Single missense mutations in Vi capsule synthesis genes confer hypervirulence to Salmonella Typhi.

Many bacterial pathogens, including the human exclusive pathogen Salmonella Typhi, express capsular polysaccharides as a crucial virulence factor. Here, through S. Typhi whole genome sequence analyses and functional studies, we found a list of single point mutations that make S. Typhi hypervirulent. We discovered a single point mutation in the Vi biosynthesis enzymes that control Vi polymerization or acetylation is enough to result in different capsule variants of S. Typhi. All variant strains are pathogenic, but the hyper Vi capsule variants are particularly hypervirulent, as demonstrated by the high morbidity and mortality rates observed in infected mice. The hypo Vi capsule variants have primarily been identified in Africa, whereas the hyper Vi capsule variants are distributed worldwide. Collectively, these studies increase awareness about the existence of different capsule variants of S. Typhi, establish a solid foundation for numerous future studies on S. Typhi capsule variants, and offer valuable insights into strategies to combat capsulated bacteria.

Exploring Disease Resistance in Pepper (Capsicum spp.) Germplasm Collection Using Fluidigm SNP Genotyping.

This study utilized a diverse Capsicum accessions (5658) sourced from various species and geographical regions, deposited at the National Agrobiodiversity Center, Genebank. We employed 19 SNP markers through a Fluidigm genotyping system and screened these accessions against eight prevalent diseases of pepper. This study revealed accessions resistant to individual diseases as well as those exhibiting resistance to multiple diseases, including bacterial spot, anthracnose, powdery mildew, phytophthora root rot, and potyvirus. The C. chacoense accessions were identified as resistant materials against bacterial spot, anthracnose, powdery mildew, and phytophthora root rot, underscoring the robust natural defense mechanisms inherent in the wild Capsicum species and its potential uses as sources of resistance for breeding. C. baccatum species also demonstrated to be a promising source of resistance to major pepper diseases. Generally, disease-resistant germplasm has been identified from various Capsicum species. Originating from diverse locations such as Argentina, Bolivia, and the United Kingdom, these accessions consistently demonstrated resistance, indicating the widespread prevalence of disease-resistant traits across varied environments. Additionally, we selected ten pepper accessions based on their resistance to multiple diseases, including CMV, Phytophthora root rot, potyviruses, and TSWV, sourced from diverse geographical regions like Hungary, Peru, the United States, and the Netherlands. This comprehensive analysis provides valuable insights into disease resistance in Capsicum, crucial for fostering sustainable agricultural practices and advancing crop improvement through breeding strategies.

Nitric oxide releasing nanofiber stimulates revascularization in response to ischemia via cGMP-dependent protein kinase.

Nitric oxide (NO) promotes angiogenesis via various mechanisms; however, the effective transmission of NO in ischemic diseases is unclear. Herein, we tested whether NO-releasing nanofibers modulate therapeutic angiogenesis in an animal hindlimb ischemia model. Male wild-type C57BL/6 mice with surgically-induced hindlimb ischemia were treated with NO-releasing 3-methylaminopropyltrimethoxysilane (MAP3)-derived or control (i.e., non-NO-releasing) nanofibers, by applying them to the wound for 20 min, three times every two days. The amount of NO from the nanofiber into tissues was assessed by NO fluorometric assay. The activity of cGMP-dependent protein kinase (PKG) was determined by western blot analysis. Perfusion ratios were measured 2, 4, and 14 days after inducing ischemia using laser doppler imaging. On day 4, Immunohistochemistry (IHC) with F4/80 and gelatin zymography were performed. IHC with CD31 was performed on day 14. To determine the angiogenic potential of NO-releasing nanofibers, aorta-ring explants were treated with MAP3 or control fiber for 20 min, and the sprout lengths were examined after 6 days. As per either LDPI (Laser doppler perfusion image) ratio or CD31 capillary density measurement, angiogenesis in the ischemic hindlimb was improved in the MAP3 nanofiber group; further, the total nitrate/nitrite concentration in the adduct muscle increased. The number of macrophage infiltrations and matrix metalloproteinase-9 (MMP-9) activity decreased. Vasodilator-stimulated phosphoprotein (VASP), one of the major substrates for PKG, increased phosphorylation in the MAP3 group. MAP3 nanofiber or NO donor SNAP (s-nitroso-n-acetyl penicillamine)-treated aortic explants showed enhanced sprouting in an ex vivo aortic ring assay, which was partially abrogated by KT5823, a potent inhibitor of PKG. These findings suggest that the novel NO-releasing nanofiber, MAP3 activates PKG and promotes therapeutic angiogenesis in response to hindlimb ischemia.

Age-related effects of Mycoplasma pneumoniae infection and subsequent asthma exacerbation in children.

BACKGROUND: Mycoplasma pneumoniae causes community-acquired pneumonia in children and increases asthma risk, but large studies are lacking. OBJECTIVE: To assess the link between M. pneumoniae infection and to asthma exacerbation, in children with allergies, and age of infection impact. METHODS: This retrospective cohort study analyzed medical records of South Korean children between January 2002 and December 2017. The study's exposure was hospitalization with an M. pneumoniae-related diagnosis, and the outcome was defined as asthma exacerbation, confirmed by hospitalization at least 6 months after M. pneumoniae infection, with alternative validation using asthma diagnosis and systemic steroid prescription records. Hazard ratios (HRs) for asthma exacerbation risk were estimated for the matched cohort using a Cox proportional hazards model stratified by allergic comorbidities. Time-dependent covariates and age-stratified exposure groups were used to calculate odds ratios. RESULTS: The study included 84,074 children with M. pneumoniae infection and 336,296 unexposed children. Follow-up for 12.2 ± 2.3 years found the exposed group had a significant risk of asthma exacerbation (HR 2.86, 95% confidence interval [CI] 2.67-3.06) regardless of allergic comorbidities. The risk was highest (over threefold) in children infected between 24 and 71 months. Sensitivity analysis using an alternative definition of the outcome showed an HR of 1.38 (95% CI 1.35-1.42), further supporting the association between M. pneumoniae infection and asthma exacerbation. CONCLUSION: M. pneumoniae infection was significantly associated with an increased risk of subsequent asthma exacerbation regardless of allergic comorbidities. Further research needed for understanding and confirmation.

Distribution and pathogen prevalence of field-collected ticks from south-western Korea: a study from 2019 to 2022.

Hard ticks are known vectors of various pathogens, including the severe fever with thrombocytopenia syndrome virus, Rickettsia spp., Coxiella burnetii, Borrelia spp., Anaplasma phagocytophilum, and Ehrlichia spp. This study aims to investigate the distribution and prevalence of tick-borne pathogens in southwestern Korea from 2019 to 2022. A total of 13,280 ticks were collected during the study period, with H. longicornis accounting for 86.1% of the collected ticks. H. flava, I. nipponensis and A. testudinarium comprised 9.4%, 3.6%, and 0.8% of the ticks, respectively. Among 983 pools tested, Rickettsia spp. (216 pools, 1.6% MIR) were the most prevalent pathogens across all tick species, with R. japonica and R. monacensis frequently detected in I. nipponensis and Haemaphysalis spp., respectively. Borrelia spp. (28 pools, 0.2% MIR) were predominantly detected in I. nipponensis (27 pools, 13.8% MIR, P < 0.001). Co-infections, mainly involving Rickettsia monacensis and Borrelia afzelii, were detected in I. nipponensis. Notably, this study identified R. monacensis for the first time in A. testudinarium in South Korea. These findings offer valuable insights into the tick population and associated pathogens in the region, underscoring the importance of tick-borne disease surveillance and prevention measures.

Sn(IV)porphyrin-Incorporated TiO2 Nanotubes for Visible Light-Active Photocatalysis.

In this study, two distinct photocatalysts, namely tin(IV)porphyrin-sensitized titanium dioxide nanotubes (SnP-TNTs) and titanium dioxide nanofibers (TNFs), were synthesized and characterized using various spectroscopic techniques. SnP-TNTs were formed through the hydrothermal reaction of NaOH with TiO2 (P-25) nanospheres in the presence of Sn(IV)porphyrin (SnP), resulting in a transformation into Sn(IV)porphyrin-imbedded nanotubes. In contrast, under similar reaction conditions but in the absence of SnP, TiO2 (P-25) nanospheres evolved into nanofibers (TNFs). Comparative analysis revealed that SnP-TNTs exhibited a remarkable enhancement in the visible light photodegradation of model pollutants compared to SnP, TiO2 (P-25), or TNFs. The superior photodegradation activity of SnP-TNTs was primarily attributed to synergistic effects between TiO2 (P-25) and SnP, leading to altered conformational frameworks, increased surface area, enhanced thermo-chemical stability, unique morphology, and outstanding visible light photodegradation of cationic methylene blue dye (MB dye). With a rapid removal rate of 95% within 100 min (rate constant = 0.0277 min-1), SnP-TNTs demonstrated excellent dye degradation capacity, high reusability, and low catalyst loading, positioning them as more efficient than conventional catalysts. This report introduces a novel direction for porphyrin-incorporated catalytic systems, holding significance for future applications in environmental remediation.

Rat Pharmacokinetics and In Vitro Metabolite Identification of KM-819, a Parkinson's Disease Candidate, Using LC-MS/MS and LC-HRMS.

FAF1 (FAS-associated factor 1) is involved in the activation of Fas cell surface death receptors and plays a role in apoptosis and necrosis. In patients with Parkinson's disease, FAF1 is overexpressed in dopaminergic neurons in the substantia nigra. KM-819, an FAF1 inhibitor, has shown potential for preventing dopaminergic neuronal cell death, promoting the degradation of α-synuclein and preventing its accumulation. This study aimed to develop and validate a quantitative analytical method for determining KM-819 levels in rat plasma using liquid chromatography-tandem mass spectrometry. This method was then applied to pharmacokinetic (PK) studies in rats. The metabolic stability of KM-819 was assessed in rat, dog, and human hepatocytes. In vitro metabolite identification and metabolic pathways were investigated in rat, dog, and human hepatocytes. The structural analog of KM-819, namely N-[1-(4-bromobenzyl)-3,5-dimethyl-1H-pyrazol-4-yl]-2-(phenylsulfanyl) acetamide, served as the internal standard (IS). Proteins were precipitated from plasma samples using acetonitrile. Analysis was carried out using a reverse-phase C18 column with a mobile phase consisting of 0.1% formic acid in distilled water and 0.1% formic acid in acetonitrile. The analytical method developed for KM-819 exhibited linearity within the concentration range of 0.002-10 µg/mL in rat plasma. The precision and accuracy of the intra- and inter-day measurements were <15% for the lower limit of quantification (LLOQ) and all quality control samples. KM-819 demonstrated stability under various sample storage conditions (6 h at room temperature (25 °C), four weeks at -20 °C, three freeze-thaw cycles, and pretreated samples in the autosampler). The matrix effect and dilution integrity met the criteria set by the Food and Drug Administration and the European Medicines Agency. This sensitive, rapid, and reliable analytical method was successfully applied in pharmacokinetic studies in rats. Pharmacokinetic analysis revealed the dose-independent kinetics of KM-819 at 0.5-5 mg/kg, with a moderate oral bioavailability of ~20% in rats. The metabolic stability of KM-819 was also found to be moderate in rat, dog, and human hepatocytes. Metabolite identification in rat, dog, and human hepatocytes resulted in the discovery of six, six, and eight metabolites, respectively. Glucuronidation and mono-oxidation have been proposed as the major metabolic pathways. Overall, these findings contribute to a better understanding of the pharmacokinetic characteristics of KM-819, thereby aiding future clinical studies.

Determinants of wearer satisfaction factors for harnesses in upper-limb assistive wearable robots.

Wearable robots are increasingly being deployed for use in industrial fields. However, only a few studies have focused on the usability of wearable robots. The present study evaluated the factors affecting the usability of a harness in securing a wearable robot to the body because the harness directly affects the work efficiency, and thus its design and use require careful consideration. A comparative evaluation of the arrangement of the Vest Exoskeleton before and after improvements was conducted, in which participants performed a benchmark assembly task while wearing the robot. Results showed that wearability decreased after the improvements due to the additional straps and buckles used, but the overall wearing satisfaction improved as a result of increased stability. Stability and convenience were the main factors affecting the overall wearing satisfaction, while sub-indicators included wearing comfort and tactile sensation. Therefore, improvements in stability, such as those related to fixation strength and tactile sensation, had a direct positive impact on the overall wearing satisfaction.

Automatic Segmentation and Radiologic Measurement of Distal Radius Fractures Using Deep Learning.

Background: Recently, deep learning techniques have been used in medical imaging studies. We present an algorithm that measures radiologic parameters of distal radius fractures using a deep learning technique and compares the predicted parameters with those measured by an orthopedic hand surgeon. Methods: We collected anteroposterior (AP) and lateral X-ray images of 634 wrists in 624 patients with distal radius fractures treated conservatively with a follow-up of at least 2 months. We allocated 507 AP and 507 lateral images to the training set (80% of the images were used to train the model, and 20% were utilized for validation) and 127 AP and 127 lateral images to the test set. The margins of the radius and ulna were annotated for ground truth, and the scaphoid in the lateral views was annotated in the box configuration to determine the volar side of the images. Radius segmentation was performed using attention U-Net, and the volar/dorsal side was identified using a detection and classification model based on RetinaNet. The proposed algorithm measures the radial inclination, dorsal or volar tilt, and radial height by index axes and points from the segmented radius and ulna. Results: The segmentation model for the radius exhibited an accuracy of 99.98% and a Dice similarity coefficient (DSC) of 98.07% for AP images, and an accuracy of 99.75% and a DSC of 94.84% for lateral images. The segmentation model for the ulna showed an accuracy of 99.84% and a DSC of 96.48%. Based on the comparison of the radial inclinations measured by the algorithm and the manual method, the Pearson correlation coefficient was 0.952, and the intraclass correlation coefficient was 0.975. For dorsal/volar tilt, the correlation coefficient was 0.940, and the intraclass correlation coefficient was 0.968. For radial height, it was 0.768 and 0.868, respectively. Conclusions: The deep learning-based algorithm demonstrated excellent segmentation of the distal radius and ulna in AP and lateral radiographs of the wrist with distal radius fractures and afforded automatic measurements of radiologic parameters.

Investigation of periodontitis, halitosis, xerostomia, and serological characteristics of patients with osteoarthritis and rheumatoid arthritis and identification of new biomarkers.

Rheumatoid arthritis (RA) and osteoarthritis (OA) are two different types of arthritis. Within RA, the subsets between seronegative RA (snRA) and seropositive RA (spRA) represent distinct disease entities; however, identifying clear distinguishing markers between them remains a challenge. This study investigated and compared the oral health conditions in patients with RA and OA to clarify the differences from healthy controls. In addition, we investigated the serological characteristics of the patients, the factors that distinguished patients with RA from those with OA, and the main factors that differentiated between snRA and spRA patients. A total of 161 participants (mean age: 52.52 ± 14.57 years, 32 males and 129 females) were enrolled in this study and categorized as: normal (n = 33), OA (n = 31), and RA (n = 97). Patients with RA were divided into the following two subtypes: snRA (n = 18) and spRA (n = 79). Demographics, oral health, and serological characteristics of these patients were compared. The prevalence of periodontal diseases was significantly higher in patients with OA (100%) and RA (92.8%) than in healthy controls (0.0%). However, the presence of periodontal diseases was not utilized as a distinguishing factor between OA and RA. Xerostomia occurred more frequently in patients with RA (84.5%) than in patients with OA (3.2%) and healthy controls (0.0%) (all p < 0.001). ROC analysis revealed that periodontal disease was a very strong predictor in the diagnosis of OA compared to healthy controls, with an AUC value of 1.00 (p < 0.001). Additionally, halitosis (AUC = 0.746, 95% CI 0.621-0.871, p < 0.001) and female sex (AUC = 0.663, 95% CI 0.529-0.797, p < 0.05) were also significant predictors of OA. The strongest predictors of RA diagnosis compared to healthy controls were periodontal diseases (AUC = 0.964), followed by xerostomia (AUC = 0.923), age (AUC = 0.923), female sex (AUC = 0.660), and halitosis (AUC = 0.615) (all p < 0.05). Significant serological predictors of RA were anti-CCP Ab (AUC = 0.808), and RF (AUC = 0.746) (all p < 0.05). In multiple logistic regression analysis, xerostomia (odds ratio, OR: 8124.88, 95% CI 10.37-6368261.97, p-value = 0.008) and Anti-CCP Ab (OR: 671.33, 95% CI 2.18-207,074.02, p = 0.026) were significant predictors for RA compared to OA. When diagnosing spRA compared to snRA, anti-CCP Ab (AUC = 1.000, p < 0.001) and RF (AUC = 0.910, 95%CI 0.854-0.967, p < 0.001) had outstanding predictive performances. Therefore, clinicians and researchers should thoroughly evaluate the oral status of both OA and RA patients, alongside serological factors, and consider these elements as potential predictors.

Unraveling the Role of Ras Homolog Enriched in Brain (Rheb1 and Rheb2): Bridging Neuronal Dynamics and Cancer Pathogenesis through Mechanistic Target of Rapamycin Signaling.

Ras homolog enriched in brain (Rheb1 and Rheb2), small GTPases, play a crucial role in regulating neuronal activity and have gained attention for their implications in cancer development, particularly in breast cancer. This study delves into the intricate connection between the multifaceted functions of Rheb1 in neurons and cancer, with a specific focus on the mTOR pathway. It aims to elucidate Rheb1's involvement in pivotal cellular processes such as proliferation, apoptosis resistance, migration, invasion, metastasis, and inflammatory responses while acknowledging that Rheb2 has not been extensively studied. Despite the recognized associations, a comprehensive understanding of the intricate interplay between Rheb1 and Rheb2 and their roles in both nerve and cancer remains elusive. This review consolidates current knowledge regarding the impact of Rheb1 on cancer hallmarks and explores the potential of Rheb1 as a therapeutic target in cancer treatment. It emphasizes the necessity for a deeper comprehension of the molecular mechanisms underlying Rheb1-mediated oncogenic processes, underscoring the existing gaps in our understanding. Additionally, the review highlights the exploration of Rheb1 inhibitors as a promising avenue for cancer therapy. By shedding light on the complicated roles between Rheb1/Rheb2 and cancer, this study provides valuable insights to the scientific community. These insights are instrumental in guiding the identification of novel targets and advancing the development of effective therapeutic strategies for treating cancer.

Oral bacteria may affect conjunctival microorganisms in brachycephalic dogs: a preliminary study.

OBJECTIVE: To evaluate the prevalence of oral bacteria in the conjunctiva of brachycephalic and nonbrachycephalic dogs. ANIMALS: 12 brachycephalic (9.58 ± 3.55 years) and 12 nonbrachycephalic (8.33 ± 4.92 years) dogs without systemic disease, regardless of breed and sex, were included in the study, and half of the dogs in each group had periodontitis. METHODS: This prospective study investigated clinical data including craniofacial ratio, ophthalmic examination results, and periodontal status of the included dogs. Bacterial samples were collected by swabbing the oral mucosa and conjunctival surfaces. The presence and quantity of bacteria were analyzed by matrix-assisted laser desorption/ionization time-of-flight mass spectrometry, 16S rRNA sequencing analysis, and the 10-fold dilution method. Statistical analyses were performed to assess correlations and factors influencing the presence of oral bacteria in the conjunctiva. RESULTS: The most common bacteria in the conjunctival flora in both groups were Micrococcus luteus, Corynebacterium spp, and Staphylococcus spp. The prevalence of oral bacteria on the conjunctival surface was 33%, with a significantly higher incidence in brachycephalic dogs (P = .027). Oral bacteria detected in the conjunctiva were predominantly Frederiksenia canicola, Neisseria spp, and Moraxella spp. Multiple regression analysis identified age, craniofacial ratio, and gingival index as factors influencing the presence of oral bacteria in the conjunctival flora. CLINICAL RELEVANCE: Oral resident bacteria have often been isolated from severe infectious corneal ulcers. This study provided evidence that brachycephalic dogs may require dental prophylaxis to reduce their oral bacterial load and that the association of oral bacteria in ocular diseases should be considered.

Antimicrobial properties of tomato juice and peptides against typhoidal Salmonella.

Tomatoes are readily available and affordable vegetables that offer a range of health benefits due to their bioactive molecules, such as antioxidants and antimicrobials. In contrast to the widely recognized antioxidant properties of tomatoes, their antimicrobial properties remain largely unexplored. Here, we present our findings on the antimicrobial properties of tomato juice and peptides, namely, tomato-derived antimicrobial peptides (tdAMPs), in relation to their effectiveness against typhoidal Salmonella. Our research has revealed that tomato juice demonstrates significant antimicrobial properties against Salmonella Typhi, a pathogen that specifically affects humans and is responsible for causing typhoid fever. By employing computational analysis of the tomato genome sequence, conducting molecular dynamics simulation, and performing functional analyses, we have successfully identified two tdAMPs, namely, tdAMP-1 and tdAMP-2. These tdAMPs have demonstrated potent antimicrobial properties by effectively disrupting bacterial membranes. The efficacy of tdAMP-2 is shown to be more effective than tdAMP-1. The efficacy of tdAMP-1 and tdAMP-2 has been demonstrated against drug-resistant S. Typhi, as well as hyper-capsular S. Typhi variants that possess hypervirulent characteristics, which are presently circulating in countries with endemicity. Tomato juice, along with the two tdAMPs, has demonstrated effectiveness against uropathogenic Escherichia coli as well. This underscores their potential as viable agents in combating certain Gram-negative pathogens. This study provides valuable insights into the development of effective and sustainable public health strategies that utilize tomato and its derivatives as lifestyle interventions.IMPORTANCEIn this study, we investigate the antimicrobial properties of tomato juice, the most widely consumed affordable vegetables, as well as tomato-derived antimicrobial peptides, in relation to their effectiveness against foodborne pathogens with an emphasis on Salmonella Typhi, a deadly human-specific pathogen.

Unraveling the link between atopic dermatitis and autoimmune diseases in children: Insights from a large-scale cohort study with 15-year follow-up and shared gene ontology analysis.

BACKGROUND: Atopic dermatitis and autoimmune diseases are highly heritable conditions that may co-occur from an early age. METHODS: The primary study is a national administrative cohort study involving 499,428 children born in 2002, tracked until 2017. Atopic dermatitis was defined as five or more principal diagnoses of atopic dermatitis and two or more topical steroid prescriptions. We estimated the risks for the occurrence of 41 autoimmune diseases, controlling for risk factors. In addition, we sourced a gene library from the National Library of Medicine to conduct a comprehensive gene ontology. We used Gene Weaver to identify gene set similarity and clustering, and used GeneMania to generate a network for shared genes. RESULTS: Exposed and unexposed groups included 39,832 and 159,328 children, respectively. During a mean follow-up of 12 years, the exposed group had an increased risk of autoimmune disease (hazard ratio, 1.27 [95 % confidence interval, 1.23-1.32]) compared to the unexposed group. The hazard ratios of autoimmune illnesses consistently increased with two- and five years lag times and alternative atopic dermatitis definitions. Shared genes between atopic dermatitis and autoimmune diseases were associated with comorbidities such as asthma, bronchiolitis, and specific infections. Genetic interactions of these shared genes revealed clustering in Th1, Th2, Th17, and non-classifiable pathways. CONCLUSIONS: Atopic dermatitis was significantly associated with an increased risk of subsequent autoimmune disease. we identified the genetically associated disease in atopic dermatitis patients comorbid with autoimmune disease and demonstrated a genetic network between atopic dermatitis and autoimmune diseases.

Single missense mutations in Vi capsule synthesis genes confer hypervirulence to Salmonella Typhi.

Many bacterial pathogens, including the human exclusive pathogen Salmonella Typhi, express capsular polysaccharides as a crucial virulence factor. Here, through S. Typhi whole genome sequence analyses and functional studies, we found a list of single point mutations that make S . Typhi hypervirulent. We discovered a single point mutation in the Vi biosynthesis enzymes that control the length or acetylation of Vi is enough to create different capsule variants of S. Typhi. All variant strains are pathogenic, but the hyper-capsule variants are particularly hypervirulent, as demonstrated by the high morbidity and mortality rates observed in infected mice. The hypo-capsule variants have primarily been identified in Africa, whereas the hyper-capsule variants are distributed worldwide. Collectively, these studies increase awareness about the existence of different capsule variants of S. Typhi, establish a solid foundation for numerous future studies on S. Typhi capsule variants, and offer valuable insights into strategies to combat capsulated bacteria.

Determination of pepsin in human saliva using pepsin-susceptible peptide reporter and colorimetric dipstick assay: a prospective, cross-sectional study.

A simple and effective pepsin detection assay is reported based on a pepsin-susceptible peptide (PSP) reporter degradation strategy. PSP, which can be specifically cleaved by pepsin, was modified with fluorescein isothiocyanate (FITC) and biotin at the N- and C-terminals to be used as a reporter for colorimetric detection of dipsticks. A universal lateral flow dipstick consisting of a streptavidin test line for biotin binding and a sample pad immobilized with a gold-labeled polyclonal (rabbit) anti-FITC antibody was used to verify PSP-based pepsin detection. When the PSP reporter reacts with pepsin in a tube, it cleaves into two fragments, and the cleaved fragments do not display any color on the test line. Therefore, the higher the concentration of pepsin is, the greater is the decrease in test line intensity (IT-line) and the higher is the control line intensity (IC-line). First, the PSP cleavage and dipstick assay conditions for pepsin detection was optimized. The ratio of color intensity (IT-line/IC-line) of PSP-based dipstick assay showed a linear relationship with log concentration of pepsin ranging between 4 and 500 ng/mL (R2 = 0.98, n = 6), with a limit of detection of 1.4 ng/mL. It also exhibited high specificity and good reproducibility. Finally, pepsin levels were quantified in saliva samples from healthy controls (n = 34) and patients with laryngopharyngeal reflux (LPR, n = 61). Salivary pepsin levels were higher in patients with LPR than in healthy controls. The salivary pepsin levels correlated with those measured using a conventional enzyme-linked immunosorbent assay kit. Therefore, this PSP-based dipstick assay is a convenient tool for assessing salivary pepsin levels.

Advanced Light: Liquid Crystals-Based Ultra-Broadband Polarization Rotator for Functional Smart Devices.

A novel ultra-broadband polarization rotator with advanced angular adjustability is proposed for functional devices such as displays and smart windows. The new solution offers dynamic control of light polarization across a broad range of wavelengths, encompassing the complete visible spectrum, ultraviolet and near-infrared. Moreover, it boasts a smaller footprint, faster response times, and lower dispersion compared to conventional rotators. The findings are remarkable in that they show that as the viewing angle increases, the hybrid alignment takes on a twist-like configuration, with the polarization rotation angle determined by the spatial variation in the twist angle. This intriguing behavior leads to an improved range of angular adjustability, as the effective polarization rotation depth is extended. The improved angular adjustability of reconfigurable smart devices surpasses the limitations of traditional polarization rotators, unlocking new innovative possibilities. For example, the rotator plays a crucial role in display technologies, allowing for effective control of viewing angles and minimizing reflection from disturbing external light. Similarly, in smart windows, it optimizes energy conservation by regulating direct sunlight transmission while ensuring clear visibility in normal conditions. It is believed that the proposed advanced ultra-broadband polarization rotator is a significant step forward in the development of reconfigurable smart devices.

Cascade of atopic dermatitis comorbidities in children after birth for 15 years.

BACKGROUND: Individuals with atopic dermatitis often develop other conditions. OBJECTIVE: This study aimed to determine how atopic dermatitis comorbidities develop in children over time. METHODS: This population-based administrative cohort study used national health insurance data. We traced individuals born in Korea between 2002 and 2003 to 2018. The date of initial atopic dermatitis diagnosis was set as the index date. Fifty-three childhood comorbidities of atopic dermatitis were identified as outcomes of interest by performing a comprehensive literature search and comparing the prevalence of diagnostic codes in children with and without atopic dermatitis. Four control children per individual in the atopic dermatitis group were randomly matched based on sex and index date. The association between atopic dermatitis and the development of each specified disease was assessed using proportional hazard assumption, followed by mapping of the temporal sequences of interconnected comorbidities. RESULTS: The atopic dermatitis and control groups contained 67,632 and 270,528 individuals, respectively. The median age at the index date was 10 months, whereas the median follow-up period was 15 years. Twenty diseases that were associated with a higher risk of atopic dermatitis were identified and a chain of interconnected conditions created. The progression began in childhood with febrile seizures, constipation, and asthma, and was later associated with the emergence of food allergy, allergic rhinitis, psychiatric disorders, and autoimmune diseases. CONCLUSION: Our study highlights the temporal nature of atopic dermatitis comorbidities in children, and indicates that an understanding of the comorbidities may inform its clinical management and treatment.

Fracture gap and working length are important actionable factors affecting bone union after minimally invasive plate osteosynthesis for the treatment of simple diaphyseal or distal metaphyseal tibia fractures.

INTRODUCTION: Indirect reduction of minimally invasive plate osteosynthesis (MIPO) can often result in delayed union in tibia fractures. This study evaluated several factors in MIPO in relation to bone union. HYPOTHESIS: We hypothesized that the fracture gap, plate - tibia distance, or working length would have a substantial effect on the tibia union rate. MATERIALS AND METHODS: Forty-one patients with simple diaphyseal or distal metaphyseal tibia fractures who underwent internal fixation surgery using the MIPO technique were divided into two groups: patients with delayed union and patients without delayed union. Non-actionable factors involving AO/OTA classification, fibula fracture and actionable factors including postoperative fracture gap, plate - tibia distance, working length in relation to parameters of bone union were compared between the two groups. Also cumulative rates of bone union and risk factors of delayed union according to variables of interest were investigated. RESULTS: AO/OTA classification, site of fibula fracture, postoperative fracture gap, working length, and bone union rate of the two groups significantly differed (p<0.05). The cumulative rate of bone union during 1-year follow-up according to 43A tibia fracture, distal fibula fracture, fracture gap, and working length significantly differed between the two groups (p<0.05). By univariate Cox proportional hazards model, 43A tibia fracture, distal fibula fracture, facture gap, and short working length were risk factors for delayed union (p<0.05). DISCUSSION: Non-actionable factors involving AO/OTA classification, distal fibula fracture and actionable factors including postoperative fracture gap, working length were significant factors affecting bone union after MIPO. The present study indicated that small fracture gap and long working length during MIPO might facilitate bone healing in tibia fracture. LEVEL OF EVIDENCE: IV; single-center retrospective cohort study.