BACKGROUND: The effect of air pollution on annual change rates in grip strength and body composition in the elderly is unknown. OBJECTIVES: This study evaluated the effects of long-term exposure to ambient air pollution on change rates of grip strength and body composition in the elderly. METHODS: In the period 2016-2020, grip strength and body composition were assessed and measured 1-2 times per year in 395 elderly participants living in the Taipei basin. Exposure to ambient fine particulate matters (PM_2.5), nitric dioxide (NO₂), and ozone (O₃) from 2015 to 2019 was estimated using a hybrid Kriging/Land-use regression model. In addition, long-term exposure to carbon monoxide (CO) was estimated using an ordinary Kriging approach. Associations between air pollution exposures and annual changes in health outcomes were analyzed using linear mixed-effects models. RESULTS: An inter-quartile range (4.1 µg/m³) increase in long-term exposure to PM_2.5 was associated with a faster decline rate in grip strength (-0.16 kg per year) and skeletal muscle mass (-0.14 kg per year), but an increase in body fat mass (0.21 kg per year). The effect of PM_2.5 remained robust after adjustment for NO₂, O₃ and CO exposure. In subgroup analysis, the PM_2.5-related decline rate in grip strength was greater in participants with older age (>70 years) or higher protein intake, whereas in skeletal muscle mass, the decline rate was more pronounced in participants having a lower frequency of moderate or strenuous exercise. The PM_2.5-related increase rate in body fat mass was higher in participants having a lower frequency of strenuous exercise or soybean intake. CONCLUSIONS Among the elderly, long-term exposure to ambient PM_2.5 is associated with a faster decline in grip strength and skeletal muscle mass, and an increase in body fat mass. Susceptibility to PM_2.5 may be influenced by age, physical activity, and dietary protein intake; however, these modifying effects vary across different health outcomes, and further research is needed to clarify their mechanisms and consistency.
Humans ; Hand Strength ; Aged ; Male ; Female ; Environmental Exposure/adverse effects* ; Follow-Up Studies ; Taiwan ; Air Pollution/adverse effects* ; Particulate Matter/adverse effects* ; Muscle, Skeletal/drug effects* ; Air Pollutants/adverse effects* ; Ozone/adverse effects* ; Aged, 80 and over ; Adipose Tissue/drug effects* ; Body Composition/drug effects* ; Nitrogen Dioxide/adverse effects*

Background: AMP-activated protein kinase (AMPK) is a key enzyme for cellular energy homeostasis and improves metabolic disorders. Brown and beige adipose tissues exert thermogenesis capacities to dissipate energy in the form of heat. Here, we investigated the beneficial effects of the antioxidant alpha-lipoic acid (ALA) in menopausal obesity and the underlying mechanisms. Methods: Female Wistar rats (8 weeks old) were subjected to bilateral ovariectomy (Ovx) and divided into four groups: Sham (n=8), Ovx (n=11), Ovx+ALA2 (n=10), and Ovx+ALA3 (n=6) (ALA 200 and 300 mg/kg/day, respectively; gavage) for 8 weeks. 3T3-L1 cells were used for in vitro study. Results: Rats receiving ALA2 and ALA3 treatment showed significantly lower levels of body weight and white adipose tissue (WAT) mass than those of the Ovx group. ALA improved plasma lipid profiles including triglycerides, total cholesterol, low-density lipoprotein cholesterol, and high-density lipoprotein cholesterol. Hematoxylin & eosin staining of inguinal WAT showed that ALA treatment reduced Ovx-induced adipocyte size and enhanced uncoupling protein 1 (UCP1) expression. Moreover, plasma levels of irisin were markedly increased in ALA-treated Ovx rats. Protein expression of brown fat-specific markers including UCP1, PRDM16, and CIDEA was downregulated by Ovx but markedly increased by ALA. Phosphorylation of AMPK, its downstream acetyl-CoA carboxylase, and its upstream LKB1 were all significantly increased by ALA treatment. In 3T3-L1 cells, administration of ALA (100 and 250 μM) reduced lipid accumulation and enhanced oxygen consumption and UCP1 protein expression, while inhibition of AMPK by dorsomorphin (5 μM) significantly reversed these effects. Conclusion ALA improves estrogen deficiency-induced obesity via browning of WAT through AMPK signaling.

Background: AMP-activated protein kinase (AMPK) is a key enzyme for cellular energy homeostasis and improves metabolic disorders. Brown and beige adipose tissues exert thermogenesis capacities to dissipate energy in the form of heat. Here, we investigated the beneficial effects of the antioxidant alpha-lipoic acid (ALA) in menopausal obesity and the underlying mechanisms. Methods: Female Wistar rats (8 weeks old) were subjected to bilateral ovariectomy (Ovx) and divided into four groups: Sham (n=8), Ovx (n=11), Ovx+ALA2 (n=10), and Ovx+ALA3 (n=6) (ALA 200 and 300 mg/kg/day, respectively; gavage) for 8 weeks. 3T3-L1 cells were used for in vitro study. Results: Rats receiving ALA2 and ALA3 treatment showed significantly lower levels of body weight and white adipose tissue (WAT) mass than those of the Ovx group. ALA improved plasma lipid profiles including triglycerides, total cholesterol, low-density lipoprotein cholesterol, and high-density lipoprotein cholesterol. Hematoxylin & eosin staining of inguinal WAT showed that ALA treatment reduced Ovx-induced adipocyte size and enhanced uncoupling protein 1 (UCP1) expression. Moreover, plasma levels of irisin were markedly increased in ALA-treated Ovx rats. Protein expression of brown fat-specific markers including UCP1, PRDM16, and CIDEA was downregulated by Ovx but markedly increased by ALA. Phosphorylation of AMPK, its downstream acetyl-CoA carboxylase, and its upstream LKB1 were all significantly increased by ALA treatment. In 3T3-L1 cells, administration of ALA (100 and 250 μM) reduced lipid accumulation and enhanced oxygen consumption and UCP1 protein expression, while inhibition of AMPK by dorsomorphin (5 μM) significantly reversed these effects. Conclusion ALA improves estrogen deficiency-induced obesity via browning of WAT through AMPK signaling.

Background: AMP-activated protein kinase (AMPK) is a key enzyme for cellular energy homeostasis and improves metabolic disorders. Brown and beige adipose tissues exert thermogenesis capacities to dissipate energy in the form of heat. Here, we investigated the beneficial effects of the antioxidant alpha-lipoic acid (ALA) in menopausal obesity and the underlying mechanisms. Methods: Female Wistar rats (8 weeks old) were subjected to bilateral ovariectomy (Ovx) and divided into four groups: Sham (n=8), Ovx (n=11), Ovx+ALA2 (n=10), and Ovx+ALA3 (n=6) (ALA 200 and 300 mg/kg/day, respectively; gavage) for 8 weeks. 3T3-L1 cells were used for in vitro study. Results: Rats receiving ALA2 and ALA3 treatment showed significantly lower levels of body weight and white adipose tissue (WAT) mass than those of the Ovx group. ALA improved plasma lipid profiles including triglycerides, total cholesterol, low-density lipoprotein cholesterol, and high-density lipoprotein cholesterol. Hematoxylin & eosin staining of inguinal WAT showed that ALA treatment reduced Ovx-induced adipocyte size and enhanced uncoupling protein 1 (UCP1) expression. Moreover, plasma levels of irisin were markedly increased in ALA-treated Ovx rats. Protein expression of brown fat-specific markers including UCP1, PRDM16, and CIDEA was downregulated by Ovx but markedly increased by ALA. Phosphorylation of AMPK, its downstream acetyl-CoA carboxylase, and its upstream LKB1 were all significantly increased by ALA treatment. In 3T3-L1 cells, administration of ALA (100 and 250 μM) reduced lipid accumulation and enhanced oxygen consumption and UCP1 protein expression, while inhibition of AMPK by dorsomorphin (5 μM) significantly reversed these effects. Conclusion ALA improves estrogen deficiency-induced obesity via browning of WAT through AMPK signaling.

Purpose: The objective of this study was to define the learning curve required to attain satisfactory oncologic outcomes of cervical cancer patients who were undergoing open or minimally invasive surgery for radical hysterectomy, and to analyze the correlation between the learning curve and tumor size. Materials and Methods: Cervical cancer patients (stage IA-IIA) who underwent open radical hysterectomy (n=280) or minimal invasive radical hysterectomy (n=282) were retrospectively reviewed. The learning curve was evaluated using cumulative sum of 5-year recurrence rates. Survival outcomes were analyzed based on the operation period (“learning period,” P1 vs. “skilled period,” P2), operation mode, and tumor size. Results: The 5-year disease-free and overall survival rates between open and minimally invasive groups were 91.8% and 89.0% (p=0.098) and 96.1% and 97.2% (p=0.944), respectively. The number of surgeries for learning period was 30 and 60 in open and minimally invasive group, respectively. P2 had better 5-year disease-free survival than P1 after adjusting for risk factors (hazard ratio, 0.392; 95% confidence interval, 0.210 to 0.734; p=0.003). All patients with tumors < 2 cm had similar 5-year disease-free survival regardless of operation mode or learning curve. Minimally invasive group presented lower survival rates than open group when tumors ≥ 2 cm in P2. Preoperative conization improved disease-free survival in patients with tumors ≥ 2 cm, especially in minimally invasive group. Conclusion Minimally invasive radical hysterectomy required more cases than open group to achieve acceptable 5-year disease-free survival. When tumors ≥ 2 cm, the surgeon’s proficiency affected survival outcomes in both groups.

INTRODUCTION: The rising prevalence of multiple chronic diseases is an important public health issue as it is associated with increased healthcare utilisation. This paper aimed to explore the annual per capita healthcare cost in primary care for patients with multiple chronic diseases (multimorbidity). METHODS: This was a retrospective cohort study conducted in a cluster of public primary care clinics in Singapore. De-identified data from electronic medical records were extracted from July 2015 to June 2017. Only patients with at least 1 chronic disease were included in the study. Basic demographic data and healthcare cost were extracted. A list of 20 chronic diseases was considered for multimorbidity. RESULTS: There were 254,377 patients in our study population, of whom 52.8% were female. The prevalence of multimorbidity was 62.4%. The median annual healthcare cost per capita for patients with multimorbidity was about twice the amount compared to those without multimorbidity (SGD683 versus SGD344). The greatest percentage increment in cost was when the number of chronic diseases increased from 2 to 3 (43.0%). CONCLUSION Multimorbidity is associated with higher healthcare cost in primary care. Since evidence for the optimal management of multimorbidity is still elusive, prevention or delay in the onset of multimorbidity in the general population is paramount.
Chronic Disease ; Comorbidity ; Cross-Sectional Studies ; Female ; Health Care Costs ; Humans ; Prevalence ; Primary Health Care ; Retrospective Studies ; Singapore/epidemiology*

Objectives: This study compared serum anti-Mullerian hormone (AMH) levels in endometriotic cysts (ECs) with those in non-ECs and analyzed changes thereof after single-port laparoscopic (SPL) ovarian cyst enucleation using vasopressin injection. Methods: In total, 180 patients (EC group, n = 112; non-EC group, n = 68) who underwent SPL ovarian cyst enucleation were retrospectively reviewed. Their AMH levels were checked preoperatively, on postoperative day 10 (POD10), and on postoperative month 3 (POM3). Changes in AMH levels were analyzed according to tumor type and vasopressin use. Results: The median initial and postoperative serum AMH levels in the EC group were significantly lower than those in the nonEC group (preoperation: 2.0 vs 3.8 ng/mL, P < 0.001; POD10: 1.0 vs 3.2 ng/mL, P < 0.001; POM3: 1.2 vs 3.6 ng/mL, P < 0.001). The postoperative decrease in AMH levels was higher in the EC group than the non-EC group on POD10 (0.8 vs 0.5 ng/mL, P = 0.011) but not on POM3 (0.7 vs 0.5 ng/mL, P = 0.164). Vasopressin injection during EC enucleation had no significant effect on the decrease in AMH levels on POD10 (vasopressin group vs non-vasopressin group: 1.0 vs 0.8 ng/mL, P = 0.253) and POM3 (vasopressin group vs nonvasopressin group: 1.4 vs 1.1 ng/mL, P = 0.242). Conclusions AMH levels were lower at baseline and had higher decreasing rates after SPL surgery in the EC group relative to the nonEC group. Vasopressin injection might not protect the ovary from the postoperative decrease in AMH levels.

BACKGROUND/AIMS: Inflammatory bowel disease (IBD) is associated with considerable impairment of patients’ health-related quality of life (HRQoL). Knowledge of factors that significantly affect IBD patients’ HRQoL can contribute to better patient care. However, the HRQoL of IBD patients in non-Western countries are limited. Hence, we assessed the HRQoL of Singaporean IBD patients and identified its determinants. METHODS: A prospective, cross-sectional study was conducted at Singapore General Hospital outpatient IBD Centre. The HRQoL of IBD patients was assessed using the short IBD questionnaire (SIBDQ), Short Form-36 physical and mental component summary (SF-36 PCS/MCS) and EuroQol 5-dimensions 3-levels (EQ-5D-3L) and visual analogue scale (VAS). Independent samples t-test was used to compare HRQoL between Crohn’s disease (CD) and ulcerative colitis (UC). Determinants of HRQoL were identified through multiple linear regression. RESULTS: A total of 195 IBD patients (103 UC, 92 CD) with a mean disease duration of 11.2 years were included. There was no significant difference in HRQoL between patients with UC and CD. Factors that significantly worsened HRQoL were presence of active disease (b=−6.293 [SIBDQ], −9.409 [PCS], −9.743 [MCS], −7.254 [VAS]), corticosteroids use (b=−7.392 [SIBDQ], −10.390 [PCS], −8.827 [MCS]), poor medication adherence (b=−4.049 [SIBDQ], −1.320 [MCS], −8.961 [VAS]), presence of extraintestinal manifestations (b=−13.381 [PCS]), comorbidities (b=−4.531 [PCS]), non-employment (b=−9.738 [MCS], −0.104 [EQ-5D-3L]) and public housing (b=−8.070 [PCS], −9.207 [VAS]). CONCLUSIONS: The HRQoL is impaired in this Asian cohort of IBD. The magnitude of HRQoL impairment was similar in UC and CD. Clinical characteristics were better determinants of patients’ HRQoL than socio-demographic factors. Recognizing the factors that impact patients’ HRQoL would improve the holistic management of IBD patients.
Adrenal Cortex Hormones ; Asian Continental Ancestry Group ; Cohort Studies ; Colitis, Ulcerative ; Comorbidity ; Cross-Sectional Studies ; Hospitals, General ; Humans ; Inflammatory Bowel Diseases ; Linear Models ; Medication Adherence ; Outpatients ; Patient Care ; Prospective Studies ; Public Housing ; Quality of Life ; Singapore

PURPOSE: Recurrence and chemoresistance (CR) are the leading causes of death in patients with high-grade serous carcinoma (HGSC) of the ovary. The aim of this study was to identify genetic changes associated with CR mechanisms using a patient-derived xenograft (PDX) mouse model and genetic sequencing. MATERIALS AND METHODS: To generate a CR HGSC PDX tumor, mice bearing subcutaneously implanted HGSC PDX tumors were treated with paclitaxel and carboplatin. We compared gene expression and mutations between chemosensitive (CS) and CR PDX tumors with whole exome and RNA sequencing and selected candidate genes. Correlations between candidate gene expression and clinicopathological variables were explored using the Cancer Genome Atlas (TCGA) database and the Human Protein Atlas (THPA). RESULTS: Three CR and four CS HGSC PDX tumor models were successfully established. RNA sequencing analysis of the PDX tumors revealed that 146 genes were significantly up-regulated and 54 genes down-regulated in the CR group compared with the CS group. Whole exome sequencing analysis showed 39 mutation sites were identified which only occurred in CR group. Differential expression of SAP25,HLA-DPA1, AKT3, and PIK3R5 genes and mutation of TMEM205 and POLR2A may have important functions in the progression of ovarian cancer chemoresistance. According to TCGA data analysis, patients with high HLA-DPA1 expression were more resistant to initial chemotherapy (p=0.030; odds ratio, 1.845). CONCLUSION: We successfully established CR ovarian cancer PDX mouse models. PDX-based genetic profiling study could be used to select some candidate genes that could be targeted to overcome chemoresistance of ovarian cancer.
Animals ; Carboplatin ; Cause of Death ; Drug Therapy ; Exome ; Female ; Gene Expression ; Genome ; Heterografts ; Humans ; Mice ; Odds Ratio ; Ovarian Neoplasms ; Ovary ; Paclitaxel ; Recurrence ; Sequence Analysis, RNA ; Statistics as Topic