In rats fed high-energy diets, taste, rather than fat content, is the key factor increasing food intake: a comparison of a cafeteria and a lipid-supplemented standard diet

Podeu consultar dades primàries associades a l'article a: http://hdl.handle.net/2445/111074Background. Food selection and ingestion both in humans and rodents, often is a critical factor in determining excess energy intake and its related disorders. Methods. Two different concepts of high-fat diets were tested for their obesogenic effects in rats; in both cases, lipids constituted about 40% of their energy intake. The main difference with controls fed standard lab chow, was, precisely, the lipid content. Cafeteria diets (K) were self-selected diets devised to be desirable to the rats, mainly because of its diverse mix of tastes, particularly salty and sweet. This diet was compared with another, more classical high-fat (HF) diet, devised not to be as tasty as K, and prepared by supplementing standard chow pellets with fat. We also analysed the influence of sex on the effects of the diets. Results. K rats grew faster because of a high lipid, sugar and protein intake, especially the males, while females showed lower weight but higher proportion of body lipid. In contrast, the weight of HF groups were not different from controls. Individual nutrient's intake were analysed, and we found that K rats ingested large amounts of both disaccharides and salt, with scant differences of other nutrients' proportion between the three groups. The results suggest that the key differential factor of the diet eliciting excess energy intake was the massive presence of sweet and salty tasting food. Conclusions. The significant presence of sugar and salt appears as a powerful inducer of excess food intake, more effective than a simple (albeit large) increase in the diet's lipid content. These effects appeared already after a relatively short treatment. The differential effects of sex agree with their different hedonic and obesogenic response to diet

Impact of COVID-19 on cancer care pathways in a comprehensive cancer center in northern Italy

The COVID-19 pandemic burdened health care systems worldwide. Health services were reorganized with the dual purpose of ensuring the most adequate continuity of care and, simultaneously, the safety of patients and health professionals. The provision of care to patients within cancer care pathways (cCPs) was not touched by such reorganization. We investigated whether the quality of care provided by a local comprehensive cancer center has been maintained using cCP indicators. A retrospective single-cancer center study was conducted on eleven cCPs from 2019 to 2021 by comparing three timeliness indicators, five care indicators and three outcome indicators yearly calculated on incident cases. Comparisons of indicators between 2019 and 2020, and 2019 and 2021, were performed to assess the performance of cCP function during the pandemic. Indicators displayed heterogeneous significant changes attributed to all cCPs over the study period, affecting eight (72%), seven (63%) and ten (91%) out of eleven cCPs in the comparison between 2019 and 2020, 2020 and 2021, and 2019 and 2021, respectively. The most relevant changes were attributed to a negative increase in time-to-treatment surgery-related indicators and to a positive increase in the number of cases discussed by cCP team members. No variations were found attributed to outcome indicators. Significant changes did not account for clinical relevance once discussed by cCP managers and team members. Our experience demonstrated that the CP model constitutes an appropriate tool for providing high levels of quality care, even in the most critical health situations

Impatto dell’ambiente materno precoce e del sesso sul comportamento e metabolismo in due modelli murini KO

Le interazioni gene-ambiente svolgono un ruolo critico nella modulazione dello sviluppo dell’organismo: in particolare l’ambiente materno precoce sembra essere un fattore chiave dello sviluppo neuro-comportamentale. Il legame tra la madre e il figlio infatti è considerato la relazione sociale più comune e duratura nei mammiferi, filogeneticamente conservato tra le diverse specie. Evidenze sperimentali indicano che l’ambiente materno precoce può modulare la regolazione dell’espressione genica; diversi studi hanno dimostrato che animali che avevano ricevuto maggiori cure materne durante il primo periodo post nascita, presentavano minori livelli di ansia, minore produzione di ACTH e corticosterone, minore invecchiamento nell’ippocampo e maggiore attività immunitaria in risposta allo stress. Negli esprimenti condotti abbiamo approfondito come l’interazione tra ambiente materno precoce e lo specifico background genetico, in relazione al sesso, agisca sul metabolismo e il comportamento. Abbiamo esaminato quindi due diversi modelli murini con modificazioni geniche: il primo è un modello caratterizzato da un knockout condizionale per il recettore Y1r nei neuroni eccitatori del proencefalo; il secondo è un knockout selettivo per TLQP21 (ΔTLQP-21), peptide derivato di VGF. Per testare l’ipotesi che gli effetti della delezione genica possono variare in relazione all’ambiente materno precoce, nel primo esperimento Npy KO e controlli di entrambi i sessi sono stati dati in adozione alla nascita a madri ad alto o basso grado di cure materne (rispettivamente CD1 swiss, FVB – C57/Bl6, Balb/c). In età adulta i topi sono stati sottoposti a test comportamentali per valutare l’aspetto emozionale, sociale ed aggressivo, e a test metabolici in risposta a dieta standard o ad alto contenuto di grassi. Nel secondo esperimento abbiamo eseguito un’analisi dettagliata dell’effetto dell’ambiente materno precoce sugli animali controllo del modello Npy Y1r KO. Nel terzo esperimento infine abbiamo osservato il comportamento materno e il successo riproduttivo in topi ΔTLQP-21 eterozigoti o omozigoti, ed eseguito una caratterizzazione della prole analizzando comportamento emozionale e simil-depressivo negli individui adulti di entrambi i sessi. In generale i risultati del primo studio hanno mostrato che i maschi, ma non le femmine, avevano un aumento dei comportamenti simil-ansiosi e pesavano meno dei loro rispettivi controlli solo quando allevati da madri adottive ad alto grado di cure materne. Nel secondo esperimento abbiamo dimostrato che l’ambiente materno agisce sullo sviluppo della prole ma l’impatto non è ascrivibile soltanto alle variazioni delle cure materne; infatti anche la quantità e la qualità del latte materno e fattori nutrizionali potrebbero essere variabili importanti che influenzano il comportamento e il metabolismo in età adulta. Infine, i risultati del terzo studio hanno indicato che la mutazione nel gene TLQP21 influenza il comportamento materno: genitori che avevano fenotipo mutante ed eterozigote mostravano un livello minore di cure materne (definito dal tempo trascorso nella posizione di arched back) se confrontati con topi wild-type. Tale differenza ha effetto anche sul fenotipo comportamentale degli animali adulti, in particolare riguardo al comportamento emozionale e alle relative differenze sessuali. Saranno dunque necessari ulteriori studi per comprendere il ruolo della nutrizione e del latte materno nello sviluppo comportamentale della prole negli animali Ko e Wt del modello Npy, e per capire in maniera dettagliata quale sia il ruolo dell’ambiente materno nei topi ΔTLQP-21.I risultati ottenuti sottolineano quanto sia importante prendere in considerazione la complessa interazione tra gene, ambiente materno precoce ed effetti legati al sesso quando si lavora con modelli murini geneticamente modificati per identificare funzioni specifiche dei geni.Interactions between genes and environment are recognized to play a critical role in modulating the development of the organism. More in details early maternal environment seems to be a key factor in shaping neuro-behavioral development; the mother-infant bond is the strongest and more common social relationship in mammal species and phylogenetically highly conserved. Experimental evidence demonstrated that maternal behavior may act on the regulation of genetic expression; in adult life, the offspring that had received high levels of maternal cares showed lower anxiety, less ACTH and Corticosterone production, less aging effect on hyppocampus and more immune activity in response to stress. In the present experiments we investigated the interaction between early maternal environment and specific genetic background, in relation to sex on metabolism and behaviour. We examined two different genetically modified mice models; the first one is a mouse model characterized by a conditional knock-out of the Y1 receptor in the excitatory neurons of the forebrain; the second one is a knockin mouse model of selective loss of the VGF peptide TLQP-21. To test the hypothesis that the effects of gene deletion may vary in relation to early maternal environment, in the first experiment male and female, Npy Ko and control mice were fostered at birth to dams that displayed high or low levels of maternal care (CD1 swiss, FVB – C57/Bl6, Balb/c respectively). As adults mice were tested for emotional, aggressive and social behavior and metabolic changes in response to standard or high fat diets. In the second experiment we performed a detailed analysis of the effect of early maternal environment on control animals of the Npy Y1r KO model. In the third experiment we observed maternal behavior and reproductive success in ΔTLQP-21 heterozygotes or homozygotes breeders and characterized their offspring by an analysis of emotional and depression-like behaviors in adult males and females. Overall the results of the first study showed that males, but not females, had an increase in axiety-like behavior and weighted less than their controls, but only when reared by foster mothers displaying high levels of maternal care. In the second experiment, we demonstrated that early maternal environment affected offspring development but its impact can not be ascribed entirely to the variation in maternal cares; in fact also maternal milk quality/quantity and nutritional factors could be important variables influencing behavior and metabolism in adult’s life. Lastly, results in the third study indicated that the mutation in TLQP21 gene influence maternal behavior, with mutant or heterozygotes breeders displaying lower amount of maternal care (defined by the time spent in the arched back position) when compared with wild type mice. Such a difference affected the offspring subsequent behavioral phenotype as adults, particularly emotional behaviour and sex related differences . Further study will be necessary to investigate the role of nutrition and maternal milk in metabolic and behavioural development of offspring in both NPY KO and WT animals, and to better understand the role of early maternal environment in ΔTLQP-21 mouse. The present findings, however, highlight the importance to take into consideration and control for the complex interaction between genes, early maternal environment and sex-related effects when working with GM mouse models to uncover specific gene functions

Learning from Adaptations to the COVID-19 Pandemic: How Teleconsultation Supported Cancer Care Pathways at a Comprehensive Cancer Center in Northern Italy

Multidisciplinary team (MDT) meetings are recognized as the gold standard for care management of cancer patients, and during the COVID-19 pandemic they were considered a priority to be maintained. Due to pandemic-related restrictions, MDT meetings were forcibly converted from in-person to telematic format. This retrospective study evaluated the annual performance of four MDT meeting indicators (MDT members’ attendance, number of discussed cases, frequency of MDT meetings, and duration) between 2019 and 2022 to report on the implementation of teleconsultation in MDT meetings related to 10 cancer care pathways (CCPs). Over the study period, MDT member participation and the number of discussed cases improved or did not change in 90% (9/10) and 80% (8/10) of the CCPs, respectively. We did not observe significant differences in any of the CCPs included in the study regarding the annual frequency and duration of MDT meeting. Considering the rapidity, extent, and intensity with which telematic tools were adopted due to the COVID-19 pandemic, the results of this study showed that MDT teleconsultation supported the CCPs, and consequently, the delivery of cancer care in COVID-19 times, helping to understand the effects of telematic tools on health care performance and the parties involved

In Rats Fed High-Energy Diets, Taste –Rather than Fat Content– Is the Key Factor Increasing Food Intake. Comparison of a Cafeteria and a Lipid-Supplemented Standard Diet (Raw data)

Dades primàries associades a un article enviat a la revista PeerJ i pendent d'avaluació (maig 2017)Podeu consultar l'article a: http://hdl.handle.net/2445/115482Background: Diet deeply affects the food selection and ingestion both in humans and rodents, often resulting in excess energy intake. Methods: We investigated this process comparing two different high-fat dietary approaches to induce obesity, in which all rats received about 40% of their energy intake as lipids. The main nutrient difference between the diets, when compared with controls fed standard lab chow, was the lipid content. Cafeteria diets (K) were devised to be tasty, and thus highly desirable to the rats, mainly for its diverse mix of tastes, particularly salty and sweet. This diet was compared with another high-fat (HF) potentially obesogenic diet, devised not to be as tasty as K, and prepared just supplementing standard chow pellets with fat. We also analysed the influence of sex on the effects of the diets. Results: K rats grew faster, especially the males, although females showed a higher proportion of body lipid, because of a high lipid, sugar and protein intake. HF weight change rates were not different from those of controls. In addition to high sugar, K rats also ingested large amounts of salt. With this study we have shown that the key factor eliciting the excess energy intake in a high-energy diet rat model was not solely or mainly their fat intake. The changes in body fat accrual were more a consequence of their appetence for the food. Conclusions: The results show that the significant presence of sugar and salt is a powerful factor promoting excess food intake, more effective than increasing diet lipid content. These effects were already observed after a relatively short treatment, additionally confirming the differential effects of sex on the hedonic and obesogenic response to diet

In rats fed high-energy diets, taste, rather than fat content, is the key factor increasing food intake: a comparison of a cafeteria and a lipid-supplemented standard diet

Podeu consultar dades primàries associades a l'article a: http://hdl.handle.net/2445/111074Background. Food selection and ingestion both in humans and rodents, often is a critical factor in determining excess energy intake and its related disorders. Methods. Two different concepts of high-fat diets were tested for their obesogenic effects in rats; in both cases, lipids constituted about 40% of their energy intake. The main difference with controls fed standard lab chow, was, precisely, the lipid content. Cafeteria diets (K) were self-selected diets devised to be desirable to the rats, mainly because of its diverse mix of tastes, particularly salty and sweet. This diet was compared with another, more classical high-fat (HF) diet, devised not to be as tasty as K, and prepared by supplementing standard chow pellets with fat. We also analysed the influence of sex on the effects of the diets. Results. K rats grew faster because of a high lipid, sugar and protein intake, especially the males, while females showed lower weight but higher proportion of body lipid. In contrast, the weight of HF groups were not different from controls. Individual nutrient's intake were analysed, and we found that K rats ingested large amounts of both disaccharides and salt, with scant differences of other nutrients' proportion between the three groups. The results suggest that the key differential factor of the diet eliciting excess energy intake was the massive presence of sweet and salty tasting food. Conclusions. The significant presence of sugar and salt appears as a powerful inducer of excess food intake, more effective than a simple (albeit large) increase in the diet's lipid content. These effects appeared already after a relatively short treatment. The differential effects of sex agree with their different hedonic and obesogenic response to diet

Targeted and selective knockout of the TLQP-21 neuropeptide unmasks its unique role in energy homeostasis

Objective: Pro-peptide precursors are processed into biologically active peptide hormones or neurotransmitters, each playing an essential role in physiology and disease. Genetic loss of function of a pro-peptide precursor results in the simultaneous ablation of all biologically-active peptides within that precursor, often leading to a composite phenotype that can be difficult to align with the loss of specific peptide components. Due to this biological constraint and technical limitations, mice carrying the selective ablation of individual peptides encoded by pro-peptide precursor genes, while leaving the other peptides unaffected, have remained largely unaddressed. Methods: We developed and characterized a mouse model carrying the selective knockout of the TLQP-21 neuropeptide (ΔTLQP-21) encoded by the Vgf gene. To achieve this goal, we used a knowledge-based approach by mutating a codon in the Vgf sequence leading to the substitution of the C-terminal Arginine of TLQP-21, which is the pharmacophore as well as an essential cleavage site from its precursor, into Alanine (R21→A). Results: We provide several independent validations of this mouse, including a novel in-gel digestion targeted mass spectrometry identification of the unnatural mutant sequence, exclusive to the mutant mouse. ΔTLQP-21 mice do not manifest gross behavioral and metabolic abnormalities and reproduce well, yet they have a unique metabolic phenotype characterized by an environmental temperature-dependent resistance to diet-induced obesity and activation of the brown adipose tissue. Conclusions: The ΔTLQP-21 mouse line can be a valuable resource to conduct mechanistic studies on the necessary role of TLQP-21 in physiology and disease, while also serving as a platform to test the specificity of novel antibodies or immunoassays directed at TLQP-21. Our approach also has far-reaching implications by informing the development of knowledge-based genetic engineering approaches to generate selective loss of function of other peptides encoded by pro-hormones genes, leaving all other peptides within the pro-protein precursor intact and unmodified