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Alessio Molfino, Giovanni Imbimbo, Alessandro Laviano Department of Translational and Precision Medicine, Sapienza University of Rome, Rome, ItalyCorrespondence: Alessandro Laviano, Department of Translational and Precision Medicine, Sapienza University of Rome, Viale dell’Università 37, Rome, 00185, Italy, Tel/Fax +39 06 49973902, Email alessandro.laviano@uniroma1.itAbstract: Malnutrition is highly common among cancer patients and is associated with a poor quality of life, increased treatment toxicities and decreased survival. The screening of malnutrition should be performed in an early stage of cancer disease and should be rapid, not expensive and highly sensitive to identify the risk of developing malnutrition. Importantly, international clinical guidelines suggest to perform screening for malnutrition in all cancer patients and if the risk is present, they recommend to perform a full nutritional assessment. During the screening phase, different nutritional parameters are considered including the loss of appetite, low food intake, body weight loss and burden of the disease. These items are present in several screening tools, such as the Nutrition Risk Screening (NRS)-2002, the Malnutrition Universal Screening Tool (MUST) and the Mini Nutritional Assessment (MNA) which represent the most widely used tools to screen for an altered nutritional status in cancer patients. Recently, the Global Leadership Initiative on Malnutrition (GLIM) developed an assessment tool for the diagnosis of malnutrition taking into account the presence of i) involuntary body weight loss, ii) body mass index, iii) low muscle mass, iv) low food intake and disease burden/inflammation; in particular, body weight loss, decreased body mass index (BMI), and low muscle mass are considered as phenotypic criteria, whereas reduced food intake, disease burden and inflammation are defined as etiologic criteria. To perform the diagnosis of malnutrition, GLIM consensus considered the presence of at least one phenotypic and one etiologic criterion. The above-mentioned screening tools were validated in different clinical settings and suggesting the use of one tool vs another is challenging considering, among others, different factors including the type and stage of cancer and the setting (i.e., inpatient or outpatient care). Recent data obtained among large cohorts of cancer patients indicate that personalized nutritional therapy reduced mortality risk and ameliorated quality of life and functionality among cancer patients with high nutritional risk, supporting the urgent need for implementing screening and diagnosis of malnutrition in this context.Keywords: malnutrition, cancer, cachexia, screening, assessment, body weight loss, anorexia

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With the prevalence of obesity soaring and the absence of an effective and safe treatment that is low-cost and always feasible, food supplements have gained attention for their potential benefits in the absence of significant safety concerns. Cinnamomum cassia (CC) and Withania somnifera (WS) are plant-based supplements reported to be effective in improving metabolic health and body composition, the first mainly acting on insulin resistance and the second on energy expenditure and leptin resistance, as shown in preclinical and some clinical studies. Their combination, which is possibly synergistic given their different mechanisms of action, has never been studied. This was a double-blind placebo-controlled study. Patients with overweight or obesity were prescribed a mildly hypocaloric diet with 300 mg CC plus 150 mg WS tid for 4 weeks in a crossover design; anthropometric parameters and safety outcomes were collected. Forty patients were enrolled, and the combination CC + WS induced significant weight loss compared with placebo (−2.66% vs. −1.28%, respectively; p = 0.0002). No significant adverse events were recorded. Our study demonstrates for the first time that the tested combination is an inexpensive yet effective strategy to enhance weight loss in patients receiving a mildly hypocaloric diet. Further studies are warranted to investigate the mechanisms underlying the weight loss effect of CC/WS in human subjects, as well as to explore potential additional metabolic effects obtained with this treatment.

Abstract Aim We tested the effects of a cancer cachexia-anorexia sydrome upon the balance of anti and pro-inflammatory cytokines in the hypothalamus of sedentary or trained tumour-bearing (Walker-256 carcinosarcoma) rats. Methods Animals were randomly assigned to a sedentary control (SC), sedentary tumour-bearing (ST), and sedentary pair-fed (SPF) groups or, exercised control (EC), exercised tumour-bearing (ET) and exercised pair-fed (EPF) groups. Trained rats ran on a treadmill (60%VO2max) for 60 min/d, 5 days/wk, for 8 wks. We evaluated food intake, leptin and cytokine (TNF-α, IL1β) levels in the hypothalamus. Results The cumulative food intake and serum leptin concentration were reduced in ST compared to SC. Leptin gene expression in the retroperitoneal adipose tissue (RPAT) was increased in SPF in comparison with SC and ST, and in the mesenteric adipose tissue (MEAT) the same parameter was decreased in ST in relation to SC. Leptin levels in RPAT and MEAT were decreased in ST, when compared with SC. Exercise training was also able to reduce tumour weight when compared to ST group. In the hypothalamus, IL-1β and IL-10 gene expression was higher in ST than in SC and SPF. Cytokine concentration in hypothalamus was higher in ST (TNF-α and IL-1β, p < 0.05), compared with SC and SPF. These pro-inflammatory cytokines concentrations were restored to control values (p < 0.05), when the animals were submitted to endurance training. Conclusion Cancer-induced anorexia leads towards a pro-inflammatory state in the hypothalamus, which is prevented by endurance training which induces an anti-inflammatory state, with concomitant decrease of tumour weight.

Abstract Objectives To determine the relationship between energy and nutrient consumption with chemosensory changes in cancer patients under chemotherapy. Methods We carried out a cross-sectional study, enrolling 60 subjects. Cases were defined as patients with cancer diagnosis after their second chemotherapy cycle (n = 30), and controls were subjects without cancer (n = 30). Subjective changes of taste during treatment were assessed. Food consumption habits were obtained with a food frequency questionnaire validated for Mexican population. Five different concentrations of three basic flavors --sweet (sucrose), bitter (urea), and a novel basic taste, umami (sodium glutamate)-- were used to measure detection thresholds and recognition thresholds (RT). We determine differences between energy and nutrient consumption in cases and controls and their association with taste DT and RT. Results No demographic differences were found between groups. Cases showed higher sweet DT (6.4 vs. 4.4 μmol/ml; p = 0.03) and a higher bitter RT (100 vs. 95 μmol/ml; p = 0.04) than controls. Cases with sweet DT above the median showed significant lower daily energy (2,043 vs.1,586 kcal; p = 0.02), proteins (81.4 vs. 54 g/day; p = 0.01), carbohydrates (246 vs.192 g/day; p = 0.05), and zinc consumption (19 vs.11 mg/day; p = 0.01) compared to cases without sweet DT alteration. Cases with sweet DT and RT above median were associated with lower completion of energy requirements and consequent weight loss. There was no association between flavors DT or RT and nutrient ingestion in the control group. Conclusion Changes of sweet DT and bitter RT in cancer patients under chemotherapy treatment were associated with lower energy and nutrient ingestion. Taste detection and recognition thresholds disorders could be important factors in malnutrition development on patients with cancer under chemotherapy treatment.

Pig feeding prior to the extensive fattening phase might affect the final lipid profile and product quality. This study evaluates how maternal supplementation with vitamin E (VITE) (100 mg/kg), hydroxytyrosol (HXT) (1.5 mg/kg), or combined administration (VE + HXT) affects the piglet’s plasma and tissues’ fatty acid profiles and lipid stability according to the sow’s parity number (PN), as well as the possible changes to the lipid profile after extensive feeding. The sows’ PN affected the total fatty acid profile of plasma, muscle, and liver of piglets, with lower Δ-9 and Δ-6 desaturase indices but higher Δ-5 in those from primiparous (P) than multiparous (M) sows. Dietary VITE was more effective at decreasing C16:0 and saturated fatty acids in the muscle of piglets born from M than P sows, and modified the liver phospholipids in a different way. Sows’ supplementation with HXT increased C18:2n-6 in triglycerides and polyunsaturated fatty acids (PUFA) in muscle phospholipids. In the liver, HXT supplementation also increased free-PUFA and free-n-3 fatty acids. However, lipid oxidation of piglets’ tissues was not affected by the antioxidant supplementation, and it was higher in the livers of piglets born from M sows. The fatty acid profile in the muscle of pigs after extensive feeding was not affected by the PN, but it was by the sows’ antioxidant supplementation, with positive effects on quality by both compounds.

The term sarcopenia was introduced in 1988. The original definition was a "muscle loss" of the appendicular muscle mass in the older people as measured by dual energy x-ray absorptiometry (DXA). In 2010, the definition was altered to be low muscle mass together with low muscle function and this was agreed upon as reported in a number of consensus papers. The Society of Sarcopenia, Cachexia and Wasting Disorders supports the recommendations of more recent consensus conferences, i.e. that rapid screening, such as with the SARC-F questionnaire, should be utilized with a formal diagnosis being made by measuring grip strength or chair stand together with DXA estimation of appendicular muscle mass (indexed for height2). Assessments of the utility of ultrasound and creatine dilution techniques are ongoing. Use of ultrasound may not be easily reproducible. Primary sarcopenia is aging associated (mediated) loss of muscle mass. Secondary sarcopenia (or disease-related sarcopenia) has predominantly focused on loss of muscle mass without the emphasis on muscle function. Diseases that can cause muscle wasting (i.e. secondary sarcopenia) include malignant cancer, COPD, heart failure, and renal failure and others. Management of sarcopenia should consist of resistance exercise in combination with a protein intake of 1 to 1.5 g/kg/day. There is insufficient evidence that vitamin D and anabolic steroids are beneficial. These recommendations apply to both primary (age-related) sarcopenia and secondary (disease related) sarcopenia. Secondary sarcopenia also needs appropriate treatment of the underlying disease. It is important that primary care health professionals become aware of and make the diagnosis of age-related and disease-related sarcopenia. It is important to address the risk factors for sarcopenia, particularly low physical activity and sedentary behavior in the general population, using a life-long approach. There is a need for more clinical research into the appropriate measurement for muscle mass and the management of sarcopenia. Accordingly, this position statement provides recommendations on the management of sarcopenia and how to progress the knowledge and recognition of sarcopenia.

Cancer threatens nutritional status, and many patients will become cachectic with a negative impact on prognosis. In the TiCaCo pilot trial, we showed a positive effect of calorie matching Nutrition Therapy on both morbidity and mortality. We attempt to validate these results in the TiCaCONCO trial. In a prospective, randomized, single-blinded, controlled trial, patients were treated with either intensive, individual biometric parameter-oriented dietary counseling (nutrition therapy or NT) for a maximum period of three months, or regular dietary counseling (control or CT), before and during conventional cancer treatment. Sixty patients were enrolled over a two-year period, with 30 receiving nutrition therapy and 30 being controls. The primary endpoint was overall survival (OS). Overall survival at 12 months in all patients was 47% (14/30 patients) in the CT group with a median OS of 45.5 weeks, and 73% (22/30 patients) in the NT group with a median OS that was undefined (i.e., cannot be calculated, as >50% of patients in the NT group were still alive at the end of the study) (p = 0.0378). The survival difference still exists when only male patients are analyzed, but is not observed in female patients. Biophysical measurements were performed at 0, 3, and 12 months in all patients. In men, the differences between CT vs NT were statistically significant for body hydration (p = 0.0400), fat mass (p = 0.0480), total energy expenditure (p = 0.0320), and median overall survival at 12 months (p = 0.0390). At 3 months (end of the intervention), the differences between CT vs NT for body hydration were 73 ± 3% vs. 75 ± 5%, for fat mass 14 ± 4% vs. 19 ± 5%, and for total energy expenditure 2231 ± 637 Kcal vs. 2408 ± 369 Kcal. In women, the differences between CT vs NT were not statistically significant for body hydration (p = 1.898), fat mass (p = 0.9495), total energy expenditure (p = 0.2875) and median overall survival at 12 months (p = 0.6486). At 3 months (end of the intervention), the differences between CT vs. NT for body hydration were 74 ± 2% vs. 78 ± 5%, for fat mass 25 ± 7% vs. 29 ± 19%, and for TEE 1657 ± 297 Kcal vs. 1917 ± 120 Kcal. Nutrition Therapy, based on patient-specific biophysical parameters, including the measurement of metabolism by indirect calorimetry and body composition measurements by BIA, improves overall survival, at least in men. The mechanism would be increasing extra energy for the body, which is necessary to fight off cancer.

Nuclear fusion technologies have re-gained momentum in the last decade thanks to their disruptive potential in different fields, such as energy production and space propulsion, and to new technological developments, especially high temperature superconductor tapes, which allow overcoming previous performance or design limits. To date, reviews of recent nuclear fusion designs are lacking. Therefore, this paper aims at giving a comprehensive overview of nuclear fusion concepts for industrial applications with a focus on the private sector. The designs are classified according to the three leading concepts for plasma confinement, namely, magnetic confinement, inertial confinement and magneto-inertial confinement. The working principles of the main devices are described in detail to highlight strengths and weaknesses of the different designs. The importance of the public sector on private projects is discussed. The technological maturity is estimated, and the main criticalities for each project are identified. Finally, the geographical distribution of the companies (or public institutions) pursuing the design of fusion devices for commercial applications is reported.

Antioxidant supplementation in critical periods may be useful for improvement of piglet early viability and development. We have evaluated the effects of maternal perinatal diet inclusion of a high vitamin E level (VE, 100 mg all-rac-α-tocopheryl acetate /kg), hydroxytyrosol (HT, 1.5 mg/kg), or their combination (VEHT), in comparison to a control diet (C, 30 mg all-rac-α-tocopheryl acetate /kg), on the offspring homeostasis and metabolism, analysing the weaned piglets' adipose tissue transcriptome and adipocyte morphology. Diets were provided to pregnant Iberian sows (n = 48, 12 per treatment) from gestation day 85 to weaning (28 days postpartum) and 48 piglets (n = 12 per treatment) were sampled 5 days postweaning for dorsal subcutaneous adipose tissue analyses. RNA obtained from 6 animals for each diet was used for paired-end RNA sequencing. Results show that supplementation of sows' diet with either vitamin E or hydroxytyrosol had substantial effects on weaned piglet adipose transcriptome, with 664 and 587 genes being differentially expressed, in comparison to C, respectively (q-value<0.10, Fold Change>1.5). Genes upregulated in C were mainly involved in inflammatory and immune response, as well as oxidative stress, and relevant canonical pathways and upstream regulators involved in these processes were predicted as activated, such as TNF, IFNB or NFKB. Vitamin E, when supplemented alone at high dose, activated lipid biosynthesis functions, pathways and regulators, this finding being accompanied by increased adipocyte size. Results suggest an improved metabolic and antioxidant status of adipose tissue in animals born from sows supplemented with individual antioxidants, while the combined supplementation barely affected gene expression, with VEHT showing a prooxidant/proinflamatory functional profile similar to C animals. Different hypothesis are proposed to explain this unexpected result. Findings allow a deeper understanding of the processes taking place in adipose tissue of genetically fat animals and the role of antioxidants in the regulation of fat cells function. [ABSTRACT FROM AUTHOR]

An adequate intestinal environment before weaning may contribute to diarrhea predisposition and piglet development. This study evaluates how the dietary supplementation of vitamin E (VE) (100 mg/kg), hydroxytyrosol (HXT) (1.5 mg/kg) or the combined administration (VE + HXT) given to Iberian sows from gestation affects the piglet’s faecal characteristics, short chain fatty acids (SCFAs), fatty acid profile or intestinal morphology as indicators of gut health; and quantify the contribution of the oxidative status and colostrum/milk composition to the piglet’s SCFAs content and intestinal health. Dietary VE increased isobutyric acid (iC4), butyric acid (C4), isovaleric acid (iC5), and ∑SCFAs, whereas HXT increased iC4 and tended to decrease ∑SCFAs of faeces. Piglets from HXT-supplemented sows also tended to have higher faecal C20:4n-6/C20:2 ratio C22:6 proportion and showed lower occludin gene expression in the duodenum. The combination of both antioxidants had a positive effect on iC4 and iC5 levels. Correlation analyses and regression equations indicate that faecal SCFAs were related to oxidative status (mainly plasma VE) and colostrum and milk composition (mainly C20:2, C20:3, C20:4 n-6). This study would confirm the superiority of VE over HXT supplementation to improve intestinal homeostasis, gut health, and, consequently piglet growth.

Different feeding strategies are being applied to sows in order to obtain homogeneous piglets’ weights and improved health status. This study evaluated how the dietary supplementation of vitamin E (VE) (100 mg/kg), hydroxytyrosol (HXT) (1.5 mg/kg) or the combined administration (VE + HXT) given to Iberian sows from day 85 of gestation affected the growth pattern of the piglets and their oxidative status; and quantified what these effects were due to. Dietary VE and HXT improved the oxidative status of sows and piglets. Both VE and HXT modified the growth pattern at birth and performances of the piglets in a different way according to the growing period. Piglets’ performances were positively correlated with plasma VE and negatively with plasma malondialdehyde (MDA) of the sow. However, the highest variation in growth patterns was explained by the colostrum composition. Significant linear equations were observed between piglets’ performances and colostrum saturated (SAT), n-7 monounsaturated fatty acids (C16:1n-7 and C18:1n-7) and different desaturases indices. This study would confirm that VE supplementation to the sow diet could be more adequate than HXT for the improved development during the first weeks of a piglet’s life. The combined administration of both antioxidants would not produce additional positive effects compared to the individual supplementation.