Intrathymic AAV delivery results in therapeutic site-specific integration at TCR loci in mice.

Adeno-associated virus (AAV) vectors have been successfully exploited in gene therapy applications for the treatment of several genetic disorders. AAV is considered an episomal vector, but it has been shown to integrate within the host cell genome after the generation of double-strand DNA breaks or nicks. Although AAV integration raises some safety concerns, it can also provide therapeutic benefit; the direct intrathymic injection of an AAV harboring a therapeutic transgene results in integration in T-cell progenitors and long-term T-cell immunity. To assess the mechanisms of AAV integration, we retrieved and analyzed hundreds of AAV integration sites from lymph node-derived mature T cells and compared these with liver and brain tissue from treated mice. Notably, we found that although AAV integrations in the liver and brain were distributed across the entire mouse genome, >90% of the integrations in T cells were clustered within the T-cell receptor α, ß, and γ genes. More precisely, the insertion mapped to DNA breaks created by the enzymatic activity of recombination activating genes (RAGs) during variable, diversity, and joining recombination. Our data indicate that RAG activity during T-cell receptor maturation induces a site-specific integration of AAV genomes and opens new therapeutic avenues for achieving long-term AAV-mediated gene transfer in dividing cells.

Breakfast quality and its sociodemographic and psychosocial correlates among Italian children, adolescents, and adults from the Italian Nutrition & HEalth Survey (INHES) study.

BACKGROUND: Breakfast quality, together with regularity of breakfast, has been suggested to be associated with cardiometabolic health advantages. We aimed to evaluate the quality of breakfast and its socioeconomic and psychosocial correlates in a large sample of the Italian population. METHODS: Cross-sectional analyses on 7,673 adult and 505 children/adolescent regular breakfast eaters from the Italian Nutrition & Health Survey (INHES; 2010-2013). Dietary data were collected through a single 24-h dietary recall. Breakfast quality was assessed through the Breakfast Quality Index (BQI) combining intake of ten food groups, energy, and nutrients of public health concern, and potentially ranging from 0 to 10. The association of sociodemographic and psychosocial factors with BQI were analyzed by multivariable-adjusted linear regression models. RESULTS: The average BQI was 4.65 (SD ± 1.13) and 4.97 (SD ± 1.00) in adults and children/adolescents, respectively. Amongst adults, older age (ß = 0.19; 95%CI 0.06 to 0.31 for > 65 vs. 20-40 years) and having a high educational level (ß = 0.13; 0.03 to 0.23; for postsecondary vs. up to elementary) were independent predictors of better breakfast quality, while men reported lower BQI (ß = -0.08; -0.14 to -0.02 vs. women). Perceived stress levels at home and work and financial stress were inversely associated with BQI. Children/adolescents living in Central and Southern Italian regions had lower BQI compared to residents in Northern Italy (ß = -0.55; -0.91 to -0.19 and ß = -0.24; -0.47 to -0.01, respectively). CONCLUSIONS: In adults, breakfast quality was associated with age, sex, and educational level. Perceived stress levels were inversely associated with the quality of breakfast. In children/adolescents, a north-south gradient in breakfast quality was observed.

Psychological distress resulting from the COVID-19 confinement is associated with unhealthy dietary changes in two Italian population-based cohorts.

PURPOSE: To examine the relationship between psychological distress resulting from the COVID-19 lockdown and dietary changes. METHODS: Cross-sectional analysis from 2 retrospective Italian cohorts recruited from May to September 2020: (1) The Moli-LOCK cohort consists of 1401 participants from the Moli-sani Study (n = 24,325) who were administered a telephone-based questionnaire to assess lifestyles and psychological factors during confinement; (2) the ALT RISCOVID-19 is a web-based survey of 1340 individuals distributed throughout Italy who self-responded to the same questionnaire using Google® forms. Psychological distress was measured by assessments of depression (PHQ-9 and depressive items from the Screening Questionnaire for Disaster Mental Health- SQD-D), anxiety (GAD-7), stress (PSS-4), and post-traumatic stress disorder (SQD-P). Diet quality was assessed either as changes in consumption of ultra-processed foods (UPF) or adherence to Mediterranean diet (MD). RESULTS: In ALT RISCOVID-19, increased UPF intake was directly associated with depression (both PHQ-9 and SQD-D; p < 0.0001), anxiety (p < 0.0001), stress (p = 0.001) and SQD-P (p = 0.001); similar results were obtained in the Moli-LOCK cohort except for perceived stress. When psychometric scales were analysed simultaneously, only depression (SQD-D) remained associated with UPF (both cohorts). In both cohorts, psychological distress poorly influenced changes toward an MD, except for depression (SQD-D) that resulted inversely associated in the ALT RISCOVID-19 participants (ß = - 0.16; 95% CI - 0.26, - 0.06). CONCLUSIONS: Psychological distress from the COVID-19 confinement is directly associated with unhealthy dietary modifications in two Italian cohorts. In view of possible future restrictive measures to contain pandemic, public health actions are warranted to mitigate the impact of psychological distress on diet quality.

Dietary factors and the risk of lumbar spinal stenosis: A case-control analysis from the PREFACE study.

BACKGROUND AND AIMS: There is a lack of knowledge on the association of dietary factors and Lumbar Spinal Stenosis (LSS). We evaluated the association of a Mediterranean diet (MD), its major food components and ultra-processed food (UPF) with the risk of LSS. METHODS AND RESULTS: Participants were recruited from the Neurosurgery Department of the IRCCS Neuromed, Italy. The study sample consisted of 156 cases of LSS, and 312 controls matched 1:2 for sex, age (±6 months) and physical activity, without a history or clinical evidence of LSS who were identified from the general population. Adherence to MD was assessed by the Mediterranean Diet Score based on 9 food groups. UPF was defined according to NOVA classification and calculated as the ratio (%) of UPF (g/d) on total food consumed (g/d). In multivariable-adjusted analysis, a 2-point increase in the MD score was not associated with LSS risk (OR: 1.02, 95% CI: 0.72-1.46). An increment of 10 g/d of fruits and nuts, cereals or fish led to lower odds of LSS (OR: 0.97, 95% CI: 0.95-0.99; OR: 0.88, 95% CI: 0.82-0.94; OR: 0.87, 95% CI: 0.76-0.99, respectively). Additionally, 1% increment in the consumption of UPF in the diet was independently associated with higher LSS risk (OR: 1.09, 95% CI: 1.04-1.14). CONCLUSION: A diet rich in fruits, cereals, fish is associated with lower risk of LSS while a large dietary share of UPF increases the risk of this disease. Further studies with a prospective design and larger sample sizes are warranted.

Association between chronotype, sleep pattern, and eating behaviours in a group of Italian adults.

A cross-sectional study was conducted to assess the possible relationship between chronotype, sleeping, and eating patterns in 74 Italian adults (71.6% women). Based on Morningness-Eveningness Questionnare (MEQ) score, participants were classified as morning (n = 24), intermediate (n = 25), and evening (n = 25) chronotypes. From analysis, no significant differences among chronotypes emerged for sleep habits. As to eating behaviours, the evening subjects showed a significant (p < 0.05) shift towards later hours of the day in the consumption of all meals, except dinner. In addition, the evening subjects had a later midpoint of energy intake (EI) of about 35 min and 1 h (p < 0.001), respectively, than the intermediate and morning subjects. Analysing the diet quality, morning subjects reported significantly (p = 0.030) lower consumption of sweets and sweeteners, and significantly (p = 0.035) lower intake of ultra-processed fats and seasonings. Evening subjects showed a significant delay in EI during the day, while morning subjects reported a better-quality diet.

Ultra-processed food consumption and its correlates among Italian children, adolescents and adults from the Italian Nutrition & Health Survey (INHES) cohort study.

OBJECTIVE: To assess ultra-processed food (UPF) consumption and its socio-demographic, psychosocial and behavioural correlates in a general population of Italian children, adolescents and adults. DESIGN: Cross-sectional telephone-based survey. SETTING: Italy, 2010-2013. PARTICIPANTS: In total, 9078 participants (5-97 years) from the Italian Nutrition & Health Survey. Dietary intakes were collected by a 1-d 24-h dietary recall. UPF was defined by the NOVA classification and expressed as percentage of total energies. RESULTS: Average energy intake from UPF (95 % CI) was 17·3 % (17·1 %, 17·6 %) among adults and 25·9 % (24·8 %, 27·0 %) in children/adolescents. Top sources of UPF were processed meats (32·5 %) and bread substitutes (16·7 %). Among adults, age (ß = -3·10; 95 % CI (-4·40, -1·80) for >65 years v. 20-40 years; ßs are dimensionless) and residing in Southern Italy (ß = -0·73; 95 % CI (-1·32, -0·14) v. Northern) inversely associated with UPF. Screen view during meals was directly linked to UPF, as well as poor self-rated health (ß = 5·32; 95 % CI (2·66, 7·99)), adverse life events (ß = 2·33; 95 % CI (1·48, 3·18)) and low sleep quality (ß = 2·34; 95 % CI (1·45, 3·23)). Boys consumed two-point percent more UPF of the total energy than girls (ß = 2·01; 95 % CI (0·20, 3·82)). For all ages, a Mediterranean diet was inversely associated with UPF (ß = -4·86; 95 % CI (-5·53, -4·20) for good v. poor adherence in adults and (ß = -5·08; 95 % CI (-8·38, -1·77) for kids). CONCLUSIONS: UPF contributes a modest proportion of energy to the diets of Italian adults while being one-quarter of the total energies in children/adolescents. UPF was associated with several psychosocial factors and eating behaviours. Increased adherence to Mediterranean diet would possibly result in lower UPF consumption.

Changes in ultra-processed food consumption during the first Italian lockdown following the COVID-19 pandemic and major correlates: results from two population-based cohorts.

OBJECTIVE: To evaluate changes in ultra-processed food (UPF) intake and its major correlates during the first Italian lockdown (9 March-3 May 2020). DESIGN: Retrospective observational study. SETTING: Italy. PARTICIPANTS: We analysed 2992 subjects (mean age 57·9 ± 15·3 years, 40·4 % men). Individual participant data were pooled from two retrospective cohorts: (1) The Moli-LOCK cohort consists of 1501 adults, a portion of the larger Moli-sani study (n 24 325; 2005-2010) who were administered a phone-based questionnaire to assess lifestyles and psychological factors during confinement and (2) the Analysis of Long Term Risk of Covid-19 Emergency is a web-based survey of 1491 individuals distributed throughout Italy who self-responded to the same questionnaire by using Google forms.UPF was defined according to NOVA classification based on degree of food processing. An UPF score was created by assigning 1 point to increased consumption, -1 to decreased and 0 point for unchanged intakes of nineteen food items, with higher values indicating an increase in UPF during confinement. RESULTS: Overall, 37·5 % of the population reported some increase in UPF (UPF score ≥1). Adults were more likely to decrease UPF (multivariable regression coefficient ß = -1·94; 95 % CI -2·72, -1·17 for individuals aged >75 years as compared with 18-39 years) as did individuals from southern Italian regions as compared with Northern inhabitants (ß = -1·32; 95 % CI -1·80, -0·84), while UPF lowering associated with increased exercise (ß = -0·90; 95 % CI -1·46, -0·35) and weight loss (ß = -1·05; 95 % CI -1·51, -0·59) during confinement. CONCLUSIONS: During the first Italian lockdown, about 40 % of our population switched to unfavourable eating as reflected by increased UPF intake and this may have long-term effects for health.

Changes in the consumption of foods characterising the Mediterranean dietary pattern and major correlates during the COVID-19 confinement in Italy: results from two cohort studies.

We investigated the effect of confinement during the COVID-19 pandemic on the consumption of foods characterising the Mediterranean dietary pattern (MDP) and its major correlates in two Italian population-based cohorts comprising 3161 subjects (mean age 57.7 ± 15.4 y). At population level, 38.8% of participants reported an improvement of diet quality during the first nationwide lockdown. Healthful dietary changes were associated with older age (ß = 0.41; 95% confidence interval [CI] 0.08, 0.73 for 56-65 vs. 18-39 y), greater wealth (ß = 0.45; 0.01, 0.89 for >40,000 ≤ 60,000 vs. ≤ 10,000 EUR/y), increased physical activity (ß = 0.52; 0.22, 0.81) and reduced body weight (ß = 0.36; 0.11, 0.62). Switching to healthy eating was also related to increased consumption of organic (ß = 1.24; 0.88, 1.60) and locally-grown food (ß = 0.74; 0.51, 0.96). The first Italian lockdown led, in a substantial part of the population, to higher intake of foods characterising a MDP; this was also accompanied by healthier lifestyle and more sustainable food choices.

Reproducibility and validity of a food-frequency questionnaire (NFFQ) to assess food consumption based on the NOVA classification in adults.

NOVA is a classification that divides foods into four groups according to processing. Since no questionnaires have been validated to assess the consumption of foods with different levels of processing in the general adult population, we tested the reliability and validity of a 94-item Food Frequency Questionnaire (NFFQ) designed to estimate the intake (g/day) and the weight ratio (%) of the NOVA food groups in Italian adults. Time reliability and validity were tested by administrating the NFFQ to 110 subjects on two different occasions and comparing it with a weighed dietary record (WDR). Strong correlations between NFFQs (r > 0.7, p < 0.001) and intraclass correlation coefficients (ICC) of 0.851-0.940 indicated good test-retest reliability. Moderate correlations between the NFFQ and the WDR (0.6

HDAC8 regulates canonical Wnt pathway to promote differentiation in skeletal muscles.

Histone deacetylase 8 (HDAC8) is a class 1 histone deacetylase and a member of the cohesin complex. HDAC8 is expressed in smooth muscles, but its expression in skeletal muscle has not been described. We have shown for the first time that HDAC8 is expressed in human and zebrafish skeletal muscles. Using RD/12 and RD/18 rhabdomyosarcoma cells with low and high differentiation potency, respectively, we highlighted a specific correlation with HDAC8 expression and an advanced stage of muscle differentiation. We inhibited HDAC8 activity through a specific PCI-34051 inhibitor in murine C2C12 myoblasts and zebrafish embryos, and we observed skeletal muscles differentiation impairment. We also found a positive regulation of the canonical Wnt signaling by HDAC8 that might explain muscle differentiation defects. These findings suggest a novel mechanism through which HDAC8 expression, in a specific time window of skeletal muscle development, positively regulates canonical Wnt pathway that is necessary for muscle differentiation.

Olive oil consumption is associated with lower cancer, cardiovascular and all-cause mortality among Italian adults: prospective results from the Moli-sani Study and analysis of potential biological mechanisms.

BACKGROUND: Olive oil consumption has been reportedly associated with lower mortality rates, mostly from cardiovascular diseases, but its potential impact on cancer death remains controversial. Moreover, biological mechanisms possibly linking olive oil consumption to mortality outcomes remain unexplored. METHODS: We longitudinally analysed data on 22,892 men and women from the Moli-sani Study in Italy (follow-up 13.1 y), to examine the association of olive oil consumption with mortality. Dietary data were collected at baseline (2005-2010) through a 188-item FFQ, and olive oil consumption was standardised to a 10 g tablespoon (tbsp) size. Diet quality was assessed through a Mediterranean diet score. Multivariable-adjusted Cox proportional hazard models, also including diet quality, were used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs). The potential mediating role of inflammatory, metabolic, cardiovascular and renal biomarkers on the association between olive oil intake and mortality was evaluated on the basis of change-in-estimate and associated p values. RESULTS: Multivariable HRs for all-cause, cancer, cardiovascular and other cause mortality associated with high (>3 tbsp/d) versus low (≤1.5 tbsp/d) olive oil consumption were 0.80 (0.69-0.94), 0.77 (0.59-0.99), 0.75 (0.58-0.97) and 0.97 (0.73-1.29), respectively. Taken together, the investigated biomarkers attenuated the association of olive oil consumption with all-cause and cancer mortality by 21.2% and 13.7%, respectively. CONCLUSIONS: Higher olive oil consumption was associated with lower cancer, cardiovascular and all-cause mortality rates, independent of overall diet quality. Known risk factors for chronic diseases only in part mediated such associations suggesting that other biological pathways are potentially involved in this relationship.

Identification and characterisation of functional Kir6.1-containing ATP-sensitive potassium channels in the cardiac ventricular sarcolemmal membrane.

BACKGROUND AND PURPOSE: The canonical Kir6.2/SUR2A ventricular KATP channel is highly ATP-sensitive and remains closed under normal physiological conditions. These channels activate only when prolonged metabolic compromise causes significant ATP depletion and then shortens the action potential to reduce contractile activity. Pharmacological activation of KATP channels is cardioprotective, but physiologically, it is difficult to understand how these channels protect the heart if they only open under extreme metabolic stress. The presence of a second KATP channel population could help explain this. Here, we characterise the biophysical and pharmacological behaviours of a constitutively active Kir6.1-containing KATP channel in ventricular cardiomyocytes. EXPERIMENTAL APPROACH: Patch-clamp recordings from rat ventricular myocytes in combination with well-defined pharmacological modulators was used to characterise these newly identified K+ channels. Action potential recording, calcium (Fluo-4) fluorescence measurements and video edge detection of contractile function were used to assess functional consequences of channel modulation. KEY RESULTS: Our data show a ventricular K+ conductance whose biophysical characteristics and response to pharmacological modulation were consistent with Kir6.1-containing channels. These Kir6.1-containing channels lack the ATP-sensitivity of the canonical channels and are constitutively active. CONCLUSION AND IMPLICATIONS: We conclude there are two functionally distinct populations of ventricular KATP channels: constitutively active Kir6.1-containing channels that play an important role in fine-tuning the action potential and Kir6.2/SUR2A channels that activate with prolonged ischaemia to impart late-stage protection against catastrophic ATP depletion. Further research is required to determine whether Kir6.1 is an overlooked target in Comprehensive in vitro Proarrhythmia Assay (CiPA) cardiac safety screens.

Effect of a subcutaneous implant of deslorelin acetate on serum testosterone concentrations in male Hermann's (Testudo hermanni sp.) and Greek (Testudo graeca sp.) tortoises.

Deslorelin acetate is a gonadotropin-releasing hormone agonist formulated in a controlled-release subcutaneous implant and designed for reversible suppression of testosterone production in dogs. It has also been demonstrated to be effective in other animal species, but no data on its effectiveness in male land tortoises are available. This study aimed to evaluate the effect of a 4.7-mg deslorelin acetate implant on serum testosterone concentrations in male Hermann's (Testudo hermanni sp.) and Greek (Testudo graeca sp.) tortoises. Twenty adult male tortoises housed under the same environmental conditions were enrolled for the study and randomly assigned to a treatment (D, n = 10) or a control (C, n = 10) group. Starting in May, males from the D group were implanted with a 4.7-mg deslorelin acetate device, whereas males from the C group did not receive any treatment. Blood samples were collected once immediately before implant application (S0-May) and at 15 days (S1-June), 2 (S2-July), and 5 (S3-October) months after application. Serum testosterone at each sampling time was measured through a solid-phase, enzyme-labeled, competitive chemiluminescent immunoassay. Median serum testosterone concentrations were not significantly different between the two groups in all sampling times, and no interaction between treatment and sampling time was observed. The present study, therefore, suggests that a single treatment with a 4.7-mg deslorelin acetate implant has no effect on testosterone circulation in male Hermann's and Greek tortoises during the following 5 months.

Ultraprocessed food consumption is associated with all-cause and cardiovascular mortality in participants with type 2 diabetes independent of diet quality: a prospective observational cohort study.

BACKGROUND: Nutritional strategies for prevention and management of type 2 diabetes traditionally emphasize dietary patterns reflecting nutrient goals, but the health implications of ultraprocessed food (UPF) for patients with type 2 diabetes remain unknown. OBJECTIVES: This study aimed to evaluate the association of UPF intake with all-cause and cardiovascular disease (CVD) mortality among participants with type 2 diabetes from the Moli-sani Study in Italy (enrollment 2005-2010). METHODS: This was a prospective observational cohort study on 1065 individuals with type 2 diabetes at baseline, followed up for 11.6 y (median). Food intake was assessed by a 188-item food-frequency questionnaire. UPF was defined following the Nova classification and calculated as the ratio (weight ratio; %) between UPF (g/d) and total food eaten (g/d). Overall diet quality was assessed through the Mediterranean Diet Score (MDS). Multivariable-adjusted Cox proportional hazards models were used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) for mortality. RESULTS: The average UPF consumption was 7.4% (±5.0%). In multivariable-adjusted Cox analyses, greater UPF intake (Q4, ≥10.5% and ≥9% of total food eaten for females and males, respectively), as opposed to the lowest (Q1, UPF <4.7% and <3.7% for females and males, respectively), was associated with higher hazards of both all-cause (HR: 1.70; 95% CI: 1.25, 2.33) and CVD mortality (HR: 2.64; 95% CI: 1.59, 4.40); inclusion of the MDS into the model did not substantially alter the magnitude of these associations (HR: 1.64; 95% CI: 1.19, 2.25 and HR: 2.55; 95% CI: 1.53, 4.24 for all-cause and CVD mortality, respectively). A linear dose-response relationship of UPF intake with both all-cause and CVD mortality was also observed. CONCLUSIONS: In participants with type 2 diabetes at study entry, higher UPF consumption was associated with reduced survival and higher CVD mortality rate, independent of diet quality. Besides prioritizing the adoption of a diet based on nutritional requirements, dietary guidelines for the management of type 2 diabetes should also recommend limiting UPF.

Association between Late-Eating Pattern and Higher Consumption of Ultra-Processed Food among Italian Adults: Findings from the INHES Study.

Late eating is reportedly associated with adverse metabolic health, possibly through poor diet quality. We tested the hypothesis that meal timing could also be linked to food processing, an independent predictor of health outcomes. We analysed data on 8688 Italians (aged > 19years) from the Italian Nutrition & HEalth Survey (INHES) established in 2010-2013 throughout Italy. Dietary data were collected through a single 24 h dietary recall, and the NOVA classification was used to categorize foods according to increasing levels of processing: (1) minimally processed foods (e.g., fruits); (2) culinary ingredients (e.g., butter); (3) processed foods (e.g., canned fish); (4) ultra-processed foods (UPFs; e.g., carbonated drinks, processed meat). We then calculated the proportion (%) of each NOVA group on the total weight of food eaten (g/d) by creating a weight ratio. Subjects were classified as early or late eaters based on the population's median timing for breakfast, lunch and dinner. In multivariable-adjusted regression models, late eaters reported a lower intake of minimally processed food (ß = -1.23; 95% CI -1.75 to -0.71), a higher intake of UPF (ß = 0.93; 0.60 to 1.25) and reduced adherence to a Mediterranean Diet (ß = -0.07; -0.12 to -0.03) as compared to early eaters. Future studies are warranted to examine whether increased UPF consumption may underpin the associations of late eating with adverse metabolic health reported in prior cohorts.

Pro-Vegetarian Food Patterns and Cancer Risk among Italians from the Moli-Sani Study Cohort.

Besides the Mediterranean diet, there is a paucity of studies examining plant-based diets in relation to cancer outcomes in Mediterranean populations. We analyzed 22,081 apparently cancer-free participants (mean age 55 ± 12 year) from the Moli-sani study (enrollment period 2005-2010; Italy). A general pro-vegetarian food pattern was computed by assigning positive or negative scores to plant- or animal-derived foods, respectively from a 188-item FFQ. A priori healthful or unhealthful pro-vegetarian food patterns distinguished between healthy plant foods (e.g., fruits, vegetables) and less-healthy plant foods (e.g., fruit juices, refined grains). Cancer incidence was defined as the earliest diagnosis of cancer from hospital discharge records over a median follow-up of 12.9 years. In multivariable-adjusted analyses, a general pro-vegetarian food pattern was associated with a lower rate of cancer incidence (HR = 0.85; 95%CI 0.75-0.97 for Q5 vs. Q1); no association was observed between the healthful or unhealthful pro-vegetarian food patterns and overall cancer incidence. A healthful pro-vegetarian pattern, however, was inversely associated with digestive cancer (HR = 0.76; 95%CI 0.58-0.99 for Q5 vs. Q1), while the unhealthful pro-vegetarian pattern was directly linked to respiratory cancer (HR = 1.68; 95%CI 1.06-2.68 for Q5 vs. Q1). Our findings in a Mediterranean population support the hypothesis that some, but not all pro-vegetarian diets, might prevent some cancers.

Food processing and risk of central nervous system tumours: A preliminary case-control analysis from the MEditerranean DIet in relation to CancEr of brAin (MEDICEA) study.

BACKGROUND: The relationship between diet and central nervous system (CNS) tumours was almost exclusively focused on food composition. We evaluated the relationship of different degrees of food processing with risk of CNS tumours. METHODS: The study sample included 44 CNS tumours cases (20 non-malignant and 24 malignant) recruited from the Neurosurgery Department at the IRCCS Neuromed (Italy), and 88 controls matched 1:2 for sex and age± 10 years, identified from the Moli-sani Study. Dietary intake was assessed using a 188-item FFQ. Food items were grouped according to the NOVA classification on the basis of processing as: (1) unprocessed/minimally processed foods; (2) processed culinary ingredients; (3) processed foods; and (4) ultra-processed food (UPF). Conditional logistic regression models were used to estimate odds ratio (OR) and 95% confidence intervals (95%CI) of dietary contributions from each NOVA group (as weight ratio on the total food eaten) and adjusting for potential confounders. RESULTS: In a multivariable conditional to match logistic regression analysis also controlled for overall diet quality, 1% increment in UPF intake was associated with higher odds of all CNS tumours (OR = 1.06; 1.01-1.13), particularly of malignant CNS tumours (OR = 1.11; 1.02-1.22), while no association with non-malignant CNS tumours was found (OR = 1.06; 0.99-1.15). In contrast, only processed food was inversely associated with risk of both CNS tumours overall (OR = 0.94; 0.90-0.98) and of malignant CNS tumours (OR = 0.90; 0.83-0.96). CONCLUSION: Increasing UPF intake was associated with higher risk of CNS tumours, especially malignant ones, independently of the overall diet quality, while only processed food (but not UPF) was inversely related to the risk of this disease.

Association between the Inflammatory Potential of the Diet and Biological Aging: A Cross-Sectional Analysis of 4510 Adults from the Moli-Sani Study Cohort.

Chronological age (CA) may not accurately reflect the health status of an individual. Rather, biological age (BA) or hypothetical underlying "functional" age has been proposed as a relevant indicator of healthy aging. Observational studies have found that decelerated biological aging or Δage (BA-CA) is associated with a lower risk of disease and mortality. In general, CA is associated with low-grade inflammation, a condition linked to the risk of the incidence of disease and overall cause-specific mortality, and is modulated by diet. To address the hypothesis that diet-related inflammation is associated with Δage, a cross-sectional analysis of data from a sub-cohort from the Moli-sani Study (2005-2010, Italy) was performed. The inflammatory potential of the diet was measured using the Energy-adjusted Dietary Inflammatory Index (E-DIITM) and a novel literature-based dietary inflammation score (DIS). A deep neural network approach based on circulating biomarkers was used to compute BA, and the resulting Δage was fit as the dependent variable. In 4510 participants (men 52.0%), the mean of CA (SD) was 55.6 y (±11.6), BA 54.8 y (±8.6), and Δage -0.77 (±7.7). In a multivariable-adjusted analysis, an increase in E-DIITM and DIS scores led to an increase in Δage (ß = 0.22; 95%CI 0.05, 0.38; ß = 0.27; 95%CI 0.10, 0.44, respectively). We found interaction for DIS by sex and for E-DIITM by BMI. In conclusion, a pro-inflammatory diet is associated with accelerated biological aging, which likely leads to an increased long-term risk of inflammation-related diseases and mortality.

Identifying brain tumor patients' subtypes based on pre-diagnostic history and clinical characteristics: a pilot hierarchical clustering and association analysis.

Introduction: Central nervous system (CNS) tumors are severe health conditions with increasing incidence in the last years. Different biological, environmental and clinical factors are thought to have an important role in their epidemiology, which however remains unclear. Objective: The aim of this pilot study was to identify CNS tumor patients' subtypes based on this information and to test associations with tumor malignancy. Methods: 90 patients with suspected diagnosis of CNS tumor were recruited by the Neurosurgery Unit of IRCCS Neuromed. Patients underwent anamnestic and clinical assessment, to ascertain known or suspected risk factors including lifestyle, socioeconomic, clinical and psychometric characteristics. We applied a hierarchical clustering analysis to these exposures to identify potential groups of patients with a similar risk pattern and tested whether these clusters associated with brain tumor malignancy. Results: Out of 67 patients with a confirmed CNS tumor diagnosis, we identified 28 non-malignant and 39 malignant tumor cases. These subtypes showed significant differences in terms of gender (with men more frequently presenting a diagnosis of cancer; p = 6.0 ×10-3) and yearly household income (with non-malignant tumor patients more frequently earning ≥25k Euros/year; p = 3.4×10-3). Cluster analysis revealed the presence of two clusters of patients: one (N=41) with more professionally active, educated, wealthier and healthier patients, and the other one with mostly retired and less healthy men, with a higher frequency of smokers, personal history of cardiovascular disease and cancer familiarity, a mostly sedentary lifestyle and generally lower income, education and cognitive performance. The former cluster showed a protective association with the malignancy of the disease, with a 74 (14-93) % reduction in the prevalent risk of CNS malignant tumors, compared to the other cluster (p=0.026). Discussion: These preliminary data suggest that patients' profiling through unsupervised machine learning approaches may somehow help predicting the risk of being affected by a malignant form. If confirmed by further analyses in larger independent cohorts, these findings may be useful to create potential intelligent ranking systems for treatment priority, overcoming the lack of histopathological information and molecular diagnosis of the tumor, which are typically not available until the time of surgery.