Drinkable in situ-forming tough hydrogels for gastrointestinal therapeutics.

Pills are a cornerstone of medicine but can be challenging to swallow. While liquid formulations are easier to ingest, they lack the capacity to localize therapeutics with excipients nor act as controlled release devices. Here we describe drug formulations based on liquid in situ-forming tough (LIFT) hydrogels that bridge the advantages of solid and liquid dosage forms. LIFT hydrogels form directly in the stomach through sequential ingestion of a crosslinker solution of calcium and dithiol crosslinkers, followed by a drug-containing polymer solution of alginate and four-arm poly(ethylene glycol)-maleimide. We show that LIFT hydrogels robustly form in the stomachs of live rats and pigs, and are mechanically tough, biocompatible and safely cleared after 24 h. LIFT hydrogels deliver a total drug dose comparable to unencapsulated drug in a controlled manner, and protect encapsulated therapeutic enzymes and bacteria from gastric acid-mediated deactivation. Overall, LIFT hydrogels may expand access to advanced therapeutics for patients with difficulty swallowing.

Comparison of 3- to 6-Month Versus 12-Month Dual Antiplatelet Therapy After Coronary Intervention Using the Contemporary Drug-Eluting Stents With Ultrathin Struts: The HOST-IDEA Randomized Clinical Trial.

BACKGROUND: Limited data are available on short-term dual antiplatelet therapy (DAPT) after percutaneous coronary intervention using third-generation drug-eluting stents with ultrathin struts and advanced polymer technology. We investigated whether 3- to 6-month DAPT was noninferior to 12-month DAPT after implantation of drug-eluting stents with ultrathin struts and advanced polymer technology. METHODS: We performed an open-label, randomized trial at 37 centers in South Korea. We enrolled patients undergoing percutaneous coronary intervention using the Orsiro biodegradable-polymer sirolimus-eluting stents or the Coroflex ISAR polymer-free sirolimus-eluting stents. Patients with ST-segment-elevation myocardial infarction were excluded. Patients were randomly assigned to receive either 3- to 6-month or 12-month DAPT after percutaneous coronary intervention. The choice of antiplatelet medications was at the physician's discretion. The primary outcome was a net adverse clinical event, a composite of cardiac death, target vessel myocardial infarction, clinically driven target lesion revascularization, stent thrombosis, or major bleeding, defined as Bleeding Academic Research Consortium type 3 or 5 at 12 months. The major secondary outcomes were target lesion failure, a composite of cardiac death, target vessel myocardial infarction, clinically driven target lesion revascularization, and major bleeding. RESULTS: A total of 2013 patients (mean age, 65.7±10.5 years; 1487 males [73.9%]; 1110 [55.1%] presented with acute coronary syndrome) were randomly assigned to 3- to 6-month DAPT (n=1002) or 12-month DAPT (n=1011). The primary outcome occurred in 37 (3.7%) patients in the 3- to 6-month DAPT group and 41 (4.1%) in the 12-month DAPT group. The noninferiority of the 3- to 6-month DAPT group to the 12-month DAPT group was met (absolute risk difference, -0.4% [1-sided 95% CI, -∞% to 1.1%]; P<0.001 for noninferiority). There were no significant differences in target lesion failure (hazard ratio, 0.98 [95% CI, 0.56-1.71], P=0.94) or major bleeding (hazard ratio, 0.82 [95% CI, 0.41-1.61], P=0.56) between the 2 groups. Across various subgroups, the treatment effect of 3- to 6-month DAPT was consistent for net adverse clinical event. CONCLUSIONS: Among patients undergoing percutaneous coronary intervention using third-generation drug-eluting stents, 3- to 6-month DAPT was noninferior to 12-month DAPT for net adverse clinical event. Further research is needed to generalize this finding to other populations and to determine the ideal regimen for 3- to 6-month DAPT. REGISTRATION: URL: https://www. CLINICALTRIALS: gov; Unique identifier: NCT02601157.

Cumulative exposure to impaired fasting glucose and gastrointestinal cancer risk: A nationwide cohort study.

BACKGROUND: Impaired fasting glucose (IFG) is associated with the risk of various cancers, but the cumulative effect of IFG on gastrointestinal cancer risk remains unclear. This study evaluated the association between the cumulative exposure to IFG and gastrointestinal cancer risk. METHODS: The authors extracted data from the Korean National Health Insurance Service and health examination data sets. Among individuals ≥40 years old who were free of diabetes or cancer, 1,430,054 who underwent national health examinations over 4 consecutive years from 2009 to 2012 were selected and followed up until gastrointestinal cancer diagnosis, death, or December 31, 2019. The IFG exposure score (range, 0-4) was based on the number of IFG diagnoses over 4 years. RESULTS: The median follow-up duration was 6.4 years. Consistent normoglycemia for 4 years was found in 44.3% of the population, whereas 5.0% had persistent IFG and 50.7% had intermittent IFG. Compared to the group with an IFG exposure score of 0, groups with IFG exposure scores of 1, 2, 3, and 4 had a 5%, 8%, 9%, and 12% increased risk of gastrointestinal cancer, respectively (score 1: adjusted hazard ratio [aHR], 1.05; 95% confidence interval [CI], 1.01-1.08; score 2: aHR, 1.08; 95% CI, 1.04-1.12; score 3: aHR, 1.09; 95% CI, 1.05-1.14; score 4: aHR, 1.12; 95% CI, 1.06-1.19). Persistent IFG exposure was also associated with higher risks of individual cancer types (colorectum, stomach, pancreas, biliary tract, and esophagus). CONCLUSIONS: Cumulative exposure to IFG is associated with an increased risk of developing gastrointestinal cancer, in a dose-dependent manner. PLAIN LANGUAGE SUMMARY: Hyperglycemia, including both diabetes and prediabetes, has been associated with an increased risk of various cancers. However, the cumulative effect of impaired fasting glucose on the risk of developing gastrointestinal cancer remains unclear. A frequent diagnosis of impaired fasting glucose was dose-dependently associated with a higher risk of developing overall gastrointestinal cancer. Furthermore, risks of individual cancer types increased with persistent impaired fasting glucose. Early detection of hyperglycemia and strict glycemic control can lower the risk of gastrointestinal cancer by reducing hyperglycemic burden. Additionally, for some individuals, lifestyle changes such as managing metabolic syndrome or abstaining from alcohol may also be helpful.

Reduction of Upper Gastrointestinal Bleeding Risk With Proton Pump Inhibitor Therapy in Asian Patients With Atrial Fibrillation Receiving Direct Oral Anticoagulant: A Nationwide Population-based Cohort Study.

BACKGROUND & AIMS: In patients with atrial fibrillation (AF) receiving direct oral anticoagulant (DOAC), upper gastrointestinal bleeding (UGIB) is a serious complication. There are limited data on the benefit of preventive proton pump inhibitor (PPI) use to reduce the risk of UGIB in DOAC users. METHODS: We included patients with AF receiving DOAC from 2015 to 2020 based on the Korean Health Insurance Review and Assessment database. The propensity score (PS) weighting method was used to compare patients with PPI use and those without PPI use. The primary outcome was hospitalization for UGIB. Weighted hazard ratios (HRs) and corresponding 95% confidence intervals (CIs) were evaluated using the Cox proportional hazards regression model. RESULTS: A total of 165,624 patients were included (mean age: 72.2 ± 10.8 years; mean CHA2DS2-VASc score: 4.3 ± 1.8; mean HAS-BLED score: 3.3 ± 1.2). Among them, 99,868 and 65,756 were in the non-PPI group and PPI group, respectively. During a median follow-up of 1.5 years, the PPI group was associated with lower risks of hospitalization for UGIB and UGIB requiring red blood cell transfusion than non-PPI group (weighted HR, 0.825; 95% CI, 0.761-0.894 and 0.798; 95% CI, 0.717-0.887, respectively, both P < .001). The benefits of PPI on the risk of hospitalization for UGIB were greater in those with older age (≥75 years), higher HAS-BLED score (≥3), prior GIB history, and concomitant use of antiplatelet agent (all P-for-interaction < .1). Low-dose PPI was consistently associated with a lower risk of significant UGIB by 43.6-49.3% (P < .001). CONCLUSIONS: In this large Asian cohort of patients with AF on DOAC, PPI co-therapy is beneficial for reducing the risk of hospitalization for UGIB, particularly in high-risk patients.

Association between dental diseases and oral hygiene care and the risk of vertebral fracture: a nationwide cohort study.

Periodontal disease and increased missing teeth were associated with incident vertebral fractures. In contrast, professional dental cleaning and frequent tooth brushing, was associated with a lower risk of vertebral fracture. Better oral hygiene care attenuated the risk associated with dental diseases. PURPOSE: To investigate the association between oral health and the risk of vertebral fractures. METHODS: We included 2,532,253 individuals aged ≥40 years who underwent the Korean National Health Insurance Service health examinations in 2008 and followed up until December 31, 2017. We performed multivariable Cox proportional hazard regression analyses to evaluate the association between dental diseases and oral hygiene care and the risk of vertebral fractures. RESULTS: Over the 9.3-year median follow-up, 1.46% (n = 36,857) experienced vertebral fractures. Individuals with dental diseases had a higher risk of vertebral fracture than those without (hazard ratio [HR] 1.04, 95% confidence interval [CI]: 1.02-1.07 for periodontal diseases; 1.02, 1.00-1.05 for dental caries; 1.12, 1.05-1.20 for ≥15 missing teeth). Good oral hygiene care was associated with a lower vertebral fracture risk (HR 0.89, 95% CI: 0.86-0.91 for ≥1 time/year [vs. <1 time/year] of professional dental cleaning; 0.90, 0.87-0.93 for ≥2 times/day [vs. 0-1 time/day] of toothbrushing). The combined dental diseases was significantly associated with an increased vertebral fracture risk, whereas combined oral hygiene care was associated with further risk reduction. Better oral hygiene care reduced vertebral fracture risk associated with dental diseases (all P <0.001). CONCLUSION: Periodontal disease, dental caries, and an increased number of missing teeth were independently associated with higher risks for vertebral fractures. Conversely, improved oral hygiene care, such as personal dental cleaning and frequent tooth brushing, may modify vertebral fracture risks associated with dental disease.

The crosstalk between PTEN-induced kinase 1-mediated mitophagy and the inflammasome in the pathogenesis of alopecia areata.

Alopecia areata (AA) is a T-cell-mediated autoimmune disease that causes chronic, relapsing hair loss; however, its precise pathogenesis remains to be elucidated. Recent studies have provided compelling evidence of crosstalk between inflammasomes and mitophagy-a process that contributes to the removal of damaged mitochondria. Our previous studies showed that the NLR family pyrin domain containing 3 (NLRP3) inflammasome is important for eliciting and progressing inflammation in AA. In this study, we detected mitochondrial DNA damage in AA-affected scalp tissues and IFNγ and poly(I:C) treated outer root sheath (ORS) cells. In addition, IFNγ and poly(I:C) treatment increased mitochondrial reactive oxygen species (ROS) levels in ORS cells. Moreover, we showed that mitophagy induction alleviates IFNγ and poly(I:C)-induced NLRP3 inflammasome activation in ORS cells. Lastly, PTEN-induced kinase 1 (PINK1) knockdown increased NLRP3 inflammasome activation, indicating that PINK1-mediated mitophagy plays a critical role in NLRP3 inflammasome activation in ORS cells. This study supports previous studies showing that oxidative stress disrupts immune privilege status and promotes autoimmunity in AA. The results emphasize the significance of crosstalk between mitophagy and inflammasomes in the pathogenesis of AA. Finally, mitophagy factors regulating mitochondrial dysfunction and inhibiting inflammasome activation could be novel therapeutic targets for AA.

Comparison of influence of intercalation and substitution of Cu on electrical and thermoelectric transport properties of InSe alloys.

Layered post-transition-metal chalcogenides, such as InSe, In4Se3, SnSe, and SnSe2, have recently been investigated as semiconducting electronic materials and thermoelectric materials owing to their adjustable electrical transport properties either by doping or alloying. Herein, the influence of intercalation doping and substitutional doping of Cu in layered InSe alloys on electrical and thermoelectric transport properties was investigated and compared by synthesizing varied compositions of CuxInSe and In1-yCuySe. It was found that Cu was intercalated in CuxInSe samples (x = 0.01 and 0.02) and behaved as an electron donor, resulting in an increase in the electron concentration and a decrease in the activation energy. Therefore, the power factor of CuxInSe samples was increased compared to that of InSe. In contrast, the substituted Cu in the In site of In1-yCuySe samples (y = 0.01 and 0.02) acted as an acceptor, and the power factor decreased owing to a decrease in the electron concentration and activation energy. Moreover, a decrease in thermal conductivity was seen for CuxInSe and In1-yCuySe samples due to increased phonon scattering after the addition of Cu. Consequently, an enhanced thermoelectric figure of merit (zT) was only observed for intercalated CuxInSe samples due to the increased power factor and decreased thermal conductivity, while substituted In1-yCuySe samples only show degraded zT. A maximum zT value of 0.062 was observed for the CuxInSe (x = 0.02) sample at 700 K, which showed a 77% enhancement compared to that of InSe.

Predicting adequate segmental lordosis correction in lumbar spinal stenosis patients undergoing oblique lumbar interbody fusion: a focus on the discontinuous segment.

PURPOSE: To identify the factors associated with a correction of the segmental angle (SA) with a total change greater than 10° in each level following minimally invasive oblique lumbar interbody fusion (MIS-OLIF). METHODS: Patients with lumbar spinal stenosis who underwent single- or two-level MIS-OLIF were reviewed. Segments with adequate correction of the SA >10° after MIS-OLIF in immediate postoperative radiograph were categorized as discontinuous segments (D segments), whereas those without such improvement were assigned as continuous segments (C segments). Clinical and radiological parameters were compared, and multivariate logistic regression analysis was performed to identify factors associated with SA correction >10° after MIS-OLIF. RESULTS: Of 211 segments included, 38 segments (18.0%) were classified as D segments. Compared with C segments, D segments demonstrated a significantly smaller preoperative SA (mean ± standard deviation [SD], - 1.1° ± 6.7° vs. 6.6° ± 6.3°, p < 0.001), larger change of SA (mean ± SD, 13.5° ± 3.4° vs. 3.1° ± 3.9°, p < 0.001), and a higher rate of presence of facet effusion (76.3% vs. 48.6%, p = 0.002). Logistic regression revealed preoperative SA (odds ratio (OR) [95% confidence interval (CI)]:0.733 [0.639-0.840], p < 0.001) and facet effusion (OR [95% CI]:14.054 [1.758-112.377], p = 0.027) as significant predictors for >10° SA correction after MIS-OLIF. CONCLUSION: Preoperative kyphotic SA and facet effusion can predict SA correction >10° following MIS-OLIF. For patients with lordotic SA and no preoperative facet effusion, supplemental procedures, such as anterior column release or posterior osteotomy, should be prepared for additional lumbar lordosis correction required for remnant global sagittal imbalance after MIS-OLIF.

Multi-Modal Multi-Array Electrochemical and Optical Sensor Suite for a Biological CubeSat Payload.

CubeSats have emerged as cost-effective platforms for biological research in low Earth orbit (LEO). However, they have traditionally been limited to optical absorbance sensors for studying microbial growth. This work has made improvements to the sensing capabilities of these small satellites by incorporating electrochemical ion-selective pH and pNa sensors with optical absorbance sensors to enrich biological experimentation and greatly expand the capabilities of these payloads. We have designed, built, and tested a multi-modal multi-array electrochemical-optical sensor module and its ancillary systems, including a fluidic card and an on-board payload computer with custom firmware. Laboratory tests showed that the module could endure high flow rates (1 mL/min) without leakage, and the 27-well, 81-electrode sensor card accurately detected pH (71.0 mV/pH), sodium ion concentration (75.2 mV/pNa), and absorbance (0.067 AU), with the sensors demonstrating precise linear responses (R2 ≈ 0.99) in various test solutions. The successful development and integration of this technology conclude that CubeSat bio-payloads are now poised for more complex and detailed investigations of biological phenomena in space, marking a significant enhancement of small-satellite research capabilities.

Zeolite application mitigates NH3 and N2O emissions from pig slurry-applied field and improves nitrogen use efficiency in Italian ryegrass-maize crop rotation system for forage production.

The present study aimed to assess the efficiency of zeolite in mitigating the nitrogen (N) losses through ammonia (NH3) and nitrous oxide (N2O) emissions from pig slurry (PS) applied to Italian ryegrass (IRG)-maize fields under a crop rotation system and the consequent effect on nitrogen use efficiency (NUE) for forage production. PS was applied at rates of 150 and 200 kg N ha-1 for the IRG and maize growing seasons, respectively, with or without zeolite. Soil mineral N content and NH3 and N2O emissions were measured periodically throughout the year-round cultivation of IRG and maize. Forage yield and nutritional composition were also analyzed at the harvest time of each crop. The PS with/without zeolite application effects were interpreted by comparison with those obtained for the negative control (no-N fertilization). Soil ammonium (NH4+) content in the PS-applied plots sharply increased within the first week, then progressively decreased in both the IRG and maize growing seasons. Soil NH4+ contents in the zeolite-amended plots were higher compared to the treatment without zeolite except for the first 1 or 2 weeks after PS application when soil nitrate (NO3-) contents significantly decreased. The increase in soil NH4+ content as affected by zeolite application was more distinct in the maize growing season than in the IRG growing season. NH3 emission was predominant at the early 2 weeks after PS application. Zeolite application reduced the cumulative emission of NH3 from PS by 16.7% and 24.4% and that of N2O by 15.6% and 31.5% in the IRG growing and maize growing seasons, respectively. NUE for dry matter (DM) and total digestible nutrients (TDN) production significantly improved in annual yield basis of the IRG-maize cropping. Zeolite application in PS-applied field may represent effective management in mitigating N losses through odorous NH3 and greenhouse gas (N2O) emissions, thereby improving NUE forage production.

Differential response of phenylpropanoid pathway as linked to hormonal change in two Brassica napus cultivars contrasting drought tolerance.

Oilseed rape (Brassica napus L.) is a significant agro-economic crop with a wide range of uses. Drought is the most frequent unfavourable environmental stressor restraining its growth and development worldwide. This study was conducted to characterize the drought-responsive phenylpropanoid pathway and its link to hormonal changes in two cultivars, drought-resistant "Saturnin" and drought-susceptible "Mosa." Drought susceptibility in cv. Mosa was confirmed by its lower water use efficiency and higher lipid peroxidation levels with reactive oxygen species (ROS) accumulation. In cv. Saturnin, higher salicylic acid (SA) levels and expression of dehydration-responsive element binding 2 (DREB2) and non-expressor of pathogenesis-related gene 1 (NPR1) led to an upregulation of production of anthocyanin pigment 1 (PAP1) and phenylpropanoid pathway-related gene (CHS, F5H and COMT1) expression, increasing hydroxycinnamic acid and flavonoid compound concentrations. However, in cv. Mosa, higher increases in the activity of lignifying enzymes (polyphenol oxidase, coniferyl alcohol peroxidase, syringaldazine peroxidase, guaiacol peroxidase) and expression of the lignin synthesis-related gene cinnamyl alcohol dehydrogenase 2 (CAD2) were found along with greater increases in abscisic acid (ABA) levels and upregulation of ABA-responsive element binding 2 (AREB2) and basic helix-loop-helix transcription factor MYC2. These results indicate that drought-induced SA-mediated activation of the hydroxycinnamic acid and flavonoid pathways contributes to drought resistance, whereas ABA-mediated lignification contributes to drought susceptibility.

Maturation of pathogenic biofilms induces enhanced resistance against gaseous chlorine dioxide.

Biofilms are surface-associated microbial clusters embedded in extracellular polymeric substances. Biofilms formed on food-contact surfaces create challenges for the food industry due to their increased tolerance to antimicrobial agents and disinfectants. This study aimed to evaluate the effect of the biofilm maturation period on their resistance to gaseous ClO2. Listeria monocytogenes, Salmonellaserotype Typhimurium, and Escherichia coli O157:H7 biofilms formed on stainless steel (SS) and high-density polyethylene (HDPE) surfaces were investigated. The total cell mass and protein content significantly increased (P < .05) between the second and the fifth day of maturation, and the biofilms' resistance to gaseous ClO2 increased as they matured. Generally, the cell counts of 0-day-old L. monocytogenes, Salm. Typhimurium, and E. coli O157:H7 biofilms on SS and HDPE reduced below the detection limit (0.48 log CFU/cm2) within 5 min. The cell counts of 2-day-old biofilms of the three pathogens were reduced by 6.22 to over 7.52 log, while those of 5-day-old biofilms were reduced by 3.64 to over 6.34 log after 20 min of treatment with 30 ppmv of gaseous ClO2. Therefore, as resistance increases with biofilm maturation, daily gaseous ClO2 treatment would maximize the antimicrobial efficacy of the cleaning strategy against biofilms.

Effect of high-pressure processing on the inactivation of foodborne pathogens in egg salad.

The objectives of this study were to determine the effect of high-pressure processing (HPP) on the survival of Listeria monocytogenes, Salmonella serotype Typhimurium, and Escherichia coli O157:H7 in egg salad and to evaluate the number of sub-lethally injured cells based on treatment conditions. HPP at 500 MPa for 30 s was sufficient for the complete inactivation of L. monocytogenes and Salm. Typhimurium directly plated on selective agar or plated after resuscitation, while 2 min treatment was required for E. coli O157:H7. HPP at 600 MPa for 30 s completely inactivated L. monocytogenes and Salm. Typhimurium, while 1 min treatment was needed for E. coli O157:H7. HPP at 400‒500 MPa injured a large number of pathogenic bacteria. No significant changes (P  > 0.05) in pH and color of egg salad were observed between HPP-treated and non-treated samples during 28 days of storage at refrigerated temperature. Our findings could be useful in predicting the HPP-mediated inactivation patterns of foodborne pathogens in egg salad for practical applications.

Effect of high hydrostatic pressure treatment on the inactivation and sublethal injury of foodborne pathogens and quality of apple puree at different pH.

The objectives of this study were to evaluate the survival of high hydrostatic pressure (HHP)-treated Salmonella Typhimurium, Escherichia coli O157:H7, and Listeria monocytogenes in apple puree, as well as to determine the levels of HHP-induced cell injury according to the pressure level, holding time, and pH of apple puree. Apple puree was inoculated with three foodborne pathogens and treated at pressures of 300-600 MPa for up to 7 min at 22 °C using HHP equipment. Increasing the pressure level and lowering the pH of apple puree led to larger microbial reductions, and E. coli O157:H7 showed higher resistance compared to S. Typhimurium and L. monocytogenes. Besides, approximately 5-log injured cells of E. coli O157:H7 were induced in apple puree at pH 3.5 and 3.8. HHP treatment at 500 MPa for 2 min effectively achieved complete inactivation of the three pathogens in apple puree at pH 3.5. For apple puree at pH 3.8, more than 2 min treatment of HHP at 600 MPa is seemingly needed to achieve complete inactivation of the three pathogens. Transmission electron microscopy analysis was conducted to identify ultrastructural changes in the injured or dead cells after HHP treatment. Plasmolysis and uneven cavities in the cytoplasm were observed in injured cells, and additional deformations, such as distorted and rough cell envelopes, and cell disruption occurred in dead cells. No changes in solid soluble content (SSC) and color of apple puree were observed after HHP treatment, and no differences were detected between control and HHP-treated samples during 10 d of storage at 5 °C. The results of this study could be useful in determining the acidity of apple purees or the treatment time at specific acidity levels when applying the HHP processing.

The Usage of Digital Health Technology Among Older Adults in Hong Kong and the Role of Technology Readiness and eHealth Literacy: Path Analysis.

BACKGROUND: Although digital health technologies (DHTs) help many people maintain a healthy life, including those of advanced age, these technologies are of little use to older adult populations if they are not being adopted in daily life. Thus, it is critical to identify ways to help older adults recognize and try new technologies and maintain their use of them to maximize the benefits of these technologies in a digital-based society. OBJECTIVE: Our study aimed (1) to assess the current usage of DHT among older adults in Hong Kong and (2) to examine how high and low levels of eHealth literacy in this group affects the relationship between the Technology Readiness and Acceptance Model (TRAM) and attitudes and intention toward DHT. METHODS: A total of 306 adults over 60 years of age in Hong Kong participated in this study. After conducting confirmatory factor analysis to validate the measurement model, the hypothesized model was tested using structural equation modeling. RESULTS: Optimism was significantly related to perceived usefulness, while optimism, innovativeness, and discomfort were significantly associated with perceived ease of use. Both perceived usefulness and perceived ease of use were significantly linked to attitude toward the use of DHTs. Meanwhile, attitude significantly predicted usage intention. Additionally, the results revealed the differences in the relationships of the TRAM between participants with high and low levels of eHealth literacy. The influence of optimism and innovativeness on perceived ease of use was stronger for the higher-level group than for the lower-level group, and the influence of discomfort for the higher-level group was much weaker. CONCLUSIONS: The findings provided partial support for the impact of eHealth literacy on encouraging older adults to use DHT and obtain health benefits from it. This study also suggests providing assistance and guidelines for older adults to narrow the aging-related technology gap and to further explore the associations of eHealth literacy, the TRAM, and actual behaviors.

Potential Biomarkers to Distinguish Type 1 Myocardial Infarction in Troponin-Elevated Diseases.

Classifying myocardial infarction by subtype is crucial for appropriate patient management. Although troponin is currently the most commonly used biomarker, it is not a specific marker for myocardial infarction and cannot distinguish subtypes. Furthermore, previous studies have confirmed that proteins known as myocardial infarction markers could function to distinguish the type of myocardial infarction. Therefore, we identify a marker that can distinguish type 1 myocardial infarction from other diseases with elevated troponin. We used mass spectrometry to compare type 1 myocardial infarction with other conditions characterized by troponin elevation and identified new candidate markers for disease classification. We then verified these markers, along with those already known to be associated with cardiovascular disease and plaque rupture. We identified α-1 acid glycoprotein 2, corticosteroid-binding globulin, and serotransferrin as potential distinguishing markers. The presence of these markers and other parameters, such as chest pain, electrocardiogram, and troponin levels from the complementary diagnostic processes, could provide valuable information to specifically diagnose type 1 myocardial infarction.

Young adults with nonalcoholic fatty liver disease, defined using the fatty liver index, can be at increased risk of myocardial infarction or stroke.

AIM: To investigate the relationship between nonalcoholic fatty liver disease (NAFLD) and cardiovascular events among a nationally representative sample of young adults in Korea. METHODS AND RESULTS: This population-based cohort study from the Korean National Health Insurance Service included adults who were aged 20 to 39 years when they underwent a health examination between 2009 and 2012. NAFLD was defined as a fatty liver index (FLI) ≥60, and participants were divided into three groups according to FLI (<30, 30-59 and ≥60) to investigate the dose-dependent effect of FLI score. Among 5 324 410 participants, 9.8% had an FLI ≥60. There were 13 051 myocardial infarctions (MIs; 0.39%) and 8573 strokes (0.26%) during a median follow-up of 8.4 years. In multivariable analysis, NAFLD was associated with a higher risk of MI and stroke (hazard ratio [HR] 1.69, 95% confidence interval [CI] 1.61-1.77 and HR  1.73, 95% CI 1.63-1.84, respectively). MI and stroke had dose-dependent relationships with FLI (HR 1.28 in participants with FLI 30-59 and 1.73 in those with FLI ≥60 for MI and HR 1.18 in participants with FLI 30-59 and 1.41 in those with FLI ≥60 for stroke, respectively). CONCLUSIONS: Nonalcholic fatty liver disease was an independent predictor of MI and stroke in young adults. These results suggest that primary prevention of cardiovascular disease should be emphasized in young adults with NAFLD.

Primary cutaneous malignant melanoma with rhabdomyosarcomatous differentiation originating from a melanocytic nevus in a patient with myelodysplastic syndrome.

Malignant melanoma (MM) may rarely exhibit divergent differentiation, in which melanocytic markers may be lost, leading to difficulty in diagnosis. A 64-year-old man recently diagnosed with myelodysplastic syndrome complained of development of a nodule in a melanocytic nevus on his scalp. On histopathologic examination, junctional nevus nests and diffuse cellular infiltrations with a sheet-like growth pattern of pleomorphic epithelioid cells were observed in the upper dermis. Junctional nevus cells were S-100 positive, and pleomorphic epithelioid cells extending from the junctional nests were weakly positive for S-100. Large polygonal cells with eccentric nuclei and intracytoplasmic hyaline inclusions were observed in the mid to deep dermis. These rhabdomyoblast-like polygonal cells diffusely expressed desmin and were focally positive for MyoD1. Some clusters of polygonal cells in the deep dermis expressed SOX10. Collectively, these clinical and histopathologic features suggested MM with rhabdomyosarcomatous differentiation. Desmin- and skeletal-muscle-specific markers should be applied to melanocytic tumors with atypical epithelioid cells resembling rhabdomyoblasts, especially if these cells are negative for melanocytic markers.

The lexicon for periprosthetic bone loss versus osteolysis after cervical disc arthroplasty: a systematic review.

BACKGROUND: Periprosthetic bone loss is a common observation following arthroplasty. Recognizing and understanding the nature of bone loss is vital as it determines the subsequent performance of the device and the overall outcome. Despite its significance, the term "bone loss" is often misused to describe inflammatory osteolysis, a complication with vastly different clinical outcomes and treatment plans. Therefore, the goal of this review was to report major findings related to vertebral radiographic bone changes around cervical disc replacements, mitigate discrepancies in clinical reports by introducing uniform terminology to the field, and establish a precedence that can be used to identify the important nuances between these distinct complications. METHODS: A systematic review of the literature was conducted following PRISMA guidelines, using the keywords "cervical," "disc replacement," "osteolysis," "bone loss," "radiograph," and "complications." A total of 23 articles met the inclusion criteria with the majority being retrospective or case reports. RESULTS: Fourteen studies reported periprosthetic osteolysis in a total of 46 patients with onset ranging from 15-96 months after the index procedure. Reported causes included: metal hypersensitivity, infection, mechanical failure, and wear debris. Osteolysis was generally progressive and led to reoperation. Nine articles reported non-inflammatory bone loss in 527 patients (52.5%), typically within 3-6 months following implantation. The reported causes included: micromotion, stress shielding, and interrupted blood supply. With one exception, bone loss was reported to be non-progressive and had no effect on clinical outcome measures. CONCLUSIONS: Non-progressive, early onset bone loss is a common finding after CDA and typically does not affect the reported short-term pain scores or lead to early revision. By contrast, osteolysis was less common, presenting more than a year post-operative and often accompanied by additional complications, leading to revision surgery. A greater understanding of the clinical significance is limited by the lack of long-term studies, inconsistent terminology, and infrequent use of histology and explant analyses. Uniform reporting and adoption of consistent terminology can mitigate some of these limitations. Executing these actionable items is critical to assess device performance and the risk of revision. LEVEL OF EVIDENCE IV: Diagnostic: individual cross-sectional studies with consistently applied reference standard and blinding.

The Prognostic Significance of Body Mass Index and Metabolic Parameter Variabilities in Predialysis CKD: A Nationwide Observational Cohort Study.

BACKGROUND: The association between variabilities in body mass index (BMI) or metabolic parameters and prognosis of patients with CKD has rarely been studied. METHODS: In this retrospective observational study on the basis of South Korea's national health screening database, we identified individuals who received ≥3 health screenings, including those with persistent predialysis CKD (eGFR <60 ml/min per 1.73 m2 or dipstick albuminuria ≥1). The study exposure was variability in BMI or metabolic parameters until baseline assessment, calculated as the variation independent of the mean and stratified into quartiles (with Q4 the highest quartile and Q1 the lowest). We used Cox regression adjusted for various clinical characteristics to analyze risks of all-cause mortality and incident myocardial infarction, stroke, and KRT. RESULTS: The study included 84,636 patients with predialysis CKD. Comparing Q4 versus Q1, higher BMI variability was significantly associated with higher risks of all-cause mortality (hazard ratio [HR], 1.66; 95% confidence interval [95% CI], 1.53 to 1.81), P [for trend] <0.001), KRT (HR, 1.20; 95% CI, 1.09 to 1.33; P<0.001), myocardial infarction (HR, 1.19; 95% CI, 1.05 to 1.36, P=0.003), and stroke (HR, 1.19; 95% CI, 1.07 to 1.33, P=0.01). The results were similar in the subgroups divided according to positive or negative trends in BMI during the exposure assessment period. Variabilities in certain metabolic syndrome components (e.g., fasting blood glucose) also were significantly associated with prognosis of patients with predialysis CKD. Those with a higher number of metabolic syndrome components with high variability had a worse prognosis. CONCLUSIONS: Higher variabilities in BMI and certain metabolic syndrome components are significantly associated with a worse prognosis in patients with predialysis CKD.