The role of a family history of lung cancer (LCFH) in screening using low-dose computed tomography (LDCT) has not been prospectively investigated with long-term follow-up.
A multicenter prospective ...study with up to three rounds of annual LDCT screening was conducted to determine the detection rate of lung cancer (LC) in asymptomatic first- or second-degree relatives of LCFH.
From 2007 to 2011, there were 1102 participants enrolled, including 805 and 297 from simplex and multiplex families (MFs), respectively (54.2% women and 70.0% never-smokers). The last follow-up date was May 5, 2021. The overall LC detection rate was 4.5% (50 of 1102). The detection rate in MF was 9.4% (19 of 202) and 4.4% (4 of 91) in never-smokers and in those who smoked, respectively. The corresponding rates for simplex families were 3.7% (21 of 569) and 2.7% (6 of 223), respectively. Of these, 68.0% and 22.0% of cases with stage I and IV diseases, respectively. LC diagnoses within a 3-year interval from the initial screening tend to be younger, have a higher detection rate, and have stage I disease; thereafter, more stage III–IV disease and 66.7% (16 of 24) with negative or semipositive nodules in initial computed tomography scans. Within the 6-year interval, only maternal (modified rate ratio = 4.46, 95% confidence interval: 2.32–8.56) or maternal relative history of LC (modified rate ratio = 5.41, 95% confidence interval: 2.84–10.30) increased the risk of LC.
LCFH is a risk factor for LC and is increased with MF history, among never-smokers, younger adults, and those with maternal relatives with LC. Randomized controlled trials are needed to confirm the mortality benefit of LDCT screening in those with LCFH.
To estimate the risks of depressive symptoms for developing frailty, accounting for baseline robust or pre-frailty status.
An incident cohort study design.
Community dwellers aged 55 years and above ...from urban and rural areas in seven regions in Taiwan.
A total of 2,717 participants from the Healthy Aging Longitudinal Study in Taiwan (HALST) were included. Subjects with frailty at baseline were excluded. The average follow-up period was 5.9 years.
Depressive symptoms were measured by the 20-item Center for Epidemiological Studies Depression (CES-D) Scale. Frailty was assessed using the Fried frailty measurement. Participants were stratified by baseline robust or pre-frailty status to reduce the confounding effects of the shared criteria between depressive symptoms and frailty. Overall and stratified survival analyses were conducted to assess risks of developing frailty as a result of baseline depressive symptoms.
One hundred individuals (3.7%) had depressive symptoms at baseline. Twenty-seven individuals (27.0%) with depressive symptoms developed frailty, whereas only 305 out of the 2,617 participants (11.7%) without depressive symptoms developed frailty during the follow-up period. After adjusting for covariates, depressive symptoms were associated with a 2.6-fold (95% CI 1.6, 4.2) increased hazard of incident frailty. The patterns of increased hazard were also observed when further stratified by baseline robust or pre-frailty status.
Depressive symptoms increased the risk of developing frailty among the older Asian population. The impact of late-life depressive symptoms on physical health was notable. These findings also replicated results from Western populations. Future policies on geriatric public health need to focus more on treatment and intervention against geriatric depressive symptoms to prevent incident frailty among older population.
Inflammation is considered as a key pathogenesis factor of dementia and epilepsy. However, epilepsy's association with dementia, particularly its role in the development of dementia, remains unclear. ...To evaluate the association between epilepsy and the risk of dementia, in Taiwan, we have now conducted a retrospective cohort study comprising 675 individuals (age, ≥50 years) with epilepsy and 2,025 matched control subjects without epilepsy. In order to match individuals diagnosed with epilepsy with those with no diagnosis of epilepsy (comparison cohort), we utilized exact matching at a ratio of 1:3. Compared with those in the comparison cohort, individuals in the epilepsy cohort had a significantly increased risk of developing dementia (adjusted hazard ratio = 2.87,
< 0.001). A similar result has been observed after stratifying for sex (adjusted hazard ratio in males = 2.95,
< 0.001; adjusted hazard ratio in females = 2.66,
< 0.001). To conclude, based on these data, epileptic individuals ≥50 years were at a greater risk of developing dementia than people who do not have epilepsy, which indicates that a diagnosis of epilepsy presents a greater risk for the development of dementia.
The effect of cardio-metabolic profile on the relationship of body mass index (BMI) with mortality is unclear. The aim of this study was to explore association between BMI and mortality at all ages, ...taking account of cardio-metabolic disorders.
We followed 377,929 individuals (≥ 20 years), who registered for health checkups in 1996-2007, until 2008 and found 9490 deaths. From multivariable Cox proportional hazards models we estimated mortality hazard ratios (HR) for those in high blood pressure, hyperglycemia, high waist circumference, dyslipidemia, and different BMIs categories (the underweight < 18.5 kg/m
, low normal weight 18.5-21.9 kg/m
, normal weight 22-23.9 kg/m
, the referent, overweight 24-26.9 kg/m
, obese1 27-29.9 kg/m
, and obese2 ≥ 30 kg/m
). Population attributable risk (PAR) provided estimates of the population mortality burden attributable to high blood pressure, hyperglycemia, high waist circumference, dyslipidemia, and deviant BMIs.
Higher blood pressure, hyperglycemia, high waist circumference, and dyslipidemia were significantly predictive of higher mortality for nearly all ages. Compared with the referent BMI, underweight (HR = 1.69, 95% confidence interval = 1.51-1.90) and low normal weight (HR = 1.19, 1.11-1.28) were significant mortality risks, while overweight (HR = 0.82, 0.76-0.89) and obese1 (HR = 0.88, 0.79-0.97) were protective against premature death. The mortality impact of obesity was largely attributable to cardio-metabolic profile and attenuated by age. The population mortality burden with high blood pressure (PAR = 7.29%), hyperglycemia (PAR = 5.15%), high waist circumference (PAR = 4.24%), and dyslipidemia (PAR = 5.66%) was similar to that in the underweight (PAR = 5.50%) or low normal weight (PAR = 6.04%) groups. Findings for non-smokers and by gender were similar.
The effect of BMI on mortality varies with age and is affected by cardio-metabolic status. Compared to any deviant BMI, abnormal cardio-metabolic status has a similar or even greater health impact at both the individual and population levels.
Aim
To develop cut‐off points of muscle mass, gait speed and handgrip strength; and to examine the prevalence of sarcopenia, and the relationship between sarcopenia stages and functional limitations ...and disability by using these cut‐off points.
Methods
We pooled individual participant data of 2867 community‐dwelling older adults from five cohort studies. We defined the cut‐off point of a muscle mass index (ASM/ht2) as the values of two standard deviations below the sex‐specific means of a young population or as the 20th percentile of the sex‐specific distribution in our study population. The gait speed and handgrip strength cut‐off points were defined as the 20th percentile of their population distributions. We also measured functional limitations, using the Short Physical Performance Battery, and the number of activities of daily living and instrumental activities of daily living difficulties.
Results
We identified the cut‐off points of ASM/ht2, gait speed and handgrip strength. By applying these cut‐off points to our study population, the prevalence of sarcopenia varied from 3.9% (2.5% in women and 5.4% in men) to 7.3% (6.5% in women and 8.2% in men). A higher sarcopenia stage was independently associated with a lower summary performance score, as well as more activities of daily living and instrumental activities of daily living difficulties (P < 0.05 for all).
Conclusions
The prevalence of sarcopenia in community‐dwelling older adults is comparable with those in other populations. A dose–response relationship exists between sarcopenia stages and functional limitations/disability. The European Working Group on Sarcopenia in Older People consensus definition using these cut‐off points is suitable for determining sarcopenia cases in the elderly population of Taiwan. Geriatr Gerontol Int 2014; 14 (Suppl. 1): 52–60.
Background and aim: Sepsis causes an uncontrolled systemic response characterized by excessive inflammation and immune suppression, leading to multiple organ failure and death. An effective ...therapeutic strategy for sepsis-related syndromes is urgently needed. Hypericum sampsonii Hance (HS) is a folk herbal plant used to treat arthritis and dermatitis, but the anti-inflammatory properties of HS and its related compounds have rarely been investigated. In this study, we aimed to explore the anti-inflammatory effects of HS. Experimental procedure: Models of bacterial lipopolysaccharide (LPS)-induced activated macrophages and endotoxemia mice were used, in which the TLR4/NF-κB signaling pathway is upregulated to trigger inflammatory responses. The HS extract (HSE) was delivered into LPS-induced endotoxemia mice via oral administration. Three compounds were purified using column chromatography and preparative thin layer chromatography and were validated by physical and spectroscopic data. Results: HSE suppressed NF-κB activation and proinflammatory molecules (TNF-a, IL-6, iNOS) in LPS-activated RAW 264.7 macrophages. Furthermore, oral administration of HSE (200 mg/kg) to LPS-treated mice improved the survival rate, restored body temperature, decreased TNF-α and IL-6 in serum, and reduced IL-6 expression in bronchoalveolar lavage fluid (BALF). In lung tissues, HSE reduced LPS-induced leukocyte infiltration and the expression of proinflammatory molecules (TNF-α, IL-6, iNOS, CCL4 and CCL5). Three pure compounds isolated from HSE, including 2,4,6-trihydroxybenzophenone-4- O-geranyl ether, 1-hydroxy-7 methoxyxanthone and euxanthone, were demonstrated to exhibit anti-inflammatory activities in LPS-stimulated RAW 264.7 macrophages. Conclusion: The present study demonstrated the anti-inflammatory effects of HS in vitro and in vivo. Further clinical studies of HS in human sepsis are warranted.
The study of cerebral metabolites relies heavily on detection methods and sample preparation. Animal experiments in vivo require anesthetic agents that can alter brain metabolism, whereas ex vivo ...experiments demand appropriate fixation methods to preserve the tissue from rapid postmortem degradation. In this study, the metabolic profiles of mouse hippocampi using proton magnetic resonance spectroscopy (
H-MRS) were compared in vivo and in situ with or without focused beam microwave irradiation (FBMI) fixation. Ten major brain metabolites, including lactate (Lac), N-acetylaspartate (NAA), total choline (tCho), myo-inositol (mIns), glutamine (Gln), glutamate (Glu), aminobutyric acid (GABA), glutathione (GSH), total creatine (tCr) and taurine (Tau), were analyzed using LCModel. After FBMI fixation, the concentrations of Lac, tCho and mIns were comparable with those obtained in vivo under isoflurane, whereas other metabolites were significantly lower. Except for a decrease in NAA and an increase in Tau, all the other metabolites remained stable over 41 hours in FBMI-fixed brains. Without FBMI, the concentrations of mIns (before 2 hours), tCho and GABA were close to those measured in vivo. However, higher Lac (P < .01) and lower NAA, Gln, Glu, GSH, tCr and Tau were observed (P < .01). NAA, Gln, Glu, GSH, tCr and Tau exhibited good temporal stability for at least 20 hours in the unfixed brain, whereas a linear increase of tCho, mIns and GABA was observed. Possible mechanisms of postmortem degradation are discussed. Our results indicate that a proper fixation method is required for in situ detection depending on the targeted metabolites of specific interests in the brain.
Systemic chronic inflammation occurs with age. The association of the leukocyte mitochondrial DNA copy number, a measure of mitochondrial function in aging, with the temporal profile of serum ...high-sensitivity C-reactive protein and mortality risk remains uncertain. The objectives of this study were to examine the association of the leukocyte mitochondrial DNA copy number with longitudinal high-sensitivity C-reactive protein levels and the association of the longitudinal high-sensitivity C-reactive protein levels with mortality risk.
This prospective cohort study included 3928 adults aged ≥ 55 years without systemic inflammation in the baseline examination of the Healthy Aging Longitudinal Study in Taiwan, which started in 2009. Each participant received leukocyte mitochondrial DNA copy number measurement using a fluorescence-based quantitative polymerase chain reaction at baseline, serum high-sensitivity C-reactive protein measurements at baseline and the follow-up examination five years later, and the ascertainment of all-cause death (until November 30, 2021). The relationships among the leukocyte mitochondrial DNA copy number, longitudinal serum high-sensitivity C-reactive protein levels, and time to all-cause mortality were examined using the joint longitudinal and survival modeling analysis.
Of the 3928 participants (mean age: 69 years; 2060 52% were women), 837 (21%) died during follow-up. In the adjusted analysis, one standard deviation lower natural log-transformed baseline leukocyte mitochondrial DNA copy number was associated with an increase of 0.05 (95% confidence interval CI, 0.02 to 0.08) standard deviation in serum high-sensitivity C-reactive protein in subsequent years. An increase of 1 standard deviation in instantaneous high-sensitivity C-reactive protein levels was associated with a hazard ratio (HR) for all-cause mortality of 1.22 (95% CI, 1.14 to 1.30). Similar results were obtained after further adjusting for baseline high-sensitivity C-reactive protein levels (HR 95% CI, 1.27 1.16 to 1.38) and after excluding those with serum high-sensitivity C-reactive protein above 10 mg/L (HR 95% CI, 1.211.11 to 1.31) or 3 mg/L (HR 95% CI, 1.19 1.06 to 1.31) during follow-up.
A lower leukocyte mitochondrial DNA copy number was associated with persistently higher high-sensitivity C-reactive protein levels. Moreover, these higher time-varying high-sensitivity C-reactive protein levels were instantaneously associated with a higher risk of death.
Glioblastoma multiforme (GBM) is one of the most challenging diseases to treat in clinical oncology due to its high mortality rates and inefficient conventional treatment methods. Difficulties with ...early detection, post-surgical recurrences, and resistance to chemotherapy and/or radiotherapy are important reasons for the poor prognosis of those with GBM. Over the past few decades, magnetic resonance (MR) theranostics using magnetic nanoparticles has shown unique advantages and great promises for the diagnosis and treatment of cancers. Magnetic nanoparticles not only serve as "molecular beacons" to enhance tumor contrast in magnetic resonance imaging (MRI), but also serve as "molecular bullets" for targeted drug delivery, controlled release, and induced hyperthermia. Moreover, multiple functions of magnetic nanoparticles can be synergistically engineered into a single nanoplatform, making it possible to simultaneously image, treat, target, and monitor the targeted lesions. The multi-functionality of nanoparticles, also called nano-theranostics, gives rises to effective new approaches for combating GBM. In this work, recent research and progress concerning the applications of MR nano-theranostics on GBM using magnetic nanoparticles will be highlighted, focusing on topics such as diagnosis, therapy, targeting, and hyperthermia, as well as outstanding challenges for MR nanotheranostics in treating GBM. The conclusions are generally applicable to other types of brain tumors.
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