Sex-specific patterns of discomfort in patients with restless legs syndrome.

STUDY OBJECTIVES: Sex differences in the prevalence of restless legs syndrome (RLS) have been reported, with a higher prevalence in women than in men. However, sex differences in clinical presentation remain unclear. We aimed to investigate the phenotypic differences in patients with RLS between sexes by comparing clinical presentations, iron status, polysomnographic parameters, and treatment. METHODS: We retrospectively evaluated 614 patients (225 men, 389 women) diagnosed with RLS. To enhance the robustness of the study, an age-matched control group of 179 men and 286 women without sleep disorders was also included. Information on demographics and sleep-related questionnaires were collected. Iron status was evaluated using blood samples, and polysomnography was performed to evaluate periodic leg movements and comorbid sleep disorders. RESULTS: Our analysis revealed no sex difference in the severity of RLS but a difference in the pattern of symptoms. Women had more frequent symptoms of pain and awakening during sleep, while men had more common motor symptoms (both self-reported symptoms and periodic leg movement on polysomnography). Women with RLS also had lower iron parameters and received more frequent iron supplementation therapy than men. In contrast to women with RLS, who presented higher sleep disturbances and depressive mood, men with RLS had a higher risk of comorbidities such as hypertension and cardiovascular disease. These sex differences were notably more pronounced than in the control group. CONCLUSIONS: This study suggests that sex differences exist in RLS phenotypes, and clinicians should consider these differences for treatment. CITATION: Kim J, Kim JR, Park HR, Joo EY. Sex-specific patterns of discomfort in patients with restless legs syndrome. J Clin Sleep Med. 2024;20(2):253-259.

Low-Molecular-Weight Fish Collagen Peptide (Valine-Glycine-Proline-Hydroxyproline-Glycine-Proline-Alanine-Glycine) Prevents Osteoarthritis Symptoms in Chondrocytes and Monoiodoacetate-Injected Rats.

The objective of this study was to investigate the effect of low-molecular-weight fish collagen (valine-glycine-proline-hydroxyproline-glycine-proline-alanine-glycine; LMWCP) on H2O2- or LPS-treated primary chondrocytes and monoiodoacetate (MIA)-induced osteoarthritis rat models. Our findings indicated that LMWCP treatment exhibited protective effects by preventing chondrocyte death and reducing matrix degradation in both H2O2-treated primary chondrocytes and cartilage tissue from MIA-induced osteoarthritis rats. This was achieved by increasing the levels of aggrecan, collagen type I, collagen type II, TIMP-1, and TIMP-3, while simultaneously decreasing catabolic factors such as phosphorylation of Smad, MMP-3, and MMP-13. Additionally, LMWCP treatment effectively suppressed the activation of inflammation and apoptosis pathways in both LPS-treated primary chondrocytes and cartilage tissue from MIA-induced osteoarthritis rats. These results suggest that LMWCP supplementation ameliorates the progression of osteoarthritis through its direct impact on inflammation and apoptosis in chondrocytes.

Antarctic Krill Oil from Euphausia superba Ameliorates Carrageenan-Induced Thrombosis in a Mouse Model.

FJH-KO obtained from Antarctic krill, especially Euphausia superba, has been reported to contain high amounts of omega-3 polyunsaturated fatty acids (n-3 PUFA) and to exhibit anticancer and anti-inflammatory properties. However, its antithrombotic effects have not yet been reported. This study aimed to investigate the antithrombotic effects of FJH-KO in carrageenan-induced thrombosis mouse models and human endothelial cells. Thrombosis was induced by carrageenan injection, whereas the mice received FJH-KO pretreatment. FJH-KO attenuated carrageenan-induced thrombus formation in mouse tissue vessels and prolonged tail bleeding. The inhibitory effect of FJH-KO was associated with decreased plasma levels of thromboxane B2, P-selectin, endothelin-1, ß-thromboglobulin, platelet factor 4, serotonin, TNF-α, IL-1ß, and IL-6. Meanwhile, FJH-KO induced plasma levels of prostacyclin I2 and plasminogen. In vitro, FJH-KO decreased the adhesion of THP-1 monocytes to human endothelial cells stimulated by TNF-α via eNOS activation and NO production. Furthermore, FJH-KO inhibited the expression of TNF-α-induced adhesion molecules such as ICAM-1 and VCAM-1 by suppressing the NF-κB signaling pathway. Taken together, our study demonstrates that FJH-KO protects against carrageenan-induced thrombosis by regulating endothelial cell activation and has potential as an antithrombotic agent.

Effects of Melatonin Supplementation on Sleep Quality in Breast Cancer Patients: A Systematic Review and Meta-Analysis.

Evidence on the effectiveness of melatonin in breast cancer patients suffering from sleep disturbances is contradictory, and there have been no meta-analyses on its use in humans with breast cancer. This study investigated the melatonin supplementation effectiveness in alleviating sleep disturbances in breast cancer patients. We searched Embase, PubMed, MEDLINE, CINAHL, Cochrane Library, Google Scholar, and Clinical trial.org databases for relevant reports by following PRISMA guidelines and collected clinical experimental studies of melatonin supplementation in breast cancer patients. Breast cancer for the population, melatonin supplementation for intervention, including sleep indicator, cancer treatment-related symptoms for outcomes, and clinical trial for humans were the searched keywords. Among the 1917 identified records, duplicates and irrelevant articles were excluded. Among the 48 full-text articles assessed, 10 studies met the criteria for inclusion in a systematic review, and five studies had sleep-related indicators and were included in the meta-analysis after quality assessment. The estimated average effect size (Hedges' g) was -0.79 (p < 0.001) in a random-effects model, thus indicating that melatonin supplementation had a moderate effect in ameliorating sleep quality in breast cancer patients. Pooled data from studies on melatonin supplementation indicate that melatonin administration may alleviate sleep problems related to treatments in breast cancer patients.

Effects of mindfulness-based stress reduction on adults with sleep disturbance: an updated systematic review and meta-analysis.

OBJECTIVE: Mindfulness-based stress reduction (MBSR) is a meditation-based therapy originally recommended for stress management. However, it is currently used to alleviate sleep disturbances. Therefore, this contemporary systematic review aimed to elucidate the clinical effects of MBSR on sleep quality and sleep-related daytime impairment in adults with sleep disturbances, including chronic insomnia disorders. DESIGN: Systematic review and meta-analysis of randomised controlled trials (RCTs). METHODS: A comprehensive search was conducted using the following databases: Ovid MEDLINE, AMED, Ovidembase, PsycINFO, Cochrane Library, CINAHL, and four domestic databases: KoreaMed, KISS, KMbase and NDSL. The final search update was performed in June 2022. Two researchers independently selected relevant studies, assessed the risk of bias and extracted the data. RESULTS: Of the 7516 records searched, 20 RCTs and 21 reports were included. In the subgroup analysis, MBSR did not improve objective or subjective sleep quality in chronic insomnia and cancers. However, MBSR versus waitlist control might have been effective in improving subjective sleep quality, but with substantial heterogeneity (standardised mean difference=-0.32; 95% CI: -0.56 to -0.08; I2=71%). In addition, MBSR compared with active control did not improve the sleep-related daytime impairments including depression, anxiety, stress, fatigue and quality of life. The overall risk of bias included in this review was a concern because of performance and detection bias. CONCLUSIONS: MBSR might be ineffective for improving sleep quality in patients with chronic insomnia and cancers. In addition, more than half of the RCTs included in this review had small sample sizes and were vulnerable to performance and detection biases. Therefore, well-designed RCTs with larger sample sizes are required to confirm the clinical effects of MBSR in adults with sleep disturbances. PROSPERO REGISTRATION NUMBER: CRD42015027963.

Herbal Medicines for the Treatment of Chronic Obstructive Airway Diseases (Asthma or Chronic Obstructive Pulmonary Disease): A Prospective Observational Study.

Background: Obstructive airway disease is a major health problem and has a great impact on global socioeconomic burden. Despite therapeutic advances in recent decades, there is still a need for effective and safe therapeutic agents for patients with asthma or chronic obstructive pulmonary disease (COPD). Methods: This prospective observational study explored the effects of herbal medicines in patients with asthma and COPD. All participants visited the hospital at least every 4 weeks for 12 weeks to receive their herbal medicines based on their pattern identification and to evaluate safety and efficacy endpoints. We followed the diagnostic criteria used by Korean medicine doctors to prescribe herbal medicines, explored variations in prescribed herbal medicines, and explored a number of clinical features in patients with asthma or COPD. Results: A total of 24 patients were enrolled: 14 were diagnosed with asthma and 10 with COPD and 19 completed the study. After 12 weeks of herbal medicine treatment, herbal medicines significantly improved the modified Clinical Asthma Measurement Scale in Oriental Medicine-V in asthma patients and the modified Medical Research Council Dyspnoea Scale and St. George's Respiratory Questionnaire in COPD patients. For all patients, modified Medical Research Council Dyspnoea Scale score and interleukin-13 were found to be significantly different after treatment. Additionally, the majority of patients were satisfied with our herbal medicine treatments, and no severe adverse events were reported during the study. Conclusions: Our study provides preliminary clinical data on the safety and efficacy of herbal medicines in patients with asthma and COPD.

Dance Intervention Using the Feldenkrais Method Improves Motor, and Non-Motor Symptoms and Gait in Parkinson's Disease: A 12-Month Study.

OBJECTIVE: The aim of this study was to assess the effects of dancing (using the Feldenkrais method) on motor and non-motor symptoms, quality of life (QoL), and objective parameters of gait at the time of intervention and at the end of the 1-year study period. METHODS: This was a single-arm study in which 12 subjects with Parkinson's disease (PD) received dance intervention during a 6-month period. Objective motor scales, gait analysis, and questionnaires on non-motor symptoms were evaluated at baseline and at 3, 6, and 12 months. RESULTS: Dance intervention decreased motor scale (Unified Parkinson's Disease Rating Scale and Tinetti scale) scores and improved gait disturbance (gait velocity and step length) without increasing levodopa equivalent dose. Furthermore, dancing decreased non-motor scale (Non-Motor Symptoms Scale and Montgomery-Asberg Depression Rating Scale) scores and improved QoL. CONCLUSION: Our findings suggest that dance intervention can be a complementary management method for PD patients.

Protective effect of Palmijihwanghwan in a mouse model of cigarette smoke and lipopolysaccharide-induced chronic obstructive pulmonary disease.

BACKGROUND: Palmijihwanghwan (PJH) is a traditional medicine and eight constituents derived from PJH possess anti-inflammatory activities. However, the scientific evidence for its potential as a therapeutic agent for inflammatory lung disease has not yet been studied. In this study, we examined the protective effect of PJH in a mouse model of chronic obstructive pulmonary disease (COPD) induced by cigarette smoke (CS) with lipopolysaccharide (LPS). METHODS: Mice received CS exposure for 8 weeks and intranasal instillation of LPS on weeks 1, 3, 5 and 7. PJH (100 and 200 mg/kg) was administrated daily 1 h before CS treatment for the last 4 weeks. RESULTS: Compared with CS plus LPS-exposed mice, mice in the PJH-treated group showed significantly decreased inflammatory cells count and reduced inflammatory cytokines including interleukin-1 beta (IL-1ß), IL-6 and tumor necrosis factor alpha (TNF-α) levels in broncho-alveolar lavage fluid (BALF) and lung tissue. PJH also suppressed the phosphorylation of nuclear factor kappa B (NF-κB) and extracellular signal-regulated kinase1/2 (ERK1/2) caused by CS plus LPS exposure. Furthermore, CS plus LPS induced increases in matrix metallopeptidase (MMP)-7, MMP-9, and transforming growth factor-ß (TGF-ß) expression and collagen deposition that were inhibited in PJH-treated mice. CONCLUSIONS: This study demonstrates that PJH prevents respiratory inflammation and airway remodeling caused by CS with LPS exposure suggesting potential therapy for the treatment of COPD.

Polyherbal formula SC-E3 inhibits rheumatoid arthritis activity in a mouse model of type-II collagen-induced arthritis.

OBJECTIVE: SC-E3 is a polyherbal formula that contains five medicinal herbs used frequently in traditional herbal medicine. In our previous study, we demonstrated the antioxidant and anti-inflammatory effects of SC-E3. The present study examined the effects of SC-E3 in a mouse model of type-II collagen-induced arthritis (CIA). METHODS: In vivo, male DBA/1J mice were immunized by intradermal injection of bovine type-II collagen and complete or incomplete Freund's adjuvant, to induce arthritis. SC-E3 was orally administered daily for 23 days. In vitro, bone marrow-derived macrophages (BMMs) were treated with macrophage colony-stimulating factor (M-CSF) and receptor activator of nuclear factor-κB ligand (RANKL) in the absence or presence of SC-E3. RESULTS: Administrations of SC-E3 were found to have anti-arthritic effects in the joints of CIA mice, as evidenced by reduced paw swelling, bone erosion and deformation, inflammatory cell infiltration, and inflammation in synovial membrane. SC-E3 also reduced serum levels of tumor necrosis factor-α, interleukin-1ß, aspartate aminotransferase and alanine aminotransferase. Furthermore, tartrate-resistant acid phosphatase-positive osteoclast numbers in the joints were significantly lower in SC-E3-treated CIA mice than in CIA mice. In addition, the differentiations of BMMs to multinucleated osteoclasts induced by M-CSF and RANKL stimulation were dose-dependently reduced by SC-E3. CONCLUSION: These results suggest that SC-E3 possesses substantial anti-arthritic activity because it inhibits pro-inflammatory cytokines and osteoclastogenesis, and that SC-E3 has potential therapeutic use for the treatment of rheumatoid arthritis.

The Burden of Cervical Cancer in Korea: A Population-Based Study.

This study used the Korean National Health Insurance (NHI) claims database from 2011 to 2017 to estimate the incidence and the incidence-based cost of cervical cancer and carcinoma in situ of cervix uteri (CIS) in Korea. The primary outcome was the direct medical cost per patient not diagnosed with cervical cancer (C53) or CIS (D06) 2 years prior to the index date in the first year after diagnosis. A regression analysis was conducted to adjust for relevant covariates. The incidence of cervical cancer tended to decrease from 2013 to 2016, while that of CIS increased. In particular, the incidence rate of CIS in women in their 20 s and 30 s increased by 56.8% and 28.4%, respectively, from 2013 to 2016. The incidence-based cost of cervical cancer and CIS was USD 13,058 and USD 2695 in 2016, respectively, which increased from 2013. Multivariate regression analysis suggested that age was the most influential variable of the cost in both patient groups, and the cost was highest in those aged over 60, i.e., the medical cost was significantly lower in younger women than their older counterparts. These findings suggest that targeting younger women in cervical cancer prevention is a reasonable option from both economic and public health perspectives.

Association of State Policies Allowing Medical Cannabis for Opioid Use Disorder With Dispensary Marketing for This Indication.

Importance: Misinformation about cannabis and opioid use disorder (OUD) may increase morbidity and mortality if it leads individuals with OUD to forego evidence-based treatment. It has not been systematically evaluated whether officially designating OUD as a qualifying condition for medical cannabis is associated with cannabis dispensaries suggesting cannabis as a treatment for OUD. Objective: To examine whether state-level policies designating OUD a qualifying condition for medical cannabis are associated with more dispensaries claiming cannabis can treat OUD. Design, Setting, and Participants: This cross-sectional, mixed-methods study of 208 medical dispensary brands was conducted in 2019 using the brands' online content. The study included dispensaries operating in New Jersey, New York, and Pennsylvania, where OUD is a qualifying condition for medical cannabis, and in Connecticut, Delaware, Maryland, Ohio, and West Virginia, where this policy does not exist. Exposures: Presence of OUD on the list of qualifying conditions for a state's medical cannabis program. Main Outcomes and Measures: Binary indicators of whether online content from the brand said cannabis can treat OUD, can replace US Food and Drug Administration-approved medications for OUD, can be an adjunctive therapy to Food and Drug Administration-approved medications for OUD, or can be used as a substitute for opioids to treat other conditions (eg, chronic pain). Results: After excluding duplicates, listings for nonexistent dispensaries, and those without online content, 167 brands across 7 states were included in the analysis (44 [26.3%] in states where OUD was a qualifying condition and 123 [73.7%] in adjacent states). A dispensary listed in a directory for West Virginia was not operational; therefore, comparison states were Connecticut, Delaware, Maryland, and Ohio. In policy-exposed states, 39% (95% CI, 23%-55%) more dispensaries claimed cannabis could treat OUD compared with unexposed states (P < .001). For replacing medications for OUD and being an adjunctive therapy, the differences were 14% (95% CI, 2%-26%; P = .002) and 28% (95% CI, 14%-42%; P < .001), respectively. The suggestion that cannabis could substitute for opioids (eg, to treat chronic pain) was made by 25% (95% CI, 9%-41%) more brands in policy-exposed states than adjacent states (P = .002). Conclusions and Relevance: In this study, state-level policies designating OUD as a qualifying condition for medical cannabis were associated with more dispensaries claiming cannabis can treat OUD. In the current policy environment, in which medical claims by cannabis dispensaries are largely unregulated, these advertisements could harm patients. Future research linking these policies to patient outcomes is warranted.

Toxicological assessments of an ethanol extract complex of Descurainia sophia and Peucedanum praeruptorum: Subacute oral toxicity and genotoxicity studies.

An ethanol extract complex of Descurainia sophia seeds and Peucedanum praeruptorum roots, called BP10A, has antitumor potential against colorectal cancer. In the present study, we evaluated the 28-day oral toxicity and the genotoxicity of BP10A. The subacute toxicity test was done through oral administration to mice. ICR mice (n = 10) received daily oral BP10A doses of 0, 500, 1000 and 2000 mg/kg for 28 consecutive days. During administration, general clinical signs, food consumption, organ weights, and hematologic, biochemical and histopathological parameters in male and female mice were assessed. No significant adverse effects up to the highest dose (2000 mg/kg) were found. The genotoxicity was evaluated using a battery of tests, including an in vitro bacterial reverse mutation (Ames) test, an in vivo micronucleus test using bone marrow cells in ICR mice and a chromosomal aberration test using CHL/IU cells. BP10A did not show any genotoxic signs in the Ames (up to 5000 µg/plate), micronucleus (up to 5000 mg/kg) and the chromosomal aberration tests (550-1750 µg/mL). Therefore, BP10A was considered safe based on the subacute toxicity and genotoxicity results, indicating that it is a useful pharmaceutical material with no adverse toxicity.

Krill Oil-Incorporated Liposomes As An Effective Nanovehicle To Ameliorate The Inflammatory Responses Of DSS-Induced Colitis.

BACKGROUND: Phosphatidylcholine (PC) and Omega-3 fatty acid (Omega-3) are promising therapeutic molecules for treating inflammatory bowel disease (IBD). PURPOSE: Based on the IBD therapeutic potential of nanoparticles, we herein sought to develop Omega-3-incorporated PC nanoparticles (liposomes) as an orally administrable vehicle for treating IBD. METHODS: Liposomes prepared with or without Omega-3 incorporation were compared in terms of colloidal stability and anitiinflammatory effects. RESULTS: The incorporation of free Omega-3 (alpha-linolenic acid, eicosapentaenoic acid or docosahexaenoic acid) into liposomes induced time-dependent membrane fusion, resulting in particle size increase from nm to µm during storage. In contrast, krill oil incorporation into liposomes (KO liposomes) did not induce the fusion and the particle size maintained <250 nm during storage. KO liposomes also maintained colloidal stability in simulated gastrointestinal conditions and exhibited a high capacity to entrap the IBD drug, budesonide (BDS). KO liposomes greatly suppressed the lipopolysaccharide-induced production of pro-inflammatory cytokines in cultured macrophages and completely restored inflammation-impaired membrane barrier function in an intestinal barrier model. In mice subjected to dextran sulfate sodium-induced colitis, oral administration of BDS-entrapped KO liposomes suppressed tumor necrosis factor-α production (by 84.1%), interleukin-6 production (by 35.3%), and the systemic level of endotoxin (by 96.8%), and slightly reduced the macroscopic signs of the disease. CONCLUSION: Taken together, KO liposomes may have great potential as a nanovehicle for oral delivery of IBD drugs.

Effects of Pet Insects on Cognitive Function among the Elderly: An fMRI Study.

Animal-assisted therapy has positive effects on cognitive function, depression, performance ability, and social functioning in elderly patients. The aim of this study was to evaluate the effects of rearing pet insects on the cognitive function of healthy elderly participants, with fMRI (functional magnetic resonance imaging) being used for this purpose. Community-dwelling right-handed elderly women (≥60 years) with normal cognitive function were enrolled and randomized at a 1:1 ratio into two groups: insect-rearing and control (n = 16) groups, with the insect-rearing group being further classified into two groups for analysis according to the subjects' scores in the Wisconsin Card Sorting Test, WCST) at the baseline fMRI: Insect-rearing group I with a relatively high score (n = 13), and insect-rearing group II with a relatively low score (n = 6). The insect-rearing groups received and reared crickets as pet insects for 8 weeks. The WCST consisted of two variations, a high level baseline (HLB) and semi-WCST version. There was a significant difference accuracy of the HLB-semi-WCST (p < 0.05) in insect-rearing group II after 8 weeks from the baseline test. In the fMRI analysis involving the WCST reaction test, increased activation was observed in the right dorsal lateral prefrontal cortex and parietal cortex in insect-rearing group II when the semi-WCST, rather than the HLB, was performed. Rearing pet insects showed positive effects on executive functions and performance improvement in elderly women. Further larger studies on the effects of pet insects on cognitive function are warranted.

Electro-Acupuncture Alleviates Cisplatin-Induced Anorexia in Rats by Modulating Ghrelin and Monoamine Neurotransmitters.

Anorexia is common in patients with cancer, mostly as a side effect of chemotherapy. The effect of electro-acupuncture (EA) on ameliorating cancer-related symptoms have been studied in animal models and in clinical trials. The aim of this study was to determine optimal conditions for the application of EA to alleviate anorexia, followed by the study of molecular mechanisms affecting its therapeutics. Anorexia was induced in male Wistar rats by injecting cisplatin, which was then followed by EA treatment at CV12, the acupuncture point located in the center of the abdominal midline. Body weight and food intake were measured daily throughout the duration of the study. The levels of monoamine neurotransmitters in the plasma were quantitatively analyzed by HPLC-ECD. Gastrointestinal hormone concentrations were elucidated with ELISA kits. RT-qPCR was performed to evaluate the mRNA expression of ghrelin (GHRL), neuropeptide Y (NPY), and pro-opiomelanocortin. The expression of c-Fos in the nucleus tractus solitarii was detected using western blotting analysis. The optimal conditions of EA to alleviate anorexia in rats was determined to be 1 unit for intensity and 10 Hz for frequency. EA treatment at CV12 reduced the levels of plasma monoamine neurotransmitters 5-hydroxytryptamine, 5-hydroxyindoleacetic acid, dopamine, and norepinephrine; as well as stimulated the expression of GHRL and NPY to alleviate cisplatin-induced anorexia in rats. EA stimulation at CV12 could be used to treat cisplatin-induced anorexia in rats.

Estrogen Receptor-Mediated Transcriptional Activities of Spent Coffee Grounds and Spent Coffee Grounds Compost, and Their Phenolic Acid Constituents.

Spent coffee grounds (SCG) are the most abundant coffee byproduct and are generally discarded as waste. The horticultural use of SCG and SCG compost (SCGC) has become popular due to a growing interest in environmentally friendly measures for waste disposal. Estrogen-like endocrine disrupting chemicals in the soil can be absorbed by plants and subsequently by humans who consume these plants. The objectives of this study are to determine the phytochemical profiles of extracts of SCG and SCGC and to evaluate the estrogen-like activities of SCG, SCGC, and the major coffee phenolic acids, specifically, 5-O-caffeoylquinic acid (CQA), caffeic acid, and ferulic acid. Their inductive effects on estrogen receptor (ER)-mediated gene transcription have been examined in cultured cell lines. CQA was the most abundant phenolic acid in SCG and SCGC and was further examined for its ER-mediated estrogen-like activity using various assays. This is the first study to report the estrogen-like signaling activities of coffee byproducts and their major constituents.

Five-year survival rate among older adults participating in the national geriatric screening program: A South Korean population-based cohort study.

INTRODUCTION: This study aimed to assess the health benefits of a geriatric screening program comprising of physical function tests, screening questionnaires for depression and cognitive impairment, and bone mineral density measurements for women as a part of the National Screening Program for Transitional Ages (NSPTA). We compared the all-cause mortality between subjects who did and did not participate in the screening program. METHODS: This was a nationwide longitudinal study with a 5-year follow-up based on a 10% sample of the National Health Insurance beneficiaries aged 60 years and older. Mortality records were obtained from the qualification dataset in the elderly cohort database of 2005-2013 provided by the National Health Insurance Service. A Cox proportional hazards model was used to analyze the mortality risk. We sampled 11,986 subjects each in the screened (intervention) and non-screened (control) groups after exact matching using propensity score. RESULTS: After adjusting for demographic and socioeconomic characteristics (age, sex, household income, smoking, alcohol drinking, physical activity, body mass index, and the Charlson Comorbidity Index), all-cause mortality rates were found to be significantly lower (a) in the intervention group compared to the control group (hazard ratio = 0.73; 95% confidence interval: 0.65, 0.82) and (b) among women compared to men (hazard ratio = 0.50; 95% confidence interval: 0.44, 0.56). Lower hazard ratios were also observed among those with a higher body mass index, fewer comorbidities, and higher income. CONCLUSION: A nationwide geriatric screening program might be helpful in reducing the incidence of premature deaths among older people.

A new herbal formula BP10A exerted an antitumor effect and enhanced anticancer effect of irinotecan and oxaliplatin in the colon cancer PDTX model.

BP10A is a novel two-herb medicine formula, consisting of Descurainiae sophia Semen and Peucedani praeruptorum Radix. This study was done to evaluate the antitumor efficacy of BP10A and its effect on the efficacy of the anticancer drugs oxaliplatin and irinotecan (CPT-11) in a colon tumor xenograft model. Chemical constituents from the ethanol extracts of BP10A were characterized with the ultra-performance liquid chromatography (UPLC) and each constituent was quantified with the UPLC-diode array detector method. Our study showed that BP10A exerted the cytotoxic effects in two colorectal cancer cell lines and its combination treatments with oxaliplatin or CPT-11 remarkably increased the in vitro cytotoxicity of each cancer drug assessed by the Ez-cytox assay. The in vivo antitumor activity of BP10A was evaluated in three colon cancer patient-derived tumor xenograft (PDTX) models with different genetic backgrounds. Oral administration with BP10A (250 and 500 mg/kg, daily) delayed tumor growth by 34-70% in the all PDTX models. Similarly, intraperitoneal injection of oxaliplatin (6 mg/kg) or CPT-11 (20 mg/kg) also suppressed tumor growth by 31.8-60.5% or by 24.3-50.4%, respectively. Furthermore, the combination treatment of BP10A with oxaliplatin or CPT-11 remarkably enhanced the antitumor activity of each anti-cancer drug and delayed tumor growth by 47.1-74.6% or by 74.4-82.9%, respectively. In accordance with the antitumor activity, the Ki-67 expression for tumor cell proliferation and the CD31 for angiogenesis were decreased, and TUNEL staining for tumor cell apoptosis was remarkably increased by the co-treatment of BP10A and the anticancer drugs as well as by each treatment of BP10A, oxaliplatin or CPT-11. Conclusively, BP10A has a strong tumor inhibitory effect against colon cancer and a synergistic effect with anticancer drugs, suggesting that BP10A could be considered as a good therapeutic candidate for the treatment of colon cancer.