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Abnormal hemoglobin levels are a risk factor for Alzheimer's disease (AD). Although the mechanism underlying these associations is elusive, inadequate micronutrients, particularly folate and vitamin B12, may increase the risk for anemia, cognitive impairment, and AD. In this study, we investigated whether the nutritional status of folate and vitamin B12 is involved in the association between low hemoglobin levels and the risk of AD mortality. Data were obtained from the 1999-2006 National Health and Nutrition Examination Survey (NHANES) and the NHANES (1999-2006) Linked Mortality File. A total of 4,688 participants aged ≥60 years with available baseline data were included in this study. We categorized three groups based on the quartiles of folate and vitamin B12 as follows: Group I (low folate and vitamin B12); Group II (high folate and low vitamin B12 or low folate and high vitamin B12); and Group III (high folate and vitamin B12). Of 4,688 participants, 49 subjects died due to AD. After adjusting for age, sex, ethnicity, education, smoking history, body mass index, the presence of diabetes or hypertension, and dietary intake of iron, significant increases in the AD mortality were observed in Quartile1 for hemoglobin (HR: 8.4, 95% CI: 1.4-50.8), and the overall risk of AD mortality was significantly reduced with increases in the quartile of hemoglobin (p for trend = 0.0200), in subjects with low levels of both folate and vitamin B12 at baseline. This association did not exist in subjects with at least one high level of folate and vitamin B12. Our finding shows the relationship between folate and vitamin B12 levels with respect to the association between hemoglobin levels and AD mortality. [ABSTRACT FROM AUTHOR]

Background: Cadmium, a ubiquitous environmental pollutant, exhibits potential neurotoxic risk. Although compelling evidence suggests cadmium accumulation has a role in the formation of amyloid-β plaques and neurofibrillary tangles, which are the hallmarks of Alzheimer's disease (AD) pathogenesis, the supporting evidence in humans is limited and conflicting. In this study, we investigated the association between blood cadmium levels and AD mortality among older adults by analyzing the prospective data from the 1999-2004 Third National Health and Nutrition Examination Survey (NHANES) and the Linked Mortality File.Methods: The data were obtained from the 1999-2004 NHANES and the NHANES (1999-2004) Linked Mortality File. A total of 4,064 participants aged ≥60 years old with available blood cadmium data and no other missing information on their questionnaires at baseline were included in this study. AD was denoted as G30 based on the ICD-10 underlying causes of death.Results: Of the 4,064 participants, 51 subjects died as a result of AD. Compared with participants with low blood cadmium levels (≤0.3 μg/L), those with high cadmium levels (>0.6 μg/L) exhibited a 3.83-fold (hazard ratio = 3.83; 95 % CI = 1.39-10.59) increased risk of AD mortality. In the Kaplan-Meier survival curves for cumulative AD mortality, higher levels of blood cadmium showed marginally significant association with increased mortality at baseline and in patients over 60 years of age (p = 0.0684).Conclusions: We observed a significant association between blood cadmium levels and AD mortality among older adults in the US. Our findings suggest that environmental exposure to cadmium may be a risk factor for AD. [ABSTRACT FROM AUTHOR]

Background/objectives: although the functional impairments of stroke survivors are associated with poor health-related quality of life (HRQoL), few studies have demonstrated the impact of individual stroke deficits on the quality of life of survivors. In this study, we investigated the association between HRQoL and stroke-related deficits, especially with respect to the number and types of deficits, in older adults. Methods: the data were obtained from the 2008 and 2009 Korean Community Health Survey. The EuroQoL 5 Dimension (EQ-5D) questionnaire used as the HRQoL index, and stroke-related information included the number of stroke deficits and five types of deficits. Results: of the 122,095 participants, 6,698 (5.5%) subjects had a history of stroke, of whom 2,222 patients (33.2%) reported one or more stroke-related deficits. After adjustments for potential variables, the EQ-5D scores of the stroke survivors with persisting deficits were significantly reduced as the number of stroke deficits increased (β = -0.080, -0.147, -0.229, -0.252 and -0.293 for one, two, three, four and five deficits, respectively). The type of stroke deficits was associated with the level of HRQoL. Specifically, the adjusted EQ-5D score of patients who suffered from hemiplegia (β = -0.143; P value < .00001) was worse than that of patients with any stroke deficits. The most frequent problems were related to mobility and pain/discomfort, regardless of the number or type of stroke deficits. Conclusion: we found that impaired HRQoL was significantly associated with the number and type of stroke deficits in older adults with a history of stroke. [ABSTRACT FROM AUTHOR]

Background: We focused on whether changes in the occupational status of older male adults can be influenced by social engagement and health status measured at the baseline. Methods: This study used a sample of the Korean Longitudinal Study of Aging (KLoSA), and the study population was restricted to 1.531 men who were aged 55 to 80 years at the 2006 baseline survey and participated in the second survey in 2008. Social engagement and health status, measured by the number of chronic diseases, grip strength, and depressive symptoms as well as covariates (age, marital status, educational level, and household income) were based on data from the 2006 baseline survey. Occupational engagement over the first and second survey was divided into four categories: 'consistently employed' (n = 892), 'employed-unemployed' (n = 152), 'unemployed-employed' (n = 138), and 'consistently unemployed' (n = 349). Results: In the multinomial model, the 'consistently employed' and 'unemployed-employed' groups had significantly higher social engagement (1.19 and 1.32 times, respectively) than the referent. The number of chronic diseases was significantly associated with four occupational changes, and the 'unemployed-employed' had the fewest chronic conditions. Conclusion: Our finding suggests that social engagement and health status are likely to affect opportunities to continue working or to start working for older male adults. [ABSTRACT FROM AUTHOR]

Objective To investigate the association between serum perfluorooctanoic acid (PFOA) concentration and cardiovascular disease, as measured by homocysteine level and blood pressure in a representative sample of US adults. Methods A cross-sectional study of 2934 adults (⩾20 years) who participated in the 2003-2004 and 2005e2006 National Health and Nutrition Examination Survey and had detectable levels of PFOA in their serum. The health effects analysed as potentially associated with PFOA exposure included homocysteine level and blood pressure. Results The geometric mean value (95% CI) of the study participants' serum PFOA concentration was 4.00 mg/l (95% CI 3.86 to 4.13). The homocysteine and systolic blood pressure were shown to increase significantly with an increase in the log-transformed serum PFOA concentration, after adjusting for potential confounding variables. Adjusted ORs comparing participants at the 80th versus the 20th percentiles were 2.62 for hypertension (95% CI 2.09 to 3.14), and a positive association was also evident in models based on quartiles or based on restricted cubic splines. Conclusion These findings suggest that background exposure to PFOA may continue a risk factor for the development of cardiovascular diseases. [ABSTRACT FROM AUTHOR]

Background. Macrolides have received considerable attention for their anti-inflammatory and immunomodulatory actions beyond the antibacterial effect. These two properties may ensure some efficacy in a wide spectrum of respiratory viral infections. We aimed to summarize the properties of macrolides and their efficacy in a range of respiratory viral infection. Methods. A search of electronic journal articles through PubMed was performed using combinations of the following keywords including macrolides and respiratory viral infection. Results. Both in vitro and in vivo studies have provided evidence of their efficacy in respiratory viral infections including rhinovirus (RV), respiratory syncytial virus (RSV), and influenza virus. Much data showed that macrolides reduced viral titers of RV ICAM-1, which is the receptor for RV, and RV infection-induced cytokines including IL-1β, IL-6, IL-8, and TNF-α. Macrolides also reduced the release of proinflammatory cytokines which were induced by RSV infection, viral titers, RNA of RSV replication, and the susceptibility to RSV infection partly through the reduced expression of activated RhoA which is an RSV receptor. Similar effects of macrolides on the influenza virus infection and augmentation of the IL-12 by macrolides which is essential in reducing virus yield were revealed. Conclusion. This paper provides an overview on the properties of macrolides and their efficacy in various respiratory diseases. [ABSTRACT FROM AUTHOR]

Objective: We assessed the outcomes of various reconstructive methods for skull base defect after endoscopic endonasal approaches (EEA) depending on the degree of intraoperative cerebrospinal fluid (CSF) leaks. Methods: Between Jan. 2008 and Sep. 2009, 122 consecutive patients underwent 124 EEA for sellar and extra-sellar lesions. Intraoperative CSF leaks were classified as grade 0, no intraoperative CSF leak; grade 1, low output; and grade 2, high-output based on the degree of CSF leakage and size of opening in the arachnoid membrane (<5 or ≥5 mm). Results: Postoperative CSF leaks or meningitis occurred in 13 of 124 cases (10.5%). In 77 patients with grade 0, there was no postoperative CSF leak. Among 20 patients with grade 1 CSF leaks, four patients developed meningitis or postoperative CSF leak. Postoperative CSF leaks occurred in nine of 26 patients (34.6%) with grade 2 leaks. Comparison of reconstructive methods revealed that gasket-seal method provided better control of CSF leaks than free-fat graft in patients with grade 2 leaks (11.8% vs. 66.7%, p = 0.028). However, in grades 0 and 1, we found no difference among the various reconstructive methods. Conclusion: The selection of reconstructive methods for skull base defects should be determined by the degree of CSF leaks. Although grade 0 or 1 leak requires relatively conservative management such as simple closure or free-tissue grafting, a more aggressive reconstructive technique is required to prevent postoperative complication in grade 2 CSF leak. [ABSTRACT FROM AUTHOR]

Background: When the skin-prick test (SPT) and in vitro test such as ImmunoCAP assay are performed simultaneously, results do not always coincide in some patients. Our objectives, therefore, were (1) to assess differences in allergic test results according to age group and (2) to establish appropriate guidelines for diagnosing mite allergy according to age. Methods: A total of 692 participants complaining of allergic rhinitis symptoms participated. Patients were divided according to age; the mean age was 32 years (range, 8-76 years). The SPT and ImmunoCAP assays were performed to detect allergies to house-dust mites (Dermatophagoides pteronyssinus and Dermatophagoides farinae). The association between age and the result of each allergy test were examined, and a cutoff age for proper application of each test was than estimated. Results: Three hundred thirty-six patients (48.6%) were allergic to D. pteronyssinus and 350 patients (50.6%) were allergic to D. farinae. In the case of D. pteronyssinus, SPT was proved to be more useful in detecting allergy for subjects <50 years old (p < 0.0001). However in case of D. farinae, ImmunoCAP was useful for all age groups, but SPT showed decreased ratio of positive result for subjects >30 years old (p < 0.0001). Conclusion: This study was the first to compare results of allergy tests according to age using true allergens. For patients >50 years of age, the ImmunoCAP was found to be the preferred method for detecting allergy to house-dust mites and for patients <30 years old, SPT is the recommended first choice. [ABSTRACT FROM AUTHOR]

Background. The aim of this study was to investigate the correlation between lymphatic vessel density in squamous cell carcinoma of the tongue and regional metastasis. Methods. Intratumoral and peritumoral lymphatic densities (ILDs and PLDs, respectively) were determined by immunohistochemical staining of lymphatic endothelial cells with podoplanin in 62 patients surgically treated for tongue cancer. Clinicopathological variables were quantified, and their correlations with regional metastasis were assessed. Results. The rate of regional metastasis was significantly higher in patients with high ILD than that in those with low ILD (21/33, 63.6% vs 8/29, 27.5%; p = .006). Perineural invasion and lymphovascular invasion were also significantly correlated with regional metastasis. By multivariate analyses, ILD was the only variable identified to be significantly correlated with regional metastasis (p = .009). On the other hand, PLD showed no correlation with regional metastasis. Conclusions. ILD showed a strong correlation with regional metastasis in patients with squamous cell carcinoma of the tongue. © 2009 Wiley Periodicals, Inc. Head Neck, 2010 [ABSTRACT FROM AUTHOR]

Background: This study was performed to investigate whether statins can enhance the recovery of the olfactory epithelium (OE) damaged by 3-methylindole (3MI), an olfactotoxicant, and to compare the effects with those of steroids. Methods: Randomized placebo-controlled trial was performed. Fifty-four healthy female Sprague-Dawley rats (aged 9-10 weeks and weighing 160-180 g each) were randomly allocated to the statin-treated, steroid-treated, or control groups. Olfactory loss was induced using i.p. injection of 3MI in adult rats. Atorvastatin (10 mg/kg for 4 weeks), prednisolone (1 mg/kg for 2 weeks), or normal saline (1 cc for 4 weeks) was then administered per os with a gastric tube. Hematoxylin and eosin (H&E) staining and immunohistochemical staining were performed to evaluate the change of thickness and the arrangement of the OE, and immunoreactivity to protein gene product (PGP) 9.5 and proliferating cell nuclear antigen (PCNA). Results: The statin-treated group showed the earliest increase of the thickness of the OE (p = 0.002 at 7 days after 3MI injection) and the immunoreactivity to PCNA (p = 0.032 at 7 days after 3MI injection) among the three groups. The immunoreactivity to PGP 9.5 showed significantly better improvement at the 7th and 28th days after 3MI injection compared with the steroid-treated or control groups (p = 0.002 and p < 0.001, respectively). Conclusion: Statins might enhance the proliferation and neuroregenesis of the OE after 3MI injection. [ABSTRACT FROM AUTHOR]

Abstract  This study evaluated age-related changes in bone mineral density (BMD) and identified the peak bone mineral density (PBMD) in Koreans. We recruited 2929 subjects, ranging in age from 5 to 86 years, from three regions: Seoul, Siwha, and Gwangyang. The BMD at the distal radius and calcaneus were measured with dual-energy X-ray absorptiometry, and anthropometric measures were also obtained. PBMD was calculated from the highest mean in each age group. The PBMD at the distal radius was 0.514 ± 0.06 g/cm2 in females and 0.598 ± 0.07 g/cm2 in males. Peak ages for both sexes were the thirties. For the calcaneus, PBMD was 0.509 ± 0.09 g/cm2 in females and 0.629 ± 0.09 g/cm2 in males. Peak ages were the thirties for females and the twenties for males. These results could facilitate international or interracial comparisons and be used as reference data to screen for osteoporosis in Koreans. [ABSTRACT FROM AUTHOR]

The article focuses on the study which investigates whether job strain had an effect on the risk of occupational injury or workers at small- to medium-sized manufacturing companies in South Korea. A follow-up survey was conducted wherein job stress was measured through the Job Demand and Decision Latitude Questionnaire. Results show that for men, the high job-demand group and high strain group showed the increased risk of occupational injury. For women, high job demand, low job control, and high job strain were significantly associated with occupational injury.

Background: Expanded polytetrafluoroethylene (ePTFE), or Gore-Tex (W.L. Gore & Associates, Flagstaff, AZ), is widely used in augmentation rhinoplasty, and the histological changes that it undergoes in the human body have been studied for decades. However, changes in the thickness of ePTFE after its use in augmentation rhinoplasty with a noninvasive object method are not well understood. Methods: We report the results of 19 patients (10 male and 9 female patients) who had undergone an uncomplicated augmentation rhinoplasty with Gore-Tex. Ultrasonography was used to evaluate changes in the thickness of Gore-Tex implants and to detect inflammatory reactions around the implants 9-67 months after surgery. Results: Gore-Tex implants were clearly distinguishable from the surrounding tissue with ultrasonography. The postoperative thickness of the implant was decreased by 29%. There was no significant correlation between the degree of change in implant thickness and the length of time after surgery. However, the amount of thickness reduction was associated with the implant's initial thickness at the time of the surgery (R = 0.448; p = 0.001). In addition, four patients (21%) showed fibrosis or granuloma formation around the implant that was detectable via ultrasonography. Conclusion: Gore-Tex implants lost thickness after nasal dorsal augmentation in proportion to their initial thickness, and ultrasonography was useful for evaluating changes in Gore-Tex thickness. [ABSTRACT FROM AUTHOR]

This study was conducted to investigate the association between depressive symptoms and job stress, as measured by the KOSS, among Korean employees in small- and medium-sized enterprises, and examined which components of stress are involved in the risk for depression among males and females. Data were collected from a work-stress survey of full-time employees of small- and medium-sized enterprises in Incheon, South Korea. A total of 3,013 participants were included in the analysis. Job stress was measured using 24 items (7 sub-scales) of the short form of Korean occupational stress scale (KOSS-SF), and depressive symptoms were evaluated using Center for epidemiologic studies depression scale (CES-D). After adjustment for confounding variables, most of subscales of job stress contributed to an increased risk of depressive symptoms, and job insecurity (male; OR = 2.02, 95%CI: 1.61–2.40, female; OR = 1.95, 95%CI: 1.42–2.70) and occupational climate (male; OR = 1.84, 95%CI: 1.49–2.28, female; OR = 1.78, 95%CI: 1.30–2.49) showed strong associations in both male and female. Other subscales revealed different effects for males and females; for males, job demands (OR = 1.68, 95%CI: 1.43–2.20), inadequate social support (OR = 1.55, 95%CI: 1.23–1.94), and lack of rewards (OR = 1.88, 95%CI: 1.48–2.37) were associated with depressive symptoms, whereas for females, organizational injustice (OR = 1.62, 95%CI: 1.14–2.30) was associated with depressive symptoms. These results indicate that job stress may play a significant role in increasing the risk of depressive symptoms, and that further preventive efforts and research are needed to reduce job stress and address health problems caused by job stress among Korean employees. [ABSTRACT FROM AUTHOR]

Abstract  The immune system is one of the targets most sensitive to lead toxicity, and the association between lead exposure and serum immunoglobulin E (IgE) has been published. Recent studies also reported that lead caused the development of IgE-mediated allergy. To investigate whether blood lead levels contribute to other allergic conditions, we examined the effect of blood lead on bronchial responsiveness (BR) in the general population. We performed a cross-sectional study with adults aged 19 to 58 years in a Korean community. Blood lead level and the methacholine provocation test were performed. The overall mean blood lead level was 2.9 μg/dl, and the mean BR index was 1.14. The percent of subjects with clinically diagnosed asthma was 21 (4%) and there was no difference in blood lead level with and without asthma. In the multiple regression model, the elevation of blood lead level was related to the increase of BR after adjusting for age, sex, height, smoking status, and the presence of asthma. Blood lead level was significantly associated with increased BR that came from the elevation of the IgE level with lead exposure. Lead may contribute to the increase of asthma and other allergic conditions. [ABSTRACT FROM AUTHOR]

Objective: To determine the long-term clinical efficacy and safety of injections of Artecoll, a soft-tissue filler consisting of a suspension of polymethyl methacrylate microspheres in a 3.5% solution of bovine collagen, into a vocal fold for managing glottal insufficiency secondary to unilateral vocal fold motion impairment. Design: Single-institution retrospective study. Setting: A single tertiary care teaching hospital of Sungkyunkwan University School of Medicine. Patients: Ninety-six patients with unilateral vocal fold motion impairment. Interventions: Percutaneous Artecoll injection laryngoplasty under local anesthesia. Main Outcome Measures: Acoustic, aerodynamic, and stroboscopic analyses were performed before injection and 1 week and 3, 6, and 12 months after injection. Two speech-language pathologists performed the perceptual assessment, and we used the subjective rating of hoarseness by the patients. Results: The maximal phonation time, shimmer (amplitude variation), jitter (frequency variation), and ratio of noise to harmonic showed significant improvement 3 months after injection; these improvements were maintained 12 months after injection (P < .05). The GRBAS scale (overall grade of hoarseness, roughness, breathiness, asthenicity, and strain) grades and subjective patient-rated scores of hoarseness improved from 1 week after injection, and the improvements were maintained 12 months after injection (P < .05).We observed no significant early or delayed adverse events. Conclusion: Injection laryngoplasty with Artecoll is a safe, useful, and durable treatment option for the management of glottal insufficiency secondary to unilateral vocal fold motion impairment. [ABSTRACT FROM AUTHOR]

Conclusion. The changes of hearing by packing after middle ear surgery should be anticipated and carefully interpreted. Objectives. To evaluate the amount and patterns of hearing loss resulting from packing in middle ear cavity (MEC) and external auditory canal (EAC) after middle ear surgery. Method. We obtained pure tone thresholds by bone (BC) and air conduction (AC) up to 12 weeks after middle ear surgery in 17 patients who had minimal middle ear pathology. To observe the effects of packing only in the EAC as in cases of explorative tympanotomy or stapes surgery, BC and AC threshold were obtained after packing only in the EAC in 18 volunteers. The changes of BC and AC thresholds in terms of pure tone average (PTA) and high frequency PTA were analyzed. Results. PTA by AC increased significantly by a maximal value of 38.7 dB at the second postoperative day, by 35.0 dB at 1 week after middle ear surgery. PTA by BC also increased maximally at the second postoperative day by 4.8 dB. The elevation of BC threshold at high frequencies (2, 3, 4 kHz) was more pronounced. Packing of EAC without MEC packing resulted in elevation of AC threshold by 43.0 dB, with similar patterns of BC threshold changes as MEC and EAC packing. [ABSTRACT FROM AUTHOR]

Objectives: In this study, we aimed to investigate the release and response of interleukin (IL)-18 to steroid treatment in a mouse model of allergic rhinitis. Methods: BALB/c mice were sensitized systemically by intraperitoneal injection of ovalbumin and locally by ovalbumin inhalation. Dexamethasone sodium phosphate was given by intraperitoneal injection in the steroid treatment group. Symptom scores, eosinophil counts, and IL-18 concentrations in the nasal and lung lavage fluids were analyzed. Results: The symptom scores and eosinophil counts of the negative control and steroid treatment groups were significantly lower than those of the positive control group (p < .01). The mean IL-18 concentrations in the nasal lavage fluid were not significantly different among the three groups (56.68 ± 9.57, 63.39 ± 8.93, and 64.47 ± 6.83 pg/mL, respectively). The IL-18 concentrations in the lung lavage fluid were significantly different between the positive control group and the steroid treatment group (430.75 ± 154.54 and 69.94 ± 14.26 pg/mL, respectively, p = .028). Conclusions: The IL-18 concentration was found to be increased in the lung lavage fluid, but not in the nasal lavage fluid, in a mouse model of allergic rhinitis. Increased IL-18 concentrations returned toward the previous concentrations after steroid treatment. These results suggest that the roles of IL-18 may be different in the pathogenesis of allergic rhinitis and the pathogenesis of asthma. [ABSTRACT FROM AUTHOR]

Both smoking and air pollution impair lung function, but little information is available regarding the combined effects on the pulmonary system. The potential effects of smoking and sulfur dioxide (SO2) were examined on lung function. Data were collected from family health examinations of 867 subjects, aged 20-86 yr, in a Korean community. The subjects responded to a questionnaire interview and completed lung function tests. Data on SO2 exposure were obtained from the Environmental Management Corporation. Studies sshowed that exposure to SO2 induced a short, marked decrease in forced vital capacity (FVC) and forced expiratory volume in 1 s (FEV1) in smokers compared with nonsmokers. The effect lasted up to 30 h after exposure. Consequently, preventive efforts are necessary to reduce the risks that air pollution and smoking pose to the respiratory system. [ABSTRACT FROM AUTHOR]

Tuberculosis of the paranasal sinus is a rare disease caused by infection with Mycobacterium tuberculosis, the causative agent of pulmonary tuberculosis. Although the worldwide incidence of tuberculosis is declining, the diagnosis of primary paranasal tuberculosis remains challenging and cannot be ruled out in patients presenting with refractory chronic rhinosinusitis after adequate surgical and medical treatment. We experienced a case of paranasal tuberculosis with no evidence of previous tuberculosis infection. It was diagnosed after a surgical biopsy revealed granulomatous inflammation and caseous necrosis. The patient responded well to antituberculosis drug therapy and became free of symptoms after 7 months of treatment. We report our findings in this case with a review of the recent literature. [ABSTRACT FROM AUTHOR]

Objectives: A cross-sectional study was conducted to investigate whether working hours mismatch is associated with workaholism.Material and Methods: This study used the data from the 17th wave (2014) of the nationwide Korean Labor and Income Panel Study. Workaholism was evaluated using the Workaholism Analysis Questionnaire. The final study involved 3157 subjects who answered questions regarding both workaholism and working hours mismatch. To identify the association between working hours mismatch and workaholism according to weekly working hours, a stratification analysis was conducted by dividing the number of working hours/week into 3 groups (≤40 h, 41-59 h, and ≥60 h). The odds ratios were calculated using a multiple logistic regression model, which was adjusted for potential confounders.Results: The workers working more hours than desired showed the greatest frequency of workaholism. As regards workaholism, in all weekly working hours groups, the odds ratios of the group working more hours than desired were 4.28, 95% CI: 2.29-7.99 (≥40 h), 2.14, 95% CI: 1.34-3.43 (41-59 h), 3.40, 95% CI: 1.60-7.21 (≤60 h), which were statistically significant compared to the reference (matched) group. There was no statistically significant relationship between working hours and workaholism when stratified according to the mismatch in working hours.Conclusions: The workers' working hours mismatch can be significantly related to workaholism. Int J Occup Med Environ Health. 2020;33(2):187-94. [ABSTRACT FROM AUTHOR]

Synergistic immunotherapy of immune checkpoint blockade (ICB) and immunogenic cell death (ICD) has shown remarkable therapeutic efficacy in various cancers. However, patients show low response rates and undesirable outcomes to these combination therapies owing to the recycling mechanism of programmed death-ligand 1 (PD-L1) and the systemic toxicity of ICD-inducing chemotherapeutic drugs. Herein, we propose all-in-one glycol chitosan nanoparticles (CNPs) that can deliver anti-PD-L1 peptide (PP) and doxorubicin (DOX) to targeted tumor tissues for a safe and more effective synergistic immunotherapy. The PP-CNPs, which are prepared by conjugating ᴅ-form PP (NYSKPTDRQYHF) to CNPs, form stable nanoparticles that promote multivalent binding with PD-L1 proteins on the targeted tumor cell surface, resulting in effective lysosomal PD-L1 degradation in contrast with anti-PD-L1 antibody, which induces recycling of endocytosed PD-L1. Consequently, PP-CNPs prevent subcellular PD-L1 recycling and eventually destruct immune escape mechanism in CT26 colon tumor-bearing mice. Moreover, the ICD inducer, DOX is loaded into PP-CNPs (DOX-PP-CNPs) for synergistic ICD and ICB therapy, inducing a large number of damage-associated molecular patterns (DAMPs) in targeted tumor tissues with minimal toxicity in normal tissues. When the DOX-PP-CNPs are intravenously injected into CT26 colon tumor-bearing mice, PP and DOX are efficiently delivered to the tumor tissues via nanoparticle-derived passive and active targeting, which eventually induce both lysosomal PD-L1 degradation and substantial ICD, resulting in a high rate of complete tumor regression (CR: 60%) by a strong antitumor immune response. Collectively, this study demonstrates the superior efficacy of synergistic immunotherapy using all-in-one nanoparticles to deliver PP and DOX to targeted tumor tissues.

Background: Falls, in older adults, can worsen physical functioning and lead to serious complications. Thus, as a means of preventive intervention, this high-risk group should be screened. The aim of the present study was to investigate whether reaction time is clinically applicable as a fall risk assessment tool. Methods: The study participants were community-dwelling older adults aged 65 years or older, who scored 24 or more in the Korean version of the Mini-Mental State Examination, and did not have difficulty with communication and comprehension. To investigate the relationship between hand reaction time and fall risk, we used items from a recently developed computerized apparatus, which includes 2 fall risk assessment tools: the Short Physical Performance Battery (SPPB) and Berg Balance Scale (BBS). Results: Reaction time was negatively correlated with the total SPPB (r=-0.314, p<0.001) and BBS scores (r=-0.164, p<0.001); the scores were higher when reaction times were lower. Multiple linear regression analyses also showed that the total SPPB (β=-0.30; 95% confidence interval [CI], -0.26 to -0.02) and BBS scores (β=-0.14; 95% CI, -0.26 to -0.02) significantly increased as the reaction time decreased. Conclusion: Reaction time was significantly correlated with the SPPB and BBS, confirming the possibility of its use in tools for fall risk assessment. [ABSTRACT FROM AUTHOR]