Lead exposure estimation through a physiologically based toxicokinetic model using human biomonitoring data and comparison with scenario-based exposure assessment: A case study in Korean adults.

Pb toxicity is linked to cardiovascular and nephrotoxicity issues. Exposure to this heavy metal can occur through food and drinking water. Therefore, this study aimed to evaluate Pb exposure and assess health risks in Korean adults using a physiologically based toxicokinetic (PBTK) model. Human blood Pb concentrations were monitored using the Korean National Environmental Health Survey (KoNEHS) Cycle 4. The average Pb exposure in Korean adults was 0.520 µg/kg bw/day. The PBTK results were compared with scenario-based results from the 2021 risk assessment report of five heavy metals, including Pb, conducted by the MFDS. Exposure determined through reverse dosimetry was approximately two times higher than scenario-based exposure (0.264 µg/kg bw/day). The higher exposure levels obtained during PBTK analysis may be attributed to sustained exposure within historically more contaminated living environments and the long half-life of Pb. These findings suggest that the PBTK-based method can quantify aggregated exposure levels in the body over time, potentially serving as a complementary tool to address the constraints of scenario-based assessment methods for integrated risk assessment. Moreover, this model is convenient and cost-effective compared with scenario-based exposure estimation. These findings can facilitate the application of model for tracking continuous national changes in hazardous substance levels.

Identification of human host factors required for beta-defensin-2 expression in intestinal epithelial cells upon a bacterial challenge.

The human intestinal tract is colonized with microorganisms, which present a diverse array of immunological challenges. A number of antimicrobial mechanisms have evolved to cope with these challenges. A key defense mechanism is the expression of inducible antimicrobial peptides (AMPs), such as beta-defensins, which rapidly inactivate microorganisms. We currently have a limited knowledge of mechanisms regulating the inducible expression of AMP genes, especially factors from the host required in these regulatory mechanisms. To identify the host factors required for expression of the beta-defensin-2 gene (HBD2) in intestinal epithelial cells upon a bacterial challenge, we performed a RNAi screen using a siRNA library spanning the whole human genome. The screening was performed in duplicate to select the strongest 79 and 110 hit genes whose silencing promoted or inhibited HBD2 expression, respectively. A set of 57 hits selected among the two groups of genes was subjected to a counter-screening and a subset was subsequently validated for its impact onto HBD2 expression. Among the 57 confirmed hits, we brought out the TLR5-MYD88 signaling pathway, but above all new signaling proteins, epigenetic regulators and transcription factors so far unrevealed in the HBD2 regulatory circuits, like the GATA6 transcription factor involved in inflammatory bowel diseases. This study represents a significant step toward unveiling the key molecular requirements to promote AMP expression in human intestinal epithelial cells, and revealing new potential targets for the development of an innovative therapeutic strategy aiming at stimulating the host AMP expression, at the era of antimicrobial resistance.

Enhancing Laser-Induced Graphene via Integration of Gold Nanoparticles and Titanium Dioxide for Sensing and Robotics Applications.

Laser-induced graphene (LIG) is a promising material for various applications due to its unique properties and facile fabrication. However, the electrochemical performance of LIG is significantly lower than that of pure graphene, limiting its practical use. Theoretically, integrating other conductive materials with LIG can enhance its performance. In this study, we investigated the effects of incorporating gold nanoparticles (AuNPs) and titanium dioxide (TiO2) into LIG on its electrochemical properties using ReaxFF molecular dynamics (MD) simulations and experimental validation. We found that both AuNPs and TiO2 improved the work function and surface potential of LIG, resulting in a remarkable increase in output voltage by up to 970.5% and output power density by 630% compared to that of pristine LIG. We demonstrated the practical utility of these performance-enhanced LIG by developing motion monitoring devices, self-powered sensing systems, and robotic hand platforms. Our work provides new insights into the design and optimization of LIG-based devices for wearable electronics and smart robotics, contributing to the advancement of sustainable technologies.

SOD1 inhibition enhances sorafenib efficacy in HBV-related hepatocellular carcinoma by modulating PI3K/Akt/mTOR pathway and ROS-mediated cell death.

Hepatitis B Virus (HBV) infection significantly elevates the risk of hepatocellular carcinoma (HCC), with the HBV X protein (HBx) playing a crucial role in cancer progression. Sorafenib, the primary therapy for advanced HCC, shows limited effectiveness in HBV-infected patients due to HBx-related resistance. Numerous studies have explored combination therapies to overcome this resistance. Sodium diethyldithiocarbamate (DDC), known for its anticancer effects and its inhibition of superoxide dismutase 1 (SOD1), is hypothesized to counteract sorafenib (SF) resistance in HBV-positive HCCs. Our research demonstrates that combining DDC with SF significantly reduces HBx and SOD1 expressions in HBV-positive HCC cells and human tissues. This combination therapy disrupts the PI3K/Akt/mTOR signalling pathway and promotes apoptosis by increasing reactive oxygen species (ROS) levels. These cellular changes lead to reduced tumour viability and enhanced sensitivity to SF, as evidenced by the synergistic suppression of tumour growth in xenograft models. Additionally, DDC-mediated suppression of SOD1 further enhances SF sensitivity in HBV-positive HCC cells and xenografted animals, thereby inhibiting cancer progression more effectively. These findings suggest that the DDC-SF combination could serve as a promising strategy for overcoming SF resistance in HBV-related HCC, potentially optimizing therapy outcomes.

Analysis of the Effect of Base Station Motion on Underwater Handovers for Base-Station-Based Underwater Wireless Acoustic Networks.

In base-station-based underwater wireless acoustic networks (B-UWANs), effective handover mechanisms are necessary to ensure seamless data services for mobile nodes such as autonomous underwater vehicles (AUVs). Unlike terrestrial base stations (BSs), moored buoy BSs in B-UWANs experience motion responses due to wave loads under environmental conditions, posing unique challenges to the handover process. This study examines how BS motion affects handover decision errors, which arise when AUVs incorrectly initiate handovers to unintended BSs due to BS motion. By utilizing the AUV-BS distance as a handover triggering parameter, our analysis reveals a significant increase in decision errors within the overlapping regions when both the current and target BSs are in motion, especially when moving in the same direction. In addition, these errors intensify with the magnitude of BS motion and are exacerbated by smaller BS network radii. Based on these simulation results, we present an analytical framework that not only measures the influence of BS motion on the AUV-BS distance but also provides strategic insights for refining underwater handover protocols, thereby enhancing operational reliability and service continuity in B-UWANs.

One-year mortality and readmission risks following hospitalization for acute exacerbation of chronic obstructive pulmonary disease based on the types of acute respiratory failure: An observational study.

Few studies have examined the risk factors associated with the type of acute respiratory failure (ARF) in patients with acute exacerbation of chronic obstructive pulmonary disease (COPD). This study evaluated the clinical characteristics and prognosis of patients hospitalized for acute exacerbation of COPD based on the type of ARF. The medical charts of hospitalized patients with acute exacerbation of COPD between 2016 and 2021 were retrospectively reviewed. We classified ARF into 2 types: type 1 ARF with PaO2 < 60 mm Hg in room air or a ratio of arterial partial pressure to fractional inspired oxygen < 300, and type 2 ARF with PaCO2 > 45 mm Hg and arterial pH < 7.35. A total of 435 patients were enrolled in study, including 170 participants without ARF, 165 with type 1 ARF, and 100 with type 2 ARF. Compared with the non-ARF group, the frequency of high-flow nasal cannula, noninvasive ventilation, intensive care unit admissions, and in-hospital deaths was higher in the ARF group compared with the non-ARF group. The ARF group had higher 1-year mortality group (hazard ratio [HR], 2.809; 95% confidence interval [CI], 1.099-7.180; P = .031) and readmission within 1-year rates (HR, 1.561; 95% CI, 1.061-2.295; P = .024) than the non-ARF group. The type 1 ARF group had a higher risk of 1-year mortality (HR, 3.022; 95% CI, 1.041-8.774; P = .042) and hospital readmission within 1-year (HR, 2.053; 95% CI, 1.230-3.428; P = .006) compared with the non-ARF group. There was no difference in mortality and readmission rates between the type 1 and type 2 ARF groups. In conclusion, patients with type 1 ARF rather than type 2 ARF had higher mortality and readmission rates than those without ARF. The prognoses of patients with type 1 and type 2 ARF were similar.

Adequacy of Dialysis and Incidence of Atrial Fibrillation in Patients Undergoing Hemodialysis.

BACKGROUND: Atrial fibrillation (AF) can lead to stroke, heart failure, and mortality and has a greater prevalence in dialysis patients than in the general population. Several studies have suggested that uremic toxins may contribute to the development of AF. However, the association between dialysis adequacy and incident AF has not been well established. METHODS: In this retrospective nationwide cohort study, we analyzed data from the Korean National Periodic Hemodialysis Quality Assessment from 2013 to 2015 of patients who received outpatient maintenance hemodialysis 3× a week. The main exposure was single pooled Kt/V (spKt/V), which is the dialysis adequacy index, and the primary outcome was the development of AF. For the primary analysis, patients were categorized into quartiles according to baseline spKt/V. The lowest quartile, representing the lowest adequacy, was used as the reference group. Fine-Gray subdistribution hazard models were used, treating all-cause mortality as a competing risk. RESULTS: Of 25 173 patients, the mean age was 60 (51-69) years, and 14 772 (58.7%) were men. During a median follow-up of 5.7 years, incident AF occurred in a total of 3883 (15.4%) patients. Participants with a higher spKt/V tended to have lower AF incidence. In survival analysis, a graded association was observed between the risk of incident AF and spKt/V quartiles: subdistribution hazard ratios and 95% CIs for the second, third, and the highest quartile compared with the lowest quartile were 0.90 (95% CI, 0.82-0.98), 0.84 (95% CI, 0.77-0.93), and 0.79 (95% CI, 0.72-0.88), respectively. CONCLUSIONS: This nationwide cohort study showed that a higher spKt/V is associated with a reduced risk of incident AF. These findings suggests that reducing uremic toxin burden through enhanced dialysis clearance may be associated with a lower risk of AF development in patients undergoing maintenance hemodialysis.

Kidney Transplantation in ≤15 kg Children: Outcomes and Prognostic Indicators-A Review of the Organ Procurement and Transplantation Database.

BACKGROUND: Approximately 2500 pediatric patients are awaiting kidney transplantation in the United States, with <5% comprising those ≤15 kg. Transplant in this cohort is often delayed by center-based growth parameters, often necessitating transplantation after the initiation of dialysis. Furthermore, prognostication remains somewhat ambiguous. In this report, we scrutinize the Organ Procurement and Transplantation Network (OPTN) data from 2001 to 2021 to help better understand specific variables impacting graft and patient outcomes in these children. METHODS: The OPTN kidney transplant dataset from 2001 to 2021 was analyzed. Inclusion criteria included age <18 years, weight ≤15 kg, and recipient of primary living donor kidney transplantation (LDKT) or deceased donor kidney transplantation (DDKT). Patient and graft survival probabilities were calculated using the Kaplan-Meier method. The Cox proportional hazards model was used to calculate hazard ratio (HR) and identify variables significantly associated with patient and graft survival. RESULTS: Two thousand one hundred sixty-eight pediatric transplant recipients met inclusion criteria. Patient survival at 1 and 3 years was 98% and 97%, respectively. Graft survival at 1 and 3 years was 95% and 92%, respectively. Dialysis was the sole significant variable impacting both patient and graft survival. Graft survival was further impacted by transplant era, recipient gender and ethnicity, and donor type. Infants transplanted at Age 1 had better graft survival compared with older children, and nephrotic syndrome was likewise associated with a better prognosis. CONCLUSION: Pediatric kidney transplantation is highly successful. The balance between preemptive transplantation, medical optimization, and satisfactory technical parameters seems to suggest a "Goldilocks zone" for many children, favoring transplantation between 1 and 2 years of age.

Expanding the Cell-Free Reporter Protein Toolbox by Employing a Split mNeonGreen System to Reduce Protein Synthesis Workload.

The cell-free system offers potential advantages in biosensor applications, but its limited time for protein synthesis poses a challenge in creating enough fluorescent signals to detect low limits of the analyte while providing a robust sensing module at the beginning. In this study, we harnessed split versions of fluorescent proteins, particularly split superfolder green fluorescent protein and mNeonGreen, to increase the number of reporter units made before the reaction ceased and enhance the detection limit in the cell-free system. A comparative analysis of the expression of 1-10 and 11th segments of beta strands in both whole-cell and cell-free platforms revealed distinct fluorescence patterns. Moreover, the integration of SynZip peptide linkers substantially improved complementation. The split protein reporter system could enable higher reporter output when sensing low analyte levels in the cell-free system, broadening the toolbox of the cell-free biosensor repertoire.

Electrophysiological Analysis of Retinal Organoid Development Using 3D Microelectrodes of Liquid Metals.

Despite of the substantial potential of human-derived retinal organoids, the degeneration of retinal ganglion cells (RGCs) during maturation limits their utility in assessing the functionality of later-born retinal cell subtypes. Additionally, conventional analyses primarily rely on fluorescent emissions, which limits the detection of actual cell functionality while risking damage to the 3D cytoarchitecture of organoids. Here, an electrophysiological analysis is presented to monitor RGC development in early to mid-stage retinal organoids, and compare distinct features with fully-mature mouse retina. This approach utilizes high-resolution 3D printing of liquid-metal microelectrodes, enabling precise targeting of specific inner retinal layers within organoids. The adaptable distribution and softness of these microelectrodes facilitate the spatiotemporal recording of inner retinal signals. This study not only demonstrates the functional properties of RGCs in retinal organoid development but also provides insights into their synaptic connectivity, reminiscent of fetal native retinas. Further comparison with fully-mature mouse retina in vivo verifies the organoid features, highlighting the potential of early-stage retinal organoids in biomedical research.

Lutimonas zeaxanthinifaciens sp. nov., a zeaxanthin-producing marine bacterium isolated from coastal sediment.

A Gram-stain-negative, yellow-pigmented, strictly aerobic, non-flagellated, motile by gliding, rod-shaped bacterium, designated strain YSD2104T, was isolated from a coastal sediment sample collected from the southeastern part of the Yellow Sea. Phylogenetic analysis based on the 16S rRNA gene sequences revealed that strain YSD2104T was closely related to three type strains, Lutimonas vermicola IMCC1616T (97.4 %), Lutimonas saemankumensis SMK-142T (96.9 %), and Lutimonas halocynthiae RSS3-C1T (96.8 %). Strain YSD2104T has a single circular chromosome of 3.54 Mbp with a DNA G+C content of 38.3 mol%. The average nucleotide identity and digital DNA-DNA hybridization values between strain YSD2104T and the three type strains (L. vermicola IMCC1616 T, L. saemankumensis SMK-142T, and L. halocynthiae RSS3-C1T) were 74.0, 86.2 and 73.6 %, and 17.9, 30.3 and 17.8 %, respectively. Growth was observed at 20-30 °C (optimum, 30 °C), at pH 6.5-8.5 (optimum, pH 7.0), and with NaCl concentrations of 1.5-3.5 % (optimum, 2.5 %). The major carotenoid was zeaxanthin, and flexirubin-type pigment was not produced. The major respiratory quinone was menaquinone-6. The major fatty acids (>10 %) were iso-C15 : 0, iso-C15 : 1 G, iso-C17 : 0 3-OH, summed feature 3 (C16 : 1 ω6c and/or C16 : 1 ω7c), and summed feature 9 (iso-C17 : 1 ω9c and/or 10-methyl C16 : 0). The major polar lipids were phosphatidylethanolamine, one unidentified aminophospholipid, two unidentified aminolipids, and eight unidentified lipids. Conclusively, based on this polyphasic approach, we classified strain YSD2104T (=KCTC 102008T=JCM 36287T) as representing a novel species of the genus Lutimonas and proposed the name Lutimonas zeaxanthinifaciens sp. nov.

Optimizing pediatric liver transplantation: Evaluating the impact of donor age and graft type on patient survival outcome.

BACKGROUND: We examined the combined effects of donor age and graft type on pediatric liver transplantation outcomes with an aim to offer insights into the strategic utilization of these donor and graft options. METHODS: A retrospective analysis was conducted using a national database on 0-2-year-old (N = 2714) and 3-17-year-old (N = 2263) pediatric recipients. These recipients were categorized based on donor age (≥40 vs <40 years) and graft type. Survival outcomes were analyzed using the Kaplan-Meier and Cox proportional hazards models, followed by an intention-to-treat (ITT) analysis to examine overall patient survival. RESULTS: Living and younger donors generally resulted in better outcomes compared to deceased and older donors, respectively. This difference was more significant among younger recipients (0-2 years compared to 3-17 years). Despite this finding, ITT survival analysis showed that donor age and graft type did not impact survival with the exception of 0-2-year-old recipients who had an improved survival with a younger living donor graft. CONCLUSIONS: Timely transplantation has the largest impact on survival in pediatric recipients. Improving waitlist mortality requires uniform surgical expertise at many transplant centers to provide technical variant graft (TVG) options and shed the conservative mindset of seeking only the "best" graft for pediatric recipients.

Temporal Muscle Thickness and Sarcopenia Components in Healthy Adults, Validated through Allgeun Diagnostic Tool.

Sarcopenia, characterized by progressive muscle loss and functional decline, poses significant risks, including falls, impaired daily activities, and increased mortality. We developed Allgeun, a novel device that measures handgrip strength, muscle mass, and physical performance. This study aimed to investigate whether temporal muscle thickness (TMT) could be used as a sarcopenia marker and to evaluate the usability of Allgeun. This prospective study enrolled 28 participants without medical or neurological disorders. They underwent three-dimensional T1-weighted imaging using a 3 Tesla magnetic resonance imaging scanner. TMT was measured based on T1-weighted images by a board-certified neuroradiologist. Allgeun was used to measure the following three key components of sarcopenia: muscle strength (handgrip strength), muscle mass (calf and thigh circumference), and physical performance (five times the chair stand test). Correlation analysis was conducted between TMT and the results of the handgrip strength, calf and thigh circumferences, and chair stand tests. There were moderate positive correlations between TMT and calf circumference (r = 0.413, p = 0.029), thigh circumference (r = 0.486, p = 0.008), and handgrip strength (r = 0.444, p = 0.018). However, no significant correlation was observed between TMT and physical performance (r = -0.000, p = 0.998). Our findings underscore TMT's potential as an indicator of sarcopenia, particularly regarding muscle mass and strength. Additionally, we demonstrated that the new device, Allgeun, is useful for screening and diagnosing the severity of sarcopenia.

Prediction of TKI response in EGFR-mutant lung cancer patients-derived organoids using malignant pleural effusion.

Patient-derived organoids (PDOs) are valuable in predicting response to cancer therapy. PDOs are ideal models for precision oncologists. However, their practical application in guiding timely clinical decisions remains challenging. This study focused on patients with advanced EGFR-mutated non-small cell lung cancer and employed a cancer organoid-based diagnosis reactivity prediction (CODRP)-based precision oncology platform to assess the efficacy of EGFR inhibitor treatments. CODRP was employed to evaluate EGFR-tyrosine kinase inhibitors (TKI) drug sensitivity. The results were compared to those obtained using area under the curve index. This study validated this index by testing lung cancer-derived organoids in 14 patients with lung cancer. The CODRP index-based drug sensitivity test reliably classified patient responses to EGFR-TKI treatment within a clinically suitable 10-day timeline, which aligned with clinical drug treatment responses. This approach is promising for predicting and analyzing the efficacy of anticancer, ultimately contributing to the development of a precision medicine platform.

Does the Surgical Approach Affect the Incidence of Post-Hepatectomy Liver Failure in Cirrhotic Patients? An Analysis of the NSQIP Database.

Background: The association between surgical approach and post-hepatectomy liver failure (PHLF) in cirrhotic patients is poorly understood. We hypothesize that patients will have similar rates of liver failure regardless of whether they undergo minimally invasive liver resection (MILR) or open liver resection (OLR) in major liver resections. In contrast, there will be lower rates of PHLF in patients undergoing minor hepatectomy via the MILR approach.Methods: Propensity score matching was used to analyze regression by matching the MILR to the OLR cohort. Patient demographics from the American College of Surgeons National Surgical Quality Improvement Program, including race, age, gender, and ethnicity, were matched. Chronic obstructive pulmonary disease, congestive heart failure, smoking, hypertension, diabetes, renal failure, dyspnea, dialysis dependence, body mass index, and American Society of Anesthesiologists (ASA) classification (>ASA III) were among the preoperative patient characteristics subject to matching. PHLF (Grade A vs B. vs C) was our primary outcome measure.Results: A total of 2129 cirrhotic patients were included in the study. In the minor hepatectomy group, patients undergoing an OLR were more likely to get discharged to a facility (7.0% vs 4.4%; P = .03), had greater hospital length of stay (5 vs 3 days; P = .02), and had a greater need for invasive postoperative interventions (10.7% vs 4.6%; P < .01). They were also noted to have higher rates of organ space superficial surgical infections (SSIs) (7.3% vs 3.7%; P = .003), Clostridium difficile infection (.9% vs .1%; P = .05), renal insufficiency (2.1% vs .1%; P < .01), unplanned intubations (3.1% vs 1.4%; P = .03), and Grade C liver failure (2.3% vs .9%; P = .03).Conclusion: A higher incidence of PHLF grade C was found in patients undergoing OLR in the minor hepatectomy group. Therefore, in cirrhotic patients who can tolerate minimally invasive approaches, MILR should be offered to prevent postoperative complications as part of their optimization plan.

Polydopamine Nanoparticles as Mimicking RPE Melanin for the Protection of Retinal Cells Against Blue Light-Induced Phototoxicity.

Exposure of the eyes to blue light can induce the overproduction of reactive oxygen species (ROS) in the retina and retinal pigment epithelium (RPE) cells, potentially leading to pathological damage of age-related macular degeneration (AMD). While the melanin in RPE cells absorbs blue light and prevents ROS accumulation, the loss and dysfunction of RPE melanin due to age-related changes may contribute to photooxidation toxicity. Herein, a novel approach utilizing a polydopamine-replenishing strategy via a single-dose intravitreal (IVT) injection is presented to protect retinal cells against blue light-induced phototoxicity. To investigate the effects of overexposure to blue light on retinal cells, a blue light exposure Nrf2-deficient mouse model is created, which is susceptible to light-induced retinal lesions. After blue light irradiation, retina degeneration and an overproduction of ROS are observed. The polydopamine-replenishing strategy demonstrated effectiveness in maintaining retinal structural integrity and preventing retina degeneration by reducing ROS production in retinal cells and limiting the phototoxicity of blue light exposure. These findings highlight the potential of polydopamine as a simple and effective replenishment for providing photoprotection against high-energy blue light exposure.

Liver transplant versus liver resection in patients with multifocal hepatocellular carcinoma.

BACKGROUND: The optimal surgical option in patients with multifocal hepatocellular carcinoma (MHCC) is an area of active research. The preference varies based on geographic variations and institutional policies. We sought to determine long-term outcomes in patients with MHCC based on surgical treatment-liver transplant (LT) vs resection (LR). METHODS: We performed a retrospective analysis of the National Cancer Database (2004-2015) and identified patients with MHCC within Milan criteria. Patients with α-fetoprotein ≥ 1000 ng/mL and those who underwent ablation were excluded. The primary outcome measure was long-term survival in patients undergoing LT vs LR. The secondary aim of our study was to determine clinicodemographic factors associated with the receipt of LT and LR. RESULTS: A total of 1546 patients were included, of whom 1211 received LT and 335 underwent LR. Patients who were non-Hispanic White (70.8% vs 54.9%; P < .01), privately insured (53.7% vs 36.7%; P < .01), and treated at academic centers (85.4% vs 71.6%; P < .01) were more likely to receive an LT. Multivariable Cox analysis revealed LT was associated with improved survival compared with LR (hazard ratio, 0.34; 95% CI, 0.28-0.42). CONCLUSION: We described clinical and sociodemographic differences in LT and LR patients and found LT to be associated with a decreased mortality risk compared with LR. The study's findings should be interpreted in the context of several limitations, including the selection of MHCC criteria within Milan criteria.

Improvement in Health-Related Quality of Life Following Antibiotic Treatment in Nontuberculous Mycobacterial Pulmonary Disease: Initial Analysis of the NTM-KOREA Cohort.

BACKGROUND: Improving health-related quality of life (HRQOL) has emerged as a priority in the management of nontuberculous mycobacterial pulmonary disease (NTM-PD). We aimed to evaluate HRQOL and its changes after 6 months' treatment in patients with NTM-PD. METHODS: The NTM-KOREA is a nationwide prospective cohort enrolling patients initiating treatment for NTM-PD in 8 institutions across South Korea. We conducted the Quality of Life-Bronchiectasis (QOL-B) at 6-month intervals and evaluated baseline scores (higher scores indicate better quality of life) and changes after 6 months' treatment. Multivariate logistic regression was performed to identify factors associated with improvement in the QOL-B physical functioning and respiratory symptoms domains. RESULTS: Between February 2022 and August 2023, 411 patients were included in the analysis. Baseline scores (95% confidence interval [CI]) for physical functioning and respiratory symptoms were 66.7 (46.7-86.7) and 81.5 (70.4-92.6), respectively. Among 228 patients who completed the QOL-B after 6 months' treatment, improvements in physical functioning and respiratory symptoms were observed in 61 (26.8%) and 71 (31.1%) patients, respectively. A lower score (adjusted odds ratio; 95% CI) for physical functioning (0.93; 0.91-0.96) and respiratory symptoms (0.92; 0.89-0.95) at treatment initiation was associated with a greater likelihood of physical functioning and respiratory symptom improvement, respectively; achieving culture conversion was not associated with improvement in physical functioning (0.62; 0.28-1.39) or respiratory symptoms (1.30; 0.62-2.74). CONCLUSIONS: After 6 months of antibiotic treatment for NTM-PD, HRQOL improved in almost one-third, especially in patients with severe initial symptoms, regardless of culture conversion. CLINICAL TRIALS REGISTRATION: ClinicalTrials.gov identifier: NCT03934034.

Development of cooking method for senior-friendly food using fruits suitable for older adults with masticatory dysfunction.

BACKGROUND/OBJECTIVES: The purpose of this study was to establish a fruit-cooking method suitable for older adults with masticatory dysfunction. MATERIALS/METHODS: Five types of fruits were selected to make fruit jelly and puree: apple, sweet persimmon, mandarin, Korean melon, and watermelon. Recipes were selected based on the Korean Industrial Standard (KS) for senior-friendly foods (KS H 4897), which classifies foods into 3 levels (L1-L3) based on their hardness and viscosity. RESULTS: In South Korea, senior-friendly foods are classified into 3 stages based on their hardness. Stage 1 is for foods that are able to eat with teeth (hardness greater than 50,000 N and less than 500,000 N), Stage 2 is for foods that are able to eat with gums (hardness greater than 20,000 N and less than 50,000 N), and Stage 3 is for foods that are able to eat with the tongue (hardness less than 20,000 N). As a result of measuring the hardness by varying the shape of the fruit, it was found that nearly all fruits could be eaten fresh by chewing with the teeth (L1) but did not meet the KS for mastication using the gums (L2) or tongue (L3), so the cooking method was selected as fruit jelly and fruit puree. Only sweet persimmon, which had a hardness of 61,624-496,393 N, was not suitable for consumption in fresh fruit, unprocessed form. Based on their hardness measurements, fruit jellies (27,869 to 36,343 N) and fruit purees (315 to 1,156 N) met the L2 and L3 requirements, respectively. The viscosity results of all fruit purees met the L3 requirement. CONCLUSION: These results offer a simple cooking method to prepare texture-modified fruits suitable for safe consumption by older adults living with masticatory difficulties in general households and nursing facilities.

Lab on a bead with oscillatory centrifugal microfluidics for fast and complete mixing enables fast and accurate biomedical assays.

Rapid mixing and precise timing are key for accurate biomedical assay measurement, particularly when the result is determined as the rate of a reaction: for example rapid immunoassay in which the amount of captured target is kinetically determined; determination of the concentration of an enzyme or enzyme substrate; or as the final stage in any procedure that involves a capture reagent when an enzyme reaction is used as the indicator. Rapid mixing and precise timing are however difficult to achieve in point-of-care devices designed for small sample volumes and fast time to result. By using centrifugal microfluidics and transposing the reaction surface from a chamber to a single mm-scale bead we demonstrate an elegant and easily manufacturable solution. Reagents (which may be, for example, an enzyme, enzyme substrate, antibody or antigen) are immobilised on the surface of a single small bead (typically 1-2 mm in diameter) contained in a cylindrical reaction chamber subjected to periodically changing rotational accelerations which promote both mixing and uniform mass-transfer to the bead surface. The gradient of Euler force across the chamber resulting from rotational acceleration of the disc, dΩdisc/dt, drives circulation of fluid in the chamber. Oscillation of Euler force by oscillation of rotational acceleration with period, T, less than that of the hydrodynamic relaxation time of the fluid, folds the fluid streamlines. Movement of the bead in response to the fluid and the changing rotational acceleration provides a dynamically changing chamber shape, further folding and expanding the fluid. Bead rotation and translation driven by fluid flow and disc motion give uniformity of reaction over the surface. Critical parameters for mixing and reaction uniformity are the ratio of chamber radius to bead radius, rchamber/rbead, and the product Trchamber(dΩdisc/dt), of oscillation period and Euler force gradient across the fluid. We illustrate application of the concept using the reaction of horse radish peroxidase (HRP) immobilised on the bead surface with its substrate tetramethylbenzidine (TMB) in solution. Acceleration from rest to break a hydrophobic valve provided precise timing for TMB contact with the bead. Solution uniformity from reaction on the surface of the bead in volumes 20-50 uL was obtained in times of 2.5 s or less. Accurate measurement of the amount of surface-bound HRP by model fitting to the measured kinetics of colour development at 10 s intervals is demonstrated.