In recent years, the wealth of basic science research supporting resveratrol's potential to treat, delay, and even prevent age-related chronic diseases has led to a number of human clinical trials. ...While such translational research has yielded promising results in clinical populations, recently published conflicting results from studies evaluating resveratrol's potential for primary prevention of chronic disease in healthy / asymptomatic individuals have generated considerable controversy and do not initially appear consistent with findings from animal models. We argue that trials targeting healthy humans are often fundamentally flawed owing to inappropriate use of paradigms only applicable to populations with overt clinical disease and the consequent misleading (typically negative) results can severely retard advancement of drug development. To appropriately perform translational research centered on resveratrol as a primary prevention agent in non-clinical populations, it is critical to utilize study designs which can provide adequate information on clinically relevant outcome measures, avoid paradigms and assumptions from interventions which are specific to clinical populations, and maintain realistic expectations compared to interventions which provide the theoretical maximal response (e.g., caloric restriction and aerobic exercise training).
Triple-negative breast cancers (TNBCs) are considered as associated with poor outcome, but prognosis of subcentimetric, node-negative disease remains controversial and evidence that adjuvant ...chemotherapy (CT) is effective in these small tumours remains limited.
Our objective was to investigate the impact of CT on survival in pT1abN0M0 TNBC. Patients were retrospectively identified from a cohort of 22,475 patients who underwent primary surgery in 15 French centres between 1987 and 2013. As rare pathological types may display very particular prognoses in these tumours, we retained only the invasive ductal carcinomas of no special type according to the last World Health Organisation (WHO) classification which is the most common TNBC histological type. End-points were disease-free survival (DFS) and metastasis-free survival (MFS). A propensity score for receiving CT was estimated using a logistic regression including age, tumour size, Scarff Bloom and Richardson (SBR) grade and lymphovascular invasion.
Of a total of 284 patients with pT1abN0M0 ductal TNBC, 144 (51%) received CT and 140 (49%) did not. Patients receiving CT had more adverse prognostic features, such as tumour size, high grade, young age, and lymphovascular invasion. CT was not associated with a significant benefit for DFS (Hazard ratio, HR = 0.77 0.40–1.46; p = 0.419, log-rank test) or MFS (HR = 1.00 0.46–2.19; p = 0.997), with 5-year DFS and MFS in the group with CT versus without of 90% 81–94% versus 84% 74–90%, and 90% 81–95% versus 90% 83%–95%, respectively. Results were consistent in all supportive analyses including multivariate Cox model and the use of the propensity score for adjustment and as a matching factor for case–control analyses.
This study did not identify a significant DFS or MFS advantage for CT in subcentimetric, node-negative ductal TNBC. Although current consensus guidelines recommend consideration of CT in all TNBC larger than 5 mm, clinicians should carefully discuss benefit/risk ratio with patients, given the unproven benefits.
•Consensus guidelines recommend consideration of treatment in patients with triple-negative breast cancer larger than 5 mm.•We did not identify significant advantage for adjuvant chemotherapy in pT1abN0M0 TNBC patients.•Clinicians should carefully discuss benefit/risk ratio with patients.
Purpose
Radioactive-iodine (RAI)-resistant differentiated thyroid cancer (DTC) patients benefit from multi-kinase inhibitors (MKIs), such as lenvatinib. Incidence of treatment-related (TR) late ...toxicities has been not yet described.
Methods
From January 2015 to June 2019 we retrospectively reviewed clinical records of patients with RAI-resistant DTC treated with lenvatinib at Istituto Nazionale dei Tumori (Milan, Italy). New side effect of any grade, appeared after 12 months of lenvatinib, was defined as late adverse event (AE). Descriptive analyses were performed. Survival curves were estimated with Kaplan–Meier method and compared with log-rank test.
Results
Thirty-seven patients were included, 65% had ≥65 years and 68% were female. Thirty patients received lenvatinib for >12 months. Lenvatinib was started at ≤20 mg/daily in 59% of patients, 64% were ≥65 years. The frequency of late AEs was 80% and cardiovascular toxicity was the most common (57%). There was no difference in the incidence of late AEs between younger/older population (77% and 82%, respectively). Median lenvatinib treatment duration (TD) was 39.96 months (95% CI 21.64-NR): 39.96 months for patients <65 years (95% CI: 13.25-NR) and 37.53 months for those ≥65 years, respectively (95% CI: 15.85-NR). Median overall survival (OS) was 39.96 months (95% CI: 21.84-NR), no statistically differences in OS was observed between younger (<65 years) and older patients (≥65 years) (HR 1.013; 95% CI 0.963–1.065;
p
= 0.62).
Conclusion
Late toxicity burden of lenvatinib is not negligible. Cardiovascular toxicity remains the principal side effect even after a prolonged lenvatinib exposition.
Disturbances within many communities are common, but the recovery of riverine fish assemblages from anthropogenic fish kills is often not well documented. Quantification of fish community recovery is ...needed to assess how rapidly or whether recovery occurs without mitigation. To address this need, we evaluated the temporal dynamics of six streams located in central Illinois, including systems impacted by fish kills and an undisturbed reference system. We found species richness and the index of biotic integrity experienced dramatic shifts within the first year after the disturbance event, while fish density varied less within most streams. Interestingly, local extinctions following a kill event were not limited to only rare species, with some dominant components of the local community also lost. Some impacted streams experienced small compositional changes, similar to those within the reference system, while other streams experienced large and continued compositional shifts following disturbance. The rate of compositional change decreased significantly with time since disturbance in all locations, especially within the first year. Most metrics of recovery reached a level of relative stasis three years after the disturbance event. Based on this, we recommend disturbed streams should be monitored for at least three years to fully document recovery dynamics and to determine whether active restoration efforts are warranted. Streams which do not recover during this time frame will likely require direct intervention to achieve recovery. Our results also highlight the importance of regular stream monitoring to document a stream's baseline composition and dynamics if a disturbance were to occur.
The recent introduction of new arboviruses in the Americas, as Zika virus (ZIKV) and Chikungunya virus (CHIKV), increased the risk of outbreaks and arboviral co-infections. Herein, we report twelve ...cases of co-infection of ZIKV and different DENV serotypes in a city located in the northwest region of São Paulo State, Brazil, which is hyper-endemic to Dengue.
Between January and November 2016, 1254 suspected cases of arboviral infection were available by our surveillance program in São José do Rio Preto. All suspected patients were examined and, when they were arboviral disease-suspectd, had sera separated and viral RNA analyzed by PCR/qPCR assays to determine the diagnosis of DENV 1-4, ZIKV, or CHIKV in the same samples. After the molecular results, twelve patients with ZIKV-DENV coinfection were identified and their clinical and laboratory characteristics were described.
The mean between symptoms onset and collected sample of 3 days. DENV-1 was identified in seven co-infected patients and DEN2 in other five. Two patients presented alarm signs of Dengue and no one was hospitalized.
The constant presence of co-circulating arboviruses increases the chance of co-infection and demonstrates the importance of the differential diagnosis, especially during periods of arboviral outbreaks. The impact of this co-infection is known individual and collectively.
Summary
Background
Recent reports have revealed the therapeutic potential of cell‐mediated immunity in neoplasms such as cutaneous squamous cell carcinoma (SCC).
Objectives
To define the antigenic ...coexpression of regulatory T cells (Tregs) and plasmacytoid dendritic cells (pDCs) and assess the CD8+/Foxp3+CD25+ cell ratio at peritumoral and intratumoral levels in order to investigate a correlation with the aggressiveness of SCC tumours.
Methods
We evaluated the content and distribution of Foxp3+CD25+ Treg and CD123+ pDC infiltration and assessed CD8+/Foxp3+CD25+ cell ratio at peritumoral and intratumoral levels in 40 SCCs (20 well‐differentiated, G1; and 20 moderately to poorly differentiated, G2–G3) to investigate a correlation with their aggressiveness. We determined the profiles of Tregs and CD123+ cells; immunostained for CD4, CD8, CD123, interleukin (IL)‐1 and transforming growth factor (TGF)‐β1; and unequivocally double stained for Foxp3CD25.
Results
Peritumorally, CD4, CD8 and Foxp3 expression showed no difference between the two groups. CD123+ cells were fewer in G2–G3 (P = 0·0005), while Foxp3+CD25+ cells were more numerous (P = 0·0005). The Foxp3+CD25+/Foxp3+ ratio was higher in G2–G3 cases (P = 0·0005), confirming the trend in this group of activated T lymphocytes towards total Treg Foxp3+ cells, while the CD8+/Foxp3+CD25+ ratio was higher in G1 (P = 0·0005). Intratumorally, CD4+ and CD8+ cells infiltrated G2–G3 (P = 0·048) more than G1 (P = 0·004), whereas almost all cells were CD123 negative. Regarding Foxp3CD25, TGF‐β1 and IL‐10, they were less expressed in G1, whereas they were positive in G2–G3 (P < 0·05). The CD8+/Foxp3+CD25+ ratio was similar to that observed in peritumoral infiltration.
Conclusions
Our data suggest that intratumoral recruitment of Tregs, high expression of TGF‐β1 and IL‐10, almost negative CD123+, and a low CD8+/Foxp3+CD25+ T‐cell ratio may contribute to the aggressiveness of cutaneous SCC, as already evidenced for other solid tumours.
What's already known about this topic?
Cell‐mediated immunity has an important therapeutic role in the clinical course of several types of malignancies, among them cutaneous squamous cell carcinoma (SCC).
What does this study add?
Our study suggests that intratumoral presence of regulatory T‐cell infiltration (evidenced by Foxp3+CD25+ double staining) and a low CD8+/Foxp3+CD25+ T‐cell ratio, together with high interleukin‐10 and transforming growth factor‐β1 expression levels, may contribute to the aggressiveness of cutaneous SCC, as evidenced for other types of cancer.
Aim
Insulin is the preferred treatment for the control of diabetes in hospital, but it raises the risk of hypoglycaemia, often because oral intake of carbohydrates in hospitalized persons is lower ...than planned. Our aim was to assess the effect on the incidence of hypoglycaemia of giving prandial insulin immediately after a meal depending on the amount of carbohydrate ingested.
Methods
A prospective pre–post intervention study in hospitalized persons with diabetes eating meals with stable doses of carbohydrates present in a few fixed foods. Foods were easily identifiable on the tray and contained fixed doses of carbohydrates that were easily quantifiable by nurses as multiples of 10 g (a ‘brick’). Prandial insulin was given immediately after meals in proportion to the amount of carbohydrates eaten.
Results
In 83 of the first 100 people treated with the ‘brick diet’, the oral carbohydrate intake was lower than planned on at least one occasion (median: 3 times; Q1–Q3: 2–6 times) over a median of 5 days. Compared with the last 100 people treated with standard procedures, postprandial insulin given on the basis of ingested carbohydrate significantly reduced the incidence of hypoglycaemic events per day, from 0.11 ± 0.03 to 0.04 ± 0.02 (P < 0.001) with an adjusted incidence rate ratio of 0.70 (95% confidence interval 0.54–0.92; P = 0.011).
Conclusions
In hospitalized persons with diabetes treated with subcutaneous insulin, the ‘brick diet’ offers a practical method to count the amount of carbohydrates ingested, which is often less than planned. Prandial insulin given immediately after a meal, in doses balanced with actual carbohydrate intake reduces the risk of hypoglycaemia.
What’s new?
People with diabetes who are in hospital often do not eat their whole meal.
In these cases, insulin treatment increases the risk of hypoglycaemia.
The ‘brick diet’ allows nurses to easily count carbohydrates ingested so that insulin can be given accordingly.
Postprandial insulin balanced against carbohydrate ingested reduces hypoglycaemic events.
Excitable temperament disrupts physiological events required for reproductive development in cattle, but no research has investigated the impacts of temperament on growth and puberty attainment in ...Bos indicus females. Hence, this experiment evaluated the effects of temperament on growth, plasma cortisol concentrations and puberty attainment in B. indicus heifers. A total of 170 Nelore heifers, weaned 4 months before the beginning of this experiment (days 0 to 91), were managed in two groups of 82 and 88 heifers each (mean ± SE; initial BW=238±2 kg, initial age=369±1 days across groups). Heifer temperament was evaluated via exit velocity on day 0. Individual exit score was calculated within each group by dividing exit velocity into quintiles and assigning heifers with a score from 1 to 5 (1=slowest; 5=fastest heifer). Heifers were classified according to exit score as adequate (ADQ, n=96; exit score⩽3) or excitable temperament (EXC, n=74; exit score>3). Heifer BW, body condition score (BCS) and blood samples were obtained on days 0, 31, 60 and 91. Heifer exit velocity and score were recorded again on days 31, 60 and 91. Ovarian transrectal ultrasonography was performed on days 0 and 10, 31 and 41, 60 and 70, 81 and 91 for puberty evaluation. Heifer was declared pubertal at the first 10-day interval in which a corpus luteum was detected. Exit velocity and exit score obtained on day 0 were correlated (r⩾0.64, P<0.01) with evaluations on days 31, 60 and 91. During the experiment, ADQ had greater (P<0.01) mean BCS and BW gain, and less (P<0.01) mean plasma cortisol concentration compared with EXC heifers. Temperament × time interactions were detected (P<0.01) for exit velocity and exit score, which were always greater (P<0.01) in EXC v. ADQ heifers. A temperament × time interaction was also detected (P=0.03) for puberty attainment, which was delayed in EXC v. ADQ heifers. At the end of the experiment, a greater (P<0.01) proportion of ADQ were pubertal compared with EXC heifers. In summary, B. indicus heifers classified as EXC had reduced growth, increased plasma cortisol concentrations and hindered puberty attainment compared to ADQ heifers. Moreover, exit velocity may serve as temperament selection criteria to optimize development of B. indicus replacement heifers.
Exergy based analyses are considered by the scientific community appropriate tools for the design and the performance evaluation and improvements of energy systems. Moreover, they are today ...recognized as proper instruments to assess economic, environmental and social externalities of energy systems. This paper presents the results of a study in which different exergy analysis methods are adopted to determine the optimal design configuration of a gas turbine operating in simple Joule Brayton cycle.
Standard exergy and Thermoeconomic analyses are performed to identify the highest thermodynamic efficiency and minimum economic cost configurations of the system, while for the environmental analysis Authors propose an innovative method in which the exergy analysis is combined with a Risk Analysis. With this method the total risk associated to the system is used as objective function in the same way as monetary cost is for standard Thermoeconomic analysis. These three methods aims therefore to determine the optimal design configurations of the system with respect to their specific objective functions, respectively: exergy cost (J/J), monetary (exergoeconomic) cost (€/J) and risk (injured/J) of the product.
Results lead to three different optimal design parameters for the system, according to the objective of each analysis procedure.
•An original implementation of Thermoeconomic framework is proposed.•Standard Exergy and Thermoeconomic analysis are performed on a case study.•A new model using exergy as allocation criteria for Risk Analysis is performed.•Different optimal configurations are obtained and compared.
Channel catfish (Ictalurus puncatus) and freshwater drum (Aplodinotus grunniens) are two commercially and recreationally important species in large rivers of the Midwestern United States. ...Understanding their population demographics is essential to managing sustainable populations. In this study, we determined and compared the size structure, individual growth, and mortality estimates of channel catfish and freshwater drum among the Illinois River and sections of the Mississippi, Ohio, and Wabash rivers to provide a current baseline for managing these populations. Results suggest that both fishes differed in size structure among rivers. Compared to all other rivers, the Mississippi River freshwater drum growth rate was the highest and the theoretical maximum length was the lowest, and the Ohio River annual mortality was lowest. Channel catfish growth did not differ among rivers, but annual mortality was significantly higher in the Mississippi River compared to the Wabash River. Given the importance of these two fishes, better understanding of their population demographics in these systems is essential to improving current and future fisheries management programs.
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