Staphylococcus aureus causes aberrant epidermal lipid composition and skin barrier dysfunction.

BACKGROUND: Staphylococcus (S) aureus colonization is known to cause skin barrier disruption in atopic dermatitis (AD) patients. However, it has not been studied how S. aureus induces aberrant epidermal lipid composition and skin barrier dysfunction. METHODS: Skin tape strips (STS) and swabs were obtained from 24 children with AD (6.0 ± 4.4 years) and 16 healthy children (7.0 ± 4.5 years). Lipidomic analysis of STS samples was performed by mass spectrometry. Skin levels of methicillin-sensitive and methicillin-resistant S. aureus (MSSA and MRSA) were evaluated. The effects of MSSA and MRSA were evaluated in primary human keratinocytes (HEKs) and organotypic skin cultures. RESULTS: AD and organotypic skin colonized with MRSA significantly increased the proportion of lipid species with nonhydroxy fatty acid sphingosine ceramide with palmitic acid ([N-16:0 NS-CER], sphingomyelins [16:0-18:0 SM]), and lysophosphatidylcholines [16:0-18:0 LPC], but significantly reduced the proportion of corresponding very long-chain fatty acids (VLCFAs) species (C22-28) compared to the skin without S. aureus colonization. Significantly increased transepidermal water loss (TEWL) was found in MRSA-colonized AD skin. S. aureus indirectly through interleukin (IL)-1ß, tumor necrosis factor (TNF)-α, IL-6, and IL-33 inhibited expression of fatty acid elongase enzymes (ELOVL3 and ELOVL4) in HEKs. ELOVL inhibition was more pronounced by MRSA and resulted in TEWL increase in organotypic skin. CONCLUSION: Aberrant skin lipid profiles and barrier dysfunction are associated with S. aureus colonization in AD patients. These effects are attributed to the inhibition of ELOVLs by S. aureus-induced IL-1ß, TNF-α, IL-6, and IL-33 seen in keratinocyte models and are more prominent in MRSA than MSSA.

Promotion of tumorigenesis by miR-1260b-targeting CASP8: Potential diagnostic and prognostic marker for breast cancer.

MicroRNAs are reported as promising biomarkers for the diagnosis and treatment of breast cancer. miR-1260b is identified as a tumor-associated noncoding microRNA in other cancers, although the role of miR-1260b and its clinical relevance in breast cancer remain unclear. In this study, miR-1260b as a potential prognostic biomarker was observed by univariate and multivariate Cox regression analyses in 102 breast tumor tissues. The tumorigenic role of miR-1260b in terms of proliferation, apoptosis, and migration of breast cancer cells was investigated using gain- and loss-of-function assays in vitro. Additionally, the potential early diagnosis and treatment monitoring marker of miR-1260b was validated in 129 plasma samples. We found that high miR-1260b expression was markedly associated with bulky tumor size, advanced stage, and lymph node invasion. Particularly, the high-miR-1260b-expression group showed shorter overall survival than the low-miR-1260b-expression group. The inhibition of oncogenic miR-1260b induced apoptosis and decreased migration and invasion of MDA-MB-231 cells. CASP8 was revealed as a direct target gene of miR-1260b, which is closely related to apoptosis. Furthermore, miR-1260b expression levels in plasma were significantly higher in patients with breast cancer than in healthy controls. The patients who tested positive for miR-1260b showed 16.3- and 18.2-fold higher risks in the early stage and locally advanced stage, respectively, compared with healthy controls, and the risk was decreased 6.2-fold after neoadjuvant chemotherapy. Taken together, miR-1260b may be a potential novel diagnostic, prognostic, and therapeutic target in breast cancer.

Synergetic Effects of Intronic Mature miR-944 and ΔNp63 Isoforms on Tumorigenesis in a Cervical Cancer Cell Line.

miR-944 is located in an intron of the tumor protein p63 gene (TP63). miR-944 expression levels in cervical cancer tissues are significantly higher than in normal tissues and are associated with tumor size, International Federation of Gynecology and Obstetrics (FIGO) stage, lymph node metastasis, and survival. However, associations of miR-944 with its host gene, TP63, which encodes TAp63 and ΔNp63, in cervical cancer have not been fully investigated. A positive correlation between miR-944 and ΔNp63 mRNA expression was identified in cervical cancer tissues. Furthermore, when the expression of miR-944 and ΔNp63 was simultaneously inhibited, cell proliferation-, differentiation- epithelial-mesenchymal transition (EMT)-, transcription-, and virus-associated gene clusters were shown to be significantly more active according to functional annotation analysis. Cell viability and migration were more reduced upon simultaneous inhibition with anti-miR-944 or ΔNp63 siRNA than with inhibition with anti-miR-944 or ΔNp63 siRNA alone, or scramble. In addition, Western blot analysis showed that the simultaneous inhibition of miR-944 and ΔNp63 reduced EMT by increasing the expression of epithelial markers such as claudin and by decreasing mesenchymal markers such as N-cadherin and vimentin. Slug, an EMT transcription factor, was also decreased by the simultaneous inhibition of miR-944 and ΔNp63. Thus, associations between miR-944 and ΔNp63 in cervical cancer could help to elucidate the function of this intronic microRNA and its role in carcinogenesis.

Identification of a possible susceptibility locus for UVB-induced skin tanning phenotype in Korean females using genomewide association study.

A two-stage genomewide association (GWA) analysis was conducted to investigate the genetic factors influencing ultraviolet (UV)-induced skin pigmentation in Korean females after UV exposure. Previously, a GWA study evaluating ~500 000 single nucleotide polymorphisms (SNPs) in 99 Korean females identified eight SNPs that were highly associated with tanning ability. To confirm these associations, we genotyped the SNPs in an independent replication study (112 Korean females). We found that a novel SNP in the intron of the WW domain-containing oxidoreductase (WWOX) gene yielded significant replicated associations with skin tanning ability (P-value = 1.16 × 10(-4) ). To understand the functional consequences of this locus located in the non-coding region, we investigated the role of WWOX in human melanocytes using a recombinant adenovirus expressing a microRNA specific for WWOX. Inhibition of WWOX expression significantly increased the expression and activity of tyrosinase in human melanocytes. Taken together, our results suggest that genetic variants in the intronic region of WWOX could be determinants in the UV-induced tanning ability of Korean females. WWOX represents a new candidate gene to evaluate the molecular basis of the UV-induced tanning ability in individuals.

Linear- and nonlinear-electromyographic analysis of supracutaneous vibration stimuli of the forearm using diverse frequencies and considering skin physiological properties.

Numerous studies have reported the efficacy of vibration in sensory feedback or substitution devices for users of myoelectric hand prostheses. Although most myoelectric hand prostheses are presently manipulated by a surface electromyogram (sEMG), only a few studies have been conducted on the effect of vibration on an sEMG. This study aimed to determine whether vibration stimulation affects the linear and nonlinear properties of surface electromyography (sEMG) considering the skin properties. The vibration stimuli, with frequencies ranging from 37 to 258 Hz, were applied to the proximal part of the arms of the eight female and seven male subjects. The skinfold thickness, hardness, and vibration threshold at the stimuli loci were measured. The root mean square (rms) and fractal dimension (DF) of the sEMG were measured at a distance of 1 cm in the upward direction from the stimuli loci. Above 223 Hz there were no differences between the rms of the genders in between the vibration stimuli (p > 0.05). Moreover, no differences were observed between the DF of the genders for any frequency (p > 0.05). Above 149 Hz, there were correlations between the rms and the skin hardness in the females. Otherwise, no correlations were observed between the rms and DF and the skin properties in both genders for most of the frequencies (all p > 0.05). These results suggest that vibration stimuli affect the linear properties of the sEMG, but not the nonlinear properties.

Incidence and risk factors of immune-related adverse events induced by immune checkpoint inhibitors among older adults with non-small cell lung cancer.

BACKGROUND: Immune checkpoint inhibitor (ICI) treatment has been linked to a variety of immune-related adverse events (irAEs), which can affect any organ system. The incidence and risk factors of irAEs have not been adequately evaluated among older adults with NSCLC. METHODS: A cohort study was conducted using 1999-2019 SEER-Medicare data among beneficiaries aged ≥65 years with a diagnosis of NSCLC who received nivolumab, pembrolizumab, or atezolizumab. Incident irAEs were identified post-ICI initiation. Demographic, cancer-related characteristics, and clinical history risk factors of irAEs were evaluated with competing events considered. RESULTS: A total of 8175 older NSCLC patients were included (with 46.8% experiencing irAEs). Pneumonitis (16.5%), hypothyroidism (10.5%), arrhythmia (11.18%), and acute kidney injury (AKI) (5.8%) were the most common irAEs. The median time to first irAE was 82 days (IQR: 29-182 days). The earliest onset of irAE occurrence was for hematologic irAEs, while the latest were gastrointestinal, dermatologic, and musculoskeletal irAEs. Fine-Gray regression modeling revealed significantly greater hazards of irAE occurrence in patients who received pembrolizumab at index, did not have CNS metastases, had a history of autoimmune disorder, and had chemotherapy in combination with ICI. Race, socioeconomic status, previous radiation therapy, and comorbidity burden were found to be associated with the occurrence of certain type of irAEs. CONCLUSION: A significant proportion of older patients with NSCLC develop an irAE after receiving ICI treatment. Factors related to cancer and treatment as well as demographics contribute to the increased risk of irAEs. Close monitoring and prediction of irAE among older patients receiving ICI is warranted.

The association between toxicity and efficacy of immune checkpoint inhibitors in older adults with NSCLC.

Aim: This cohort study evaluated the association between immune checkpoint inhibitors (ICIs)-induced immune-related adverse events (irAEs) and mortality as well as ICI discontinuation among older adults with NSCLC.Methods: 2007-2019 Surveillance, Epidemiology and End Results-Medicare linked database was used and survival analysis with time-varying exposure of irAEs was applied to estimate the associations.Results & conclusion: A total of 8,175 individuals were included, with 46.8% of whom developed an irAE. Cox regression models showed the occurrence of any irAEs was associated with increased risk of mortality (HR: 1.73, 95% CI: 1.63-1.82) and treatment discontinuation (HR: 1.87, 95% CI: 1.78-1.97). Some variability was observed in the effect on the two outcomes depending on the type of irAE.

A few studies have suggested that certain adverse events related to the immune system (called immune-related adverse events, or irAEs) following treatment of immune checkpoint inhibitors (ICIs) are linked to better clinical outcomes associated with ICI treatment. In contrast, this study of older adults with lung cancer found that patients suffering from irAEs were more likely to die and discontinue ICI treatment. Adverse events such as pneumonitis, arrhythmia, acute kidney injury, hepatitis and colitis were found to be associated with worse outcomes, while hypothyroidism and dermatologic irAEs were not. To prevent life-threatening outcomes for older adults with lung cancer, it is important to closely monitor for the development of irAEs following the initiation of ICI therapy.

Perceptions and preferences for environmentally sustainable food and associated factors: a cross-sectional analysis of a nationally representative survey of United States consumers.

BACKGROUND: Consumers are increasingly interested in environmentally sustainable dietary patterns. However, specific signals (e.g., language, labels, logos, or packaging) American consumers use to identify environmentally sustainable products are yet to be explored. OBJECTIVES: To determine perception and preferences for environmentally sustainable food and associated health and demographic factors associated with consumers' use of signals for environmentally sustainable food products in a nationally representative survey of United States consumers. METHODS: Repeated cross-sectional data were collected for the 2019 and 2020 annual online Food and Health Survey by the International Food Information Council. Three questions were analyzed: 1) the stated importance of environmentally sustainable food products, 2) signals consumers use to identify environmentally sustainable food/beverage products, and 3) the impact of environmental sustainability on food/beverage purchase decisions. Questions 2 and 3 were asked only from participants who stated environmental sustainability is important in question 1. Options provided for signals for environmentally sustainable products were recyclable packaging, minimal packaging, labeled organic, labeled locally grown, labeled sustainably sourced, and labeled non-genetically modified organisms (GMOs)/not bioengineered. Poisson regression and logistic regressions were performed to assess associations. RESULTS: Of 1905 completers, 1059 (55.6%) answered that it was somewhat or very important that food products purchased/consumed were environmentally sustainable. Of those, 94% used ≥1 of the 6 signals to determine environmental sustainability when shopping. Some signals were selected despite little association with environmental sustainability (e.g., locally grown and non-GMO/not bioengineered). The number of signals consumers used was associated with education, race/ethnicity, health status, and the level of impact they reported that sustainability plays in their decisions. Associations between consumer characteristics and the use of different signals for environmental sustainability were heterogeneous. CONCLUSIONS: Even among consumers who value environmental sustainability in food products, specific signals used by different respondents varied across demographics and health characteristics.

Development of a Digital Healthcare Management System for Lower-Extremity Amputees: A Pilot Study.

The research, which was designed as a "pre- and post-single group" study, included patients with lower-limb amputation and aimed to evaluate the effectiveness of self-directed physical-strength training and cardiovascular exercise using a novel digital healthcare management service three times a week for 12 weeks. Muscle strength, thigh circumference, lipid profile and glycated hemoglobin levels, pulmonary function, quality of life, and physical activity level were evaluated before and after the intervention, while satisfaction was measured after the study. Among the 14 included patients, the proportion of adherence to the physical-strength training and physical-strengthening activity were 85.2% and 75.8%, respectively. The level of satisfaction with the digital healthcare management system was high. Significant changes were observed in the muscle-strength tests (dominant grip power and muscle strength of knee flexion and extension of the intact side), thigh circumference, and glycated hemoglobin levels. Further, the quality-of-life score showed improvement, although without significant differences. Individualized exercise management using the novel digital healthcare management system for lower-limb amputees could induce interest in self-care and promote physical activity and healthy behavior. Through this effect, we can expect a reduction in the incidence of cardiovascular diseases, diabetes mellitus, dyslipidemia, and severe injuries from falling.

Dietary saturated and monounsaturated fats protect against acute acetaminophen hepatotoxicity by altering fatty acid composition of liver microsomal membrane in rats.

BACKGROUND: Dietary polyunsaturated fats increase liver injury in response to ethanol feeding. We evaluated the effect of dietary corn oil (CO), olive oil (OO), and beef tallow (BT) on fatty acid composition of liver microsomal membrane and acute acetaminophen hepatotoxicity. METHODS: Male Sprague-Dawley rats were fed 15% (wt/wt) CO, OO or BT for 6 weeks. After treatment with acetaminophen (600 mg/kg), samples of plasma and liver were taken for analyses of the fatty acid composition and toxicity. RESULTS: Treatment with acetaminophen significantly elevated levels of plasma GOT and GPT as well as hepatic TBARS but reduced hepatic GSH levels in CO compared to OO and BT groups. Acetaminophen significantly induced protein expression of cytochrome P450 2E1 in the CO group. In comparison with the CO diet, lower levels of linoleic acid, higher levels of oleic acids and therefore much lower ratios of linoleic to oleic acid were detected in rats fed OO and BT diets. CONCLUSIONS: Dietary OO and BT produces similar liver microsomal fatty acid composition and may account for less severe liver injury after acetaminophen treatment compared to animals fed diets with CO rich in linoleic acid. These findings imply that types of dietary fat may be important in the nutritional management of drug-induced hepatotoxicity.

Phase-Specific and Lifetime Costs of Multiple Myeloma Among Older Adults in the US.

Importance: Health care costs associated with diagnosis and care among older adults with multiple myeloma (MM) are substantial, with cost of care and the factors involved differing across various phases of the disease care continuum, yet little is known about cost of care attributable to MM from a Medicare perspective. Objective: To estimate incremental phase-specific and lifetime costs and cost drivers among older adults with MM enrolled in fee-for-service Medicare. Design, Setting, and Participants: A retrospective cohort study was conducted using population-based registry data from the 2007-2015 Surveillance, Epidemiology, and End Results database linked with 2006-2016 Medicare administrative claims data. Data analysis included 4533 patients with newly diagnosed MM and 4533 matched noncancer Medicare beneficiaries from a 5% sample of Medicare to assess incremental MM lifetime and phase-specific costs (prediagnosis, initial care, continuing care, and terminal care) and factors associated with phase-specific incremental MM costs. The study was conducted from June 1, 2019, to April 30, 2021. Main Outcomes and Measures: Incremental MM costs were calculated for the disease lifetime and the following 4 phases of care: prediagnosis, initial, continuing care, and terminal. Results: Of the 4533 patients with MM included in the study, 2374 were women (52.4%), 3418 (75.4%) were White, and mean (SD) age was 75.8 (6.8) years (2313 [51.0%] aged ≥75 years). The characteristics of the control group were similar; however, mean (SD) age was 74.2 (8.8) years (2839 [62.6%] aged ≤74 years). Mean adjusted incremental MM lifetime costs were $184 495 (95% CI, $183 099-$185 968). Mean per member per month phase-specific incremental MM costs were estimated to be $1244 (95% CI, $1216-$1272) for the prediagnosis phase, $11 181 (95% CI, $11 052-$11 309) for the initial phase, $5634 (95% CI, $5577-$5694) for the continuing care phase, and $6280 (95% CI, $6248-$6314) for the terminal phase. Although inpatient and outpatient costs were estimated as the major cost drivers for the prediagnosis (inpatient, 55.8%; outpatient, 40.2%), initial care (inpatient, 38.1%; outpatient, 35.5%), and terminal (inpatient, 33.0%; outpatient, 34.6%) care phases, prescription drugs (44.9%) were the largest cost drivers in the continuing care phase. Conclusions and Relevance: The findings of this study suggest that there is substantial burden to Medicare associated with diagnosis and care among older adults with MM, and the cost of care and cost drivers vary across different phases of the cancer care continuum. The study findings might aid policy discussions regarding MM care and coverage and help further the development of alternative payment models for MM, accounting for differential costs across various phases of the disease continuum and their drivers.

Development and validation of bioimpedance prediction equations for fat-free mass in unilateral male amputees.

BACKGROUND: Metabolic disease due to increased fat mass is observed in amputees (APTs), thereby restricting their activity. Systemic health management with periodic body composition (BC) testing is essential for healthy living. Bioelectrical impedance analysis (BIA) is a non-invasive and low-cost method to test BC; however, the APTs are classified as being exempted in the BIA. OBJECTIVE: To develop segmental estimated regression equations (sEREs) for determining the fat-free mass (FFM, kg) suitable for APTs and improve the accuracy and validity of the sERE. METHODS: Seventy-five male APTs participated in this cross-sectional study. Multiple regression analysis was performed to develop highly accurate sEREs of BIA based on independent variables derived from anthropometric measurements, dual-energy X-ray absorptiometry (DXA), and BIA parameters. The difference in validity between the predicted DXA and sum of the segmentally-predicted FFM values by sEREs (Sum_sEREs) values was evaluated using bivariate linear regression analysis and the Bland-Altman plot. RESULTS: The coefficient of determination (R2 ) and total error (TE) between DXA and Sum_sEREs were 71% and 5.4 (kg) in the cross-validation analysis. CONCLUSIONS: We confirmed the possibility of evaluating the FFM of APTs through the sEREs developed in this study. We also identified several independent variables that should be considered while developing such sEREs. Further studies are required to determine the validity of our sEREs and the most appropriate BIA frequencies for measuring FFM in APTs.

Evaluation of the QuantaMatrix Multiplexed Assay Platform for Molecular Diagnosis of Multidrug- and Extensively Drug-Resistant Tuberculosis Using Clinical Strains Isolated in Myanmar.

BACKGROUND: Although the incidence of tuberculosis (TB) is decreasing, cases of multidrug-resistant (MDR) TB and extensively drug-resistant (XDR) TB continue to increase. As conventional phenotype drug susceptibility testing (pDST) takes six to eight weeks, molecular assays are widely used to determine drug resistance. we developed QuantaMatrix Multiplexed Assay Platform (QMAP) MDR/XDR assay (QuantaMatrix Inc., Seoul, Korea) that can simultaneously detect mutations related to both first- and second-line drug resistance (rifampin, isoniazid, ethambutol, fluoroquinolones, second-line injectable drugs, and streptomycin). METHODS: We used 190 clinical Mycobacterium tuberculosis (MTB) strains isolated from Myanmar, compared QMAP and pDST results, and determined concordance rates. Additionally, we performed sequence analyses for discordant results. RESULTS: QMAP results were 87.9% (167/190) concordant with pDST results. In the 23 isolates with discordant results, the QMAP and DNA sequencing results completely matched. CONCLUSIONS: The QMAP MDR/XDR assay can detect all known DNA mutations associated with drug resistance for both MDR- and XDR-MTB strains. It can be used for molecular diagnosis of MDR- and XDR-TB to rapidly initiate appropriate anti-TB drug therapy.

Identification of Circulating miR-22-3p and miR-93-5p as Stable Endogenous Control in Tuberculosis Study.

The diagnosis and prognosis of tuberculosis remains challenging and necessitates the development of a new test that can accurately diagnose and monitor treatment responses. In this regard, miRNA is becoming a potential diagnostic and prognostic biomarker which differentiates treatment respondents from non-respondents for various non-infectious and infectious diseases, including tuberculosis. The concentration of miRNAs varies based on cell type, disease, and site of infection, implicating that selection of an optimal reference gene is crucial, and determines the quantification of transcript level and biological interpretation of the data. Thus, the study evaluated the stability and expression level of five candidate miRNAs (let-7i-5p, let-7a-5p, miRNA-16-5p, miRNA-22-3p and miRNA-93-5p), including U6 Small Nuclear RNA (RNU6B) to normalize circulating miRNAs in the plasma of 68 participants (26 healthy controls, 23 latent, and 19 pulmonary tuberculosis infected) recruited from four health centers and three hospitals in Addis Ababa, Ethiopia. The expression levels of miRNAs isolated from plasma of culture confirmed newly diagnosed pulmonary tuberculosis patients were compared with latently infected and non-infected healthy controls. The qPCR data were analyzed using four independent statistical tools: Best Keeper, Genorm, Normfinder and comparative delta-Ct methods, and the data showed that miRNA-22-3p and miRNA-93-5p were suitable plasma reference miRNAs in a tuberculosis study.

Antigen-Specific Cytokine and Chemokine Gene Expression for Diagnosing Latent and Active Tuberculosis.

Tuberculosis infection exhibits different forms, namely, pulmonary, extrapulmonary, and latent. Here, diagnostic markers based on the gene expression of cytokines and chemokines for differentiating between tuberculosis infection state(s) were identified. Gene expression of seven cytokines (Interferon gamma (IFN-γ), Interferon gamma-induced protein 10 (IP-10), Interleukin-2 receptor (IL-2R), C-X-C Motif Chemokine Ligand 9 (CXCL-9), Interleukin 10 (IL-10), Interleukin 4 (IL-4), and Tumor Necrosis Factor alpha (TNF-α)) in response to tuberculosis antigen was analyzed using real-time polymerase reaction. The sensitivity and specificity of relative quantification (2^-ΔΔCt) of mRNA expression were analyzed by constructing receiver operating characteristic curves and measuring the area under the curve (AUC) values. Combinations of cytokines were analyzed using the R statistical software package. IFN-γ, IP-10, IL2R, and CXCL-9 showed high expression in latent and active tuberculosis patients (p = 0.001), with a decrease in IL10 expression, and no statistical difference in IL-4 levels among all the groups (p = 0.999). IL-10 differentiated pulmonary tuberculosis patients from latent cases with an AUC of 0.731. IL10 combined with CXCL-9 distinguished pulmonary tuberculosis patients from extrapulmonary cases with a sensitivity, specificity, and accuracy of 85.7%, 73.9%, and 81.0%, respectively. IL-10 together with IP-10 and IL-4 differentiated pulmonary tuberculosis from latent cases with a sensitivity and specificity of 77.1% and 88.1%, respectively. Decision tree analysis demonstrated that IFN-γ IL-2R, and IL-4 can diagnose tuberculosis infection with a sensitivity, specificity, and accuracy of 89.7%, 96.1%, and 92.7%, respectively. A combination of gene expression of cytokines and chemokines might serve as an effective marker to differentiate tuberculosis infection state(s).

Comparison of Quantamatrix Multiplexed Assay Platform and GenoType MTBDR Assay Using Smear-Positive Sputum Specimens From Patients With Multidrug- Resistant/Extensively Drug-Resistant Tuberculosis in South Korea.

Rapid detection of drug-resistant tuberculosis (DR-TB) is crucial for timely treatment and management. The GenoType MTBDRplus and MTBDRsl (MTBDR) assays have been endorsed by the World Health Organization (WHO) for the detection of DR-TB. However, MTBDR assays cannot simultaneously detect multidrug-resistant TB (MDR-TB) and extensively drug-resistant TB (XDR-TB). Furthermore, interpretation of the MTBDR assay requires trained people, and the assay has low sample throughput, processing only up to 12 samples in parallel. We have developed the Quantamatrix Multiplexed Assay Platform (QMAP) to detect MDR-/XDR-TB simultaneously. The interpretation of QMAP results is automated, and the platform can process up to 96 samples in parallel. To compare the performance of QMAP with MTBDR assays, we performed QMAP and the MTBDR assay on 76 smear-positive, Mycobacterium tuberculosis culture-positive sputum specimens. Compared with phenotypic drug susceptibility testing (DST) results, the sensitivity and specificity of QMAP were 100 and 98% for rifampin resistance, 80 and 100% for isoniazid resistance, 44.4 and 100% for ethambutol resistance, 100 and 100% for fluoroquinolone resistance, and 100 and 100% for second-line injectable drug resistance, respectively. The sensitivity and specificity of MTBDR assays were 100 and 98% for rifampin resistance, 80 and 100% for isoniazid resistance, 44.4 and 98.1% for ethambutol resistance, 100 and 100% for fluoroquinolone resistance, and 100 and 100% for second-line injectable drug resistance, respectively. The sensitivity and specificity of QMAP were 85.0 and 100%, respectively, for the detection of MDR-TB and 100 and 100%, respectively, for XDR-TB. The sensitivity and specificity of MTBDR assays was consistent with those of QMAP. Our study showed that the QMAP assay has sensitivity and specificity equivalent to that of MTBDR assays in smear-positive sputum specimens. In combination with phenotypic DST, QMAP might be useful as a supplementary DST assay for rapid detection of MDR-/XDR-TB.

Food Insecurity and Perceived Diet Quality Among Low-Income Older Americans with Functional Limitations.

OBJECTIVE: To evaluate how functional limitations are associated with food insecurity and perceived diet quality in low-income older Americans. DESIGN: Nationwide repeated cross-sectional surveys regarding health and nutritional status. SETTING: The National Health and Nutrition Examination Surveys, 2007-2008, 2009-2010, and 2011-2012. PARTICIPANTS: Individuals aged ≥65 years with household incomes ≤130% of the federal poverty level (n = 1,323). MAIN OUTCOME MEASURES: Dependent variables included dichotomous indicators of food insecurity and poor-quality diet, measured with the household food security survey module and respondents' own ratings, respectively. Independent variable was presence of limitations in physical functioning. ANALYSIS: Weighted logistic regressions with nested controls and interaction terms. RESULTS: Functional limitations in low-income older adults were associated with 1.69 times higher odds of food insecurity (P < .01) and 1.65 times higher odds of poor-quality diet (P < .01) after accounting for individuals' health care needs and socioeconomic conditions. These associations were greatest among those living alone (odds ratio = 3.38 for food insecurity; 3.07 for poor-quality diet; P < .05) and smallest among those living with a partner. CONCLUSIONS AND IMPLICATIONS: Low-income older adults who live alone with functional limitations are exposed to significant nutritional risk. Resources should be directed to facilitating their physical access to healthful foods.

Comparison of segmental analysis and sacral marker methods for determining the center of mass during level and slope walking.

BACKGROUND: A human's center of mass (COM) is a widely used parameter in both clinical and practical applications. The segmental analysis method for determining the COM is considered the gold standard but is difficult to apply in a real environment. RESEARCH QUESTION: The purpose of this study was to confirm the efficacy of an alternative COM determination method-the sacral marker method-by comparing segmental analysis and sacral marker method results in three dimensions during level or slope walking. METHODS: Ten healthy young subjects (age = 24.0 ±â€¯4.5 yr, height = 174.5 ±â€¯5.9 cm, and weight = 66.9 ±â€¯9.4 kg) participated in the study. Each participant was monitored using a Helen Hayes full-body marker set and asked to walk on level and sloped (7°) terrain. The markers' trajectories were subsequently recorded. Each participant's COM was determined using segmental analysis and sacral marker methods via calculation and direct measurement, respectively. RESULTS: Comparative results indicated no significant differences (p > 0.05) between the segmental analysis and sacral marker method results for the COM displacement, velocity, or acceleration in the fore-aft and vertical directions. Conversely, significant differences (p < 0.05) between the two methods were observed for the COM displacement and acceleration in the medial-lateral direction, suggesting kinematic differences. SIGNIFICANCE: Based on this latter finding, caution should be exercised when determining COM kinematics using the sacral marker method.

Direct Detection of Rifampin-Resistant Mycobacterium tuberculosis in Respiratory Specimens Using Quantamatrix Multiplexed Assay Platform (QMAP) System: A Multicenter Study in Korea.

Rapid and accurate detection of rifampin-resistant Mycobacterium tuberculosis (MTB) is of primary importance for infection control and selection of anti-tuberculosis drugs. The aim of this study was to evaluate the usefulness of a newly developed multiplexed, bead-based bioassay (Quantamatrix Multiplexed Assay Platform, QMAP) for the direct detection of rifampin-resistant MTB in respiratory specimens. A total of 400 respiratory specimens collected from patients with clinically suspected tuberculosis or non-tuberculous mycobacteria (NTM) infections were tested with the culture-based conventional Mycobacterium species identification and QMAP system. Among 400 specimens, 154 samples were evaluated using phenotypic anti-tuberculosis drug susceptibility test (DST) and the QMAP system for the detection of rifampin resistance. Detection agreement rate between the culture-based conventional identification and QMAP system for MTB and NTM according to acid-fast bacillus smear positivity was as follows: 97.0% (131/135) and 93.6% (88/94) in 229 smear-positive samples and 69.4% (25/36) and 73.0% (65/89) in 171 smear-negative samples. Based on culture as the gold standard, the overall sensitivity and specificity of the QMAP system for Mycobacterium identification were 87.3 and 97.8%, respectively. The categorical agreement rate between phenotypic DST and QMAP system for rifampin was as follows: complete agreement, 92.9% (143/154); very major error, 0%; and major error, 0.6% (1/154). The overall sensitivity of the QMAP system for the detection of rifampin resistance was 97.1% (34/35). The QMAP system is a useful screening method for the early diagnosis of tuberculosis and selection of anti-tuberculosis drug, as it may detect rifampin-resistant MTB directly from respiratory specimens.

Possible Role of Single Stranded DNA Binding Protein 3 on Skin Hydration by Regulating Epidermal Differentiation.

BACKGROUND: Skin hydration is a common problem both in elderly and young people as dry skin may cause irritation, dermatological disorders, and wrinkles. While both genetic and environmental factors seem to influence skin hydration, thorough genetic studies on skin hydration have not yet been conducted. OBJECTIVE: We used a genome-wide association study (GWAS) to explore the genetic elements underlying skin hydration by regulating epidermal differentiation and skin barrier function. METHODS: A GWAS was conducted to investigate the genetic factors influencing skin hydration in 100 Korean females along with molecular studies of genes in human epidermal keratinocytes for functional study in vitro. RESULTS: Among several single nucleotide polymorphisms identified in GWAS, we focused on Single Stranded DNA Binding Protein 3 (SSBP3) which is associated with DNA replication and DNA damage repair. To better understand the role of SSBP3 in skin cells, we introduced a calcium-induced differentiation keratinocyte culture system model and found that SSBP3 was upregulated in keratinocytes in a differentiation dependent manner. When SSBP3 was overexpressed using a recombinant adenovirus, the expression of differentiation-related genes such as loricrin and involucrin was markedly increased. CONCLUSION: Taken together, our results suggest that genetic variants in the intronic region of SSBP3 could be determinants in skin hydration of Korean females. SSBP3 represents a new candidate gene to evaluate the molecular basis of the hydration ability in individuals.