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"Chen, Kong"
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Apatinib combined with temozolomide in diffuse midline glioma: a novel and effective therapy
Purpose
Diffuse midline glioma (DMG), H3 K27M-mutant is a type of diffuse high-grade glioma that occurs in the brain midline carrying an extremely poor prognosis under the best efforts of surgery, radiation, and other therapies. For better therapy, we explored the efficacy and toxicity of a novel therapy that combines apatinib and temozolomide in DMG.
Methods
A retrospective analysis of 32 patients with DMG who underwent apatinib plus temozolomide treatment was performed. Apatinib was given 500 mg in adults, 250 mg in pediatric patients once daily. Temozolomide was administered at 200 mg/m
2
/d according to the standard 5/28 days regimen. The main clinical data included basic information of patients, radiological and pathological characteristics of tumors, treatment, adverse reactions, prognosis.
Results
The objective response rate was 24.1%, and the disease control rate was 79.3%. The median PFS of all patients was 5.8 months, and median OS was 10.3 months. A total of 236 cycles of treatment were available for safety assessment and the toxicity of the combination therapy was relatively well tolerated. The most common grade 3 toxicities were myelosuppression including leukopenia (5.08%), neutropenia (4.24%), lymphopenia (2.12%), thrombocytopenia (1.69%) and anemia (1.27%). Grade 4 toxicities included neutropenia (2.12%), thrombocytopenia (2.12%) and proteinuria (1.69%). All the adverse events were relieved after symptomatic treatment or dose reduction.
Conclusions
Apatinib plus temozolomide could be an effective regimen with manageable toxicities and favorable efficacy and may outperform temozolomide monotherapy, particularly in newly diagnosed adults with tumors located outside the pons. The novel therapy deserves further investigation in adult DMG patients.
Key points
1. The novel therapy that combines apatinib and temozolomide could be an effective regimen with manageable toxicities in DMGs.
2. Apatinib plus temozolomide is a therapeutic improved with favorable efficacy and at least superior to temozolomide monotherapy.
3. It was confirmed that some adult and thalamic subgroup patients with DMG could benefit from the application of apatinib plus temozolomide.
Journal Article
Less screen time and more frequent vigorous physical activity is associated with lower risk of reporting negative mental health symptoms among Icelandic adolescents
Few studies have explored the potential interrelated associations of screen time and physical activity with mental health in youth, particularly using objective methods. We examined cross-sectional associations of these variables among Icelandic adolescents, using objective and subjective measurements of physical activity.
Data were collected in the spring of 2015 from 315 tenth grade students (mean age 15.8 years) in six elementary schools in metropolitan Reykjavík, Iceland. Participants reported, via questionnaire, on demographics, weekly frequency of vigorous physical activity, daily hours of screen time and mental health status (symptoms of depression, anxiety and somatic complaints, self-esteem and life satisfaction). Total physical activity was measured over one week with wrist-worn accelerometers. Body composition was determined by DXA-scanning. Poisson regression analysis was used to explore independent and interactive associations of screen time and physical activity with mental health variables, adjusting for gender, body fat percentage and maternal education.
Less screen time (below the group median of 5.3 h/day) and more frequent vigorous physical activity (≥4x/week) were each associated with reporting fewer symptoms of depression, anxiety, low self-esteem, and life dissatisfaction. No significant associations were observed between objectively measured physical activity and mental health outcomes. Interactive regression analysis showed that the group reporting both less screen time and more frequent vigorous physical activity had the lowest risk of reporting symptoms of depression, anxiety, low self-esteem, and life dissatisfaction.
Reports of less screen time and more frequent vigorous physical activity were associated with lower risk of reporting mental health problems among Icelandic adolescents. Those who reported a combination of engaging in less screen time and more frequent vigorous physical activity had the lowest risk, suggesting a synergistic relationship between the two behaviors on mental health outcomes. Our results support guiding youth towards more active and less sedentary/screen-based lifestyle.
Journal Article
Estimation of Daily Energy Expenditure in Pregnant and Non-Pregnant Women Using a Wrist-Worn Tri-Axial Accelerometer
Few studies have compared the validity of objective measures of physical activity energy expenditure (PAEE) in pregnant and non-pregnant women. PAEE is commonly estimated with accelerometers attached to the hip or waist, but little is known about the validity and participant acceptability of wrist attachment. The objectives of the current study were to assess the validity of a simple summary measure derived from a wrist-worn accelerometer (GENEA, Unilever Discover, UK) to estimate PAEE in pregnant and non-pregnant women, and to evaluate participant acceptability.
Non-pregnant (N = 73) and pregnant (N = 35) Swedish women (aged 20-35 yrs) wore the accelerometer on their wrist for 10 days during which total energy expenditure (TEE) was assessed using doubly-labelled water. PAEE was calculated as 0.9×TEE-REE. British participants (N = 99; aged 22-65 yrs) wore accelerometers on their non-dominant wrist and hip for seven days and were asked to score the acceptability of monitor placement (scored 1 [least] through 10 [most] acceptable).
There was no significant correlation between body weight and PAEE. In non-pregnant women, acceleration explained 24% of the variation in PAEE, which decreased to 19% in leave-one-out cross-validation. In pregnant women, acceleration explained 11% of the variation in PAEE, which was not significant in leave-one-out cross-validation. Median (IQR) acceptability of wrist and hip placement was 9(8-10) and 9(7-10), respectively; there was a within-individual difference of 0.47 (p<.001).
A simple summary measure derived from a wrist-worn tri-axial accelerometer adds significantly to the prediction of energy expenditure in non-pregnant women and is scored acceptable by participants.
Journal Article
Association of Sedentary Time with Mortality Independent of Moderate to Vigorous Physical Activity
Sedentary behavior has emerged as a novel health risk factor independent of moderate to vigorous physical activity (MVPA). Previous studies have shown self-reported sedentary time to be associated with mortality; however, no studies have investigated the effect of objectively measured sedentary time on mortality independent of MVPA. The objective our study was to examine the association between objectively measured sedentary time and all-cause mortality.
7-day accelerometry data of 1906 participants aged 50 and over from the U.S. nationally representative National Health and Nutrition Examination Survey (NHANES) 2003-2004 were analyzed. All-cause mortality was assessed from the date of examination through December 31, 2006.
Over an average follow-up of 2.8 years, there were 145 deaths reported. In a model adjusted for sociodemographic factors, lifestyle factors, multiple morbidities, mobility limitation, and MVPA, participants in third quartile (hazard ratio (HR):4.05; 95%CI:1.55-10.60) and fourth quartile (HR:5.94; 95%CI: 2.49-14.15) of having higher percent sedentary time had a significantly increased risk of death compared to those in the lowest quartile.
Our study suggests that sedentary behavior is a risk factor for mortality independent of MVPA. Further investigation, including studies with longer follow-up, is needed to address the health consequences of sedentary behavior.
Journal Article
Mapping of human brown adipose tissue in lean and obese young men
Human brown adipose tissue (BAT) can be activated to increase glucose uptake and energy expenditure, making it a potential target for treating obesity and metabolic disease. Data on the functional and anatomic characteristics of BAT are limited, however. In 20 healthy young men [12 lean, mean body mass index (BMI) 23.2 ± 1.9 kg/m²; 8 obese, BMI 34.8 ± 3.3 kg/m²] after 5 h of tolerable cold exposure, we measured BAT volume and activity by 18F-labeled fluorodeoxyglucose positron emission tomography/computerized tomography (PET/CT). Obese men had less activated BAT than lean men (mean, 130 vs. 334 mL) but more fat in BAT-containing depots (mean, 1,646 vs. 855 mL) with a wide range (0.1–71%) in the ratio of activated BAT to inactive fat between individuals. Six anatomic regions had activated BAT—cervical, supraclavicular, axillary, mediastinal, paraspinal, and abdominal—with 67 ± 20% of all activated BAT concentrated in a continuous fascial layer comprising the first three depots in the upper torso. These nonsubcutaneous fat depots amounted to 1.5% of total body mass (4.3% of total fat mass), and up to 90% of each depot could be activated BAT. The amount and activity of BAT was significantly influenced by region of interest selection methods, PET threshold criteria, and PET resolutions. The present study suggests that active BAT can be found in specific adipose depots in adult humans, but less than one-half of the fat in these depots is stimulated by acute cold exposure, demonstrating a previously underappreciated thermogenic potential.
Journal Article
Redox control in the pathophysiology of influenza virus infection
Triggered in response to external and internal ligands in cells and animals, redox homeostasis is transmitted via signal molecules involved in defense redox mechanisms through networks of cell proliferation, differentiation, intracellular detoxification, bacterial infection, and immune reactions. Cellular oxidation is not necessarily harmful per se, but its effects depend on the balance between the peroxidation and antioxidation cascades, which can vary according to the stimulus and serve to maintain oxygen homeostasis. The reactive oxygen species (ROS) that are generated during influenza virus (IV) infection have critical effects on both the virus and host cells. In this review, we outline the link between viral infection and redox control using IV infection as an example. We discuss the current state of knowledge on the molecular relationship between cellular oxidation mediated by ROS accumulation and the diversity of IV infection. We also summarize the potential anti-IV agents available currently that act by targeting redox biology/pathophysiology.
Journal Article
The Complex Effects of Light on Metabolism in Humans
Light is an essential part of many life forms. The natural light–dark cycle has been the dominant stimulus for circadian rhythms throughout human evolution. Artificial light has restructured human activity and provided opportunities to extend the day without reliance on natural day–night cycles. The increase in light exposure at unwanted times or a reduced dynamic range of light between the daytime and nighttime has introduced negative consequences for human health. Light exposure is closely linked to sleep–wake regulation, activity and eating patterns, body temperature, and energy metabolism. Disruptions to these areas due to light are linked to metabolic abnormalities such as an increased risk of obesity and diabetes. Research has revealed that various properties of light influence metabolism. This review will highlight the complex role of light in human physiology, with a specific emphasis on metabolic regulation from the perspective of four main properties of light (intensity, duration, timing of exposure, and wavelength). We also discuss the potential influence of the key circadian hormone melatonin on sleep and metabolic physiology. We explore the relationship between light and metabolism through circadian physiology in various populations to understand the optimal use of light to mitigate short and long-term health consequences.
Journal Article
Effect of a plant-based, low-fat diet versus an animal-based, ketogenic diet on ad libitum energy intake
The carbohydrate–insulin model of obesity posits that high-carbohydrate diets lead to excess insulin secretion, thereby promoting fat accumulation and increasing energy intake. Thus, low-carbohydrate diets are predicted to reduce ad libitum energy intake as compared to low-fat, high-carbohydrate diets. To test this hypothesis, 20 adults aged 29.9 ± 1.4 (mean ± s.e.m.) years with body mass index of 27.8 ± 1.3 kg m
−2
were admitted as inpatients to the National Institutes of Health Clinical Center and randomized to consume ad libitum either a minimally processed, plant-based, low-fat diet (10.3% fat, 75.2% carbohydrate) with high glycemic load (85 g 1,000 kcal
−1
) or a minimally processed, animal-based, ketogenic, low-carbohydrate diet (75.8% fat, 10.0% carbohydrate) with low glycemic load (6 g 1,000 kcal
−1
) for 2 weeks followed immediately by the alternate diet for 2 weeks. One participant withdrew due to hypoglycemia during the low-carbohydrate diet. The primary outcomes compared mean daily ad libitum energy intake between each 2-week diet period as well as between the final week of each diet. We found that the low-fat diet led to 689 ± 73 kcal d
−1
less energy intake than the low-carbohydrate diet over 2 weeks (
P
< 0.0001) and 544 ± 68 kcal d
−1
less over the final week (
P
< 0.0001). Therefore, the predictions of the carbohydrate–insulin model were inconsistent with our observations. This study was registered on ClinicalTrials.gov as
NCT03878108
.
In an inpatient, randomized controlled crossover trial, participants consumed 550–700 kcal day
−1
fewer calories when following a plant-based, low-fat diet with a high glycemic load compared with an animal-based, low-carbohydrate diet with a low glycemic load; weight loss was comparable between the two diets and there were no significant differences in hunger or enjoyment of the meals.
Journal Article