Because sustained physical activity is important for a healthy life, this paper examined whether a greater diversity of sport activities during adolescence predicts higher levels of leisure‐time ...physical activity (LTPA) in adulthood. From sport activity participation reported by 17‐year‐old twins, we formed five groups: 1, 2, 3, 4, and 5+ different sport activities. At follow‐up in their mid‐thirties, twins were divided into four activity classes based on LTPA, including active commuting. Multinomial regression analyses, adjusted for several confounders, were conducted separately for male (N=1288) and female (N=1770) participants. Further, conditional logistic regression analysis included 23 twin pairs discordant for both diversity of sport activities in adolescence and LTPA in adulthood. The diversity of leisure‐time sport activities in adolescence had a significant positive association with adulthood LTPA among females. Membership in the most active adult quartile, compared to the least active quartile, was predicted by participation in 2, 3, 4, and 5+ sport activities in adolescence with odds ratios: 1.52 (P=.11), 1.86 (P=.02), 1.29 (P=.39), and 3.12 (P=5.4e‐05), respectively. Within‐pair analyses, limited by the small sample of twins discordant for both adolescent activities and adult outcomes, did not replicate the association. A greater diversity of leisure‐time sport activities in adolescence predicts higher levels of LTPA in adulthood in females, but the causal nature of this association remains unresolved.
Puumala hantavirus (PUUV) causes most cases of haemorrhagic fever with renal syndrome (HFRS) in Europe. PUUV infection is characterised by acute kidney injury, thrombocytopenia and increased ...capillary leakage. Typical symptoms are fever, headache, nausea, abdominal and back pain. This study aimed to evaluate the amount and distribution of intraperitoneal, retroperitoneal and pleural fluid and the association of fluid collections to the symptoms and clinical findings in patients with acute PUUV infection.
Abdominal magnetic resonance imaging (MRI) was performed on 27 hospitalised patients with acute PUUV infection. The clinical and laboratory findings and patients' symptoms were analysed in relation to the imaging findings. The thickness of the fluid collections was measured in millimetres (mm) from axial images.
Fluid collections were found in all patients. The amount of intraperitoneal fluid correlated positively with plasma C-reactive protein (CRP) level (r = 0.586, p = .001), while it had an inverse correlation with serum creatinine concentration (r = −0.418, p = .030). Retroperitoneal fluid also correlated inversely with serum creatinine and cystatin C concentrations (r = −0.501, p = .008 and r = −0.383, p = .048, respectively). The amount of fluid was not greater in patients with abdominal or back pain. Patients with back pain had higher serum creatinine compared with patients without back pain, 452 µmol/L (range 88-1071) vs. 83 µmol/L (range 60-679), p = .004.
Fluid collections were found in all patients. A greater amount of intraperitoneal fluid associates with higher CRP concentrations but not with higher serum creatinine levels. Back pain associates with higher creatinine level but not with the presence of fluids.
KaroBio AB and Departments of Biosciences and of Medical Nutrition,
Karolinska Institute, NOVUM; Department of Pathology, Huddinge
Hospital, Huddinge, Sweden; and Institute of Biomedicin Department
...of Anatomy, University of Turku, Turku,
Finland
Nilsson, Stefan,
Sari Mäkelä,
Eckardt Treuter,
Michel Tujague,
Jane Thomsen,
Göran Andersson,
Eva Enmark,
Katarina Pettersson,
Margaret Warner, and
Jan-Åke Gustafsson.
Mechanisms of Estrogen Action. Physiol. Rev. 81: 1535-1565, 2001. Our
appreciation of the physiological functions of estrogens and the
mechanisms through which estrogens bring about these functions has
changed during the past decade. Just as transgenic mice were produced
in which estrogen receptors had been inactivated and we thought that we
were about to understand the role of estrogen receptors in physiology
and pathology, it was found that there was not one but two distinct and
functional estrogen receptors, now called ER and ER . Transgenic
mice in which each of the receptors or both the receptors are inactive
have revealed a much broader role for estrogens in the body than was
previously thought. This decade also saw the description of a male
patient who had no functional ER and whose continued bone growth
clearly revealed an important function of estrogen in men. The
importance of estrogen in both males and females was also demonstrated
in the laboratory in transgenic mice in which the aromatase gene was
inactivated. Finally, crystal structures of the estrogen receptors with
agonists and antagonists have revealed much about how ligand binding
influences receptor conformation and how this conformation influences
interaction of the receptor with coactivators or corepressors and hence
determines cellular response to ligands.
Lakes play an important role in catchment carbon (C) balances. However, the role of lakes in landscape C cycling in changing climate is highly uncertain. We studied C pools in a chain of five boreal ...lakes and compared the C fluxes during a wet and a dry year. The included pools were dissolved inorganic carbon (DIC) and total organic carbon (TOC) in lake water, as well as C pools in littoral macrophytes and lake sediments. The estimated C fluxes consisted of hydrological input and output of DIC and TOC, emission of carbon dioxide (CO2) to the atmosphere, DIC incorporated as organic carbon in primary production of phytoplankton and littoral macrophytes, and sedimentation of C. The riverine input of C into the lakes increased remarkably (40–210%) in the year with high precipitation. Simultaneously, there was a clear increase in the flux of CO2 to the atmosphere from the three small uppermost lakes, whereas in two large lowland lakes the CO2 fluxes were higher during the warm dry year. On the landscape scale, the role of small lakes (area <1 km2) was emphasized in net C accumulation, whereas the large lowland lakes released more CO2 to the atmosphere. In parallel, the concentration of TOC in the water column decreased downstream the lake chain whereas DIC increased. The largest pool of C (>98%) in all the lakes was in the sediment. Sediment C store, calculated relative to the lake area, was positively correlated with lake water TOC (r2 = 0.93, P < 0.05) and Fe (r2 = 0.96, P < 0.05) concentrations. Lake water Fe content was also a good predictor for the long‐term accumulation (r2 = 0.99, P < 0.01), as well as gross sedimentation rate of organic carbon (r2 = 0.48, P < 0.01).
Key Points
Lake C budgets show highly variable patterns during dry and wet years
The role of small lakes was emphasized in net C accumulation
Large lakes released more CO2 to the atmosphere than did the small lakes
Phosphorus (P) is an essential element for plant growth and development. Finding new P sources and ways to improve crop P utilization are necessary due to the depletion of phosphate reserves. Five ...crop species, buckwheat (Fagopyrum esculentum L.), maize (Zea mays L.), oilseed rape (Brassica napus L. ssp. oleifera (Moench) Metzg.), spelt wheat (Triticum spelta L.), and white lupine (Lupinus albus L.), were grown in pots containing sandy soil with chemical nutrients, digestate, and meat bone meal (MBM) without added nutrients. Thirty days after the seeding plants were harvested, the growth stage, soil-plant analysis development (SPAD) value, biomass, P content of the plants, colonization of the roots with endomycorrhiza, and soil pH were analyzed, and the number of fungal spores in the soil was counted. All species showed interaction with the P sources for measured traits, except for the rhizosphere pH. A high biomass was recorded in all species fertilized with various P sources compared to the unfertilized treatment. Buckwheat and spelt wheat showed a higher P uptake with MBM, and the mycorrhizal symbiosis improved with digestate or MBM compared to synthetic P. The results indicate that different species have adaptative mechanisms to various P sources which could improve the resilience and sustainability of cropping systems.
•Aromatase reporter activity was increased in the subcutaneous and gonadal fat of obese male hARO-Luc mice.•Obesity-induced adipose tissue inflammation was associated with enhanced aromatase reporter ...expression.•Glucocorticoids, TNFα, and forskolin induced aromatase reporter activity in adipose tissue and mesenchymal stromal cells.•Plant polyphenol mixture attenuated adipose tissue inflammation and aromatase reporter activity in obese male subcutaneous fat.•Bioavailable polyphenols, nortrachelogenin and pinosylvin, modified aromatase reporter activity in mesenchymal stromal cells.
Obesity and white adipose tissue (WAT) inflammation are associated with enhanced aromatization in women, but little is known about the regulation of aromatase (CYP19A1) gene expression in male WAT. We investigated the impact of weight gain and WAT inflammation on the regulation of CYP19A1 in males, by utilizing the hARO-Luc aromatase reporter mouse model containing a >100-kb 5′-region of the human CYP19A1 gene. We show that hARO-Luc reporter activity is enhanced in WAT of mice with increased adiposity and inflammation. Dexamethasone and TNFα, as well as forskolin and phorbol 12-myristate 13-acetate, upregulate hARO-Luc activity, suggesting the involvement of promoters I.4 and I.3/II. Furthermore, we show that diet enriched with antioxidative plant polyphenols attenuates WAT inflammation and hARO-Luc activity in obese males. In conclusion, our data suggest that obesity-associated WAT inflammation leads to increased peripheral CYP19A1 expression in males, and that polyphenol-enriched diet may have the potential to attenuate excessive aromatization in WAT of obese men.
Research focusing on the nitrogen (N) application and N use of forage maize (Zea mays L.) in the boreal region is either limited or non-existent. The aim of this study was to investigate the response ...of yield, quality and N recovery efficiency (NRE) of forage maize to an increase in the N application rate and different climatic conditions in two locations in Finland. The field experiment was conducted in southern (Helsinki; 60° N) and central (Maaninka; 63° N) Finland in 2019 and 2020. Dry matter (DM) yield, forage quality and NRE were determined for N application rates of 100, 150 and 200 N kg ha−1. The DM yield was similar to all studied N application rates. Moreover, there were no marked differences in the studied forage quality traits or the NRE following the N application rates. However, the NRE of maize was generally low at 45%. The current study recommends a N application rate of 100–150 N kg ha−1 for forage maize in the boreal region. There is no need to increase the N application from current recommendations since climate conditions seem to limit the growth, development and NRE of forage maize. The observed low NRE of forage maize warrants further research in the future.
Objectives
Urokinase‐type plasminogen activator receptor (uPAR) is upregulated during inflammation and known to bind to β3‐integrins, receptors used by pathogenic hantaviruses to enter endothelial ...cells. It has been proposed that soluble uPAR (suPAR) is a circulating factor that causes focal segmental glomerulosclerosis and proteinuria by activating β3‐integrin in kidney podocytes. Proteinuria is also a characteristic feature of hantavirus infections. The aim of this study was to evaluate the relation between urine suPAR levels and disease severity in acute Puumala hantavirus (PUUV) infection.
Design
A single‐centre, prospective cohort study.
Subjects and methods
Urinary suPAR levels were measured twice during the acute phase and once during convalescence in 36 patients with serologically confirmed PUUV infection. Fractional excretion of suPAR (FE suPAR) and of albumin (FE alb) was calculated.
Results
The FE suPAR was significantly elevated during the acute phase of PUUV infection compared to the convalescent phase (median 3.2%, range 0.8–52.0%, vs. median 1.9%, range 1.0–5.8%, P = 0.005). Maximum FE suPAR was correlated markedly with maximum FE alb (r = 0.812, P < 0.001) and with several other variables that reflect disease severity. There was a positive correlation with the length of hospitalization (r = 0.455, P = 0.009) and maximum plasma creatinine level (r = 0.780, P < 0.001) and an inverse correlation with minimum urinary output (r = −0.411, P = 0.030). There was no correlation between FE suPAR and plasma suPAR (r = 0.180, P = 0.324).
Conclusion
Urinary suPAR is markedly increased during acute PUUV infection and is correlated with proteinuria. High urine suPAR level may reflect local production of suPAR in the kidney during the acute infection.
Programmed cell death protein 1 (PD-1) blocking monoclonal antibodies improve the overall survival of patients with advanced melanoma but the optimal duration of treatment has not been established.
...This academic real-world cohort study investigated the outcome of 185 advanced melanoma patients who electively discontinued anti-PD-1 therapy with pembrolizumab (N=167) or nivolumab (N=18) in the absence of disease progression (PD) or treatment limiting toxicity (TLT) at 14 medical centres across Europe and Australia.
Median time on treatment was 12months (range 0.7–43). The best objective tumour response at the time of treatment discontinuation was complete response (CR) in 117 (63%) patients, partial response (PR) in 44 (24%) patients and stable disease (SD) in 16 (9%) patients; 8 (4%) patients had no evaluable disease (NE). After a median follow-up of 18months (range 0.7–48) after treatment discontinuation, 78% of patients remained free of progression. Median time to progression was 12months (range 2–23). PD was less frequent in patients with CR (14%) compared with patients with PR (32%) and SD (50%). Six out of 19 (32%) patients who were retreated with an anti-PD-1 at the time of PD obtained a new antitumour response.
In this real-world cohort of advanced melanoma patients discontinuing anti-PD-1 therapy in the absence of TLT or PD, the duration of anti-PD-1 therapy was shorter when compared with clinical trials. In patients obtaining a CR, and being treated for >6months, the risk of relapse after treatment discontinuation was low. Patients achieving a PR or SD as best tumour response were at higher risk for progression after discontinuing therapy, and defining optimal treatment duration in such patients deserves further study. Retreatment with an anti-PD-1 at the time of progression may lead to renewed antitumour activity in some patients.
NCT02673970 (https://clinicaltrials.gov/ct2/show/NCT02673970?cond=melanoma&cntry=BE&city=Jette&rank=3)
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