Aquaculture has become an agronomic activity with noticeable development around the world to respond to the simultaneous decrease of fish captures and the increasing demand of aquatic products for ...human consumption. However, different problems limit the development of this industry and one of those is the time required for most of the cultured fish species to achieve economically viable the commercial size. The knowledge up to date of the regulatory systems involved in controlling growth has improved very much but, it is still necessary to devote efforts to transform the basic information in application to fish culture production. The aim of the present review is to summarize the knowledge acquired with the studies about the GH/IGF axis and other hormones regarding their function on the regulation of fish muscle development and growth. To this end, GH and IGFs effects in muscle cells on metabolism and development are examined, as well as the contribution of IGF-I binding proteins, IGF-I receptors and their downstream regulated molecules like TOR and its relation with cell proliferation and differentiation and the myogenic regulatory factors. The effect of regulatory molecules on cultured myocytes are reviewed as well as in vivo responses, including the model of sustained and maintained swimming. Key aspects we consider should be further investigated to complete the scenario of the regulation of fish muscle are also proposed.
•The GH/IGF axis regulates growth and metabolism in fish muscle•Thyroid hormones and steroids exert important roles controlling muscle growth•IGF-I and IGF-II stimulate nutrients uptake and differentially regulate myogenesis•TOR and proteolytic systems' members can be valuable markers of growth condition•Moderate and sustained swimming provokes in fish better growth and flesh quality
Schedules of survival, growth and reproduction are key life‐history traits. Data on how these traits vary among species and populations are fundamental to our understanding of the ecological ...conditions that have shaped plant evolution. Because these demographic schedules determine population growth or decline, such data help us understand how different biomes shape plant ecology, how plant populations and communities respond to global change and how to develop successful management tools for endangered or invasive species. Matrix population models summarize the life cycle components of survival, growth and reproduction, while explicitly acknowledging heterogeneity among classes of individuals in the population. Matrix models have comparable structures, and their emergent measures of population dynamics, such as population growth rate or mean life expectancy, have direct biological interpretations, facilitating comparisons among populations and species. Thousands of plant matrix population models have been parameterized from empirical data, but they are largely dispersed through peer‐reviewed and grey literature, and thus remain inaccessible for synthetic analysis. Here, we introduce the compadre Plant Matrix Database version 3.0, an open‐source online repository containing 468 studies from 598 species world‐wide (672 species hits, when accounting for species studied in more than one source), with a total of 5621 matrices. compadre also contains relevant ancillary information (e.g. ecoregion, growth form, taxonomy, phylogeny) that facilitates interpretation of the numerous demographic metrics that can be derived from the matrices. Synthesis. Large collections of data allow broad questions to be addressed at the global scale, for example, in genetics (genbank), functional plant ecology (try, bien, d3) and grassland community ecology (nutnet). Here, we present compadre, a similarly data‐rich and ecologically relevant resource for plant demography. Open access to this information, its frequent updates and its integration with other online resources will allow researchers to address timely and important ecological and evolutionary questions.
The specific role of different strength measures on mortality risk needs to be clarified to gain a better understanding of the clinical importance of different muscle groups, as well as to inform ...intervention protocols in relation to reducing early mortality. The aim of the systematic review and meta‐analysis was to determine the relationship between muscular strength and risk of cancer mortality. Eligible cohort studies were those that examined the association between muscular strength, as assessed using validated tests, and cancer mortality in healthy youth and adults. The hazard ratio (HR) estimates obtained were pooled using random effects meta‐analysis models. The outcome was cancer mortality assessed using the HR (Cox proportional hazards model). Eleven prospective studies with 1 309 413 participants were included, and 9787 cancer‐specific deaths were reported. Overall, greater handgrip (HR = 0.97, 95% CI, 0.92‐1.02; P = .055; I2 = 18.9%) and knee extension strength (HR = 0.98, 95% CI, 0.95‐1.00; P = .051; I2 = 60.6%) were barely significant associated with reduced risk of cancer mortality. Our study suggests that higher level of muscular strength is not statistically associated with lower risk of cancer mortality.
Benznidazole is recommended for treatment of Chagas infection. Effects of combination therapy with benznidazole and posaconazole have not been tested in Trypanosoma cruzi carriers.
The purpose of ...this study was to determine whether posaconazole alone or combined with benznidazole were superior to benznidazole monotherapy in eliminating T. cruzi parasites measured by real time polymerase chain reaction (RT-PCR) in asymptomatic Chagas carriers.
A prospective, multicenter randomized placebo-controlled study was conducted in 120 subjects from Latin America and Spain who were randomized to 4 groups: posaconazole 400 mg twice a day (b.i.d.); benznidazole 200 mg + placebo b.i.d.; benznidazole 200 mg b.i.d. + posaconazole 400 mg b.i.d.; or placebo 10 mg b.i.d. T. cruzi deoxyribonucleic acid was detected by RT-PCR at 30, 60, 90, 120, 150, 180, and 360 days. The primary efficacy outcome is the proportion of subjects with persistent negative RT-PCR by day 180; the secondary outcome was negative RT-PCR at 360 days.
Only 13.3% of those receiving posaconazole and 10% receiving placebo achieved the primary outcome, compared with 80% receiving benznidazole + posaconazole and 86.7% receiving benznidazole monotherapy (p < 0.0001 vs. posaconazole/placebo). Posaconazole monotherapy or posaconazole combined with benznidazole achieved high RT-PCR conversion rates during treatment (30 days; 93.3% and 88.9% and 60 days; 90%, and 92.3%) that were similar to benznidazole (89.7% and 89.3%); all were superior to placebo or posaconazole (10% and 16.7%, p < 0.0001). This was not observed at 360 days; benznidazole + posaconazole and benznidazole monotherapy (both 96%) versus placebo (17%) and posaconazole (16%, p < 0.0001). Serious adverse events were rare (6 patients) and were observed in the benznidazole-treated patients. Permanent discontinuation was reported in 19 patients (31.7%) receiving either benznidazole monotherapy or combined with posaconazole.
Posaconazole demonstrated trypanostatic activity during treatment, but it is ineffective long-term in asymptomatic T. cruzi carriers. Benznidazole monotherapy is superior to posaconazole, with high RT-PCR conversion rates sustained at 1 year. Side effects lead to therapy discontinuation in 32%. No advantages were observed with combined therapy versus benznidazole monotherapy. (A Study of the Use of Oral Posaconazole POS in the Treatment of Asymptomatic Chronic Chagas Disease P05267 STOP CHAGAS: NCT01377480).
Antibodies that block programmed death 1 (PD-1) protein improve survival in patients with advanced non-small-cell lung cancer (NSCLC) but have not been tested in resectable NSCLC, a condition in ...which little progress has been made during the past decade.
In this pilot study, we administered two preoperative doses of PD-1 inhibitor nivolumab in adults with untreated, surgically resectable early (stage I, II, or IIIA) NSCLC. Nivolumab (at a dose of 3 mg per kilogram of body weight) was administered intravenously every 2 weeks, with surgery planned approximately 4 weeks after the first dose. The primary end points of the study were safety and feasibility. We also evaluated the tumor pathological response, expression of programmed death ligand 1 (PD-L1), mutational burden, and mutation-associated, neoantigen-specific T-cell responses.
Neoadjuvant nivolumab had an acceptable side-effect profile and was not associated with delays in surgery. Of the 21 tumors that were removed, 20 were completely resected. A major pathological response occurred in 9 of 20 resected tumors (45%). Responses occurred in both PD-L1-positive and PD-L1-negative tumors. There was a significant correlation between the pathological response and the pretreatment tumor mutational burden. The number of T-cell clones that were found in both the tumor and peripheral blood increased systemically after PD-1 blockade in eight of nine patients who were evaluated. Mutation-associated, neoantigen-specific T-cell clones from a primary tumor with a complete response on pathological assessment rapidly expanded in peripheral blood at 2 to 4 weeks after treatment; some of these clones were not detected before the administration of nivolumab.
Neoadjuvant nivolumab was associated with few side effects, did not delay surgery, and induced a major pathological response in 45% of resected tumors. The tumor mutational burden was predictive of the pathological response to PD-1 blockade. Treatment induced expansion of mutation-associated, neoantigen-specific T-cell clones in peripheral blood. (Funded by Cancer Research Institute-Stand Up 2 Cancer and others; ClinicalTrials.gov number, NCT02259621 .).
The tolerance of fish to fasting offers a model to study the regulatory mechanisms and changes produced when feeding is restored. Gilthead sea bream juveniles were exposed to a 21-days fasting period ...followed by 2 h to 7-days refeeding. Fasting provoked a decrease in body weight, somatic indexes, and muscle gene expression of members of the Gh/Igf system, signaling molecules (akt, tor and downstream effectors), proliferation marker pcna, myogenic regulatory factors, myostatin, and proteolytic molecules such as cathepsins or calpains, while most ubiquitin-proteasome system members increased or remained stable. In bone, downregulated expression of Gh/Igf members and osteogenic factors was observed, whereas expression of the osteoclastic marker ctsk was increased. Refeeding recovered the expression of Gh/Igf system, myogenic and osteogenic factors in a sequence similar to that of development. Akt and Tor phosphorylation raised at 2 and 5 h post-refeeding, much faster than its gene expression increased, which occurred at day 7. The expression in bone and muscle of the inhibitor myostatin (mstn2) showed an inverse profile suggesting an inter-organ coordination that needs to be further explored in fish. Overall, this study provides new information on the molecules involved in the musculoskeletal system remodeling during the early stages of refeeding in fish.
Neoadjuvant anti-PD-1 may improve outcomes for patients with resectable NSCLC and provides a critical window for examining pathologic features associated with response. Resections showing major ...pathologic response to neoadjuvant therapy, defined as ≤10% residual viable tumor (RVT), may predict improved long-term patient outcome. However, %RVT calculations were developed in the context of chemotherapy (%cRVT). An immune-related %RVT (%irRVT) has yet to be developed.
The first trial of neoadjuvant anti-PD-1 (nivolumab, NCT02259621) was just reported. We analyzed hematoxylin and eosin-stained slides from the post-treatment resection specimens of the 20 patients with non-small-cell lung carcinoma who underwent definitive surgery. Pretreatment tumor biopsies and preresection radiographic ‘tumor’ measurements were also assessed.
We found that the regression bed (the area of immune-mediated tumor clearance) accounts for the previously noted discrepancy between CT imaging and pathologic assessment of residual tumor. The regression bed is characterized by (i) immune activation—dense tumor infiltrating lymphocytes with macrophages and tertiary lymphoid structures; (ii) massive tumor cell death—cholesterol clefts; and (iii) tissue repair—neovascularization and proliferative fibrosis (each feature enriched in major pathologic responders versus nonresponders, P<0.05). This distinct constellation of histologic findings was not identified in any pretreatment specimens. Histopathologic features of the regression bed were used to develop ‘Immune-Related Pathologic Response Criteria’ (irPRC), and these criteria were shown to be reproducible amongst pathologists. Specifically, %irRVT had improved interobserver consistency compared with %cRVT median per-case %RVT variability 5% (0%–29%) versus 10% (0%–58%), P=0.007 and a twofold decrease in median standard deviation across pathologists within a sample (4.6 versus 2.2, P=0.002).
irPRC may be used to standardize pathologic assessment of immunotherapeutic efficacy. Long-term follow-up is needed to determine irPRC reliability as a surrogate for recurrence-free and overall survival.
This study tests the effects of feeding different vegetable oils (VO) in gilthead sea bream with the aim of improving sustainable aquafeeds. Juveniles were fed ad libitum with ten isonitrogenous ...(46%) and isolipidic (22%) diets with a 75% fish oil (FO) replacement, differing in VO composition leading to two experimental blocks: fish fed with VO blends or mono-substituted diets. Growth parameters, skin and muscle colour, muscle texture, plasma metabolites, digestive capacities, and transcript levels of intestinal lipid transport, muscle dynamics and lipid metabolism-related genes in white muscle and adipose tissue were studied. In fish fed high-palm oil diets, final body weight and mesenteric fat significantly increased, while effects were not found in hepatosomatic index, reflecting tissue-specific lipid accumulation. Relative intestinal length increased significantly with dietary soya oil (SO) content, suggesting a compensatory mechanism to improve nutrient absorption capacity. Plasma parameters showed few changes upon dietary treatments. Lipase activity was unaltered, while intestinal fatp1b expression increased in animals fed blended diets high in rapeseed oil (RO). In adipose tissue, expression of nuclear receptors pparβ and lxr was modified by dietary fatty acids (FA) profile; however, regarding lipid metabolism and β-oxidation genes, only lpl showed significant differences, suggesting that FA uptake and oxidation, but not de novo lipogenesis is what appears to determine the increase in adipose tissue mass. In fish fed blended VO diets, lpl expression showed a positive correlation with MUFA dietary content, suggesting that some FA present in RO enhance its expression, according to data from fish fed mono-substituted diets. In muscle, fish fed blended VO diets also showed a positive correlation of lpl expression with dietary MUFA, whereas in mono-substituted, it was significantly higher in fish fed SO, suggesting other mechanisms are involved in LPL regulation. Concerning β-oxidation genes in muscle, significant differences were detected in cpt1a expression for fish fed blended VO diets, whereas hadh and cpt1b were unaltered, suggesting slight FA uptake regulation in mitochondria. Expression levels of genes related to myogenic processes were not greatly modified by dietary lipid sources except for myogenin in blended VO diets-fed fish, showing a similar profile as that in body weight and opposite with the differentiation marker mhc. This study provides new information regarding the effects of dietary VO, demonstrating moderate effects in lipid homeostasis without adverse effects on growth performance, leading to a transversal view of the responses and interactions from intestine to muscle growth and flesh quality.
•Transversal view of responses from intestine, adipose tissue to muscle to dietary vegetable oils substitution in seabream.•Relative intestinal length and fatty acid transporters expression showed adaptations to specific vegetable oils.•Palm oil had positive effects on growth but caused a higher accumulation of visceral fat in this species.•High proportion of dietary MUFA could favor the lpl expression in adipose and muscle tissues.
The human ageing process is universal, ubiquitous and inevitable. Every physiological function is being continuously diminished. There is a range between two distinct phenotypes of ageing, shaped by ...patterns of living - experiences and behaviours, and in particular by the presence or absence of physical activity (PA) and structured exercise (i.e., a sedentary lifestyle). Ageing and a sedentary lifestyle are associated with declines in muscle function and cardiorespiratory fitness, resulting in an impaired capacity to perform daily activities and maintain independent functioning. However, in the presence of adequate exercise/PA these changes in muscular and aerobic capacity with age are substantially attenuated. Additionally, both structured exercise and overall PA play important roles as preventive strategies for many chronic diseases, including cardiovascular disease, stroke, diabetes, osteoporosis, and obesity; improvement of mobility, mental health, and quality of life; and reduction in mortality, among other benefits. Notably, exercise intervention programmes improve the hallmarks of frailty (low body mass, strength, mobility, PA level, energy) and cognition, thus optimising functional capacity during ageing. In these pathological conditions exercise is used as a therapeutic agent and follows the precepts of identifying the cause of a disease and then using an agent in an evidence-based dose to eliminate or moderate the disease. Prescription of PA/structured exercise should therefore be based on the intended outcome (e.g., primary prevention, improvement in fitness or functional status or disease treatment), and individualised, adjusted and controlled like any other medical treatment. In addition, in line with other therapeutic agents, exercise shows a dose-response effect and can be individualised using different modalities, volumes and/or intensities as appropriate to the health state or medical condition. Importantly, exercise therapy is often directed at several physiological systems simultaneously, rather than targeted to a single outcome as is generally the case with pharmacological approaches to disease management. There are diseases for which exercise is an alternative to pharmacological treatment (such as depression), thus contributing to the goal of deprescribing of potentially inappropriate medications (PIMS). There are other conditions where no effective drug therapy is currently available (such as sarcopenia or dementia), where it may serve a primary role in prevention and treatment. Therefore, this consensus statement provides an evidence-based rationale for using exercise and PA for health promotion and disease prevention and treatment in older adults. Exercise prescription is discussed in terms of the specific modalities and doses that have been studied in randomised controlled trials for their effectiveness in attenuating physiological changes of ageing, disease prevention, and/or improvement of older adults with chronic disease and disability. Recommendations are proposed to bridge gaps in the current literature and to optimise the use of exercise/PA both as a preventative medicine and as a therapeutic agent.
Fish growth is strongly influenced by environmental and nutritional factors and changing culture conditions can help optimize it. The importance of early-life experience on the muscle phenotype later ...in life is well known. Here, we study the effects of 5 weeks of moderate and sustained swimming activity (5 BL s
−1
) in gilthead sea bream during early development. We analysed growth and body indexes, plasma IGF-I and GH levels, feed conversion, composition proximate and isotopic (
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N/
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C) and metabolic key enzymes (COX, CS, LDH, HOAD, HK, ALAT, ASAT) of white muscle. Moderate and continuous exercise in fingerlings of gilthead sea bream increased plasma IGF-I, whereas it reduced plasma GH. Under these conditions, growth rate improved without any modification to feed intake through an increase in muscle mass and a reduction in mesenteric fat deposits. There were no changes in the content and turnover of muscle proteins and lipid reserves. Glycogen stores were maintained, but glycogen turnover was higher in white muscle of exercised fish. A lower LDH/CS ratio demonstrated an improvement in the aerobic capacity of white muscle, while a reduction in the COX/CS ratio possibly indicated a functional adaptation of mitochondria to adjust to the tissue-specific energy demand and metabolic fuel availability in exercised fish. We discuss the synergistic effects of dietary nutrients and sustained exercise on the different mitochondrial responses.
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