Doxorubicin causes cachexia, sarcopenia, and frailty characteristics in mice.

While chemotherapy treatment can be lifesaving, it also has adverse effects that negatively impact the quality of life. To investigate the effects of doxorubicin chemotherapy on body weight loss, strength and muscle mass loss, and physical function impairments, all key markers of cachexia, sarcopenia, and frailty. Seventeen C57/BL/6 mice were allocated into groups. 1) Control (n = 7): mice were exposed to intraperitoneal (i.p.) injections of saline solution. 2) Dox (n = 10): mice were exposed to doxorubicin chemotherapy cycles (total dose of 18 mg/kg divided over 15 days). The body weight loss and decreased food intake were monitored to assess cachexia. To assess sarcopenia, we measured muscle strength loss using a traction method and evaluated muscle atrophy through histology of the gastrocnemius muscle. To evaluate physical function impairments and assess frailty, we employed the open field test to measure exploratory capacity. Doxorubicin administration led to the development of cachexia, as evidenced by a significant body weight loss (13%) and a substantial decrease in food intake (34%) over a 15-day period. Furthermore, 90% of the mice treated with doxorubicin exhibited sarcopenia, characterized by a 20% reduction in traction strength (p<0,05), a 10% decrease in muscle mass, and a 33% reduction in locomotor activity. Importantly, all mice subjected to doxorubicin treatment were considered frail based on the evaluation of their overall condition and functional impairments. The proposed model holds significant characteristics of human chemotherapy treatment and can be useful to understand the intricate relationship between chemotherapy, cachexia, sarcopenia, and frailty.

Chemotherapy periodization to maximize resistance training adaptations in oncology.

INTRODUCTION: Engaging in exercise programs during cancer treatment is challenging due to the several chemotherapy-induced side effects. Using a pre-clinical model that mimics chemotherapy treatment, we investigated if a periodized-within-chemotherapy training strategy can maximize resistance training (RT) adaptations such as increasing muscle mass and strength. METHODS: Swiss mice were randomly allocated into one of the following five groups (n = 14): control (C), resistance training (RT), chemotherapy-treated non-exercised group (Ch), resistance training chemotherapy treated (RTCh), and resistance training periodized-within-chemotherapy (RTPCh). Doxorubicin (i.p.) was weekly injected for a total of 3 weeks (total dose of 12 mg/kg). Resistance training consisted of ladder climbing with progressive intensity, three times a week for 3 weeks, during chemotherapy treatment. RTPCh prescriptions considered "bad day" adjustments while RTCh did not. "Bad day" adjustments considered the presence or absence of clinical signs (e.g., severe weight loss, diarrhea, mice refusing to train) to replace RT sessions. At the end of the third week, animals were euthanized. RESULTS: Weekly doxorubicin injection promoted progressive body weight loss, muscle atrophy, strength loss, local oxidative stress, and elevated inflammatory mediators, such as TNF-α and IL-6. Non-periodized-within-chemotherapy RT promoted mild protection against doxorubicin-induced skeletal muscle disturbances; moreover, when periodized-within-chemotherapy was applied, RT prevented elevated skeletal muscle inflammatory mediators and oxidative damage markers and promoted muscle mass and strength gains. CONCLUSION: Considering chemotherapy-induced side effects is a crucial aspect when prescribing resistance exercise during cancer, it will maximize the effectiveness of exercise in enhancing muscle mass and strength.

Creatine Supplementation Potentiates Exercise Protective Effects against Doxorubicin-Induced Hepatotoxicity in Mice.

We tested the hypothesis that creatine supplementation may potentiate exercise's protective effects against doxorubicin-induced hepatotoxicity. Thirty-eight Swiss mice were randomly allocated into five groups: control (C, n = 7), exercised (Ex, n = 7), treated with doxorubicin (Dox, n = 8), treated with doxorubicin and exercised (DoxEx, n = 8), and treated with doxorubicin, exercised, and supplemented with creatine (DoxExCr, n = 8). Doxorubicin was administered weekly (i.p.) for a total dose of 12 mg/kg. Creatine supplementation (2% added to the diet) and strength training (climbing stairs, 3 times a week) were performed for a total of 5 weeks. The results demonstrated that doxorubicin caused hepatotoxicity, which was evidenced by increased (p < 0.05) hepatic markers of inflammation (i.e., TNF-α and IL-6) and oxidative damage, while the redox status (GSH/GSSG) was reduced. The plasma concentrations of liver transaminases were also significantly (p < 0.05) elevated. Furthermore, doxorubicin-treated animals presented hepatic fibrosis and histopathological alterations such as cellular degeneration and the infiltration of interstitial inflammatory cells. Exercise alone partly prevented doxorubicin-induced hepatotoxicity; thus, when combined with creatine supplementation, exercise was able to attenuate inflammation and oxidative stress, morphological alterations, and fibrosis. In conclusion, creatine supplementation potentiates the protective effects of exercise against doxorubicin-induced hepatotoxicity in mice.

Creatine supplementation protects against diet-induced non-alcoholic fatty liver but exacerbates alcoholic fatty liver.

AIMS: This work investigated the effects of creatine supplementation on different pathways related to the pathogenesis of non-alcoholic fatty liver disease and alcoholic liver disease. MAIN METHODS: To induce alcoholic liver disease, male Swiss mice were divided into three groups: control, ethanol and ethanol supplemented with creatine. To induce non-alcoholic fatty liver disease, mice were divided into three groups: control, high-fat diet and high-fat diet supplemented with creatine. Each group consisted of eight animals. In both cases, creatine monohydrate was added to the diets (1 %; weight/vol). KEY FINDINGS: Creatine supplementation prevented high-fat diet-induced non-alcoholic fatty liver disease progression, demonstrated by attenuated liver fat accumulation and liver damage. On the other hand, when combined with ethanol, creatine supplementation up-regulated key genes related to ethanol metabolism, oxidative stress, inflammation and lipid synthesis, and exacerbated ethanol-induced liver steatosis and damage, demonstrated by increased liver fat accumulation and histopathological score, as well as elevated oxidative damage markers and inflammatory mediators. SIGNIFICANCE: Our results clearly demonstrated creatine supplementation exerts different outcomes in relation to non-alcoholic fatty liver disease and alcoholic liver disease, namely it protects against high-fat diet-induced non-alcoholic fatty liver disease but exacerbates ethanol-induced alcoholic liver disease. The exacerbating effects of the creatine and ethanol combination appear to be related to oxidative stress and inflammation-mediated up-regulation of ethanol metabolism.

Resistance Training Attenuates Activation of STAT3 and Muscle Atrophy in Tumor-Bearing Mice.

Purpose: Although the role of signal transducers and activators of transcription (STAT3) in cachexia due to the association of circulating IL-6 and muscle wasting has been extensively demonstrated, the effect of resistance training on STAT3 in mediating muscle atrophy in tumor-bearing mice is unknown. The aim of this study is to investigate the effects of resistance exercise training on inflammatory cytokines and oxidative-mediated STAT3 activation and muscle loss prevention in tumor-bearing mice. Methods: Male Swiss mice were inoculated with Ehrlich tumor cells and exposed or not exposed to resistance exercise protocol of ladder climbing. Skeletal muscle STAT3 protein content was measured, compared between groups, and tested for possible association with plasma interleukins and local oxidative stress markers. Components of the ubiquitin-proteasome and autophagy pathways were assessed by real-time PCR or immunoblotting. Results: Resistance training prevented STAT3 excessive activation in skeletal muscle mediated by the overabundance of plasma IL-6 and muscle oxidative stress. These mechanisms contributed to preventing the increased key genes and proteins of ubiquitin-proteasome and autophagy pathways in tumor-bearing mice, such as Atrogin-1, LC3B-II, and Beclin-1. Beyond preventing muscle atrophy, RT also prevented strength loss and impaired locomotor capacity, hallmarks of sarcopenia. Conclusion: Our results suggest that STAT3 inhibition is central in resistance exercise protective effects against cancer-induced muscle atrophy and strength loss.

Effect of running exercise on titanium dioxide (TiO2)-induced chronic arthritis and sarcopenia in mice. A titanium prosthesis loosening injury model study.

AIMS: This study aimed to investigate if titanium dioxide (TiO2) joint administration is a useful pre-clinical model to study sarcopenia-related chronic arthritis, and if exercise is a useful therapeutic approach against the pathogenesis of TiO2-induced arthritis and sarcopenia in mice. MAIN METHODS: Two experiments were conducted. Firstly, 36 female Swiss mice were randomly divided into a control group (n = 12) and two groups who received intra-articular TiO2 injections of 0.3-mg (n = 12) and 3-mg (n = 12), respectively. Mice were euthanized 4 and 8 weeks after TiO2 injections. Based on data of the first experiment, mice were exposed to four groups: control (C, n = 10), exercised (Ex, n = 10), injected with 3-mg of TiO2 (TiO2, n = 10), and injected with 3-mg of TiO2 and exercised (TiO2 + Ex, n = 10) for a total of 8-weeks. KEY FINDINGS: Eight-week of 3 mg of TiO2 joint administration promoted characteristics of chronic inflammation such as elevated histopathological score, inflammation, edema and pain. Hallmarks of sarcopenia were also observed such as muscle atrophy and loss of strength. Furthermore, voluntary exercise running reduced TiO2-induced chronic inflammation and pain, attenuating chronic arthritis-related muscle atrophy, strength loss and impairment of locomotion capacity. In addition, exercise was also able to prevent TiO2-induced collagen degradation, an important marker of functional and structural integrity loss of cartilage and chronic arthritis disease progression. SIGNIFICANCE: TiO2 joint administration mimed titanium prosthesis release-induced joint chronic arthritis and sarcopenia-related chronic arthritis, disturbances that were attenuated by voluntary exercise.

Resistance Training's Ability to Prevent Cancer-induced Muscle Atrophy Extends Anabolic Stimulus.

PURPOSE: This study aimed to determine the role of mammalian target of rapamycin (mTORC1) activation and catabolic markers in resistance training's (RT) antiatrophy effect during cachexia-induced muscle loss. METHODS: Myofiber atrophy was induced by injecting Walker 256 tumor cells into rats exposed or not exposed to the RT protocol of ladder climbing. The role of RT-induced anabolic stimulation was investigated in tumor-bearing rats with the mTORC1 inhibitor rapamycin, and cross-sectional areas of skeletal muscle were evaluated to identify atrophy or hypertrophy. Components of the mTORC1 and ubiquitin-proteasome pathways were assessed by real-time polymerase chain reaction or immunoblotting. RESULTS: Although RT prevented myofiber atrophy and impaired the strength of tumor-bearing rats, in healthy rats, it promoted activated mTORC1, as demonstrated by p70S6K's increased phosphorylation and myofiber's enlarged cross-sectional area. However, RT promoted no changes in the ratio of p70S6K to phospho-p70S6K protein expression while prevented myofiber atrophy in tumor-bearing rats. Beyond that, treatment with rapamycin did not preclude RT's preventive effect on myofiber atrophy in tumor-bearing rats. Thus, RT's ability to prevent cancer-induced myofiber atrophy seems to be independent of mTORC1's and p70S6K's activation. Indeed, RT's preventive effect on cancer-induced myofiber atrophy was associated with its capacity to attenuate elevated tumor necrosis factor α and interleukin 6 as well as to prevent oxidative damage in muscles and an elevated abundance of atrogin-1. CONCLUSIONS: By inducing attenuated myofiber atrophy independent of mTORC1's signaling activation, RT prevents muscle atrophy during cancer by reducing inflammation, oxidative damage, and atrogin-1 expression.

Resources for assessing parents' vaccine hesitancy: a systematic review of the literature.

The concept of Vaccine Hesitancy has begun to appear in the scientific landscape, referring to the reluctance of a growing proportion of people to accept the vaccination offer. A variety of factors were identified as being associated with vaccine hesitancy but there was no universal algorithm and currently there aren't any established metrics to assess either the presence or impact of vaccine hesitancy. The aim of this study was to systematically review the published questionnaires evaluating parental vaccine hesitancy, to highlight the differences among these surveys and offer a general overview on this matter. This study offers a deeper perspective on the available questionnaires, helping future researches to identify the most suitable one according to their own aim and study setting.

Mild-cold water swimming does not exacerbate white adipose tissue browning and brown adipose tissue activation in mice.

The present study investigated the effects of swimming physical training either thermoneutral or below thermoneutral water temperature on white (WAT) and brown (BAT) adipose tissue metabolism, morphology, and function. C57BL/6J male mice (n = 40; weight 25.3 ± 0.1 g) were divided into control (CT30), cold control (CT20), trained (TR30), and cold trained (TR20) groups. Swimming training consisted of 30-min exercise at 30°C (control) or 20°C (cold) water temperature. After 8-week training, adipose tissues were excised and inguinal (ingWAT) and BAT were processed for histology, lipolysis, and protein contents of total OXPHOS, PGC1α, and UCP1 by western blotting analysis. Swimming training reduced body weight gain independently of water temperature (P < 0.05). ingWAT mass was decreased for TR30 in comparison to other groups (P < 0.05), while for BAT, there was a significant increase in CT20 in relation to CT30, and both trained groups were significantly increased in relation to control groups (P < 0.05). ingWAT mean adipocyte area was smaller for trained groups, and seemed to present multilocular adipocytes. Lipolytic activity and protein content of UCP1, PGC1α, and mitochondrial markers were increased in trained groups for ingWAT (P < 0.05), independent of water temperature (P > 0.05), and these patterns were not observed for BAT (P > 0.05). Our findings suggest that mild-cold water exposure and swimming physical exercise seem to, independently, promote browning in ingWAT with no effects on BAT; however, the association of exercise and mild-cold water did not exacerbate these effects.

Creatine supplementation does not promote tumor growth or enhance tumor aggressiveness in Walker-256 tumor-bearing rats.

OBJECTIVES: This study aimed to analyze the effect of creatine (Cr) supplementation on tumor microenvironment, evaluating the parameters of tumor aggressiveness. METHODS: Sixteen male Wistar rats were randomly assigned to 2 groups (n = 8/group): Tumor-bearing (T) and tumor-bearing supplemented with Cr (TCr). Cr supplementation was provided in drinking water for a total of 21 d. After 11 d of Cr supplementation (TCr group) or water (T group), Walker-256 tumor cells were inoculated subcutaneously in the right flank of all rats, which kept receiving Cr supplementation (TCr group) or water (T group) for 10 more days. The total period of the experiment was 21 d. RESULTS: Tumor weight corresponded with approximately 3.5% ± 0.9% of animal body weight in the T group. Cr supplementation did not accelerate tumor growth or increase tumor size. The histopathological analysis demonstrated the presence of nuclear pleomorphisms and atypical nuclei, with the presence of low-differentiated tumor cells, in both groups. Cr supplementation did not alter apoptosis and cell proliferation markers, nor tumor capsule thickness and viable tumor area. CONCLUSIONS: Cr supplementation in Walker-256 tumor-bearing rats did not induce significant changes in tumor development, and did not interfere with the parameters of tumor aggressiveness, such as the level of cell differentiation and proliferation.

Healthcare Students' Flu Vaccine Uptake in the Last 5 Years and Future Vaccination Acceptance: Is There a Possible Association?

BACKGROUND: Despite the free-of-charge offer of influenza vaccines to at-risk subgroups, vaccine coverage remains low and far from the target, probably due to the false myths and misperceptions. We aimed to explore the healthcare students' vaccination behavior and beliefs to find any association between vaccination uptake during the last 5 years and future vaccination acceptance. STUDY DESIGN: A multicentre cross-sectional study. METHODS: From Oct 2017 to Nov 2018, the Italian healthcare students from 14 different universities in 2017/2018 were enrolled, through an online and anonymous questionnaire previously validated. Absolute and relative frequencies were calculated and Pearson's Chi-square test was used. A multinomial logistic regression model was performed. Results are expressed as relative Risk Ratio (RR) with 95% Confidence Intervals (95% CI). The level of significance chosen was P-value <0.05. RESULTS: A total of 3137 students were enrolled and 3131 questionnaires were analysed. 82.7% of the sample declared they had not received any flu vaccination during the last 5 years. Students who received flu vaccination 4 times or more during the last 5 years were more likely to do it again next year as well (95.1% vs 4.9%). The regression model showed that having received flu vaccination over the last 5 years was statistically associated with the intention of getting vaccinated during next season. CONCLUSION: Frequency of flu vaccination is predictive for future acceptance among healthcare students. This association could have both implications for the organization of vaccination campaigns and improve educational strategies for this category of students.

Creatine supplementation in Walker-256 tumor-bearing rats prevents skeletal muscle atrophy by attenuating systemic inflammation and protein degradation signaling.

PURPOSE: The aim of this study was to investigate the effects of creatine supplementation on muscle wasting in Walker-256 tumor-bearing rats. METHODS: Wistar rats were randomly assigned into three groups (n = 10/group): control (C), tumor bearing (T), and tumor bearing supplemented with creatine (TCr). Creatine was provided in drinking water for a total of 21 days. After 11 days of supplementation, tumor cells were implanted subcutaneously into T and TCr groups. The animals' weight, food and water intake were evaluated along the experimental protocol. After 10 days of tumor implantation (21 total), animals were euthanized for inflammatory state and skeletal muscle cross-sectional area measurements. Skeletal muscle components of ubiquitin-proteasome pathways were also evaluated using real-time PCR and immunoblotting. RESULTS: The results showed that creatine supplementation protected tumor-bearing rats against body weight loss and skeletal muscle atrophy. Creatine intake promoted lower levels of plasma TNF-α and IL-6 and smaller spleen morphology changes such as reduced size of white pulp and lymphoid follicle compared to tumor-bearing rats. In addition, creatine prevented increased levels of skeletal muscle Atrogin-1 and MuRF-1, key regulators of muscle atrophy. CONCLUSION: Creatine supplementation prevents skeletal muscle atrophy by attenuating tumor-induced pro-inflammatory environment, a condition that minimizes Atrogin-1 and MuRF-1-dependent proteolysis.

Moderate vs high-load resistance training on muscular adaptations in rats.

AIMS: The main aim of this study was to investigate the moderate versus high-load resistance training on muscle strength, hypertrophy and protein synthesis signaling in rats. METHODS: Twenty rats were randomly allocated into three groups as follow: control group (C, n = 6), high-load training (HL, n = 7) and moderate-load training (ML, n = 7). A ladder climb exercise was used to mimic resistance exercise. ML resistance training consisted of a moderate load, allowing performance at higher volume of load inherent to higher number of repetitions (8-16 climbing). HL resistance training consisted of progressively increase training load, with low volume of load (4-8 climbing). C group remained with physical activity restricted to their cage space. This experiment was conducted over a six-weeks period. Forty-eight hours after the last resistance training session the animals were euthanized for tissue collection. RESULTS: Both HL and ML regimens promoted similar increases in muscle strength, elevated protein synthesis signaling demonstrated by increased skeletal muscle total/phosphorylated P-70S6K ratio and similar increases in plantaris and FHL muscle hypertrophy, all compared to control. All these similarities were demonstrated even though testosterone/cortisol ratio was higher in HL group compared to ML and control. ML regimen caused higher total training volume and soleus muscle hypertrophy, which was not demonstrated in HL group. CONCLUSION: In conclusion, results suggest that both HL and ML induce muscle hypertrophy and increase on strength in a similar way. ML moreover seems to favor slow fiber hypertrophy due the higher training volume.

Resistance Exercise Counteracts Tumor Growth in Two Carcinoma Rodent Models.

PURPOSE: Although resistance exercise (RE) is now recognized as an adjuvant in cancer treatment because of its capacity to prevent muscle wasting, weakness, and cachexia, it is unknown whether RE can mitigate tumor development. Two solid adenocarcinoma models (Walker-256 and Ehrlich) were used to investigate the effects of RE on tumor cell proliferation, growth, and aggressiveness parameters in tumor-bearing animals' life span. METHODS: Walker-256 tumor-bearing rats and Ehrlich tumor-bearing mice were subjected to RE, which consisted of climbing a ladder apparatus with loads tied to their tails. After 4 wk, animals were euthanized, and tumors were excised and assessed for tumor microenvironment evaluation such as cell proliferation and apoptosis determination, collagen deposit, and presence of malignant tumor morphology. RESULTS: Our data demonstrate that RE mitigated tumor growth and favored tumor end points such as lower Scarff-Bloom-Richardson histological grade tumor, denoting slow cell aberrant form and division, decreased tumor cell proliferation (evaluated by nucleus marked with antigen ki-67), and lower viable tumor area in both types of tumors studied. In addition, RE stimulated tumor microvessel density in Walker-256 tumor-bearing rats, but there was no change in their life span. CONCLUSION: RE may mitigate tumor growth and tumor malignancy parameters such as lower histopathological grade, assuming less nuclear pleomorphism and mitotic cells, smaller viable tumor area, and decreased tumor cell proliferation in both adenocarcinomas. In addition, RE induced tumor vascularization.

Acute exercise alters homocysteine plasma concentration in an intensity-dependent manner due increased methyl flux in liver of rats.

PURPOSE: We aimed to determine the effects of different intensities of acute exercise on Hcy plasma levels, and the exercise-induced changes in Hcy liver metabolism. METHOD: First, thirty-two Wistar rats were randomly submitted to an acute bout of swimming exercise carrying a load of 2% (n=8), 4% (n=8) and 6% (n=8) of their total body weight attached in their tail. Control rats remained rested (n=8). Blood samples were taken from tail vein for plasma S-containing amino acids determination before (Rest) and post, 1, 2, 3, 4, 6, and 10h after acute swimming exercise. Second, 56 exercised rats (4% loads) were euthanized before (Rest) and1, 2, 3, 4, 6, and 10h after acute swimming exercise. Blood and liver samples were collected for amino acids and keys genes involved in the Hcy metabolism assay. RESULTS: Acute exercise increases (P<0.05) plasma Hcy concentration in an intensity-dependent manner (rest 7.7±0.8; 6% load 13.8±3.6; 4% load 12.2±2.9±and 2% load 10.1±2.6, µmol/L); this increase is transient and does not promote hyperhomocysteinemia (<15µmol/L).Exercise-induced increased plasma Hcywas accompanied by the decreased liver S-adenosylmethionine/S-adenosylhomocysteine ratio and elevated MAT1a mRNA content. Acute exercise also caused elevated mRNA of key enzymes of transsulfuration (CBS) and remethylation (BHMT and the MTRR). CONCLUSION: Our data provided evidence that acute exercise increases plasma Hcy concentration due to the augmented requirement for methylated compounds that increases liver SAM consumption. Also, Hcy remethylation and transsulfuration are coordinately regulated to maintain methyl balance.

Oral creatine supplementation attenuates muscle loss caused by limb immobilization: a systematic review / Suplementação oral de creatina atenua a perda de massa muscular causada pela imobilização de membros: uma revisão sistemática

Abstract Introduction: Recent studies have pointing creatine supplementation as a promising therapeutic alterna- tive in several diseases, especially myopathies and neurodegenerative disorder. Objective: elucidate the role of creatine supplementation on deleterious effect caused by limb immobilization in humans and rats. Methods: Analyzed articles were searched by three online databases, PubMed, SportDicus e Scielo. After a review and analysis, the studies were included in this review articles on effect of creatine supplementation on skeletal muscle in humans and rat, before, during and after a period of limb immobilization. Results: Studies analyzed demonstrated positive points in use of creatine supplementation as a therapeutic tool to mitigating the deleterious effects of limb immobilization, in humans and rat. Conclusion: The dataset of this literature review allows us to conclude that creatine supplementation may reduce muscle loss and/or assist in the recovery of muscle atrophy caused by immobilization and disuse in rats and humans. Also, we note that further research with better methodological rigor is needed to clarify the mechanisms by which creatine support the recovery of muscle atrophy. Moreover, these effects are positive and promising in the field of muscle rehabilitation, especially after member's immobilization.

Resumo Introdução: Estudos recentes apontam a suplementação de creatina como promissora alternativa terapêuti- ca em desordens de diversos tipos, especialmente miopatias e desordens neurodegenerativas. Objetivo: Essa revisão tem o objetivo de elucidar o papel da creatina sobre a perda da massa muscular causada pela imobili- zação de membros em seres humanos e ratos. Métodos: Os artigos analisados foram buscados em três bases de dados on-line, PubMed, SportDiscus e Scielo. Após análise dos estudos, foram incluídos na presente revisão os efeitos da suplementação de creatina na musculatura esquelética, envolvendo seres humanos e roedores, antes, durante e depois de um período de imobilização e desuso. Resultados: Os estudos analisados apresentaram pontos positivos sobre a utilização de creatina, sobretudo quando combinado com outro recurso terapêutico, atenuando a atrofia muscular causada pela imobilização de membros. Conclusão: Em suma, o conjunto de dados ainda que limitantes apresentado por essa revisão de literatura nos permite concluir que a suplemen- tação com creatina é capaz de amenizar a perda de massa muscular e/ou auxiliar na recuperação da atrofia muscular causada pela imobilização e desuso em ratos e humanos. Ainda, salientamos que mais investigações com melhor rigor metodológico são necessárias para o esclarecimento sobre os mecanismos pelo qual a creati- na favorece a recuperação da atrofia muscular. Alem disso, esses efeitos são positivos e promissores na área da reabilitação muscular, especialmente após a imobilização de membros.

Syngeneic B16F10 Melanoma Causes Cachexia and Impaired Skeletal Muscle Strength and Locomotor Activity in Mice.

Muscle wasting has been emerging as one of the principal components of cancer cachexia, leading to progressive impairment of work capacity. Despite early stages melanomas rarely promotes weight loss, the appearance of metastatic and/or solid tumor melanoma can leads to cachexia development. Here, we investigated the B16F10 tumor-induced cachexia and its contribution to muscle strength and locomotor-like activity impairment. C57BL/6 mice were subcutaneously injected with 5 × 104 B16F10 melanoma cells or PBS as a Sham negative control. Tumor growth was monitored during a period of 28 days. Compared to Sham mice, tumor group depicts a loss of skeletal muscle, as well as significantly reduced muscle grip strength and epididymal fat mass. This data are in agreement with mild to severe catabolic host response promoted by elevated serum tumor necrosis factor-alpha (TNF-α), interleukin-6 (IL-6) and lactate dehydrogenase (LDH) activity. Tumor implantation has also compromised general locomotor activity and decreased exploratory behavior. Likewise, muscle loss, and elevated inflammatory interleukin were associated to muscle strength loss and locomotor activity impairment. In conclusion, our data demonstrated that subcutaneous B16F10 melanoma tumor-driven catabolic state in response to a pro-inflammatory environment that is associated with impaired skeletal muscle strength and decreased locomotor activity in tumor-bearing mice.

Infant immunization coverage in Italy (2000-2016).

BACKGROUND: In Italy, national-level immunization polices are included in the National Immunization Prevention Plan (PNPV), whose latest edition - 2017-2019 PNPV - was finally approved in February 2017. Coverage rates are a key measure of immunization system performance; it can inform and support national and regional polices' implementation monitoring, as well as measure the impact of interventions aimed at increasing vaccine uptake. METHODS: We collected, analysed and critically interpreted 2000-2016 Italian national infant immunization coverage trends, by different vaccine, target population, and by Region. Data were provided by the Directorate General for Prevention of the Italian Ministry of Health. RESULTS: In 2016, none of the mandatory or recommended vaccines reached the 95% national coverage target set in the PNPV. Weighted average national coverage for currently mandatory vaccines (against Polio, Tetanus, Diphtheria, Hepatitis B) and other antigens included in the hexavalent vaccine (Pertussis, and Haemophilus influenzae type b) ranged between 93.0% for Hepatitis B and 93.7% for Tetanus; it was lower for Measles, Mumps and Rubella vaccines (87.2%), pneumococcal (88.4%) and meningococcal C conjugate vaccines (80.7%), with a high degree of heterogeneity by Region. Both hexavalent and MMR vaccines coverage rates have been decreasing in the last years, respectively from 2012 (-2.8%) and from 2010 (-3.6%). DISCUSSION: Further efforts are needed to increase vaccine uptake in Italy, to improve data collection and reporting, as well as to fight the growing phenomenon of the vaccine hesitancy so that PNPV's objectives and targets can be met in the near future.

Flu vaccination in elite athletes: A survey among Serie A soccer teams.

Scant data is available on immunization policies and practices among professional athletes. Following up on a recent review on the topic, we conducted a survey among Italian Serie A soccer teams during the influenza season 2015-16, to explore vaccination practices and attitudes as well as influenza vaccine uptake. The survey covered a sample of over 600 professional athletes from 20 teams and was carried out in collaboration with the Italian Association of Physicians of Professional Football Teams (L.A.M.I.CA.). For each team, the head of the medical staff was interviewed (structured telephone interviews, 100% response rate). Seasonal influenza vaccine was actively offered in 75% of Serie A teams with a median coverage rate of 40% (range 0%-100%). Vaccines are often administered after matches or training sessions. We report vaccine hesitancy associated with fear of adverse events, poor communication and other selected determinants. Vaccination in elite athletes, if correctly managed, represents a powerful, cost-effective and long lasting preventive tool. In times where vaccines are losing public confidence, our findings are a useful basis to inform the planning, implementation and evaluation of interventions to promote prevention in sports medicine.