Introduction
We used data from MOBI-Kids, a 14-country international collaborative case–control study of brain tumors (BTs), to study clinical characteristics of the tumors in older children ...(10 years or older), adolescents and young adults (up to the age of 24).
Methods
Information from clinical records was obtained for 899 BT cases, including signs and symptoms, symptom onset, diagnosis date, tumor type and location.
Results
Overall, 64% of all tumors were low-grade, 76% were neuroepithelial tumors and 62% gliomas. There were more males than females among neuroepithelial and embryonal tumor cases, but more females with meningeal tumors. The most frequent locations were cerebellum (22%) and frontal (16%) lobe. The most frequent symptom was headaches (60%), overall, as well as for gliomas, embryonal and ‘non-neuroepithelial’ tumors; it was convulsions/seizures for neuroepithelial tumors other than glioma, and visual signs and symptoms for meningiomas. A cluster analysis showed that headaches and nausea/vomiting was the only combination of symptoms that exceeded a cutoff of 50%, with a joint occurrence of 67%. Overall, the median time from first symptom to diagnosis was 1.42 months (IQR 0.53–4.80); it exceeded 1 year in 12% of cases, though no particular symptom was associated with exceptionally long or short delays.
Conclusions
This is the largest clinical epidemiology study of BT in young people conducted so far. Many signs and symptoms were identified, dominated by headaches and nausea/vomiting. Diagnosis was generally rapid but in 12% diagnostic delay exceeded 1 year with none of the symptoms been associated with a distinctly long time until diagnosis.
Emerging evidence indicates that metabolic dysregulation drives prostate cancer (PCa) progression and metastasis. AMP-activated protein kinase (AMPK) is a master regulator of metabolism, although its ...role in PCa remains unclear. Here, we show that genetic and pharmacological activation of AMPK provides a protective effect on PCa progression in vivo. We show that AMPK activation induces PGC1α expression, leading to catabolic metabolic reprogramming of PCa cells. This catabolic state is characterized by increased mitochondrial gene expression, increased fatty acid oxidation, decreased lipogenic potential, decreased cell proliferation, and decreased cell invasiveness. Together, these changes inhibit PCa disease progression. Additionally, we identify a gene network involved in cell cycle regulation that is inhibited by AMPK activation. Strikingly, we show a correlation between this gene network and PGC1α gene expression in human PCa. Taken together, our findings support the use of AMPK activators for clinical treatment of PCa to improve patient outcome.
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•Chronic genetic activation of AMPK protects against prostate cancer in vivo•AMPK activation induces PGC1α and catabolic reprogramming of prostate cancer cells•The catabolic state correlates with inhibition of a network of cell cycle genes•AMPK activation decreases storage of neutral lipids in prostate cancer cells
Penfold et al. show that AMPK activation protects against prostate cancer progression in vivo. AMPK activation switches prostate cancer cells to a tumor-suppressive catabolic state, increasing PGC1α expression and mitochondrial biogenesis while inhibiting lipogenic potential. In parallel, AMPK inhibits a cell cycle gene network associated with prostate cancer progression.
The effectiveness of repeated vaccination for influenza to prevent severe cases remains unclear. We evaluated the effectiveness of influenza vaccination on preventing admissions to hospital for ...influenza and reducing disease severity.
We conducted a case-control study in 20 hospitals in Spain during the 2013/14 and 2014/15 influenza seasons. Community-dwelling adults aged 65 years or older who were admitted to hospital for laboratory-confirmed influenza were matched with inpatient controls by sex, age, hospital and admission date. The effectiveness of vaccination in the current and 3 previous seasons in preventing influenza was estimated for inpatients with nonsevere influenza and for those with severe influenza who were admitted to intensive care units (ICUs) or who died.
We enrolled 130 inpatients with severe and 598 with nonsevere influenza who were matched to 333 and 1493 controls, respectively. Compared with patients who were unvaccinated in the current and 3 previous seasons, adjusted effectiveness of influenza vaccination in the current and any previous season was 31% (95% confidence interval CI 13%-46%) in preventing admission to hospital for nonsevere influenza, 74% (95% CI 42%-88%) in preventing admissions to ICU and 70% (95% CI 34%-87%) in preventing death. Vaccination in the current season only had no significant effect on cases of severe influenza. Among inpatients with influenza, vaccination in the current and any previous season reduced the risk of severe outcomes (adjusted odds ratio 0.45, 95% CI 0.26-0.76).
Among older adults, repeated vaccination for influenza was twice as effective in preventing severe influenza compared with nonsevere influenza in patients who were admitted to hospital, which is attributable to the combination of the number of admissions to hospital for influenza that were prevented and reduced disease severity. These results reinforce recommendations for annual vaccination for influenza in older adults.
Life satisfaction is a cognitive and stable construct that comprises the subjective well-being and an accurate indicator of the perception of life circumstances among adolescents. Previous studies ...demonstrate that adolescents’ life satisfaction is associated with developmental outcomes and positive psychological variables as well as protection against risk factors, such as bullying. Several international studies demonstrate that adolescents’ life satisfaction can be negatively affected by bullying; consequently this behavior has become a matter of public concern. Our study hypothesized that the perception of safety plays a protective role against bullying and therefore maintains life satisfaction levels in adolescents. We examined a cohort of 1955 Chilean and 1789 Brazilian adolescents that participated in the International Survey of Children’s Well-Being (ISCWeB) 3rd Wave in Latin America. Using multiple regression and moderation analyses we found that the interaction victim × feeling safety predicts adolescents life satisfaction. Hence, adolescents that report high victim scores and high safety also report high life satisfaction levels, versus adolescents that report high victim scores and low safety that report lower levels of life satisfaction; suggesting a protective role of the perception of safety against victim scores. Our results confirm the importance and the protective role of the perception of safety (i.e. “feeling safe”) on adolescents’ life satisfaction. Particularly, we provide evidence that supports the promotion of safer environments at schools, within families, and in our communities in Latin America.
The bloom-forming toxic dinoflagellate
was first detected in southern Chile (39.5-55° S) 50 years ago and is responsible for most of the area's cases of paralytic shellfish poisoning (PSP). Given the ...complex life history of
, which includes benthic sexual cysts, in this study, we examined the potential link between latitude, toxicity, and sexual compatibility. Nine clones isolated from Chilean Patagonia were used in self- and out-crosses in all possible combinations (
= 45). The effect of latitude on toxicity, reproductive success indexes, and cyst production was also determined. Using the toxin profiles for all strains, consisting of C1, C2, GTX4, GTX1, GTX3, and NeoSTX, a latitudinal gradient was determined for their proportions (%) and content per cell (pg cell
), with the more toxic strains occurring in the north (-40.6° S). Reproductive success also showed a latitudinal tendency and was lower in the north. None of the self-crosses yielded resting cysts. Rather, the production of resting cysts was highest in pairings of clones separated by distances of 1000-1650 km. Our results contribute to a better understanding of PSP outbreaks in the region and demonstrate the importance of resting cysts in fueling new toxic events. They also provide additional evidence that the introduction of strains from neighboring regions is a cause for concern.
Abstract Objective To evaluate the effectiveness and safety of anti-tumor necrosis factor therapy in patients with amyloid A amyloidosis. Methods Multicenter, controlled, dynamic prospective cohort ...study of 36 patients with amyloid A amyloidosis (94% kidney involvement) treated with anti-tumor necrosis factor agents (drug exposure of 102.97 patient-years). As an external control group, 35 propensity score-matched non-amyloid patients were chosen from the Base de Datos de Productos Biológicos de la Sociedad Española de Reumatología registry. The end points were kidney response and progression, anti-tumor necrosis factor continuation rate, patient survival, and adverse events. Results At the end of follow-up, a kidney response was observed in 12 of 22 patients (54.5%) and a kidney progression was observed in 6 of 36 patients (17%). The kidney amyloidosis remained stable in 16 of 36 patients (44%). The level of acute phase reactants diminished but did not reach the normal level. The continuation rates of anti-tumor necrosis factor drugs among patients with amyloid A amyloidosis after 1, 2, 3, and 4 or more years were 80%, 80%, 61%, and 52%, respectively, comparable to controls. The 5-year cumulative survival of amyloid A amyloidosis cases was 90.6%, and the 10-year survival was 78.5%. In a multivariate Cox regression analysis, the duration of amyloidosis and the level of proteinuria at the onset of anti-tumor necrosis factor treatment were independent predictors of treatment failure, whereas the level of proteinuria was the only factor that predicts mortality. Most adverse events were similar in both groups, although the number of infections was 3 times higher in amyloid A amyloidosis cases. Conclusion Anti-tumor necrosis factor drugs are effective in treating amyloid A amyloidosis, although they might increase the risk of infection.
From 1985 to 2016, the prevalence of underweight decreased, and that of obesity and severe obesity increased, in most regions, with significant variation in the magnitude of these changes across ...regions. We investigated how much change in mean body mass index (BMI) explains changes in the prevalence of underweight, obesity, and severe obesity in different regions using data from 2896 population-based studies with 187 million participants. Changes in the prevalence of underweight and total obesity, and to a lesser extent severe obesity, are largely driven by shifts in the distribution of BMI, with smaller contributions from changes in the shape of the distribution. In East and Southeast Asia and sub-Saharan Africa, the underweight tail of the BMI distribution was left behind as the distribution shifted. There is a need for policies that address all forms of malnutrition by making healthy foods accessible and affordable, while restricting unhealthy foods through fiscal and regulatory restrictions.
Optimal growth and development in childhood and adolescence is crucial for lifelong health and well-being
. Here we used data from 2,325 population-based studies, with measurements of height and ...weight from 71 million participants, to report the height and body-mass index (BMI) of children and adolescents aged 5-19 years on the basis of rural and urban place of residence in 200 countries and territories from 1990 to 2020. In 1990, children and adolescents residing in cities were taller than their rural counterparts in all but a few high-income countries. By 2020, the urban height advantage became smaller in most countries, and in many high-income western countries it reversed into a small urban-based disadvantage. The exception was for boys in most countries in sub-Saharan Africa and in some countries in Oceania, south Asia and the region of central Asia, Middle East and north Africa. In these countries, successive cohorts of boys from rural places either did not gain height or possibly became shorter, and hence fell further behind their urban peers. The difference between the age-standardized mean BMI of children in urban and rural areas was <1.1 kg m
in the vast majority of countries. Within this small range, BMI increased slightly more in cities than in rural areas, except in south Asia, sub-Saharan Africa and some countries in central and eastern Europe. Our results show that in much of the world, the growth and developmental advantages of living in cities have diminished in the twenty-first century, whereas in much of sub-Saharan Africa they have amplified.
Influenza vaccination may limit the impact of influenza in the community. The aim of this study was to assess the effectiveness of influenza vaccination in preventing hospitalisation in individuals ...aged ≥ 65 years in Spain. A multicentre case-control study was conducted in 20 Spanish hospitals during 2013/14 and 2014/15. Patients aged ≥ 65 years who were hospitalised with laboratory-confirmed influenza were matched with controls according to sex, age and date of hospitalisation. Adjusted vaccine effectiveness (VE) was calculated by multivariate conditional logistic regression. A total of 728 cases and 1,826 matched controls were included in the study. Overall VE was 36% (95% confidence interval (CI): 22-47). VE was 51% (95% CI: 15-71) in patients without high-risk medical conditions and 30% (95% CI: 14-44) in patients with them. VE was 39% (95% CI: 20-53) in patients aged 65-79 years and 34% (95% CI: 11-51) in patients aged ≥ 80 years, and was greater against the influenza A(H1N1)pdm09 subtype than the A(H3N2) subtype. Influenza vaccination was effective in preventing hospitalisations of elderly individuals.
Seasonal influenza causes significant morbidity and mortality in people aged ≥65 years. Antiviral treatment can reduce complications and disease severity. The objective of this study was to ...investigate the effect of antiviral treatment in patients aged ≥65 years hospitalized with confirmed influenza in preventing intensive care unit (ICU) admission or death. A retrospective cohort study was carried out in 20 hospitals from seven Spanish regions during 2013–2015 in patients aged ≥65 years. Hospitalized cases of laboratory-confirmed influenza were selected. To assess the association between antiviral treatment and ICU admission or death, the adjusted odds ratios (aOR) and their 95% confidence intervals (CI) were calculated using multivariate logistic regression. We included 715 hospitalized patients, of whom 640 (87.9%) received antiviral treatment, 77 (10.8%) required ICU admission and 66 (9.2%) died. In the 64–74 years age group, receipt of antiviral treatment ≤48 h (aOR 0.20; 95% CI 0.04–0.89), 3–4 days (aOR 0.23; 95% CI 0.05–0.92) and 5–7 days (aOR 0.24; 95% CI 0.03–0.91) after clinical symptom onset was associated with reduced mortality. Receipt of treatment >7 days after symptom onset was not associated with reduced mortality. No association of antiviral treatment with reduced mortality was observed in the >74 years age group or with the prevention of ICU admission in any age group. Antiviral treatment had a protective effect in avoiding death in patients aged 65–74 years hospitalized due to influenza when administered ≤48 h after symptom onset and when no more than 7 days had elapsed.
•Antiviral treatment reduces deaths in hospitalized patients aged 65–74 years.•Antiviral treatment ≤48 hours after symptom onset and when no more than 6 days have elapsed is effective in avoiding deaths.•No association between antiviral treatment and the prevention of mortality was observed in patients aged >74 years.•No association between antiviral treatment and the prevention of ICU admission was observed.
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