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Background: Growing evidence indicates an association between ambient air pollution and decreased human reproductive potential. This study aims to systematically review the association between air pollutants and female ovarian reserve., Methods: The literature was searched in six electronic databases through June 2024. Screening the 136 articles retrieved for inclusion criteria resulted in the selection of 15 human observational studies that evaluated the effect of environmental pollutants on ovarian reserve markers. The study protocol was registered on the International Prospective Register of Systematic Reviews (PROSPERO, registration code: CRD42023474218)., Results: The study design of the selected studies was found to be cross-sectional (2 of 15), retrospective cohort (10 of 15), prospective cohort (2 of 15), and case-control (1 of 15). The study population was distributed as follows: Asians (53%, eight studies), Americans (33%, five studies), and Europeans (14%, two studies). The main findings showed a higher body of evidence for the environmental pollutants PM2.5, PM10, and NO 2 , while a low body of evidence for PM1, O 3 , SO 2 , and a very low body of evidence for benzene, formaldehyde, and benzo(a)pyrene, yet consistently showing significant inverse association data. The overall methodological quality of the selected studies was rated moderated across the 14 domains of the National Institutes of Health (NIH) toolkit., Conclusion: The data suggest that increased exposure to air pollutants seems to be associated with reduced ovarian reserve, with the most substantial evidence for pollutants such as PM2.5, PM10, and NO 2 . However, more evidence is needed to draw conclusions about causality., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Zupo, Castellana, Nawrot, Lampignano, Bortone, Murgia, Campobasso, Gruszecka Kosowska, Giannico and Sardone.)

Polyphenols are secondary metabolites found in plants, foods, and drinks, occurring in small quantities and showcasing antioxidant and anti-inflammatory qualities. The primary polyphenols consist of flavonoids, phenolic acids, stilbenes, and lignans. However, there is currently no comprehensive quantitative analysis of epidemiological data on overall death rates. This systematic review with meta-analysis aims to identify the exposure-response relationship between dietary polyphenol intake and all-cause mortality. The literature was reviewed from its earliest study to May 2024, utilizing six distinct electronic databases. No specific criteria were used to choose participants based on the recruiting environment, their general health condition, country, or ethnicity. The inclusion criteria for studies were as follows: a longitudinal design, exposure to dietary polyphenols, all-cause mortality as the outcome, and hazard risk (HR) as the impact measure. The Newcastle-Ottawa Scale was used to evaluate the methodological rigor of the study. The hazard risks (HRs) and 95% confidence intervals (CIs) were estimated by pooling data using common effects models. A protocol has been registered on PROSPERO with the identification number CRD42024545524. The meta-analysis comprised seven cohort studies that involved 178,657 adult people aged 18 years and older. These studies examined the relationship between total dietary polyphenol consumption and the risk of all-cause death. The recruitment settings exclusively used community-based approaches, with a preference for Europe (71%) in terms of geographic distribution. The study's quality was assessed to be moderate to high. The meta-analysis showed consistent evidence that increased dietary exposure to polyphenols reduces the risk of all-cause mortality by 7% (HR 0.93, 95% CI 0.91-0.95, I 2 : 48%). Pooled data from the available evidence consistently show that individuals exposed to an antioxidant diet rich in polyphenol sources may be at lower risk of all-cause mortality.

The well-established anti-inflammatory and antioxidant properties of red fruits leave room for a biological pathway of improved muscle health promoted by berries in the diet. Our objective was to systematically review the number of trials conducted on human and animal species around the relationship between a berry diet and muscle health outcomes. Two independent examiners conducted a search for studies that utilized keywords associated with muscle health outcomes and a berry-based diet in both human and animal trials, in accordance with the PRISMA statement guidelines. The literature was searched through six electronic databases until December 2023. Screening of 152 retrieved articles resulted in a final selection of 16 reports investigating the effect of exposure to a berry-based diet and skeletal muscle health outcomes. The study protocol was registered on PROSPERO (CRD42023479682). Among the selected studies, nine involved humans and seven animal models (rats and mice). Overall, most of the studies reported positive effects on performance or muscle health. Specifically, five studies investigated the possible effects of blackcurrant on active human subjects or athletes; three studies focused on blueberry and presented results on running performance (human sample) and muscle health (rat models). The rest of the studies involved raspberries (two studies, rat models), aronia (one study, rat models), elderberry (one study, rat models), and a mixed compound (one study, rat models). In conclusion, there is some early evidence that a berry-rich diet may increase performance or muscle health, but more research is needed to fully understand the underlying biological trajectories, and thus, no firm conclusions can yet be drawn.

Background: The rising diffusion of vascular resections during complex pancreatectomy for malignancy, for both oncological and technical matters, brought with it the use of vascular shunts, either temporary or definitive, to prevent bowel congestion and liver ischemia. This study aimed to systematically review the literature on the technical feasibility of vascular shunts during advanced pancreatic surgery, analyzing intraoperative and postoperative outcomes., Methods: A systematic literature search was performed on PubMed, Scopus, Web of Science, and the Cochrane Library Central, according to PRISMA guidelines. Studies published before 2006 were excluded, considering the lack of a standardized definition of locally advanced pancreatic cancer. The main outcomes evaluated were the overall complication rate and shunt patency., Results: Among 789 papers retrieved from the database search, only five fulfilled the inclusion criteria and were included in the review, amounting to a total of 145 patients undergoing a shunt creation at the time of pancreatectomy. Pancreatic adenocarcinoma (PDAC) was found to be the most common diagnosis and pancreaticoduodenectomy was the main surgical procedure, accounting for 88% and 83% of the overall cohort, respectively. The distal splenorenal shunt was the most performed. Overall, 44 out of 145 patients (30%) experienced postoperative complications; the long-term patency of definitive shunts was 83% (110 out of 120 patients)., Conclusions: An increasing number of patients with borderline resectable or locally advanced PDAC are becoming amenable to resection and shunt creation may facilitate vascular resection with clear margins, becoming a valid tool of modern pancreatic surgery.

Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Introduction: In the last decade, the efforts conducted for discovering Alzheimer's Disease (AD) treatments targeting the best-known pathogenic factors [amyloid-β (Aβ), tau protein, and neuroinflammation] were mostly unsuccessful. Given that a systemic failure of Aβ clearance was supposed to primarily contribute to AD development and progression, disease-modifying therapies with anti-Aβ monoclonal antibodies (e.g. solanezumab, bapineuzumab, gantenerumab, aducanumab, lecanemab and donanemab) are ongoing in randomized clinical trials (RCTs) with contrasting results., Areas Covered: The present Drug Discovery Case History analyzes the failures of RCTs of solanezumab on AD. Furthermore, the authors review the pharmacokinetics, pharmacodynamics, and tolerability effect of solanezumab from preclinical studies with its analogous m266 in mice. Finally, they describe the RCTs with cognitive, cerebrospinal fluid and neuroimaging findings in mild-to-moderate AD (EXPEDITION studies) and in secondary prevention studies (A4 and DIAN-TU)., Expert Opinion: Solanezumab was one of the first anti-Aβ monoclonal antibodies to be tested in preclinical and clinical AD showing to reduce brain Aβ level by acting on soluble monomeric form of Aβ peptide without significant results on deposits. Unfortunately, this compound showed to accelerate cognitive decline in both asymptomatic and symptomatic trial participants, and this failure of solanezumab further questioned the Aβ cascade hypothesis of AD.

Objective: To review the evidence on the association between maternal exposure to ultra-processed food (UPF) categories, UPF diet items, and overall diet quality, as assessed by recognized dietary indices, and neurodevelopmental outcomes in offspring., Methods: PubMed, MEDLINE, EMBASE, Scopus, Ovid, and Scholar databases were searched for original articles on female gestational exposure to UPF categories, individual elements of the UPF diet, or indices of diet quality, in relation to outcomes regarding their offspring's neurocognitive development, according to neuropsychometric and behavioral scales, anthropometric/psychomotor indices, and symptoms/diagnosis of neurodevelopmental disorders (NDDs)., Results: Fourteen articles were selected and underwent the quantitative analysis. Six of these examined diet quality, and eight exposure to UPF categories or specific UPF foods. The maternal population was adult (18+). Child cognitive development was negatively impacted by a diet featuring many processed foods, saturated fats, and sugars. Conversely, a Med-diet led to better neurodevelopment, particularly verbal intelligence and executive functions, in middle childhood., Discussion: A maternal diet with many UPFs, saturated fats, and total sugars (especially those added or hidden in packaged carbonated beverages) can adversely affect a child's cognitive development. Knowledge needs to be further extended and managed from a prevention perspective in light of the well-known negative effects of UPFs on human health in all age groups.

The conceptual change of frailty, from a physical to a biopsychosocial phenotype, expanded the field of frailty, including social and behavioral domains with critical interaction between different frailty models. Environmental exposures - including physical exercise, psychosocial factors and diet - may play a role in the frailty pathophysiology. Complex underlying mechanisms involve the progressive interactions of genetics with epigenetics and of multimorbidity with environmental factors. Here we review the literature on possible mechanisms explaining the association between epigenetic hallmarks (i.e., global DNA methylation, DNA methylation age acceleration and microRNAs) and frailty, considered as biomarkers of aging. Frailty could be considered the result of environmental epigenetic factors on biological aging, caused by conflicting DNA methylation age and chronological age.

Sporadic Alzheimer's disease (AD) derives from an interplay among environmental factors and genetic variants, while epigenetic modifications have been expected to affect the onset and progression of its complex etiopathology. Carriers of one copy of the apolipoprotein E gene ( APOE ) ε4 allele have a 4-fold increased AD risk, while APOE ε4/ε4 -carriers have a 12-fold increased risk of developing AD in comparison with the APOE ε3 -carriers. The main longevity factor is the homozygous APOE ε3/ε3 genotype. In the present narrative review article, we summarized and described the role of APOE epigenetics in aging and AD pathophysiology. It is not fully understood how APOE variants may increase or decrease AD risk, but this gene may affect tau- and amyloid-mediated neurodegeneration directly or indirectly, also by affecting lipid metabolism and inflammation. For sporadic AD, epigenetic regulatory mechanisms may control and influence APOE expression in response to external insults. Diet, a major environmental factor, has been significantly associated with physical exercise, cognitive function, and the methylation level of several cytosine-phosphate-guanine (CpG) dinucleotide sites of APOE .

In 2011, the European Food Safety Authority (EFSA) accorded a health claim to olive oil polyphenols in that they protected LDL particles from oxidative damage. However, limited scientific evidence has so far failed to confer any claim of function on the maintenance of normal lipid metabolism. We performed a systematic review and meta-analysis of human RCTs, evaluating the effect of olive oil polyphenol administration on lipid profiles. Previous literature was acquired from six electronic databases until June 2023. A total of 75 articles were retrieved and screened for inclusion criteria, which resulted in the selection of 10 RCTs that evaluated the effect of daily exposure to olive oil polyphenols on serum lipids in adults. Meta-analyses were built by tertiles of outcomes, as follows: low (0-68 mg/kg), medium (68-320 mg/kg), and high (320-600 mg/kg) polyphenols for HDL and LDL cholesterol (HDL-C and LDL-C, respectively), and low (0-59.3 mg/kg), medium (59.3-268 mg/kg), and high (268-600 mg/kg) polyphenols for total cholesterol (TC). The study protocol was registered on PROSPERO (registration code: CRD42023403383). The study design was predominantly cross-over ( n = 8 of 10) but also included parallel ( n = 2 of 10). The study population was predominantly European and healthy. Daily consumption of olive oil polyphenols did not affect TC levels and only slightly significantly reduced LDL-C, with WMD statistically significant only for high daily consumption of olive oil polyphenols (WMD -4.28, 95%CI -5.78 to -2.77). Instead, our data found a statistically significant HDL-C enhancing effect (WMD pooled effect model: 1.13, 95%CI 0.45; 1.80, heterogeneity 38%, p = 0.04) with WMD by daily exposure level showing a statistically significant improvement effect for low (WMD 0.66, 95%CI 0.10-1.23), medium (WMD 1.36, 95%CI 0.76-1.95), and high (WMD 1.13, 95%CI 0.45-1.80) olive oil polyphenol consumptions. Olive oil polyphenols contribute toward maintaining lipid metabolism. Thus, food labeling regulations should stress this health feature of olive oil, whereby a declaration of the olive oil polyphenol content should be added to products on the market. Consumers need to be aware of the quality and possible health effects of any products they consume, and enforcement of nutrition labels offers the best way of providing this information.

Background: To date, no standardized protocols nor a quantitative assessment of the near-infrared fluorescence angiography with indocyanine green (NIR-ICG) are available. The aim of this study was to evaluate the timing of fluorescence as a reproducible parameter and its efficacy in predicting anastomotic leakage (AL) in colorectal surgery., Methods: A consecutive cohort of 108 patients undergoing minimally invasive elective procedures for colorectal cancer was prospectively enrolled. The difference between macro and microperfusion (ΔT) was obtained by calculating the timing of fluorescence at the level of iliac artery division and colonic wall, respectively., Results: Subjects with a ΔT ≥ 15.5± 0.5 s had a higher tendency to develop an AL ( p < 0.01). The ΔT/heart rate interaction was found to predict AL with an odds ratio of 1.02 ( p < 0.01); a cut-off threshold of 832 was identified (sensitivity 0.86, specificity 0.77). Perfusion parameters were also associated with a faster bowel motility resumption and a reduced length of hospital stay., Conclusions: The analysis of the timing of fluorescence provides a quantitative, easy evaluation of tissue perfusion. A ΔT/HR interaction ≥832 may be used as a real-time parameter to guide surgical decision making in colorectal surgery.

Background and Aims: Non-alcoholic hepatic steatosis affects 25% of adults worldwide and its prevalence increases with age. There is currently no definitive treatment for NAFLD but international guidelines recommend a lifestyle-based approach, including a healthy diet. The aim of this study was to investigate the interactions between eating habits and the risk of steatosis and/or hepatic fibrosis, using a machine learning approach, in a non-institutionalized elderly population., Methods and Results: We recruited 1929 subjects, mean age 74 years, from the population-based Salus in Apulia Study. Dietary habits and the risk of steatosis and hepatic fibrosis were evaluated with a validated food frequency questionnaire, the Fatty Liver Index (FLI) and the FIB-4 score, respectively. Two dietary patterns associated with the risk of steatosis and hepatic fibrosis have been identified. They are both similar to a "western" diet, defined by a greater consumption of refined foods, with a rich content of sugars and saturated fats, and alcoholic and non-alcoholic calorie drinks., Conclusion: This study further supports the concept of diet as a factor that significantly influences the development of the most widespread liver diseases. However, longitudinal studies are needed to better understand the causal effect of the consumption of particular foods on fat accumulation in the liver., Competing Interests: Conflicts of Interest The authors have no conflicts of interest to declare., (Copyright © 2023 The Italian Diabetes Society, the Italian Society for the Study of Atherosclerosis, the Italian Society of Human Nutrition and the Department of Clinical Medicine and Surgery, Federico II University. Published by Elsevier B.V. All rights reserved.)

Background: Med-Index is a one-health front-of-pack (FOP) label, based on Mediterranean diet (MedDiet) principles, developed to summarize information about the nutritional properties and related-health benefits of any food as well as its sustainable production processes, and the associated food company's social responsibility parameters in a new "Planeterranean" perspective. Thus, Med-Index can be adopted in and by any European region and authority as well as worldwide; this is achieved by consumption and cooking of locally available and sourced foods that respect MedDiet principles, both in terms of healthy nutrition and sustainable production. The huge body of scientific evidence about the health benefits of the MedDiet model and principles requires a comprehensive framework to encompass the scientific reliability and robustness of this tool. A systematic review was carried out to examine the association between human health and adherence to MedDiet patterns upon which the "Med-Index" tool was subsequently developed., Methods: MEDLINE and PubMed databases were searched for eligible publications from 1990 to April 2023. Systematic literature reviews, with or without meta-analysis, of clinical trials and observational studies were screened by two independent investigators for eligibility, data extraction, and quality assessment. English language and the time interval 1990-2023 were applied. A registry code CRD42023464807 was generated on PROSPERO and approved for this search protocol. The corrected covered area (CCA), calculated to quantify the degree of overlap between reviews, gave a slight overlap (CCA = 4%)., Results: A total of 84 systematic reviews out of 6681 screened records were selected. Eligible reviews included studies with predominantly observational designs (61/84, 72.6%%), of which 26/61 referenced studies of mixed observational and RCT designs, while 23/84 (27.4%) were RCT-only systematic reviews. Seventy-nine different entries were identified for health outcomes, clustered into 10 macro-categories, each reporting a statistically significant association with exposure to the MedDiet. Adherence to MedDiet was found to strongly benefit age-related chronic diseases (21.5%), neurological disorders (19%), and obesity-related metabolic features (12.65), followed by CVDs (11.4%), cancer (10.1%), diabetes (7.5%), liver health (6.3%), inflammation (5%), mortality (5%), and renal health (1.2%). The quality of the studies was moderate to high., Conclusion: In the context of a "Planeterranean" framework and perspective that can be adopted in any European region and worldwide, MedDiet represents a healthy and sustainable lifestyle model, able to prevent several diseases and reduce premature mortality. In addition, the availability of a FOP, such as Med-Index, might foster more conscious food choices among consumers, paying attention both to human and planetary health., (© 2023. The Author(s).)

The literature shows how sarcopenia often occurs along with different phenotypes based either on the concomitant presence of adipose tissue excess (i.e., sarcopenic obesity, SO), or osteopenia/osteoporosis (osteosarcopenia, OS), or the combination of the two conditions, so-called osteosarcopenic obesity (OSO). This research aimed to assess the prevalence of sarcopenia phenotypes (SO, OS, OSO), their associated risk factors and their health impact in a population of out- and inpatients living in the North of Italy. Male and female subjects aged ≥18 years were enrolled for the study. A blood sample was collected to measure targeted blood makers. A comprehensive anthropometric clinical assessment (height, weight, Body Mass Index, BMI and Dual Energy X-ray Absorptiometry, DXA) was performed to measure ponderal, bone, fat, and muscle status. A total of 1510 individuals participated to the study (females, n = 1100; 72.85%). Sarcopenia was the most prevalent phenotype (17%), followed by osteosarcopenia (14.7%) and sarcopenic obesity. Only 1.9% of the sample was affected by OSO. According to logistic regression analysis, sarcopenia was associated with age, erythrocyte sedimentation rate (ESR), C-reactive protein (CRP) (positively) and BMI, Iron (Fe), Total Cholesterol, albumin (%), albumin (g), and gamma proteins (negatively). Sarcopenic obesity was associated with age, ferritin, ESR, CRP (positively) and BMI, Fe, and albumin (%) (negatively). Osteosarcopenia was associated with age, ESR (positively) and BMI, Total Cholesterol, albumin (%), albumin (g), and Ca (negatively). Osteosarcopenic obesity was associated with glycemia and gamma-glutamyl transferase (gGT) (positively). According to random forest analysis, a higher BMI was the most important protective factor for sarcopenia, for sarcopenic obesity (along with Iron) and for osteosarcopenia (along with albumin). Moreover, osteosarcopenic obesity was positively associated with GgT and glycaemia. The possibility of gaining such information, especially in the younger population, could help to prevent the onset of such diseases and best fit the patient's needs, according to a precision-medicine approach.

Background: The assessment of oral health-related quality of life (OHRQoL) evaluated the impact of an individual's oral health on the patient's physical and psychosocial status. We evaluated the association between subjective OHRQoL, measured with the Oral Health Impact Profile-14 (OHIP-14) questionnaire, and unfavorable body mass index (BMI) (i.e., too high or too low) in a large population-based study on older adults from Southern Italy. Moreover, we assessed which of the seven OHIP-14 domains was the most strongly associated with an unfavorable BMI., Methods: We used data on a subpopulation of the Salus in Apulia Study, including 216 older adults. BMI < 18.4 kg/m 2 and >30 kg/m 2 were classified as unfavorable, while values between 18.5 and 30 kg/m 2 were classified as ideal., Results: A higher OHIP-14 total score increased the risk of an unfavorable BMI (odds ratio (OR): 1.08, 95% confidence interval (CI): 1.01-1.15). In the model adjusted for age, sex, education, hypertension, carbohydrate consumption, and alcohol consumption, this finding was confirmed with a higher OHIP-14 total score increasing the risk of an unfavorable BMI (OR: 1.10, 95% CI: 1.01-1.22), and higher age linked to a decreased risk of an unfavorable BMI (OR: 0.89, 95% CI: 0.82-0.97). In a random forest regression model, the most important predictive domains/sub-scales of OHIP-14 in the mean decrease in the Gini coefficient for unfavorable BMI were, in order of decreasing importance, physical pain, functional limitation, psychological discomfort, physical disability, social disability, psychological disability, and handicap., Conclusions: In older age, negative OHRQoL, particularly linked to the physical pain domain, increased the risk of being underweight or overweight and obesity.

Frailty is a multidisciplinary public health issue and nutrition is key concern. Given the scientific consistency about inflammation as shared pathway to poor nutrition and frailty, food processing seems a suitable target to gain evidence in frailty prevention nutrition settings. This study aimed to assess diet in relation to nutritional frailty using the NOVA classification. Browsing the dataset of the Salus in Apulia, 2185 older adults were found to have completed the nutritional assessment, providing eligible data for this study goal. A validated construct, based on the co-presence of physical frailty by CHS criteria plus nutritional imbalance, was applied to characterize nutritional frailty phenotypes. Using the NOVA classification, daily food and beverage intakes from an 85-item self-administered FFQ were assigned to three categories, and effect sizes were tested among groups according to nutritional frailty status (presence/absence). Raw and adjusted logistic regression models were run to assess associations between NOVA food categories by quintiles of daily exposure (very-low, low, mild, moderate, high) and nutritional frailty. Nutritional frailty prevalence was 27%, being more frequent in males. Eating more unprocessed or minimally processed foods was inversely related to nutritional frailty, even after adjustment (OR: 0.10, 95%CI 0.07-0.16), showing a downward ORs behavior toward lower consumption quintiles. Listing in the quintile of moderate consumption of processed foods meant a nearly 50% increase in nutritional frailty probability (OR: 1.46, 95%CI 1.03-2.06), while the probability was double for the highest quintile against the lowest (OR: 3.22, 95%CI 2.27-4.58). A growing probability of nutritional frailty was found for increasing consumption of ultra-processed foods, but significance was lacking. The contribution of food processing to poor nutrition needs to be considered when promoting a better understanding of effective nutritional screening in aging. Therefore, food processing should be accounted for when composing diet guidelines for the older population within the framework of multidisciplinary efforts to ease the frailty healthcare burden., (© 2023. The Author(s).)

Introduction: Chronic liver disease is often combined with a morbidity burden that strongly affects the functional domain. In liver cirrhosis (LC), qualitative and quantitative muscle wasting, known as sarcopenia, poses an added clinical burden, together with comorbidities and a poor quality of life., Methods: We conducted a systematic review and meta-analysis of the prevalence of sarcopenia in LC. The literature was screened through 6 electronic databases from the study's inception to January 2023. No exclusion criteria were applied to language, operative tools for diagnosing sarcopenia, population age, general health status, country, and study setting (cohort or cross-sectional). Two independent researchers applied the inclusion criteria in parallel to evaluate the eligibility of the 44 retrieved articles; only 36 met the eligibility requirements., Results: The total sample (N = 8,821) was slightly dominated by men (N = 4,941). The cross-sectional design predominated over the longitudinal, and the hospital setting was prevalent. The pooled prevalence of sarcopenia across the selected studies was 33% (95% confidence interval [CI] 0.32-0.34), with high heterogeneity ( I2 = 96%). A further meta-analysis using the Child-Pugh (CP) score to stage LC was conducted on 24 entries, and the results showed that for the LC populations classified with the CP-A, CP-B, and CP-C staging, respectively, the overall mean prevalence was 33% (95% CI 0.31-0.35), 36% (95% CI 0.34-0.39) and 46% (95% CI 0.43-0.50). The risk of bias was moderate. In LC, 1 in 3 patients suffers sarcopenia., Discussion: Poor management of muscle mass loss plays a role in the prognosis of death and quality of life of patients with LC. Clinicians in the field are recommended, when screening for sarcopenia, to pay close attention by carefully assessing body composition as part of the monitoring scheme., (Copyright © 2023 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of The American College of Gastroenterology.)

Introduction: Tauopathies are clinicopathological entities with increased and pathological deposition in glia and/or neurons of hyperphosphorylated aggregates of the microtubule-binding protein tau. In secondary tauopathies, i.e. Alzheimer's disease (AD), tau deposition can be observed, but tau coexists with another protein (amyloid-β). In the last 20 years, little progress has been made in developing disease-modifying drugs for primary and secondary tauopathies and available symptomatic drugs have limited efficacy., Areas Covered: The present review summarized recent advances about the development and challenges in treatments for primary and secondary tauopathies, with a focus on passive tau-based immunotherapy., Expert Opinion: Several tau-targeted passive immunotherapeutics are in development for treating tauopathies. At present, 14 anti-tau antibodies have entered clinical trials, and 9 of them are still in clinical testing for progressive supranuclear palsy syndrome and AD (semorinemab, bepranemab, E2814, JNJ-63733657, Lu AF87908, APNmAb005, MK-2214, PNT00, and PRX005). However, none of these nine agents have reached Phase III. The most advanced anti-tau monoclonal antibody for treating AD is semorinemab, while bepranemab is the only anti-tau monoclonal antibody still in clinical testing for treating progressive supranuclear palsy syndrome. Further evidence on passive immunotherapeutics for treating primary and secondary tauopathies will come from ongoing Phase I/II trials.

Objectives: Individuals with late-life depression (LLD) may have shorter survival, but there is a lack of findings in population-based settings about health-related outcomes of LLD and its subtypes: early-onset depression (EOD) and late-onset depression (LOD). We aimed to evaluate the risk of all-cause mortality of individuals with LLD and its subtypes in an older population-based cohort. Moreover, we investigated whether inflammatory, cognitive, genetic features and multimorbidity could modify the effect of this association., Design: Longitudinal population-based study with 8-year follow-up., Setting and Participants: We analyzed data on a sample of 1479 participants, all aged >65 years, in the Salus in Apulia Study., Methods: LLD was diagnosed through DSM-IV-TR criteria and LOD and EOD according to the age of onset. Multimorbidity status was defined as the copresence of 2 or more chronic diseases., Results: The overall prevalence of LLD in this older sample from Southern Italy was 10.2%, subdivided into 3.4% EOD and 6.8% LOD. In multivariable Cox models adjusted for age, gender, education, global cognition, apolipoprotein E ε4 allele, physical frailty, interleukin-6, and multimorbidity, LLD showed a greater risk of all-cause mortality. LOD differed from EOD regarding gender, education, cognitive dysfunctions, and diabetes mellitus. There was a significantly increased risk of all-cause mortality for participants with LOD (hazard ratio:1.99; 95% CI 1.33-2.97) in the time of observation between enrollment date and death date (7.31 ± 2.17 months)., Conclusions and Implication: In older age, individuals with LOD but not with EOD had a significantly decreased survival, probably related to increased inflammation, multimorbidity, and cognitive impairments., (Copyright © 2022 AMDA – The Society for Post-Acute and Long-Term Care Medicine. Published by Elsevier Inc. All rights reserved.)

Introduction: Tauopathies represent clinicopathological entities with increased and abnormal glial and/or neuronal inclusions of tau, a microtubule-binding protein. Antisense oligonucleotides (ASOs) are a promising therapeutic approach for treating tauopathies as they can target tau mRNA to reduce total human tau expression or tau exon 10 expression and 4 R tau. Additionally, targeting the tau specifically with peptides may be a unique pharmacological approach, between small molecules and proteins., Areas Covered: The present review investigates the chemical basis of designing ASOs and peptides currently known to treat tauopathies. Among ASOs targeting tau expression, BIIB080 was the first to enter clinical trial development for treating mild Alzheimer's disease (AD). Furthermore, the therapeutic potential of peptide 021 (P021, Ac-DGGLAG-NH2) in tauopathies is discussed based on preclinical studies., Expert Opinion: ASOs are a promising therapeutic approach for tauopathies, particularly because ASOs may suppress the expression of harmful genes and are directly delivered to the brain, showing little systemic side effects. However, whether a generalized brain tau decrease will produce positive clinical effects remains unclear. A Phase II trial of BIIB080 is ongoing in mild AD. Neurotrophic and neurogenic peptide mimetic compounds have also shown potential as treatment options for AD and other tauopathies.

Epidemiological and public health resonance of sarcopenia in late life requires further research to identify better clinical markers useful for seeking proper care strategies in preventive medicine settings. Using a machine-learning approach, a search for clinical and fluid markers most associated with sarcopenia was carried out across older populations from northern and southern Italy. A dataset of adults >65 years of age ( n = 1971) made up of clinical records and fluid markers from either a clinical-based subset from northern Italy (Pavia) and a population-based subset from southern Italy (Apulia) was employed ( n = 1312 and n = 659, respectively). Body composition data obtained by dual-energy X-ray absorptiometry (DXA) were used for the diagnosis of sarcopenia, given by the presence of either low muscle mass (i.e., an SMI < 7.0 kg/m 2 for males or <5.5 kg/m 2 for females) and of low muscle strength (i.e., an HGS < 27 kg for males or <16 kg for females) or low physical performance (i.e., an SPPB ≤ 8), according to the EWGSOP2 panel guidelines. A machine-learning feature-selection approach, the random forest (RF), was used to identify the most predictive features of sarcopenia in the whole dataset, considering every possible interaction among variables and taking into account nonlinear relationships that classical models could not evaluate. Then, a logistic regression was performed for comparative purposes. Leading variables of association to sarcopenia overlapped in the two population subsets and included SMI, HGS, FFM of legs and arms, and sex. Using parametric and nonparametric whole-sample analysis to investigate the clinical variables and biological markers most associated with sarcopenia, we found that albumin, CRP, folate, and age ranked high according to RF selection, while sex, folate, and vitamin D were the most relevant according to logistics. Albumin, CRP, vitamin D, and serum folate should not be neglected in screening for sarcopenia in the aging population. Better preventive medicine settings in geriatrics are urgently needed to lessen the impact of sarcopenia on the general health, quality of life, and medical care delivery of the aging population.

Purpose: Growing awareness of the biological and clinical value of nutrition in frailty settings calls for further efforts to investigate dietary gaps to act sooner to achieve focused management of aging populations. We cross-sectionally examined the eating habits of an older Mediterranean population to profile dietary features most associated with physical frailty., Methods: Clinical and physical examination, routine biomarkers, medical history, and anthropometry were analyzed in 1502 older adults (65 +). CHS criteria were applied to classify physical frailty, and a validated Food Frequency Questionnaire to assess diet. The population was subdivided by physical frailty status (frail or non-frail). Raw and adjusted logistic regression models were applied to three clusters of dietary variables (food groups, macronutrients, and micronutrients), previously selected by a LASSO approach to better predict diet-related frailty determinants., Results: A lower consumption of wine (OR 0.998, 95% CI 0.997-0.999) and coffee (OR 0.994, 95% CI 0.989-0.999), as well as a cluster of macro and micronutrients led by PUFAs (OR 0.939, 95% CI 0.896-0.991), zinc (OR 0.977, 95% CI 0.952-0.998), and coumarins (OR 0.631, 95% CI 0.431-0.971), was predictive of non-frailty, but higher legumes intake (OR 1.005, 95%CI 1.000-1.009) of physical frailty, regardless of age, gender, and education level., Conclusions: Higher consumption of coffee and wine, as well as PUFAs, zinc, and coumarins, as opposed to legumes, may work well in protecting against a physical frailty profile of aging in a Mediterranean setting. Longitudinal investigations are needed to better understand the causal potential of diet as a modifiable contributor to frailty during aging., (© 2022. The Author(s).)

Background: Like other parts of the body, the retina and its neurovascular system are also affected by age-related changes. The rising age of populations worldwide makes it important to study the pathologies related to age and their potential risk factors, such as diet and eating habits. The aim of this study was to investigate the predictive power of food groups versus retinal features among noninstitutionalized older adults from Southern Italy using a machine learning approach., Methods: We recruited 530 subjects, with a mean age of 74 years, who were drawn from the large population of the Salus in Apulia Study. In the present cross-sectional study, eating habits were assessed with a validated food frequency questionnaire. For the visual assessment, a complete ophthalmic examination and optical coherence tomography-angiography analyses were performed., Results: The analyses identified 13 out of the 28 food groups as predictors of all our retinal variables: grains, legumes, olives-vegetable oil, fruiting vegetables, other vegetables, fruits, sweets, fish, dairy, low-fat dairy, red meat, white meat, and processed meat., Conclusions: Eating habits and food consumption may be important risk factors for age-related retinal changes. A diet that provides the optimal intake of specific nutrients with antioxidant and anti-inflammatory powers, including carotenoids and omega-3 fatty acids, could have beneficial effects.

Growing evidence suggests that inflammation contributes to brain aging and neurodegeneration. This study investigates the relationship between global cognitive as well executive function and the inflammatory markers IL-6, CRP, and TNF-α in a population-based study of older adults. A population-based sample, of older people in Southern Italy, was enrolled. We measured serum levels of IL-6, CRP, and TNF-α. We also administered two neuropsychological tests: Mini-Mental State Examination and Frontal Assessment Battery. Rank-based regression models were performed to investigate the relationship between inflammatory markers and cognitive functions, including major demographic and clinical confounders for adjustment. The sample consisted of 1929 subjects aged between 65 and 95 years. Multivariate linear regression analysis revealed that higher serum levels of IL-6 were associated with lower MMSE and FAB scores even after adjustment for demographic data and cardiovascular risk factors. No significant associations were found between cognitive functioning and serum levels of CRP and TNF-α. Our results suggest that higher levels of IL-6 were associated with cognitive impairment in an older adult population of Southern Italy., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2023 The Authors.)

The thyroid gland requires iodine to synthesize thyroid hormones, and iodine deficiency results in the inadequate production of thyroxine and related thyroid, metabolic, developmental, and reproductive disorders. Iodine requirements are higher in infants, children, and during pregnancy and lactation than in adult men and non-pregnant women. Iodine is available in a wide range of foods and water and is susceptible to almost complete gastric and duodenal absorption as an iodide ion. A healthy diet usually provides a daily iodine consumption not exceeding 50% of the recommended intake. Iodine supplementation is usually necessary to prevent iodine deficiency disorders (IDDs), especially in endemic areas. The community-based strategy of iodine fortification in salt has eradicated IDDs, such as endemic goiter and cretinism, in countries providing adequate measures of iodine prophylaxis over several decades in the 20th century. Iodized salt is the cornerstone of iodine prophylaxis in endemic areas, and the continuous monitoring of community iodine intake and its related clinical outcomes is essential. Despite the relevant improvement in clinical outcomes, subclinical iodine deficiency persists even in Western Europe, especially among girls and women, being an issue in certain physiological conditions, such as pregnancy and lactation, and in people consuming unbalanced vegetable-based or salt-restricted diets. Detailed strategies to implement iodine intake (supplementation) could be considered for specific population groups when iodized salt alone is insufficient to provide adequate requirements.

Very low-calorie ketogenic diets (VLCKD) are widely employed in successful weight-loss strategies. Herein, we evaluated the efficacy and safety of a VLCKD on non-alcoholic fatty liver disease (NAFLD) and parameters commonly associated with this condition in overweight and obese subjects who did not take any drugs. This prospective, real-life study included thirty-three participants who followed a VLCKD for 8 weeks. NAFLD was diagnosed using transient elastography (FibroScan). Data on anthropometric measurements, bioimpedance analysis, and biochemical assays were gathered both before and after the dietary intervention. BMI (kg/m 2 ) (from 33.84 ± 6.55 to 30.89 ± 6.38, p < 0.01), waist circumference (cm) (from 106.67 ± 15.51 to 98.64 ± 16.21, p < 0.01), and fat mass (Kg) (from 38.47 ± 12.59 to 30.98 ± 12.39, p < 0.01) were significantly lower after VLCKD. CAP (db/m), the FibroScan parameter quantifying fatty liver accumulation, showed a significant reduction after VLCKD (from 266.61 ± 67.96 to 223 ± 64.19, p < 0.01). After VLCKD, the fatty liver index (FLI), a benchmark of steatosis, also revealed a significant decline (from 62.82 ± 27.46 to 44.09 ± 31.24, p < 0.01). Moreover, fasting blood glucose, insulin, triglycerides, total cholesterol, LDL-cholesterol, ALT, γGT, and FT3 blood concentrations, as well as insulin resistance (quantified by HOMAIR) and systolic and diastolic blood pressure levels, were significantly lower after VLCKD ( p < 0.01 for all the parameters). By contrast, HDL-cholesterol, 25 (OH) vitamin D, and FT4 blood concentrations were higher after VLCKD ( p < 0.01 for all parameters). The variation (δ) of CAP after VLCKD did not show a correlation with the δ of any other parameter investigated in this study. We conclude that VLCKD is a helpful approach for NAFLD independent of changes in factors commonly associated with NAFLD (obesity, fat mass, insulin resistance, lipids, and blood pressure) as well as vitamin D and thyroid hormone levels.

Background: Due to the COVID-19 pandemic, current epidemiological conditions may exacerbate the risk of new-onset, recurrence and relapse of eating disorders. This perspective aims to better analyse the phenomenon., Results: Some data suggest that new-onset and recurrence/relapse of eating disorders are increasing due to the pandemic. Government restrictions, self-confinement, social isolation, restriction to healthcare facilities access, delayed access to diagnosis and cure, fear of contagion, distress and difficulties related to the telemedicine approach contribute to this burden. The Immune system dysfunction usually observed in undernourishment (e.g., anorexia nervosa) could delay the diagnosis of respiratory infections, including COVID-19, and predispose to possible bacterial superinfections. Conversely, patients with binge eating, obesity or metabolic syndrome are susceptible to high-grade systemic inflammation and poor prognosis once the infection has occurred., Discussion: More detailed data combining research on eating disorders and COVID-19 are required despite some evidence. Many data show that telemedicine has beneficial aspects, but its impact on long-term mental health is still poorly understood. Short- and long-term consequences of COVID-19 in patients with eating disorders are unknown, but they will likely become more apparent over time., Conclusion: Working on emotion regulating strategies in a post-pandemic world, when people have inadequate control over the background of negative emotions, could be a future treatment strategy. Long-term studies with a larger sample size are essential to assess the long-term consequences of the blockade on patients and their healthcare providers and identify useful strategies to improve clinical management., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

In older age, frailty is a detrimental transitional status of the aging process featuring an increased susceptibility to stressors defined by a clinical reduction of homoeostatic reserves. Multidimensional frailty phenotypes have been associated with all-cause dementia, mild cognitive impairment (MCI), Alzheimer's disease (AD), AD neuropathology, vascular dementia, and non-AD dementias. In the present article, we reviewed current evidence on the existing links among depressive and biopsychosocial frailty phenotypes and late-life cognitive disorders, also examining common pathways and mechanisms underlying these links. The depressive frailty phenotype suggested by the construct of late-life depression (LLD) plus physical frailty is poorly operationalized. The biopsychosocial frailty phenotype, with its coexistent biological/physical and psychosocial dimensions, defines a biological aging status and includes motivational, emotional, and socioeconomic domains. Shared biological pathways/substrates among depressive and biopsychosocial frailty phenotypes and late-life cognitive disorders are hypothesized to be inflammatory and cardiometabolic processes, together with multimorbidity, loneliness, mitochondrial dysfunction, dopaminergic neurotransmission, specific personality traits, lack of subjective/objective social support, and neuroendocrine dysregulation. The cognitive frailty phenotype, combining frailty and cognitive impairment, may be a risk factor for LLD and vice versa, and a construct of depressive frailty linking physical frailty and LLD may be a good dementia predictor. Frailty assessment may enable clinicians to better target the pharmacological and psychological treatment of LLD. Given the epidemiological links of biopsychosocial frailty with dementia and MCI, multidomain interventions might contribute to delay the onset of late-life cognitive disorders and other adverse health-related outcomes, such as institutionalization, more frequent hospitalization, disability, and mortality.

Background: Epidemiological studies have shown that food is a compelling means of maintaining a state of well-being and preventing diseases. Many malignant diseases are related to nutrition, and the nutrient-organism interaction could define the balance between health and disease. Nutrients and dietary components influence epigenetic phenomena and modify drug response so that food-organism interactions may influence individual predisposition to disease and its potential therapeutic response., Aims: In this review, we highlighted emerging opinions and data on a large cluster of nutraceuticals, as well as functional foods and specific dietary patterns, with respect to cancer, including breast, pancreas, prostate, and colorectal. Only those nutraceuticals and nutritional supplements yielding sufficient and convincing data have been reported in this review; molecules with inconclusive clinical evidence will not be discussed., Conclusion: Growing and accumulating evidence is validating the use of nutraceuticals in cancer settings. However, a knowledge gap remains in terms of causal evidence for several compounds where a window for further clinical studies is left., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Background: Age is a leading contributor to the liver fibrosis rate and a gradual deterioration of optical function, but this association in older populations is still under-explored. The present study aimed to explore the link between vascular and neural retinal characteristics and the risk of liver fibrosis in 731 older adults from the population-based Salus in Apulia study., Methods: Retinal features were obtained using optical coherence tomography (OCT) and OCT-angiography (OCT-A). Liver fibrosis risk was taken as the fibrosis-4 (FIB-4) score. Generalized linear models (logistic regression) were used to estimate the association effect between each unit increase of OCT and OCT-A parameters as independent variables and a FIB-4 ≥ 2.67 score as an outcome. Generalized additive models were used to assess the non-linear association between OCT-A features and the linear FIB-4 score., Results: Increased gangliar cell complex (GCC) thickness was inversely associated with a FIB-4 score above the cut-off in both the raw model (OR: 0.98; 95% CI: 0.96-0.99; SE: 0.01) and after adjustment for age, sex, education, hypertension, diabetes, total cholesterol, and triglycerides (OR: 0.98; 95% CI: 0.97-0.99; SE: 0.01)., Conclusion: Our findings add to the growing volume of scientific literature demonstrating that liver fibrosis is associated with retinal neurodegeneration. This study raises a number of new questions, including whether OCT-A may be used to track the progression of metabolic abnormalities and define exact thresholds for predicting and classifying liver disease., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Lampignano, Niro, Castellana, Bortone, Zupo, Tirelli, Tatoli, Griseta, De Nucci, Sila, De Pergola, Conte, Alessio, Boscia, Sborgia, Eye Clinic Research Group, Giannelli and Sardone.)

Background: Possible relationships between suicidal ideation and biopsychosocial predictors in older age are unclear. In the population-based Salus in Apulia Study, we investigated the relationships among biomarkers, socio-demographic, psychopathological, inflammatory and metabolic characteristics and suicidal ideation in 1252 older subjects., Methods: Suicidal ideation was evaluated with the brief version of the Columbia-Suicide Severity Rating Scale. Apolipoprotein E (APOE) genotype and inflammatory profile [interleukin (IL)-6, tumor necrosis factor (TNF)-α, C-reactive protein (CRP)] were evaluated. A machine learning algorithm, the Random Forest (RF), selected potential biopsychosocial factors associated to suicidal ideation., Results: Suicidal ideators accounted for 2.32 % of subjects, were female, smokers, and obese with multimorbidity. After adjusting for age, gender, education and social dysfunction, logistic regression analyses revealed that suicidal ideation was associated to late-life depression (LLD) (odds ratio:21.71,95 % confidence interval:9.22-51.14). In the full RF model, asthma was the most important contributor to suicidal ideation. In the final RF model, education, age, and mild cognitive impairment followed by gender and global cognition were considered the most important contributors. Among biomarkers, in the final RF model, IL-6 followed by TNF-α, APOE ε4 allele presence, CRP and high-density lipoprotein cholesterol contributed most to suicidal ideation., Limitations: A relatively small number of older subjects with suicidal ideation (2.3 %); we did not distinguish between active and passive suicidal ideation., Conclusions: Although LLD is a strong determinant of suicidal ideation, other non-psychiatric factors, i.e., serum inflammation biomarkers, APOE ε4 allele, and multimorbidity, should be taken into account when evaluating a suicidal ideation phenotype in older age., Competing Interests: Conflict of Interest The authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article., (Copyright © 2022 Elsevier B.V. All rights reserved.)