inoculum and was previously incubated with doxorubicin 10(-3) M and with increasing concentrations of Congo Red ranging from 10(-7) to 10(-2) M. This study shows for the first time that doxorubicin, and confirms that Congo Red, may interact with pathological PrP monomers modifying their infectious properties. Pre-incubation of infected brain homogenate with Congo Red resulted in prolonged incubation time and survival, independently of Congo Red concentration (p&lt;0.05). Doxorubicin and Congo Red effects do not depend upon interaction with PrP amyloid material

No association between frailty index and epigenetic clocks in Italian semi-supercentenarians

Centenarians experience successful ageing, although they still present high heterogeneity in their health status. The frailty index is a biomarker of biological age, able to capture such heterogeneity, even at extreme old age. At the same time, other biomarkers (e.g., epigenetic clocks) may be informative the biological age of the individual and potentially describe the ageing status in centenarians. In this article, we explore the relationship between epigenetic clocks and frailty index in a cohort of Italian centenarians. No association was reported, suggesting that these two approaches may describe different aspects of the same ageing process

Laparoscopic paraesophageal hernia repair with absorbable mesh: a systematic review

Background: Laparoscopic repair is the standard of care for patients with paraesophageal hernia (PEH). Different prosthetic materials have been proposed to bolster the hiatus thus theoretically minimizing the probability for hernia recurrence. The use of non-absorbable mesh has been reported however, their safety profile has been questioned because the noteworthy mesh-related complication rate. Opposite, absorbable mesh (synthetic and biologic) seems associated with mitigated mesh-related complications and comparable hernia recurrence in the short- and medium-term. Methods: PubMed, MEDLINE, EMBASE, Scopus, Google Scholar, and ClinicalTrials.gov were executed according to the PRISMA statement until May 2022. Primary endpoints were technical details and surgical outcomes of adult patients (&gt;= 18 years old) that underwent laparoscopic PEH repair and crural reinforcement with absorbable mesh. The ROBINS-I tool was used to assess the methodological quality of included studies. Results: Thirty-nine studies (3,103 patients) were included. The age of the patient population ranged from 18 to 93 years old and 62.8% were females. Posterior cruroplasty was performed in all patients. U-shape (83.7%), circumferential (8.1%), keyhole (5.4%) and starburst (2.8%) mesh configuration were described. Different methods for mesh fixation (sutures vs. fibrin glue vs. absorbable tacks) were adopted while Nissen (75.1%) and Toupet (21.1%) fundoplication were mainly fashioned. The overall postoperative complication rate was 2.5%. Pulmonary and cardiac complication rates were 1.8% and 0.9%, respectively while in-hospital mortality was 0.2%. Postoperative follow-up ranged from 12 to 166 months. Mesh-related complication rate was 0.06% (esophageal stricture related to fibrosis). Hernia recurrence rate was 12.7% while re-do surgery was required in 1.9% of patients. Postoperative dysphagia rate was 5.1%. Discussion: Consensus concerning the optimal mesh material for crural buttressing is lacking. Given the potential for tissue ingrowth rather than encapsulation and reduced degree of perivisceral inflammation, absorbable meshes are mostly preferred over non-absorbable meshes. The use of absorbable mesh seems safe and effective with low overall and mesh-related complications, acceptable recurrence rate and low need for re-do surgery in the short/medium-term. Because heterogeneity related to different hernia characteristics, intraoperative technical variations (i.e., method for mesh fixation, etc.), definition of hernia recurrence and diverse follow-up, a conclusive evidence is still to be defined

A comparison of data mining approaches in the categorization of oral anticoagulation patients

Oral anticoagulation therapy, largely performed bywarfarin-based drugs, is commonly used for patientswith a high risk of blood clotting which can lead to stroke or thrombosis. The state of the patient, with respect to anticoagulation, is captured by the index INR, which is to be kept within a therapeutic range. The patients\u2019 response is marked by high interindividual and inter-temporal variability, which can lead to serious adverse events. Polymorphisms of two genes CYP2C9 and VKORC1, considered markers of lower dosage requirements, still account for a relatively minor part of this variability. In this work, authors show that classification methods can identify groups of patients homogeneous with respect to the dynamics of INR. In particular, authors use classification methods in order to characterize patients according to their warfarin metabolism and hence their sensitivity to different doses. Finally a Markov model to capture the dynamics of the patient\u2019sresponse over the years is propose

Remodelling of biological parameters during human ageing: evidence for complex regulation in longevity and in type 2 diabetes.

Factor structure analyses have revealed the presence of specific biological system markers in healthy humans and diseases. However, this type of approach in very old persons and in type 2 diabetes (T2DM) is lacking. A total sample of 2,137 Italians consisted of two groups: 1,604 healthy and 533 with T2DM. Age (years) was categorized as adults (≤65), old (66-85), oldest old (>85-98) and centenarians (≥99). Specific biomarkers of routine haematological and biochemical testing were tested across each age group. Exploratory factorial analysis (EFA) by principal component method with Varimax rotation was used to identify factors including related variables. Structural equation modelling (SEM) was applied to confirm factor solutions for each age group. EFA and SEM identified specific factor structures according to age in both groups. An age-associated reduction of factor structure was observed from adults to oldest old in the healthy group (explained variance 60.4% vs 50.3%) and from adults to old in the T2DM group (explained variance 57.4% vs 44.2%). Centenarians showed three-factor structure similar to those of adults (explained variance 58.4%). The inflammatory component became the major factor in old group and was the first one in T2DM. SEM analysis in healthy subjects suggested that the glucose levels had an important role in the oldest old. Factorial structure change during healthy ageing was associated with a decrease in complexity but showed an increase in variability and inflammation. Structural relationship changes observed in healthy subjects appeared earlier in diabetic patients and later in centenarians

Pitch as the Main Determiner of Italian Lexical Stress Perception Across the Lifespan : Evidence From Typical Development and Dyslexia

The study deals with the issue of lexical stress perception in both a developmental (comparing children and adults with typical development) and a clinical perspective (comparing typically developing children and children with dyslexia). The three parameters characterizing the acoustic profiles of words and non-words in a certain language are duration, pitch and intensity of its syllables. Based on (sparse) previous literature on Italian and other European languages, it was expected that syllable duration would be the parameter predominantly determining the perception of stress position. It was furthermore anticipated that children with dyslexia may be found to have an altered perception of lexical stress, due to their impairments in auditory processing of either pitch, duration or (more controversial) intensity. Systematic manipulation of the pitch, duration and intensity profiles of three Italian trisyllabic non-words produced a series of 81 stimuli, that were judged with respect to stress position (perceived on the ultimate, penultimate, or antepenultimate syllable) by the three groups of participants. The results showed, contrarily to expectations, that the pitch component is the most reliable acoustic cue in stress perception for both adults, in whom this dominance is very strong, and typically developing children, who showed a similar but quantitatively less marked pattern. As to children with dyslexia, they did not seem to rely on any parameter for their judgments, and rather gave random responses, which point to a general inability to process the various acoustic modulations that normally contribute to stress perception. Performance on the stress perception task strongly correlates with language (morphosyntactic) measures in the whole sample of children, and with reading abilities in the group with dyslexia, confirming the strict relationship between the two sets of skills. These findings seem to support a language-specific approach, suggesting that the set of acoustic parameters required for the development of stress perception is language-dependent rather than universal

Association between pain intensity and depressive symptoms in community-dwelling adults: longitudinal findings from the Survey of Health, Ageing and Retirement in Europe (SHARE)

Purpose: To investigate the longitudinal associations between pain and depressive symptoms in adults. Methods: Prospective cohort study on data from 28,515 community-dwelling adults ≥ 50 years, free from depression at baseline (Wave 5), with follow-up in Wave 6 of the Survey of Health, Ageing and Retirement in Europe (SHARE). Significant depressive symptoms were defined by a EURO-D score ≥ 4. The longitudinal association between baseline pain intensity and significant depressive symptoms at follow-up was analysed using logistic regression models; odds ratios (ORs) and confidence intervals (CI) were calculated, adjusting for socio-demographic and clinical factors, physical inactivity, loneliness, mobility and functional impairments. Results: Mean age was 65.4 years (standard deviation 9.0, range 50–99); 14,360 (50.4%) participants were women. Mean follow-up was 23.4 (standard deviation 3.4) months. At baseline, 2803 (9.8%) participants reported mild pain, 5253 (18.4%) moderate pain and 1431 (5.0%) severe pain. At follow-up, 3868 (13.6%) participants—1451 (10.3%) men and 2417 (16.8%) women—reported significant depressive symptoms. After adjustment, mild, moderate and severe baseline pain, versus no pain, were associated with an increased likelihood of significant depressive symptoms at follow-up: ORs (95% CI) were 1.20 (1.06–1.35), 1.32 (1.20–1.46) and 1.39 (1.19–1.63), respectively. These associations were more pronounced in men compared to women, and consistent in participants aged 50–64 years, those without mobility or functional impairment, and those without loneliness at baseline. Conclusion: Higher baseline pain intensity was longitudinally associated with a greater risk of significant depressive symptoms at 2-year follow-up, in community-dwelling adults without baseline depression