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Infertility has been characterized as a disease by the World Health Organization (WHO) and reportedly affects about 10-12% of couples worldwide, while the incidence is even higher in Italy, at about 15%. The issue of iatrogenic infertility arising from treatments that can compromise an individual's reproductive capacity, it is necessary to inform patients of the possible damage on their future fertility and on the possibilities to preserve it. The complexities inherent in the various techniques and approaches aimed at preserving fertility should be expounded upon thoroughly to the patients, who should also receive proper psychological assistance and counseling, which ought to take into account the ethical distinctive challenges and the possible misgivings that may be caused in patients. Ovarian Tissue Cryopreservation (OTC) and ovarian tissue transplantation (OTT) can constitute a valuable part of the clinical armamentarium for preserving fertility, although the data are still inconclusive, particularly in over-36 patients. The multidisciplinary nature of the healthcare teams involved in such interventions is of paramount importance to optimize results. [ABSTRACT FROM AUTHOR]

Advanced glycation end products (AGEs) have been implicated in chronic diseases in adults, but their role in paediatric populations remains uncertain. This study, conducted on the Italian sample of the I.Family project, aimed to investigate the relationship between dietary and urinary fluorescent AGEs in children and adolescents. The secondary objective was to investigate the sources of dietary AGEs (dAGEs) and their association with dietary composition and anthropometric parameters. Dietary data were collected from 1048 participants via 24 h dietary recall in 2013/2014 to estimate dAGEs intake, while urinary fluorescent AGE levels were measured in 544 individuals. Participants were stratified based on dAGEs intake and compared with respect to urinary fluorescent AGE levels, anthropometric measurements, and dietary intake. The results showed no significant correlation between dietary and urinary fluorescent AGE levels, nor between dAGEs and anthropometric parameters. Notably, higher dAGEs were associated with a diet richer in protein (especially from meat sources) and fat and lower in carbohydrates. In addition, the consumption of ultra-processed foods was lower in participants with a higher DAGE intake. This study highlights the lack of a clear association between dietary and urinary fluorescent AGEs in children, but suggests a distinctive dietary pattern associated with increased dAGEs intake. Further investigation is warranted to elucidate the potential health implications of dAGEs in paediatric populations.

Mucinous appendicular neoplasms are a rare and heterogeneous group of tumors, whose treatment may vary based on histologic features and extent. We present a case of low-grade appendiceal mucinous neoplasm mimicking an acute appendicitis scenario. The patient underwent appendectomy along with resection of the caecal fundus. Choosing the correct treatment according to the case by following current guidelines is crucial to avoid under- or overtreatment., (Published by Oxford University Press and JSCR Publishing Ltd. © The Author(s) 2024.)

Invasive lobular cancer (ILC) is the most common of the breast cancer special types, accounting for up to 15% of all breast malignancies. The distinctive biological features of ILC include the loss of the cell adhesion molecule E-cadherin, which drives the tumor's peculiar discohesive growth pattern, with cells arranged in single file and dispersed throughout the stroma. Typically, such tumors originate in the lobules, are more commonly bilateral compared to invasive ductal cancer (IDC) and require a more accurate diagnostic examination through imaging. They are luminal in molecular subtype, and exhibit estrogen and progesterone receptor positivity and HER2 negativity, thus presenting a more unpredictable response to neoadjuvant therapies. There has been a significant increase in research focused on this distinctive breast cancer subtype, including studies on its pathology, its clinical and surgical management, and the high-resolution definition of its genomic profile, as well as the development of new therapeutic perspectives. This review will summarize the heterogeneous pattern of this unique disease, focusing on challenges in its comprehensive clinical management and on future insights and research objectives., Competing Interests: Declaration of competing interest No financial/personal interest from all Authors with the exception of Prof. Giuseppe Curigliano., (Copyright © 2024 Elsevier Inc. All rights reserved.)

A breast unit is a multidisciplinary center specialized in the management of women with breast diseases, including breast cancer (BC). It represents a care path, passing from screening activities to diagnostic investigations, from surgery to the definition of the therapeutic strategy, from psychophysical rehabilitation to long-term checks (follow-up), and up to genetic counseling. Since 2006, following a resolution issued by the European Parliament to urge member states to activate multidisciplinary breast centers by 2016, work has been underway throughout Italy to improve the management of women with BC. In Italy, the State-Regions agreement was signed on 18 December 2014, sanctioning the establishment of breast units. These centers must adhere to specific quality criteria and requirements. In 2020, the experts of the EUSOMA group (European Society of Breast Cancer Specialists), in their latest document published, expanded the requirements of the breast units. Furthermore, Senonetwork was founded in 2012 with the aim of allowing BC to be treated in breast units that comply with European requirements to ensure equal treatment opportunities for all Italian women. Indeed, the available data indicate that the BC patient has a greater chance of better treatment in the breast units with a multidisciplinary team, thus increasing the survival rate with a better quality of life, compared to those managed in nonspecialized structures. The present review is a perspective on the current Italian reality of breast units, updated with the available literature and the most recent epidemiological data from Senonetwork and AgeNaS., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)

Childhood obesity is a complex disorder that appears to be influenced by an interacting system of many factors. Taking this complexity into account, we aim to investigate the causal structure underlying childhood obesity. Our focus is on identifying potential early, direct or indirect, causes of obesity which may be promising targets for prevention strategies. Using a causal discovery algorithm, we estimate a cohort causal graph (CCG) over the life course from childhood to adolescence. We adapt a popular method, the so-called PC-algorithm, to deal with missing values by multiple imputation, with mixed discrete and continuous variables, and that takes background knowledge such as the time-structure of cohort data into account. The algorithm is then applied to learn the causal structure among 51 variables including obesity, early life factors, diet, lifestyle, insulin resistance, puberty stage and cultural background of 5112 children from the European IDEFICS/I.Family cohort across three waves (2007-2014). The robustness of the learned causal structure is addressed in a series of alternative and sensitivity analyses; in particular, we use bootstrap resamples to assess the stability of aspects of the learned CCG. Our results suggest some but only indirect possible causal paths from early modifiable risk factors, such as audio-visual media consumption and physical activity, to obesity (measured by age- and sex-adjusted BMI z-scores) 6 years later., (© 2024. The Author(s).)

The underlying cause of Spinal Muscular Atrophy (SMA) is in the reduction of survival motor neuron (SMN) protein levels due to mutations in the SMN1 gene. The specific effects of SMN protein loss and the resulting pathological alterations are not fully understood. Given the crucial roles of the SMN protein in snRNP biogenesis and its interactions with ribosomes and translation-related proteins and mRNAs, a decrease in SMN levels below a specific threshold in SMA is expected to affect translational control of gene expression. This review covers both direct and indirect SMN interactions across various translation-related cellular compartments and processes, spanning from ribosome biogenesis to local translation and beyond. Additionally, it aims to outline deficiencies and alterations in translation observed in SMA models and patients, while also discussing the implications of the relationship between SMN protein and the translation machinery within the context of current and future therapies., (© 2024 The Author(s).)

Dietary diversity (DD) plays a crucial role in fostering high-quality diets, but its association with health outcomes, particularly body adiposity and non-communicable diseases (NCDs), is inconsistent. This may be due to a lack of a standardized method for estimating DD. Our study investigates the association between two DD indices, namely the dietary diversity score (DDS) and food variety score (FVS), and anthropometric measures, biochemical parameters, and diet quality in a large population sample from the I.Family study across research centers in eight European countries. In our cross-sectional analysis of 3035 participants, DDSs varied among countries, with a higher prevalence in the third DDS tertile among those with higher education. DDS showed a positive association with diet quality across all age groups. Higher DDS tertile individuals showed increased fiber, fruit, and vegetable intake, greater meal frequency, and lower ultra-processed food consumption. No relevant biochemical differences were observed across DDS tertiles, and a higher DDS was associated with lower overweight/obesity prevalence only in adults. No significant associations were found with FVS. Our findings emphasize the need to consider food groups for a more accurate estimation of diet quality. This aligns with studies suggesting DDS alone is not an independent risk factor for obesity in children and adolescents. Public health programs should prioritize food diversity to promote improved nutrition and overall well-being in communities.

Context: Vitamin D status has previously been associated with cardiometabolic risk markers in children and adolescents. In particular, it has been suggested that children with obesity are more prone to vitamin D deficiency and unfavorable metabolic outcomes compared with healthy-weight children., Objective: To conduct a longitudinal study assessing this association in children and stratify by body mass index (BMI) category., Methods: Children from the pan-European IDEFICS/I.Family cohort with at least one measurement of serum 25-hydroxyvitamin D [25(OH)D] at cohort entry or follow-up (n = 2171) were included in this study. Linear mixed-effect models were used to assess the association between serum 25(OH)D as an independent variable and z-scores of cardiometabolic risk markers (waist circumference, systolic [SBP] and diastolic blood pressure [DBP], high- [HDL] and low-density lipoprotein, non-HDL, triglycerides [TRG], apolipoprotein A1 [ApoA1] and ApoB, fasting glucose [FG], homeostatic model assessment for insulin resistance [HOMA-IR], and metabolic syndrome score) as dependent variables., Results: After adjustment for age, sex, study region, smoking and alcohol status, sports club membership, screen time, BMI, parental education, and month of blood collection, 25(OH)D levels were inversely associated with SBP, DBP, FG, HOMA-IR, and TRG. The HOMA-IR z-score decreased by 0.07 units per 5 ng/mL increase in 25(OH)D. The 25(OH)D level was consistently associated with HOMA-IR irrespective of sex or BMI category., Conclusion: Low serum 25(OH)D concentrations are associated with unfavorable levels of cardiometabolic markers in children and adolescents. Interventions to improve vitamin D levels in children with a poor status early in life may help to reduce cardiometabolic risk., (© The Author(s) 2023. Published by Oxford University Press on behalf of the Endocrine Society. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Amyotrophic lateral sclerosis (ALS) is a progressive, lethal neurodegenerative disease mostly affecting people around 50-60 years of age. TDP-43, an RNA-binding protein involved in pre-mRNA splicing and controlling mRNA stability and translation, forms neuronal cytoplasmic inclusions in an overwhelming majority of ALS patients, a phenomenon referred to as TDP-43 proteinopathy. These cytoplasmic aggregates disrupt mRNA transport and localization. The axon, like dendrites, is a site of mRNA translation, permitting the local synthesis of selected proteins. This is especially relevant in upper and lower motor neurons, whose axon spans long distances, likely accentuating their susceptibility to ALS-related noxae. In this work we have generated and characterized two cellular models, consisting of virtually pure populations of primary mouse cortical neurons expressing a human TDP-43 fusion protein, wt or carrying an ALS mutation. Both forms facilitate cytoplasmic aggregate formation, unlike the corresponding native proteins, giving rise to bona fide primary culture models of TDP-43 proteinopathy. Neurons expressing TDP-43 fusion proteins exhibit a global impairment in axonal protein synthesis, an increase in oxidative stress, and defects in presynaptic function and electrical activity. These changes correlate with deregulation of axonal levels of polysome-engaged mRNAs playing relevant roles in the same processes. Our data support the emerging notion that deregulation of mRNA metabolism and of axonal mRNA transport may trigger the dying-back neuropathy that initiates motor neuron degeneration in ALS., 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 © 2023 Pisciottani, Croci, Lauria, Marullo, Savino, Ambrosi, Podini, Marchioretto, Casoni, Cremona, Taverna, Quattrini, Cioni, Viero, Codazzi and Consalez.)

Background and Aims: Evidence shows that migrant children have a higher risk of developing obesity than those with native parents. We aimed to investigate the association between parental migration background and cardiometabolic health in children and adolescents in Europe., Methods and Results: We included 8745 children aged 2-17 from the second follow-up of the European IDEFICS/I.Family cohort. Linear regression models were used to investigate the association between parental migration background (one or two migrant parent(s) vs native parents) and body mass index (BMI), metabolic syndrome (MetS) score and its individual components. Outcome variables were parametrized as age and sex-specific z-scores. We adjusted for age, sex, country, and parental education, and additionally for parental income, lifestyle including dietary factors, and maternal BMI. On average, children with two migrant parents had higher z-scores of BMI (+0.24 standard deviation (SD)) and MetS score (+0.30 SD) compared to those with native parents, whereas no significant differences were seen for children with one migrant parent. Associations were attenuated when controlling for maternal BMI and sports club activity. Parental education modified the associations with BMI and MetS z-scores such that they were more pronounced in children with low parental education., Conclusion: Children with two migrant parents were at higher risk for adverse cardiometabolic health compared to children with native parents, especially in families with low parental education. These associations were explained by lower physical activity and maternal body weight and encourages early intervention strategies by schools and communities., (© 2023. The Author(s).)

Vascular approach during elective laparoscopic left colectomy impacts post-operative outcomes. The aim of our study was to evaluate how different approaches impact positively defecatory, urinary and sexual functions and quality of life during elective laparoscopic left colectomy. A prospective non-randomized controlled trial at two tertiary center was conducted. All patients who underwent elective laparoscopic left colonic resection from January 2019 to July 2022 were analyzed. They were divided into two groups based on Inferior Mesenteric Artery (IMA) preservation with distal ligation of sigmoid branches close to a colonic wall for complicated diverticular disease and IMA high tie ligation for oncological disease. Patients were asked to fulfil standardized, validated questionnaires to evaluate pre and post-operative defecatory, urinary and sexual functions and quality of life. Defecatory disorders were assessed by high-resolution anorectal manometry preoperatively and six months after surgery. A total of 122 patients were included in the study. The 62 patients with IMA preservation showed a lower incidence of defecatory disorders also confirmed by manometer data, minor incontinence and less lifestyle alteration than the 60 patients with IMA high tie ligation. No urinary disorders such as incomplete emptying, frequency, intermittence or urgency were highlighted after surgery in the IMA preservation group. Evidence of any sexual disorders remained controversial. The IMA-preserving vascular approach seems to be an effective strategy to prevent postoperative functional disorders. It is a safe and feasible technique especially for diverticular disease. New prospective randomized and highly probative studies are needed to confirm the effectiveness in specific clinical situations., (© 2023. Italian Society of Surgery (SIC).)

Modern dietary habits are linked to high exposure to Advanced Glycation End products (AGEs) mainly due to the dramatic increase in the consumption of highly processed foods in recent years. Body levels of these compounds vary with food intake and are almost interconnected with age and health status, formally embodying indicators of oxidative stress and inflammation in adults. However, the relationship between AGEs and health issues has not been definitively understood in children, and several pediatric investigations have produced conflicting evidence. Besides, despite extensive research, there are no universally accepted analytical techniques for measuring AGE levels in the human body, with several approaches available, each with its advantages and disadvantages. This pilot study aimed to investigate the association between urinary AGEs, measured using spectrofluorimetry-based assays, and circulating microRNAs (c-miRNAs) in a subsample ( n = 22) of Italian children participating in the I.Family Study. Anthropometric measurements, biochemical markers, and miRNA profiles were assessed. The first indication of a relationship between urinary AGEs and c-miRNAs in the context of obesity was found. Specifically, four miRNAs, hsa-miR-10b-5p, hsa-miR-501-5p, hsa-miR-874-3p, and hsa-miR-2355-5p were significantly associated with levels of urinary AGEs. The association between AGEs, obesity, inflammation markers, and specific miRNAs highlights the complex interplay between these factors and their potential impact on cellular and tissue homeostasis. The discovery of altered c-miRNAs profiling has the potential to offer innovative methods for assessing early changes in the body's AGE pool and allow recognition of an increased risk of disease susceptibility, routinely undetected until metabolic complications are identified.

Cancer is highly infiltrated by myeloid-derived suppressor cells (MDSCs). Currently available immunotherapies do not completely eradicate MDSCs. Through a genome-wide analysis of the translatome of prostate cancers driven by different genetic alterations, we demonstrate that prostate cancer rewires its secretome at the translational level to recruit MDSCs. Among different secreted proteins released by prostate tumor cells, we identified Hgf, Spp1 and Bgn as the key factors that regulate MDSC migration. Mechanistically, we found that the coordinated loss of Pdcd4 and activation of the MNK/eIF4E pathways regulate the mRNAs translation of Hgf, Spp1 and Bgn. MDSC infiltration and tumor growth were dampened in prostate cancer treated with the MNK1/2 inhibitor eFT508 and/or the AKT inhibitor ipatasertib, either alone or in combination with a clinically available MDSC-targeting immunotherapy. This work provides a therapeutic strategy that combines translation inhibition with available immunotherapies to restore immune surveillance in prostate cancer., (© 2023. The Author(s), under exclusive licence to Springer Nature America, Inc.)

The last decade has witnessed massive advancements in high-throughput techniques capable of producing increasingly complex gene expression datasets across time and space and at the resolution of single cells. Yet, the large volume of big data available and the complexity of experimental designs hamper an easy understanding and effective communication of the results. We present expressyouRcell , an easy-to-use R package to map the multi-dimensional variations of transcript and protein levels in dynamic cell pictographs. expressyouRcell visualizes gene expression variations as pictographic representations of cell-type thematic maps. expressyouRcell visually reduces the complexity of displaying gene expression and protein level changes across multiple measurements (time points or single-cell trajectories) by generating dynamic representations of cellular pictographs. We applied expressyouRcell to single cell, bulk RNA sequencing (RNA-seq), and proteomics datasets, demonstrating its flexibility and usability in the visualization of complex variations in gene expression. Our approach improves the standard quantitative interpretation and communication of relevant results., Competing Interests: GV has been scientific advisor of IMMAGINA Biotechnology s.r.l. until November 2022., (© 2023 The Author(s).)

Regeneration of the neuromuscular junction (NMJ) leverages on extensive exchange of factors released from motor axon terminals (MATs), muscle fibers and perisynaptic Schwann cells (PSCs), among which hydrogen peroxide (H 2 O 2 ) is a major pro-regenerative signal. To identify critical determinants of NMJ remodeling in response to injury, we performed temporal transcriptional profiling of NMJs from 2 month-old mice during MAT degeneration/regeneration, and cross-referenced the differentially expressed genes with those elicited by H 2 O 2 in SCs. We identified an enrichment in extracellular matrix (ECM) transcripts, including Connective Tissue Growth Factor (Ctgf), which is usually expressed during development. We discovered that Ctgf levels are increased in a Yes-associated protein (YAP)-dependent fashion in response to rapid, local H 2 O 2 signaling generated by stressed mitochondria in the injured sciatic nerve, a finding highlighting the importance of signals triggered by mechanical force to motor nerve repair. Through sequestration of Ctgf or inactivation of H 2 O 2 , we delayed the recovery of neuromuscular function by impairing SC migration and, in turn, axon-oriented re-growth. These data indicate that H 2 O 2 and its downstream effector Ctgf are pro-regenerative factors that enable axonal growth, and reveal a striking ECM remodeling process during nerve regeneration upon local H 2 O 2 signaling. Our study identifies key transcriptomic changes at the regenerating NMJ, providing a rich source of pro-regenerative factors with potential for alleviating the consequences of peripheral nerve injuries., (© 2022. The Author(s).)

A significant body of literature has been generated related to the detection of measurable residual disease (MRD) at the time of achieving complete remission (CR) in patients with hairy cell leukemia (HCL). However, due to the indolent nature of the disease as well as reports suggesting long-term survival in patients treated with a single course of a nucleoside analog albeit without evidence of cure, the merits of detection of MRD and attempts to eradicate it have been debated. Studies utilizing novel strategies in the relapse setting have demonstrated the utility of achieving CR with undetectable MRD (uMRD) in prolonging the duration of remission. Several assays including immunohistochemical analysis of bone marrow specimens, multi-parameter flow cytometry and molecular assays to detect the mutant BRAF V600E gene or the consensus primer for the immunoglobulin heavy chain gene (IGH) rearrangement have been utilized with few comparative studies. Here we provide a consensus report on the available data, the potential merits of MRD assessment in the front-line and relapse settings and recommendations on future role of MRD assessment in HCL., (© 2022. The Author(s).)

Background: This study aimed to examine associations of early childhood physical fitness and physical activity (PA) with PA during later childhood/early adolescence while accounting for gender differences., Methods: We selected data of N = 4329 children from the IDEFICS/I. Family cohort (age 2.4-11.7 years) with data on baseline fitness and accelerometer measurements. At baseline, physical fitness tests were conducted including Flamingo balance, Backsaver sit and reach, Handgrip strength, Standing Long Jump, 40-m sprint and 20-m Shuttle run (to estimate cardio-respiratory fitness levels). PA was measured with Actigraph accelerometers over 3 days at baseline (ActiTrainer or GT1M) and 7 days at follow-up (GT3X). Evenson cutpoints were used to determine moderate-to-vigorous PA (MVPA) time, and children with ≥60mins/day of average MVPA were deemed as having met WHO guidelines at baseline and follow-up. Linear and logistic regressions were performed to examine longitudinal associations between meeting WHO guidelines, MVPA, and physical fitness tests at baseline with meeting WHO guidelines and MVPA at follow-up. Models were conducted on the entire sample, the sex-stratified sample, and stratified by sex and pubertal status at follow-up., Results: Results showed that meeting WHO guidelines for MVPA at baseline was positively associated with MVPA (Standardized Beta (B) = 0.13, 95%CI:(5.6;11.1)) and meeting WHO guidelines at follow-up for the entire sample (OR = 2.1, 95%CI:(1.5; 3.14), and stratified by males (OR = 2.5, 95%CI:(1.5; 4.1)) and females (OR = 1.8, 95%CI:(1.0; 3.2)). This was also found for both male pre/early pubertal and pubertal groups but only in the female pre/early pubertal group, and not the female pubertal group (MVPA: B = .00, 95%CI:(- 6.1; 5.6), WHO: OR = 0.61, 95%CI:(0.23;1.6)). Models indicated that Standing Long jump, 40-m sprint, Shuttle run and Flamingo balance at baseline were associated with MVPA and meeting the guidelines at follow-up., Conclusions: Meeting WHO guidelines and certain fitness tests at baseline were strongly associated with MVPA and meeting WHO guidelines at follow-up, but this association varied with sex and pubertal status. Consequently, these findings underline the importance of ensuring sufficient physical activity in terms of quality and quantity for children at the earliest stages of life., Trial Registration: ISRCTN62310987., (© 2022. The Author(s).)

Background: Living in single parent and blended families or as an only child-compared to living in two-parent biological families or with siblings, respectively-is associated with a higher body mass index (BMI) in cross-sectional studies. However, longitudinal research addressing the children's BMI in this context is scarce. Further, little is known about the association between family structure and metabolic health., Objectives: This study aimed at investigating the association between both aspects of family structure with BMI and a metabolic score (MetS)., Methods: Cross-sectional data from 7804 children participating in the European multi-center I.Family study (2013/2014) and longitudinal data from 5621 children who also participated previously in the IDEFICS study (2007-2010) were used. Family structure was assessed by a detailed interview. BMI z-score and the MetS were based on measured anthropometry, blood pressure, high-density lipoprotein, blood glucose, and triglycerides. Linear regressions were performed to model associations between family structure with BMI and MetS., Results: Children from single-parent families had higher BMI z-scores in the cross-sectional (β = 0.09, 95% confidence interval [CI]: 0.001 to 0.18) and longitudinal analyses compared to those from two-parent families. Cross-sectionally, the number of siblings was associated with lower BMI z-scores (β = -0.07, 95% CI: -0.10 to -0.03) and lower MetS (β = -0.14, 95% CI: -0.26 to -0.01). Longitudinally, only children between baseline and follow-up had higher BMI z-scores at follow-up (β = 0.07, 95% CI: 0.01 to 0.14) compared to stable siblings., Conclusion: Obesity prevention measures should focus on single-parent households and families with an only child., (© 2022 The Authors. Pediatric Obesity published by John Wiley & Sons Ltd on behalf of World Obesity Federation.)

Advanced Glycation End Products (AGEs) have been positively correlated with inflammation in adults, while inconsistent evidence is available in children. We evaluated the association between urinary AGEs, measured by fluorescence spectroscopy, and biomarkers of subclinical inflammation in 676 healthy children/adolescents (age 11.8 ± 1.6 years, M ± SD) from the Italian cohort of the I.Family project. Urinary fluorescent AGEs were used as independent variable and high-sensitivity C-reactive protein (hs-CRP) was the primary outcome, while other biomarkers of inflammation were investigated as secondary outcomes. Participants with urinary AGEs above the median of the study population showed statistically significantly higher hs-CRP levels as compared to those below the median (hs-CRP 0.44 ± 1.1 vs. 0.24 ± 0.6 mg/dL, M ± SD p = 0.002). We found significant positive correlations between urinary AGEs and hs-CRP ( p = 0.0001), IL-15 ( p = 0.001), IP-10 ( p = 0.006), and IL-1Ra ( p = 0.001). At multiple regression analysis, urinary AGEs, age, and BMI Z-score were independent variables predicting hs-CRP levels. We demonstrated for the first time, in a large cohort of children and adolescents, that the measurement of fluorescent urinary AGEs may represent a simple, noninvasive, and rapid technique to evaluate the association between AGEs and biomarkers of inflammation. Our data support a role of AGEs as biomarkers of subclinical inflammation in otherwise healthy children and adolescents.

We aimed to describe differences in taste sensitivity in children according to age across 7- to 11-year-old children from eight European countries. We further compared taste sensitivity between boys vs. girls and under-/normal weight vs. overweight/obese children. Within the European multicentre IDEFICS (Identification and prevention of dietary and lifestyle-induced health effects in children and infants) study, 1938 school children participated in sweet, bitter, salty and umami detection threshold tests between 2007 and 2010, using the paired comparison staircase method. The lowest concentration at which the child was able to detect a difference to water was determined as taste detection threshold as a proxy of taste sensitivity. Mean taste thresholds were calculated stratified for sex, age groups, weight groups and country. BMI was calculated using measured height and weight; socio-demographic information was collected using questionnaires. Ordinal logistic regressions were conducted to investigate the association between sex, weight status (as categorical exposure variable) and age (as continuous exposure variable) and the taste sensitivity for the four taste modalities (as outcome), separately. Older children were more taste sensitive for sweet and salty and less taste sensitive for umami and bitter than younger children. Girls were more sensitive to sweet taste than boys. Overweight or obese children were less sensitive to sweet and salty taste compared to normal weight children This was the first study comparing taste sensitivity by measuring taste thresholds in children across different European countries. We conclude that taste thresholds are associated with weight status, children become more sensitive to sweet and salty tastes with increasing age, and girls might be more sensitive to sweet than boys., (Copyright © 2022. Published by Elsevier Ltd.)

We herein report the case of a voluminous splenic artery aneurysm (SAA) diagnosed in a 48 year-old Caucasian male patient. After endovascular treatment failure, considering the volumetric aneurysm increase and recurrent symptoms, a laparoscopic splenic artery aneurysmectomy with partial splenectomy guided by indocyanine green fluorescence (ICG) was performed. This conservative strategy leads to save a spleen volume of about 10 cm 3 to avoid postsplenectomy thrombocytosis and infections, potential immunodeficiency and overwhelming postsplenectomy infection syndrome (OPSS) and to preserve pancreatic vascularization preventing distal pancreas injuries.

Abstract: Infertility has been characterized as a disease by the World Health Organization (WHO) and reportedly affects about 10-12% of couples worldwide, while the incidence is even higher in Italy, at about 15%. The issue of iatrogenic infertility arising from treatments that can compromise an individual's reproductive capacity, it is necessary to inform patients of the possible damage on their future fertility and on the possibilities to preserve it. The complexities inherent in the various techniques and approaches aimed at preserving fertility should be expounded upon thoroughly to the patients, who should also receive proper psychological assistance and counseling, which ought to take into account the ethical distinctive challenges and the possible misgivings that may be caused in patients. Ovarian Tissue Cryopreservation (OTC) and ovarian tissue transplantation (OTT) can constitute a valuable part of the clinical armamentarium for preserving fertility, although the data are still inconclusive, particularly in over-36 patients. The multidisciplinary nature of the healthcare teams involved in such interventions is of paramount importance to optimize results.

Unhealthy diets represent a major risk for the pathogenesis of metabolic and chronic inflammatory diseases. Improving the quality of diet is important to prevent chronic diseases, and diet-induced modifications of the gut microbiota (GM) community likely play an important role. The EU-funded Stance4Health project aims at performing a randomized clinical trial based on a nutritional intervention program in the context of normal weight and overweight adults as well as children with obesity and gluten-related disorders or allergy/intolerance to cow's milk. The trial will evaluate the efficacy of a Smart Personalised Nutrition (SPN) service in modifying GM composition and metabolic function and improving consumer empowerment through technology adoption.

Anastomotic leakage is the most-feared complication of rectal surgery. Transanal devices have been suggested for anastomotic protection as an alternative to defunctioning stoma, although evidence is conflicting, and no single device is widely used in clinical practice. The aim of this paper is to investigate the safety and efficacy of a transanal tube for the prevention of leakage following laparoscopic rectal cancer resection. A transanal tube was used in the cases of total mesorectal excision with low colorectal or coloanal anastomosis, undamaged doughnuts, and negative intraoperative air-leak test. The transanal tube was kept in place until the seventh postoperative day. A total of 195 consecutive patients were retrieved from a prospective surgical database and included in the study. Of these, 71.8% received preoperative chemoradiotherapy. The perioperative mortality rate was 1.0%. Anastomotic leakage occurred in 19 patients, accounting for an incidence rate of 9.7%. Among these, 13 patients underwent re-laparoscopy and ileostomy, while 6 patients were managed conservatively. Overall, the stoma rate was 6.7%. The use of a transanal tube may be a suitable strategy for anastomotic protection following restorative rectal cancer resection. This approach could avoid the burden of a stoma in selected patients with low anastomoses.

Increasing data suggest that overnutrition-induced obesity may trigger an inflammatory process in adipose tissue and upturn in the innate immune system. Numerous players have been involved in governing the inflammatory response, including epigenetics. Among epigenetic players, miRNAs are emerging as crucial regulators of immune cell development, immune responses, autoimmunity, and inflammation. In this study, we aimed at identifying the involvement of candidate miRNAs in relation to inflammation-associated biomarkers in a subsample of European children with overweight and obesity participating in the I.Family study. The study sample included individuals with increased adiposity since this condition contributes to the early occurrence of chronic low-grade inflammation. We focused on the acute-phase reagent C-reactive protein (CRP) as the primary outcome and selected cytokines as plausible biomarkers of inflammation. We found that chronic low-grade CRP elevation shows a highly significant association with miR-26b-3p and hsa-miR-576-5p in boys. Furthermore, the association of CRP with hsa-miR-10b-5p and hsa-miR-31-5p is highly significant in girls. We also observed major sex-related associations of candidate miRNAs with selected cytokines. Except for IL-6, a significant association of hsa-miR-26b-3p and hsa-miR-576-5p with TNF-α, IL1-Ra, IL-8, and IL-15 levels was found exclusively in boys. The findings of this exploratory study suggest sex differences in the association of circulating miRNAs with inflammatory response biomarkers, and indicate a possible role of miRNAs among the candidate epigenetic mechanisms related to the process of low-grade inflammation in childhood obesity.

Most RNA footprinting approaches that require ribonuclease cleavage generate RNA fragments bearing a phosphate or cyclic phosphate group at their 3' end. Unfortunately, current library preparation protocols rely only on a 3' hydroxyl group for adaptor ligation or poly-A tailing. Here, we developed circAID-p-seq, a PCR-free library preparation for selective 3' phospho-RNA sequencing. As a proof of concept, we applied circAID-p-seq to ribosome profiling, which is based on sequencing of RNA fragments protected by ribosomes after endonuclease digestion. CircAID-p-seq, combined with the dedicated computational pipeline circAidMe, facilitates accurate, fast and highly efficient sequencing of phospho-RNA fragments from eukaryotic cells and tissues. We used circAID-p-seq to portray ribosome occupancy in transcripts, providing a versatile and PCR-free strategy to possibly unravel any endogenous 3'-phospho RNA molecules., (© The Author(s) 2021. Published by Oxford University Press on behalf of Nucleic Acids Research.)

Background: Muscular and cardiorespiratory fitness (MF and CRF) have been related to inflammation. Thus, the aim of this study was to assess the relationship between fitness and high-sensitivity C-reactive protein (hs-CRP) in European children both in the cross-sectional and longitudinal analysis., Methods: Three hundred and fifty-seven children (46.2% males) aged 2-9 years with hs-CRP measured, data from MF and CRF, diet quality, objectively measured physical activity (PA) and screen time at baseline and follow-up after 2 years were included. Body mass index z-score (zBMI), waist circumference (WC) and fat mass index (FMI) were assessed. MF and CRF were also dichotomized as follows: low-medium quartiles (Q1-Q3) and highest quartile (Q4)., Results: At follow-up, children with the highest CRF (Q4) showed a lower probability of having high hs-CRP. In the longitudinal analysis, children who improved their CRF over time showed a significantly lower probability (p < 0.05) of being in the highest hs-CRP category at follow-up, independently of the body composition index considered: odds ratio (OR) = 0.22 for zBMI, OR = 0.17 for WC, and OR = 0.21 for FMI., Conclusions: Improving CRF during childhood reduces the odds of an inflammatory profile, independently of body composition and lifestyle behaviours. These highlight the importance of enhancing fitness, especially CRF, to avoid an inflammatory state in children., Impact: Improvements in the cardiorespiratory profile during childhood could reverse an unfavourable inflammatory status. There is a longitudinal and inverse association between CRF and inflammation in children. This is the first longitudinal study assessing the relationship between fitness and inflammation during childhood that takes also into account the lifestyle behaviours. Results from the present study suggest a protective role of fitness already in childhood. Efforts to improve fitness in children should be aimed at as inflammation could trigger future cardiovascular disease., (© 2021. The Author(s), under exclusive licence to the International Pediatric Research Foundation, Inc.)

Introduction: Unbalanced dietary intake has been increasingly recognized as an important modifiable risk factor for asthma. In this study, we assessed whether a pro-inflammatory diet is associated with higher asthma burden in three steps: (1) identification of asthma latent classes (LC) based on symptoms, indoor exposures, and pulmonary function; (2) identification of risk factors associated with LC membership; and (3) estimation of the probabilities of LC membership with variation in DII., Methods: A cross-sectional study on 415 children aged 5-14 years (266 with persistent asthma and 149 controls). LC analysis was performed in asthmatic children. The DII was calculated based on a semiquantitative food frequency questionnaire. Elastic net logistic regression was used to investigate whether increasing DII was associated with worse asthma burden., Results: Two LCs were identified. Children in Class 1, "high burden," had higher symptom burden and worse lung function. Children in Class 2, "low burden," had lower symptom burden and less impaired lung function but were more subject to indoor exposures. DII was the only risk factor significantly associated with Class 1 membership. As the DII increased (from -4.0 to +4.0), the probability of Class 1 membership increased from 32% to 65% when compared with control group, whereas it increased from 41% to 72% when compared with Class 2., Conclusions: We identified two phenotypes of persistent asthma associated with different disease burden linked to indoor exposures. An increasing DII was associated with high-burden asthma, providing further evidence about the role of a pro-inflammatory diet in asthma morbidity., (© 2021 EAACI and John Wiley and Sons A/S. Published by John Wiley and Sons Ltd.)

Introduction: Over the past decades, children have been increasingly using screen devices, while at the same time their sleep duration has decreased. Both behaviors have been associated with excess weight, and it is possible they act as mutually reinforcing behaviors for weight gain. The aim of the study was to explore independent, prospective associations of screen time and sleep duration with incident overweight in a sample of European children., Methods: Data from 4,285 children of the IDEFICS/I.Family cohort who were followed up from 2009/2010 to 2013/2014 were analyzed. Hours per day of screen time and of sleep duration were reported by parents at baseline. Logistic regression analyses were carried out in separate and mutually adjusted models controlled for sex, age, European country region, parental level of education, and baseline BMI z-scores., Results: Among normal weight children at baseline (N = 3,734), separate models suggest that every hour increase in screen time and every hour decrease in sleep duration were associated with higher odds of the child becoming overweight or obese at follow-up (OR = 1.16, 95% CI: 1.02-1.32 and OR = 1.23, 95% CI: 1.05-1.43, respectively). In the mutually adjusted model, both associations were attenuated slightly ( screen time OR = 1.13, 95% CI: 0.99-1.28; sleep duration OR = 1.20, 95% CI: 1.03-1.40), being consistently somewhat stronger for sleep duration., Discussion/conclusion: Both screen time and sleep duration increased the incidence of overweight or obesity by 13-20%. Interventions that include an emphasis on adequate sleep and minimal screen time are needed to establish their causal role in the prevention of overweight and obesity among European children., (© 2021 The Author(s). Published by S. Karger AG, Basel.)

Cancer is one of the main causes of death worldwide, and, among the most frequent cancer types, osteosarcoma accounts for 56% of bone neoplasms observed in children and colorectal cancer for 10.2% of tumors diagnosed in the adult population. A common and frequent hurdle in cancer treatment is the emergence of resistance to chemo- and radiotherapy whose biological causes are largely unknown. In the present work, human osteosarcoma (SAOS) and colorectal adenocarcinoma (HT29) cell lines were γ-irradiated at doses mimicking the sub-lethal irradiation in clinical settings to obtain two radio-resistant cellular sub-populations named SAOS400 and HT500, respectively. Since "therapy-induced senescence" (TIS) is often associated with tumor response to radiotherapy in cancer cells, we measured specific cellular and biochemical markers of senescence in SAOS400 and HT500 cells. In detail, both cell lines were characterized by a higher level of expression of cyclin-dependent kinase inhibitors p16 INK4 and p21 CIP1 and increased positivity to SAβ-gal (senescence-associated β-galactosidase) with respect to parental cells. Moreover, the intracellular levels of reactive oxygen species in the resistant cells were significantly lower compared to the parental counterparts. Subsequently, we demonstrated that senolytic agents were able to sensitize SAOS400 and HT500 to cell death induced by γ-irradiation. Employing two natural flavonoids, fisetin and quercetin, and a BH3-mimetic, ABT-263/navitoclax, we observed that their association with γ-irradiation significantly reduced the expression of p16 INK4 , p21 CIP1 and synergistically (combination index < 1) increased cell death compared to radiation mono-alone treatments. The present results reinforce the potential role of senolytics as adjuvant agents in cancer therapy.

The European Commission funded project Stance4Health (S4H) aims to develop a complete personalised nutrition service. In order to succeed, sources of information on nutritional composition and other characteristics of foods need to be as comprehensive as possible. Food composition tables or databases (FCT/FCDB) are the most commonly used tools for this purpose. The aim of this study is to describe the harmonisation efforts carried out to obtain the Stance4Health FCDB. A total of 10 FCT/FCDB were selected from different countries and organizations. Data were classified using FoodEx2 and INFOODS tagnames to harmonise the information. Hazard analysis and critical control points analysis was applied as the quality control method. Data were processed by spreadsheets and MySQL. S4H's FCDB is composed of 880 elements, including nutrients and bioactive compounds. A total of 2648 unified foods were used to complete the missing values of the national FCDB used. Recipes and dishes were estimated following EuroFIR standards via linked tables. S4H's FCDB will be part of the smartphone app developed in the framework of the Stance4Health European project, which will be used in different personalized nutrition intervention studies. S4H FCDB has great perspectives, being one of the most complete in terms of number of harmonized foods, nutrients and bioactive compounds included.

Background: Elevated cardiometabolic risk (CMR) is an important factor for cardiovascular diseases later in life while physical fitness seems to decrease CMR., Objective: Thus, the aim of the present study is to assess the association between muscular fitness (MF) and cardiorespiratory fitness (CRF) on CMR in European children, both cross-sectional and longitudinally., Methods: A total of 289 children (49.5% males) from eight European countries, aged 6 to 9, with longitudinal information on blood pressure, triglycerides, total cholesterol, HDL-cholesterol, homoeostasis model assessment, body mass index, data on fitness level, objectively measured physical activity (PA), diet quality, and total screen time were included. A CMR score was calculated and dichotomized. MF and CRF were also dichotomized. Cross-sectional and longitudinal multilevel logistic regressions adjusting for lifestyle behaviours were performed., Results: Reaching a high level of MF during childhood as well as remaining in that level over-time were associated with an 82% and 62% lower probability of high CMR at follow-up, respectively. Also, children who became top CRF over time, showed a 77% lower probability (P < 0.05) of being in the highest CMR quartile at follow-up, independently of sociodemographic and lifestyle indicators., Conclusions: A high MF at early childhood and during childhood reduces the odds of having CMR. Same occurs with the improvement of CRF during childhood. These findings highlight the importance of enhancing fitness to avoid CMR already in children., (© 2021 The Authors. Pediatric Obesity published by John Wiley & Sons Ltd on behalf of World Obesity Federation.)