Low-dose daily folic acid (400 µg) supplementation does not affect regulation of folate transporters found present throughout the terminal ileum and colon of humans: a randomized clinical trial.

BACKGROUND: Folic acid supplementation during the periconceptional period reduces the risk of neural tube defects in infants, but concern over chronic folic acid exposure remains. An improved understanding of folate absorption may clarify potential risks. Folate transporters have been characterized in the small intestine, but less so in the colon of healthy, free-living humans. The impact of folic acid fortification or supplementation on regulation of these transporters along the intestinal tract is unknown. OBJECTIVE: The objective was to characterize expression of folate transporters/receptor (FT/R) and folate hydrolase, glutamate carboxypeptidase II (GCPII), from the terminal ileum and throughout the colon of adults and assess the impact of supplemental folic acid. METHODS: In this 16-wk open-labeled randomized clinical trial, adults consumed a low folic acid-containing diet, a folate-free multivitamin, and either a 400 µg folic acid supplement or no folic acid supplement. Dietary intakes and blood were assessed at baseline, 8 wk, and 16 wk (time of colonoscopy). Messenger RNA (mRNA) expression and protein expression of FT/R and GCPII were assessed in the terminal ileum, cecum, and ascending and descending colon. RESULTS: Among 24 randomly assigned subjects, no differences in dietary folate intake or blood folate were observed at baseline. Mean ± SD red blood cell folate at 16 wk was 1765 ± 426 and 911 ± 242 nmol/L in the 400 and 0 µg folic acid group, respectively (P < 0.0001). Reduced folate carrier, proton-coupled folate transporter, and folate-receptor alpha expression were detected in the terminal ileum and colon, as were efflux transporters of breast cancer resistance protein and multidrug resistance protein-3. Other than a higher mRNA expression of FR-alpha and GCPII in the 400 µg supplement group in the ascending colon, no treatment differences were observed (P < 0.02). CONCLUSIONS: Folate transporters are present throughout the terminal ileum and colon; there is little evidence that a low dose of folic acid supplementation affects colonic absorption. This trial was registered at clinicaltrials.gov as NCT03421483.

A Multi-Functional CMOS Biosensor Array With On-Chip DEP-Assisted Sensing for Rapid Low-Concentration Analyte Detection and Close-Loop Particle Manipulation With No External Electrodes.

This article presents a fully-integrated dielectrophoresis (DEP)-assisted multi-functional CMOS biosensor array chip with 4096 working electrodes (WEs), 12288 photodiodes (PDs), reference electrodes (REs), and counter electrodes (CEs), while each WE and photodiode can be reconfigured to support on-chip DEP actuation, electrochemical potentiostat, optical shadow imaging, and complex impedance sensing. The proposed CMOS biosensor is an example of an actuation-assisted label-free biosensor for the rapid sensing of low-concentration analytes. The DEP actuator of the proposed CMOS biosensor does not require any external electrode. Instead, on-chip WE pairs can be re-used for DEP actuation to simplify the sensor array design. The CMOS biosensor is implemented in a standard 130-nm BiCMOS process. Theoretical analyses and finite element method (FEM) simulations of the on-chip DEP operations are conducted as proof of concept. Biological assay measurements (DEP actuation/electrochemical potentiostat/impedance sensing) with E.coli bacteria and microbeads (optical shadow imaging) demonstrate rapid detection of low-concentration analytes and simultaneous manipulation and detection of large particles. The on-chip DEP operations draw the analytes closer to the sensor electrode surface, which overcomes the diffusion limit and accelerates low-concentration analyte sensing. Moreover, the DEP-based movement of large particles can be readily detected by on-chip photodiode arrays to achieve close-loop manipulation and sensing of particles and droplets. These show the unique advantages of the DEP-assisted multi-functional biosensor.

Anti-Bordetella bronchiseptica effects of targeted bacteriophages via microbiome and metabolic mediated mechanisms.

Bordetella bronchiseptica poses a significant challenge in the context of respiratory infections, particularly in weanling pigs. In this study, we investigated the impact of a novel targeted bacteriophage in controlling B. bronchiseptica challenge (BBC) in an experimental design involving five distinct treatment groups: NC (no challenge), PC (BBC challenge), BF (108 pfu bacteriophage/kg diet + BBC), BN (2 × 107 pfu/day bacteriophage by nasal spray + BBC), and AT (antibiotic + BBC). The experiment was conducted for 2 weeks. The highest turbinate score was observed in the PC. The BF treatment showed higher plasma IL (interleukine)-1ß and IL-6 compared with the BN and AT treatments. Plasma concentrations of IL-1ß were increased in the BF pigs compared with the BN, AT, and NC. Among the BBC groups, the PC treatment exhibited a higher abundance of Staphylococcus. aureus and B. bronchiseptica in the lung. A lower S. aureus, Streptococcus. suis, and B. bronchiseptica colonization was detected in the AT compared with the BF and BN treatments. The BF showed lower plasma zonulin compared with the BN and AT. A higher plasma concentration of superoxide dismutase was observed in the BF and AT compared with PC and BN. The BN influenced the glycine, serine-threonine metabolism; glycerolipid metabolism; glyoxylate-dicarboxylate metabolism; and arachidonic acid metabolism compared with the NC. In conclusion, nasal-sprayed bacteriophage effectively controlled B. bronchiseptica infection, however, their efficiency was lower than the antibiotic.

Exploring horticultural traits and disease resistance in Capsicum baccatum through segmental introgression lines.

KEY MESSAGE: Segmental introgression and advanced backcross lines were developed and validated as important tools for improving agronomically important traits in pepper, offering improved sensitivity in detecting quantitative trait loci for breeding. Segmental introgression lines (SILs) and advanced backcross lines (ABs) can accelerate genetics and genomics research and breeding in crop plants. This study presents the development of a complete collection of SILs and ABs in pepper using Capsicum annuum cv. 'CM334' as the recipient parent and Capsicum baccatum 'PBC81', which displays various agronomically important traits including powdery mildew and anthracnose resistance, as donor parent. Using embryo rescue to overcome abortion in interspecific crosses, and marker-assisted selection with genotyping-in-thousands by sequencing (GT-seq) to develop SILs and ABs containing different segments of the C. baccatum genome, we obtained 63 SILs and 44 ABs, covering 94.8% of the C. baccatum genome. We characterized them for traits including powdery mildew resistance, anthracnose resistance, anthocyanin accumulation, trichome density, plant architecture, and fruit morphology. We validated previously known loci for these traits and discovered new sources of variation and quantitative trait loci (QTLs). A total of 15 QTLs were identified, including four for anthracnose resistance with three novel loci, seven for plant architecture, and four for fruit morphology. This is the first complete collection of pepper SILs and ABs validated for agronomic traits and will enhance QTL detection and serve as valuable breeding resources. Further, these SILs and ABs will be useful for comparative genomics and to better understand the genetic mechanisms underlying important agronomic traits in pepper, ultimately leading to improved crop productivity and sustainability.

Effectiveness of a Smartphone Application for Dietary Sodium Intake Measurement.

Accurate estimation of sodium intake is a key requirement for evaluating the efficacy of interventional strategies to reduce salt intake. The effectiveness of a smartphone application in measuring dietary sodium intake was assessed. This study included 46 participants who consented to register in Noom's food-logging program. All participants were followed up for six months from the day of enrollment. The mean age of the participants was 40.2 ± 12.3 years, and 22 (48%) participants were male. The average number of times/weeks the meals were logged was 16.2 ± 10.3. At baseline, the mean 24-h urine sodium was 124.3 mmol/24 h. The mean sodium intake measured by the smartphone application and calculated using the 24-h urine sodium was 2020.9 mg/24 h and 2857.6 mg/24 h, respectively. During the second visit, the mean 24-h urine sodium was 117.4 mmol/24 h. The mean sodium intake measured by the smartphone application and calculated using the 24-h urine sodium was 1456.0 mg/24 h and 2698.3 mg/24 h, respectively. Sodium intake measured using the smartphone application positively correlated with that calculated using the 24-h urine sodium at baseline (r = 0.464; p < 0.001) and follow-up (r = 0.334; p= 0.023). Dietary sodium intake measured using a smartphone application correlated well with that estimated using 24-h urine sodium level.

Potential of a bivalent vaccine for broad protection against enterovirus 71 and coxsackie virus 16 infections causing hand, foot, and mouth disease.

Hand, foot, and mouth disease (HFMD) is a highly contagious viral infection that is mainly caused by enterovirus 71 (EV71) and coxsackievirus 16 (CVA16). As there are no specific therapeutics for HFMD, the development of a bivalent vaccine is required to cover a broad range of infections. In this study, the effectiveness of novel monovalent and bivalent vaccines targeting EV71 C4a and CVA16 was investigated for their ability to prevent viral infections in neonatal human scavenger receptor class B member 2 (hSCARB2) transgenic mice. As hSCARB2 serves as a key viral receptor for EV71, these transgenic mice are susceptible to EV71 strains and facilitate viral binding, internalization, and uncoating processes. Antisera prepared by vaccine immunization were transferred to 2-day-old hSCARB2 transgenic mice, which were then infected with EV71 C4a or CVA16 virus. The antisera generated by each monovalent or bivalent vaccine effectively protected against EV71 C4a and CVA16 infections. The examination of tissue damage and viral contents in various organs indicated that both monovalent and bivalent antisera reduced EV71 C4a viral load in the brainstem, and no significant tissue damage was observed. During CVA16 infection, the monovalent and bivalent antisera significantly reduced viral contents in both the brainstem and muscles. These results suggest that passive immunity by monovalent and bivalent antisera can effectively protect against EV71 C4a and CVA16 infections. Thus, the development of a bivalent vaccine that can provide broad protection against both CV and EV infections may be a promising strategy in preventing HFMD.

Microplastic contamination in groundwater of rural area, eastern part of Korea.

Microplastics (MPs) are emerging contaminants in agricultural regions owing to the widespread use of plastics in farming activities. Groundwater has a vital role in farming activities, and it can be contaminated by MPs, fragmented from plastic products used in agricultural activities. Following an appropriate sampling protocol, this study investigated the distribution of MPs in shallow to deep aquifers (well depths: 3-120 m) and cave water of an agricultural region in Korea. Our investigation found that MPs contamination can penetrate up to the deep bedrock aquifer. The abundance of MPs was lower during the wet season (0.014-0.554 particles/L) than during the dry season (0.042-1.026 particles/L), which may be attributed to the dilution effect of precipitation in the groundwater. The abundance of MPs increased as the MPs size decreased at all sampling points, and size ranges were 20.3-869.6 and 20.3-673.0 µm in the dry and wet seasons, respectively. Our findings showed lower MPs abundance compared to previous studies, and we inferred that it might be due to differences in groundwater sampling volume, low agricultural intensity, and the non-application of sludge fertilizers. Our findings suggest that repeated and long-term investigations are needed to identify better the factors that influence the results of MPs distribution in groundwater, including sampling methods and hydrogeological and hydrological conditions.

A Bivalent Inactivated Vaccine Prevents Enterovirus 71 and Coxsackievirus A16 Infections in the Mongolian Gerbil.

Hand-foot-and-mouth disease (HFMD) is a viral infectious disease that occurs in children under 5 years of age. Its main causes are coxsackievirus (CV) and enterovirus (EV). Since there are no efficient therapeutics for HFMD, vaccines are effective in preventing the disease. To develop broad coverage against CV and EV, the development of a bivalent vaccine form is needed. The Mongolian gerbil is an efficient and suitable animal model of EV71 C4a and CVA16 infection used to investigate vaccine efficacy following direct immunization. In this study, Mongolian gerbils were immunized with a bivalent inactivated EV71 C4a and inactivated CVA16 vaccine to test their effectiveness against viral infection. Bivalent vaccine immunization resulted in increased Ag-specific IgG antibody production; specifically, EV71 C4a-specific IgG was increased with medium and high doses and CVA16-specific IgG was increased with all doses of immunization. When gene expression of T cell-biased cytokines was analysed, Th1, Th2, and Th17 responses were found to be highly activated in the high-dose immunization group. Moreover, bivalent vaccine immunization mitigated paralytic signs and increased the survival rate following lethal viral challenges. When the viral RNA content was determined from various organs, all three doses of bivalent vaccine immunization were found to significantly decrease viral amplification. Upon histologic examination, EV71 C4a and CVA16 induced tissue damage to the heart and muscle. However, bivalent vaccine immunization alleviated this in a dose-dependent manner. These results suggest that the bivalent inactivated EV71 C4a/CVA16 vaccine could be a safe and effective candidate HFMD vaccine.

Microplastic contamination in groundwater on a volcanic Jeju Island of Korea.

Microplastic (MPs) contamination in groundwater has received massive attention since plastic waste has been released directly into the environment. This study investigates MPs contamination in groundwater on the Jeju volcanic Island, Korea. To the best of our knowledge, this is the first study to identify MPs in groundwater from volcanic islands. A total of 21 sites were sampled for groundwater wells and springs in July and September (2021). Sampling was performed without cross-contamination through quality assurance and quality control. The results showed that MPs abundance ranged from 0.006 to 0.192 particles/L in groundwater samples. Additionally, MPs were detected in deep groundwater wells where the groundwater level was 143 m below ground surface. Eight MPs polymer types, including polypropylene, polyethylene, polyethylene terephthalate, polyvinyl chloride, polystyrene, polyamide, acrylonitrile butadiene styrene, and polyurethane, were detected using Micro-Fourier Transform Infrared Spectroscopy (µ-FT-IR). Most of the detected MPs size ranged from 20 to 100 µm, accounting for 95% of the total. Fragments and fiber shaped MPs were detected, with the majority of them being fragmented in groundwater samples. The concentrations of MPs and major ions in groundwater showed a positive correlation. A negative correlation was observed between MPs concentration and topographic elevation (r = -0.59, p = 0.01). The source of MPs contamination is most likely attributed to agricultural activities, such as plastic mulching and greenhouses, which account for most of the land use in the study area. In this study, MPs entered the aquifer through the soil at the surface and seeped through cracks in fractured rock on basalt with sealed groundwater wells. This study takes 500 L of samples to prevent sample bias, reveal plastic contamination in groundwater, and indicating the characteristics and sources of contaminated plastics.

Intranasal immunization with curdlan induce Th17 responses and enhance protection against enterovirus 71.

Mucosal surfaces are in contact with the external environment and protect the body from infection by various microbes. To prevent infectious diseases at the first line of defense, the establishment of pathogen-specific mucosal immunity by mucosal vaccine delivery is needed. Curdlan, a 1,3-ß-glucan has a strong immunostimulatory effect when delivered as a vaccine adjuvant. Here, we investigated whether intranasal administration of curdlan and antigen (Ag) could induce sufficient mucosal immune responses and protect against viral infections. Intranasal co-administration of curdlan and OVA increased OVA-specific IgG and IgA Abs in both serum and mucosal secretions. In addition, intranasal co-administration of curdlan and OVA induced the differentiation of OVA-specific Th1/Th17 cells in the draining lymph nodes. To investigate the protective immunity of curdlan against viral infection, intranasal co-administration of curdlan with recombinant VP1 of EV71 C4a was administered and showed enhanced protection against enterovirus 71 in a passive serum transfer model using neonatal hSCARB2 mice, although intranasal administration of VP1 plus curdlan increased VP1-specific helper T cells responses but not mucosal IgA. Next, Mongolian gerbils were intranasally immunized with curdlan plus VP1, and they had effective protection against EV71 C4a infection, while decreasing viral infection and tissue damage by inducing Th17 responses. These results indicated that intranasal curdlan with Ag improved Ag-specific protective immunity by enhancing mucosal IgA and Th17 against viral infection. Our results suggest that curdlan is an advantageous candidate as a mucosal adjuvant and delivery vehicle for the development of mucosal vaccines.

Remnant cholesterol, low-density lipoprotein cholesterol, and incident cardiovascular disease among Koreans: a national population-based study.

AIMS: The synergistic association of remnant cholesterol (remnant-C) and low-density lipoprotein cholesterol (LDL-C) levels with incident cardiovascular disease (CVD) in various subgroups of Koreans was investigated. METHODS AND RESULTS: Using the national health insurance data, we included subjects aged between 40 and 70 years without a history of CVD and at least two health screenings between 2009 and 2011. The subjects were divided into four groups by LDL-C and remnant-C levels. The primary outcome was CVD, which occurred between 2014 and 2017. Among 3 686 034 (45.6% women) subjects, 144 004 cardiovascular events occurred. Individuals in both high LDL-C and high remnant-C [hazard ratio (HR) 1.266, 95% confidence interval (CI) 1.243-1.289; 7.9%], high LDL-C only (HR 1.098, 95% CI 1.083-1.113; 21.2%), and high remnant-C only groups (HR 1.102, 95% CI 1.087-1.118; 19.1%) had higher risks of CVD than those in the reference group (LDL-C < 3.4 mmol/L and remnant-C < 0.8 mmol/L; 51.8%). A continuous and linear increase in CVD risk was found in those with higher remnant-C levels after adjustment for several confounders, including LDL-C levels. The association of remnant-C ≥ 0.8 mmol/L with an increased CVD risk was consistent across various strata. CONCLUSIONS: Combined high remnant-C and LDL-C levels confer a higher CVD risk than that individually. Elevated remnant-C values independent of LDL-C levels were associated with a risk of incident CVD. Remnant cholesterol levels in addition to LDL-C levels are important considerations in risk stratification for the primary prevention of CVD.

Since remnant-C has recently emerged as a potential risk factor for CVD, the synergistic association of LDL-C and remnant-C with CVD has been investigated among 3 686 034 Koreans (45.6% women) without preceding CVD using nationwide population-based big data. Remnant cholesterol remained proportional to the risk of incident CVD after adjusting for multiple variables, including LDL-C levels.Low-density lipoprotein cholesterol and remnant-C synergistically contributed to incident CVD.

An early interactive human coaching via a mobile application to improve quality of life in patients who underwent gastrectomy for gastric cancer: Design and protocol of a randomized controlled trial.

BACKGROUND: After gastrectomy, patients may experience the postgastrectomy syndrome and face difficulties adapting to everyday diet. Recently, human health coaching via a mobile application (app) has been used for obese patients or patients with chronic diseases, with significant improvements in clinical outcomes. The aim of this study is to evaluate and compare the effects of human health coaching via a mobile app and conventional face-to-face counseling in patients who underwent gastrectomy for gastric cancers. METHODS: This study is a single-institution, prospective randomized controlled trial comparing the mobile health and face-to-face counselling groups. After randomization, participants assigned to the mobile health coaching group will receive health coaching via a mobile app for 3 months after discharge, and the assigned coaches will provide personalized advice based on the self-recorded health data. Participants in the face-to-face group will have 1- and 3-months postoperative dietary consultations with a clinical dietitian. The primary endpoint is the food restriction score on the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-STO22, and secondary endpoints included all other quality of life scale scores and nutritional parameters. The calculated sample size is 180, and the outcomes will be measured until 1-year post-surgery. SIGNIFICANCE: This study will show the efficacy of human health coaching via a mobile app on dietary adaptation in patients who underwent gastrectomy. A relational approach based on personal data and timely intervention using a mobile platform could reduce patients' trial and error and improve quality of life. TRIAL REGISTRATION: ClinicalTrials.gov, NCT04394585, Registered 19 May, 2020 -Retrospectively registered, http://clinicaltrials.gov/ct2/show/NCT040394585.

Barriers and facilitators on the HIV care continuum among adults living with HIV in high-income countries: a scoping review protocol.

BACKGROUND: As the life expectancy of people living with HIV increases with the advancements in antiretroviral treatment, the continuity of long-term therapy and health care for people living with HIV has gained more importance. However, the estimated proportion of people living with HIV who have access to treatment or are virally suppressed is unsatisfactory. Therefore, it is necessary to build strategies to improve treatment continuity by identifying the barriers and facilitators that affect the HIV care continuum. To enable this, we will conduct a scoping review to explore the barriers and facilitators related to the care continuum in high-income countries for adults living with HIV. METHODS: The review question will be identified based on the JBI guidelines for the development of scoping review protocols. Studies exploring the barriers to and facilitators of the HIV care continuum among adults living with HIV in high-income countries will be included in this review. A literature search will be conducted on the databases (platform) of MEDLINE (Ovid), Cumulative Index to Nursing and Allied Health Literature (EBSCO), Embase (Ovid), and the Cochrane Central Register of Controlled Trials (Cochrane Library). Four researchers will screen articles for inclusion and subsequently build a charting form and collate the data to provide results. DISCUSSION: The results of this scoping review will provide comprehensive evidence for the barriers and facilitators to be considered in the care continuum of people living with HIV. Importantly, the results will provide insight for healthcare providers and researchers to develop interventions and research the continuity in caring for people living with HIV.

The Effectiveness of a Mobile Health Care App and Human Coaching Program in Primary Care Clinics: Pilot Multicenter Real-World Study.

BACKGROUND: As the global burden of chronic conditions increases, their effective management is a concern. Although the need for chronic disease management using mobile self-management health care apps is increasing, there are still many barriers to their practical application in the primary care field. OBJECTIVE: This study evaluated the effectiveness of primary care services combining a mobile self-management health care app with human coaching for patients with chronic diseases in the current primary care system. METHODS: A total of 110 patients (mean age 53.2, SD 9.2 years; 64 of 110, 58.2% female) with hypertension, diabetes, dyslipidemia, or metabolic syndrome who visited one of 17 participating primary care clinics from September to November 2020 were included in this study. All participants recorded data regarding changes in body weight, sleep conditions, quality of life, depression, anxiety, stress, BMI, waist circumference, blood sugar levels, blood pressure, and blood lipids levels. The app user group (n=65) used a mobile self-management health care app with human coaching for 12 weeks, and the control group (n=45) underwent conventional self-managed health care. RESULTS: Patients in the app user group reported significantly more weight loss than those in the control group-the body weight of the app user group decreased by 1.43 kg (95% CI -2.07 to -0.79) and that of the control group decreased by 0.13 kg (95% CI -0.67 to 0.41; P=.002). The weight loss was markedly greater after using the app for 9 weeks than that when used for 4 weeks or 5-8 weeks (P=.002). Patients in the app user group reported better sleep quality (P=.04) and duration (P=.004) than those in the control group. CONCLUSIONS: The combination of primary care clinics and a mobile self-management health care app with human coaching results in better management of chronic conditions. This study shows that the primary care services combining a mobile self-management health care app with human coaching are effective in the current primary care system. An implication of this study is the possibility that a mobile self-management health care app with human coaching is a treatment option in the current primary care system.

Identification of Genetic Factors Controlling the Formation of Multiple Flowers Per Node in Pepper (Capsicum spp.).

Flower production provides the foundation for crop yield and increased profits. Capsicum annuum is a pepper species with a sympodial shoot structure with solitary flowers. By contrast, C. chinense produces multiple flowers per node. C. annuum accounts for 80% of pepper production worldwide. The identification of C. chinense genes that control multiple flowers and their transfer into C. annuum may open the way to increasing fruit yield. In this study, we dissected the genetic factors were dissected controlling the multiple-flower-per-node trait in Capsicum. 85 recombinant inbred lines (RILs) between the contrasting C. annuum 'TF68' and C. chinense 'Habanero' accessions were phenotyped and genotyped. Quantitative Trait Loci (QTL) analysis identified four novel QTLs on chromosomes 1, 2, 7, and 11 that accounted for 65% of the total phenotypic variation. Genome-wide association study was also performed on a panel of 276 genotyped and phenotyped C. annuum accessions, which revealed 28 regions significantly associated with the multiple-flower trait, of which three overlapped the identified QTLs. Five candidate genes involved in the development of the shoot and flower meristems were identified and these genes could cause multiple flowers per node in pepper. These results contribute to our understanding of multiple flower formation in Capsicum and will be useful to develop high-yielding cultivars.

Comparison of Energy and Macronutrients Between a Mobile Application and a Conventional Dietary Assessment Method in Korea.

BACKGROUND: The use of mobile apps for dietary evaluation avoids some of the disadvantages of costly and time-consuming traditional diet assessment. However, few studies have compared dietary intake data in smartphone apps with a conventional diet assessment. OBJECTIVE: This study aimed to compare the dietary data collected on energy and macronutrients (proteins, fats, and carbohydrates) consumed for 3 nonconsecutive days using both a mobile application (Noom) and a conventional dietary assessment tool (CAN Pro). DESIGN: This was a cross-sectional study. PARTICIPANTS/SETTING: A total of 119 healthy adults (68 males and 51 females) aged 19 to 65 years were recruited from the National Cancer Center in Korea between May and September 2019. MAIN OUTCOME MEASURES: The mean daily energy and macronutrient intake data were obtained for the dietary intakes consumed for 3 nonconsecutive days using Noom and CAN Pro. STATISTICAL ANALYSIS PERFORMED: The estimates of energy and macronutrient intake between the two tools were compared using correlation coefficients and cross-classification. RESULTS: Although mean daily fat intake and percent total energy from carbohydrate estimated by Noom were comparable with values provided by CAN Pro, mean daily estimated energy intake (kcal), protein (g, percent total energy), and carbohydrate (g) were significantly higher with Noom than with CAN Pro. The correlation coefficients ranged from 0.79 to 0.99 for crude intake and from 0.77 to 0.88 for energy-adjusted values of intake after adjustment for sex and age. The percentages of participants classified into quartiles of "exact agreement and plus adjacent" varied between 95% and 99% for crude intake and between 93% and 97% for energy-adjusted values of intake. CONCLUSIONS: The findings indicate that Noom may be useful for monitoring the dietary intake of energy and macronutrients and reducing workload compared with a traditional dietary assessment in Korea. However, further research is needed to assess the validity and usability of Noom for estimating intake of micronutrients and other dietary components.

Weight Loss Trajectories and Related Factors in a 16-Week Mobile Obesity Intervention Program: Retrospective Observational Study.

BACKGROUND: In obesity management, whether patients lose ≥5% of their initial weight is a critical factor in clinical outcomes. However, evaluations that take only this approach are unable to identify and distinguish between individuals whose weight changes vary and those who steadily lose weight. Evaluation of weight loss considering the volatility of weight changes through a mobile-based intervention for obesity can facilitate understanding of an individual's behavior and weight changes from a longitudinal perspective. OBJECTIVE: The aim of this study is to use a machine learning approach to examine weight loss trajectories and explore factors related to behavioral and app use characteristics that induce weight loss. METHODS: We used the lifelog data of 13,140 individuals enrolled in a 16-week obesity management program on the health care app Noom in the United States from August 8, 2013, to August 8, 2019. We performed k-means clustering with dynamic time warping to cluster the weight loss time series and inspected the quality of clusters with the total sum of distance within the clusters. To identify use factors determining clustering assignment, we longitudinally compared weekly use statistics with effect size on a weekly basis. RESULTS: The initial average BMI value for the participants was 33.6 (SD 5.9) kg/m2, and it ultimately reached 31.6 (SD 5.7) kg/m2. Using the weight log data, we identified five clusters: cluster 1 (sharp decrease) showed the highest proportion of participants who reduced their weight by >5% (7296/11,295, 64.59%), followed by cluster 2 (moderate decrease). In each comparison between clusters 1 and 3 (yo-yo) and clusters 2 and 3, although the effect size of the difference in average meal record adherence and average weight record adherence was not significant in the first week, it peaked within the initial 8 weeks (Cohen d>0.35) and decreased after that. CONCLUSIONS: Using a machine learning approach and clustering shape-based time series similarities, we identified 5 weight loss trajectories in a mobile weight management app. Overall adherence and early adherence related to self-monitoring emerged as potential predictors of these trajectories.

Human Epidural AD-MSC Exosomes Improve Function Recovery after Spinal Cord Injury in Rats.

Spinal cord injury (SCI) interferes with the normal function of the autonomic nervous system by blocking circuits between the sensory and motor nerves. Although many studies focus on functional recovery after neurological injury, effective neuroregeneration is still being explored. Recently, extracellular vesicles such as exosomes have emerged as cell-free therapeutic agents owing to their ability of cell-to-cell communication. In particular, exosomes released from mesenchymal stem cells (MSCs) have the potential for tissue regeneration and exhibit therapeutic effectiveness in neurological disorders. In this study, we isolated exosomes from human epidural adipose tissue-derived MSCs (hEpi AD-MSCs) using the tangential flow filtration method. The isolated exosomes were analyzed for size, concentration, shape, and major surface markers using nanoparticle tracking analysis, transmission electron microscopy, and flow cytometry. To evaluate their effect on SCI recovery, hEpi AD-MSC exosomes were injected intravenously in SCI-induced rats. hEpi AD-MSC exosomes improved the locomotor function of SCI-induced rats. The results of histopathological and cytokine assays showed that hEpi AD-MSC exosomes regulated inflammatory response. Genetic profiling of the rat spinal cord tissues revealed changes in the expression of inflammation-related genes after exosome administration. Collectively, hEpi AD-MSC exosomes are effective in restoring spinal functions by reducing the inflammatory response.

Contribution of Protein Kinase D1 on Acute Pulmonary Inflammation and Hypersensitivity Pneumonitis Induced by Saccharopolyspora rectivirgula.

Protein kinase D1 (PKD1), a ubiquitously expressed serine/threonine kinase, regulates diverse cellular processes such as oxidative stress, gene expression, cell survival, vesicle trafficking, Ag receptor signaling, and pattern recognition receptor signaling. We found previously that exposure to hypersensitivity pneumonitis (HP) inciting Ag Saccharopolyspora rectivirgula leads to the activation of PKD1 in a MyD88-dependent manner in various types of murine cells in vitro and in the mouse lung in vivo. However, it is currently unknown whether PKD1 plays a role in the S. rectivirgula-induced HP. In this study, we investigated contributions of PKD1 on the S. rectivirgula-induced HP using conditional PKD1-insufficient mice. Compared to control PKD1-sufficient mice, PKD1-insufficient mice showed substantially suppressed activation of MAPKs and NF-κB, expression of cytokines and chemokines, and neutrophilic alveolitis after single intranasal exposure to S. rectivirgula The significantly reduced levels of alveolitis, MHC class II surface expression on neutrophils and macrophages, and IL-17A and CXCL9 expression in lung tissue were observed in the PKD1-insufficient mice repeatedly exposed to S. rectivirgula for 5 wk. PKD1-insuficient mice exposed to S. rectivirgula for 5 wk also showed reduced granuloma formation. Our results demonstrate that PKD1 plays an essential role in the initial proinflammatory responses and neutrophil influx in the lung after exposure to S. rectivirgula and substantially contribute to the development of HP caused by repeated exposure to S. rectivirgula Our findings suggest that PKD1 can be an attractive new molecular target for therapy of S. rectivirgula-induced HP.

An Impedance Readout IC with Ratio-Based Measurement Techniques for Electrical Impedance Spectroscopy.

This paper presents an error-tolerant and power-efficient impedance measurement scheme for bioimpedance acquisition. The proposed architecture measures the magnitude and the real part of the target complex impedance, unlike other impedance measurement architectures measuring either the real/imaginary components or the magnitude and phase. The phase information of the target impedance is obtained by using the ratio between the magnitude and the real components. This can allow for avoiding direct phase measurements, which require fast, power-hungry circuit blocks. A reference resistor is connected in series with the target impedance to compensate for the errors caused by the delay in the sinusoidal signal generator and the amplifier at the front. Moreover, an additional magnitude measurement path is connected to the reference resistor to cancel out the nonlinearity of the proposed system and enhance the settling speed of the low-pass filter by a ratio-based detection. Thanks to this ratio-based detection, the accuracy is enhanced by 30%, and the settling time is improved by 87.7% compared to the conventional single-path detection. The proposed integrated circuit consumes only 513 µW for a wide frequency range of 10 Hz to 1 MHz, with the maximum magnitude and phase errors of 0.3% and 2.1°, respectively.