Utility of epitope-specific IgE, IgG4, and IgG1 antibodies for the diagnosis of wheat allergy.

BACKGROUND: The bead-based epitope assay has been used to identify epitope-specific (es) antibodies and successfully used to diagnose clinical allergy to milk, egg, and peanut. OBJECTIVE: We sought to identify es-IgE, es-IgG4, and es-IgG1 of wheat proteins and determine the optimal peptides to differentiate wheat-allergic from wheat-tolerant using the bead-based epitope assay. METHODS: Children and adolescents who underwent an oral food challenge to confirm their wheat allergy status were enrolled. Seventy-nine peptides from α-/ß-gliadin, γ-gliadin, ω-5-gliadin, and high- and low-molecular-weight glutenin were commercially synthesized and coupled to LumAvidin beads (Luminex Corporation, Austin, Tex). Machine learning methods were used to identify diagnostic epitopes, and performance was evaluated using the DeLong test. RESULTS: The analysis included 122 children (83 wheat-allergic and 39 wheat-tolerant; 57.4% male). Machine learning coupled with simulations identified wheat es-IgE, but not es-IgG4 or es-IgG1, to be the most informative for diagnosing wheat allergy. Higher es-IgE binding intensity correlated with the severity of allergy phenotypes, with wheat anaphylaxis exhibiting the highest es-IgE binding intensity. In contrast, wheat-dependent exercise-induced anaphylaxis showed lower es-IgG1 binding intensity than did all the other groups. A set of 4 informative epitopes from ω-5-gliadin and γ-gliadin were the best predictors of wheat allergy, with an area under the curve of 0.908 (sensitivity, 83.4%; specificity, 88.4%), higher than the performance exhibited by wheat-specific IgE (area under the curve = 0.646; P < .001). The predictive ability of our model was confirmed in an external cohort of 71 patients (29 allergic, 42 nonallergic), with an area under the curve of 0.908 (sensitivity, 75.9%; specificity, 90.5%). CONCLUSIONS: The wheat bead-based epitope assay demonstrated greater diagnostic accuracy compared with existing specific IgE tests for wheat allergy.

Effect of personalized extracorporeal biofeedback device for pelvic floor muscle training on urinary incontinence after robot-assisted radical prostatectomy: A randomized controlled trial.

AIMS: To investigate the effectiveness of a novel personalized extracorporeal biofeedback device (Anykegel) for pelvic floor muscle training (PFMT) on the recovery of postprostatectomy urinary incontinence (PPI) after robot-assisted laparoscopic radical prostatectomy (RARP) through a randomized controlled trial. METHODS: A total of 84 patients who underwent RARP were randomized either to the intervention group (42) (receiving biofeedback-PFMT using a novel device in addition to verbal and written instruction) or to the control group (42). Patients were evaluated 1, 2, and 3 months after surgery. Incontinence severity was measured by the 24-hour pad test. The International Prostate Symptom Score (IPSS) and the International Index of Erectile Function (IIEF-5) questionnaire were also assessed. RESULTS: The intervention group showed a significantly smaller volume of urine loss at the 1-month follow-up than the control group on a 24-hour pad test (71.0 g vs 120.8 g; P = .028). However, from the 2-month follow-up visit, no significant differences were observed between the two groups. In addition, in the 1-month follow-up data of the IPSS-total score, the intervention group demonstrated significantly favorable changes from baseline with improved scores compared to the control group (0.25 ± 9.15 vs -3.81 ± 8.98; P = .046). Regarding the IIEF-5 score changes, no significant differences were reported throughout the study periods. CONCLUSIONS: The personalized extracorporeal biofeedback device for PFMT offers a significant positive effect on the recovery of PPI after RARP, especially in the early postoperative period. Furthermore, patients can be offered more convenience through performing the regular exercise at any place with ease.

Evaluation of caffeine as inhibitor against collagenase, elastase and tyrosinase using in silico and in vitro approach.

Skin ageing results from enhanced activation of intracellular enzymes such as collagenases, elastases and tyrosinase, stimulated by intrinsic ageing and photoageing factors. Recently, caffeine-based cosmetics are introduced that demonstrates to slow down skin photoageing process. However, no attempts have been done so for to understand caffeine functional inhibitory activity against photoageing related enzymes. Hence, this study established the caffeine molecular interaction and inhibition activity profiles against respective enzymes using in silico and in vitro methods, respectively. Results from in silico study indicates that caffeine has comparatively good affinity with collagenase (-4.6 kcal/mol), elastase (-3.36 kcal/mol) and tyrosinase (-2.86 kcal/mol) and formed the stable protein-ligand complex as validated by molecular dynamics simulation (protein-ligand contacts, RMSD, RMSF and secondary structure changes analysis). Moreover, in vitro data showed that caffeine (1000 µg/mL) has statistically significant maximum inhibition activity of 41.86, 36.44 and 13.72% for collagenase, elastase and tyrosinase, respectively.

Arteriovenous graft patency outcomes and prognostic factors.

OBJECTIVES: Arteriovenous graft for hemodialysis shows poorer outcomes than arteriovenous fistula, due to frequent stenosis and thrombosis. We investigated arteriovenous graft patency outcomes and prognostic factors for these outcomes. METHODS: We included a single-center cohort of patients receiving arteriovenous graft for hemodialysis access from 2010 to 2014. Demographics, laboratory data, comorbidities, and medications were collected from medical records. Surgical factors related to graft operation including the type and diameter of connected vessels, graft location, and type of operation (elective or emergency) were also recorded. Outcomes included primary and secondary patency. Survival analysis was conducted using the Kaplan-Meier method; univariate and multivariate analyses were used to evaluate the prognostic factors. RESULTS: Data from 225 grafts were analyzed. During the follow-up period (mean: 583 days, range: 1-1717 days), 138 (61%) grafts required intervention and 46 (20%) permanently failed. Primary patency at one, two, and three years was 42%, 20%, and 16%, respectively. Secondary patency at one, two, and three years was 85%, 72%, and 64%, respectively. Multivariate analysis showed that primary patency was negatively associated with increasing age and location of vessel anastomosis (reference-brachiobrachial anastomosis; brachiobasilic - HR, 0.569; 95% CI, 0.376-0.860; p = 0.007; brachioaxillary anastomosis - HR 0.407; 95% CI, 0.263-0.631; p < 0.0001); secondary patency was positively associated with diastolic blood pressure, serum albumin level, and hemoglobin over 10 g/dL. Adverse events other than stenosis or thrombosis, such as infection/inflammation or pseudoaneurysm were observed in approximately 20% of grafts. CONCLUSIONS: Factors associated with diminished primary arteriovenous graft patency included increased patient age and location of vessel anastomosis (brachiobrachial type compared to brachiobasilic or brachioaxillary type); diminished secondary patency was associated with low diastolic blood pressure, low serum albumin, and hemoglobin level under 10 g/dL. Among these factors, diastolic blood pressure, serum albumin, and hemoglobin level may be modifiable and could improve arteriovenous graft patency outcomes.

Role of Saw1 in Rad1/Rad10 complex assembly at recombination intermediates in budding yeast.

The Saccharomyces cerevisiae Rad1/Rad10 complex is a multifunctional, structure-specific endonuclease that processes UV-induced DNA lesions, recombination intermediates, and inter-strand DNA crosslinks. However, we do not know how Rad1/Rad10 recognizes these structurally distinct target molecules or how it is incorporated into the protein complexes capable of incising divergent substrates. Here, we have determined the order and hierarchy of assembly of the Rad1/Rad10 complex, Saw1, Slx4, and Msh2/Msh3 complex at a 3' tailed recombination intermediate. We found that Saw1 is a structure-specific DNA binding protein with high affinity for splayed arm and 3'-flap DNAs. By physical interaction, Saw1 facilitates targeting of Rad1 at 3' tailed substrates in vivo and in vitro, and enhances 3' tail cleavage by Rad1/Rad10 in a purified system in vitro. Our results allow us to formulate a model of Rad1/Rad10/Saw1 nuclease complex assembly and 3' tail removal in recombination.

DA-1229, a dipeptidyl peptidase IV inhibitor, protects against renal injury by preventing podocyte damage in an animal model of progressive renal injury.

Although dipeptidyl peptidase IV (DPPIV) inhibitors are known to have renoprotective effects, the mechanism underlying these effects has remained elusive. Here we investigated the effects of DA-1229, a novel DPPIV inhibitor, in two animal models of renal injury including db/db mice and the adriamycin nephropathy rodent model of chronic renal disease characterized by podocyte injury. For both models, DA-1229 was administered at 300 mg/kg/day. DPPIV activity in the kidney was significantly higher in diabetic mice compared with their nondiabetic controls. Although DA-1229 did not affect glycemic control or insulin resistance, DA-1229 did improve lipid profiles, albuminuria and renal fibrosis. Moreover, DA-1229 treatment resulted in decreased urinary excretion of nephrin, decreased circulating and kidney DPPIV activity, and decreased macrophage infiltration in the kidney. In adriamycin-treated mice, DPPIV activity in the kidney and urinary nephrin loss were both increased, whereas glucagon-like peptide-1 concentrations were unchanged. Moreover, DA-1229 treatment significantly improved proteinuria, renal fibrosis and inflammation associated with decreased urinary nephrin loss, and kidney DPP4 activity. In cultured podocytes, DA-1229 restored the high glucose/angiotensin II-induced increase of DPPIV activity and preserved the nephrin levels in podocytes. These findings suggest that activation of DPPIV in the kidney has a role in the progression of renal disease, and that DA-1229 may exert its renoprotective effects by preventing podocyte injury.

Designing of the fixed-dose gastroretentive bilayer tablet for sustained release of metformin and immediate release of atorvastatin.

Patients with type 2 diabetes mellitus have a high risk of cardiovascular disease mainly caused by dyslipidemia. Metformin and atorvastatin are preferentially used to treat type 2 diabetes mellitus and dyslipidemia, respectively. The aim of this study was to develop a once-a-day fixed-dose combination tablet containing metformin and atorvastatin. For this purpose, we designed gastroretentive bilayer tablets consisting of 500 mg metformin in a sustained release layer and 10 mg atorvastatin in an immediate release layer. In addition, we modified the formulation to maintain a dual release pattern for the kinetically different layers for once-daily dosing. The gastroretentive bilayer tablet was developed using polyethylene oxide as a swellable polymer and ammonium methacrylate copolymer as a granule-coating polymer with minimal use of excipients. In vitro release patterns of metformin and atorvastatin from the developed formulation were similar to those of the reference drugs, Glucophage XR for metformin and Lipitor for atorvastatin, with satisfactory dissolution similarity factor (f2) values. The pharmacokinetic study showed the sustained and immediate absorptions of metformin and atorvastatin, respectively, in beagle dogs. The 90% confidence intervals of the ratios of ln values of AUCs of test formulation F3 and respective reference formulations of metformin and atorvastatin were 0.93-1.12 and 0.89-1.17, respectively, compared with their respective reference drugs. This formulation could contribute to improving the compliance and therapeutic outcome of patients with metabolic diseases.

Ventral posterolateral deep brain stimulation treatment for neuropathic pain shortens pain response after cold stimuli.

Neuropathic pain is often severe. Deep brain stimulation (DBS) is a treatment method for neuropathic pain, but its mechanism of action remains unclear. Patients with neuropathic pain are affected by various stimulations, such as mechanical and cold stimuli, but studies of cold allodynia showed the associated pain to be less than that caused by mechanical stimuli. This study focused on the effects of DBS on cold allodynia in rats. To observe the effects of DBS, we established three groups: a normal group (normal), a neuropathic pain group (pain), and a DBS with neuropathic pain group (DBS). The stimulation target was the ventral posterolateral nucleus (VPL). We observed differences in the degree of cold allodynia elicited between a conventional method that measured the number of pain responses and our altered novel method that measured the duration of pain responses. Cold allodynia after DBS did not differ when conventional analysis was applied, but the pain response duration was decreased. We suggest that VPL DBS was partially effective in cold allodynia, implicating complex pathways of pain signaling.

Home-Based Remote Rehabilitation Leads to Superior Outcomes for Older Women With Knee Osteoarthritis: A Randomized Controlled Trial.

OBJECTIVES: To examine the effects of a home-based lower-extremity strengthening exercise program in community-dwelling older women with knee osteoarthritis. DESIGN: Randomized controlled trial. SETTING AND PARTICIPANTS: Women aged ≥60 years with knee osteoarthritis and Kellgren-Lawrence grade 1 or 2 on anteroposterior/lateral radiographs of both knee joints. METHODS: Patients (n = 36) were randomly divided into experimental (EG) and control (CG) groups. The EG performed home-based remote rehabilitation lower-extremity strengthening exercises for 8 weeks, whereas the CG received no intervention. Assessment was performed at baseline and week 8. The primary outcome was the five-times sit-to-stand test (FTSST) result. Secondary outcomes included timed up-and-go (TUG) test results, knee extensor and flexor strength, quadriceps (rectus femoris) muscle activity, skeletal muscle index, blood pressure (BP), visual analog scale (VAS) scores, C-reactive protein level, and erythrocyte sedimentation rate. RESULTS: A statistically significant difference in the FTSST times was observed between the groups after 8 weeks of intervention (EG: 7.95 ± 1.08 seconds, CG: 10.01 ± 2.03 seconds, P < .001). In the EG, the TUG test score decreased by 0.75 ± 0.80 seconds (P = .002), right and left knee flexor strength increased by 4.69 ± 6.05 kg (P = .007) and 3.98 ± 6.98 kg (P = .038), respectively, and the right knee extensor root mean square (RMS) ratio increased by 1.24 ± 0.39 (P = .027). Additionally, systolic and diastolic BP decreased by 9.50 ± 10.75 mm Hg (P = .005) and 4.25 ± 4.91 mm Hg (P = .003), respectively. In the CG, the VAS scores decreased by 9.10 ± 13.68 mm (P = .022). CONCLUSIONS AND IMPLICATIONS: The home-based exercise program using a remote rehabilitation medical device was effective in improving lower extremity strength and function in community-dwelling older women with knee osteoarthritis. This finding suggests that the remote rehabilitation medical device may be used as an alternative to exercise interventions for patients with knee osteoarthritis.

Identification, structural, and biochemical characterization of a group of large Csn2 proteins involved in CRISPR-mediated bacterial immunity.

Many prokaryotic organisms acquire immunity against foreign genetic material by incorporating a short segment of foreign DNA called spacer into chromosomal loci, termed clustered regularly interspaced short palindromic repeats (CRISPRs). The encoded RNAs are processed into small fragments that guide the silencing of the invading genetic elements. The CRISPR-associated (Cas) proteins are the main executioners of these processes. Herein, we report the crystal structure of Stu0660 of Streptococcus thermophilus, a Cas protein involved in the acquisition of new spacers. By homotetramerization, Stu0660 forms a central channel which is decorated with basic amino acids and binds linear double-stranded DNA (dsDNA), but not circular dsDNA. Despite undetectably low sequence similarity, two N-terminal domains of Stu0660 are similar to the entire structure of an Enterococcus faecalis Csn2 protein, which also forms a homotetramer and binds dsDNA. Thus, this work identifies a previously unknown group of Stu0660-like Csn2 proteins (∼350 residues), which are larger than the known canonical Csn2 proteins (∼220 residues) by containing an extra C-terminal domain. The commonly present central channel in the two subgroups appears as a design to selectively interact with linear dsDNA.

The Effect of Convergence Gamification Training in Community-Dwelling Older People: A Multicenter, Randomized Controlled Trial.

OBJECTIVES: It is necessary to improve the health of older adults through exercise, but there is no concrete way to implement it or an environment in which they can exercise continuously. Our objective was to confirm the safety and efficacy of information technology (IT) convergence gamification exercise equipment for older adults. We tried to demonstrate equivalence to conventional exercise by comparing the functional improvement. DESIGN: Randomized controlled trial, with 8-week-long IT convergence exercises 3 times a week vs conventional exercise. SETTING AND PARTICIPANTS: 40 community-dwelling participants aged 60-85 years. METHOD: Participants were randomly divided into a conventional exercise group (group 1) and an IT convergence exercise group (group 2). Both groups were trained for 8 weeks, and functional assessment was performed before training (pre-evaluation), after training, and after 4 weeks of rest. RESULTS: There were functional improvements in both groups. A comparison of the differences in the functional assessment between pre-evaluation and after 8 weeks of training yielded the following results. In group 1, the mean Five Times Sit to Stand Test-30 seconds was scored as 3.60 ± 2.56 (P < .015); Five Times Sit to Stand Test-5 times, -1.75 ± 2.04 s (P < .015); Berg Balance Scale, 1.05 ± 1.39 (P < .015); Timed Up-and-Go test, -0.64 ± 0.64 s (P < .015); and 10-m Walking Test, -0.35 ± 0.47 s (P < .015). And in group 2, the mean Five Times Sit to Stand Test-30 seconds (s) was scored as 3.70 ± 2.62 (P < .015), Five Times Sit to Stand Test-5 times, -1.65 ± 1.59 s (P < .015); Berg Balance Scale, 1.05 ± 1.00 (P < .015); Timed Up-and-Go test, -0.93 ± 0.68 s (P < .015); 10-m Walking Test, -0.41 ± 0.489 s (P < .015); Chair Sit and Reach test, 2.23 ± 3.19 cm (P < .015); and Korean version of the Falls Efficacy Scale-International, -1.05 ± 1.43 (P < .015). CONCLUSION AND IMPLICATIONS: The results of this study suggest that the IT convergence gamification exercise equipment such as balpro110 has exercise effects similar to conventional exercise and also has advantages as an alternative to exercise for older adults in the next generation.

Effects of RETN polymorphisms on treatment response in rheumatoid arthritis patients receiving TNF-α inhibitors and utilization of machine-learning algorithms.

This study was designed to investigate the effects of polymorphisms in RETN on remission in RA patients receiving TNF-α inhibitors. In addition, machine learning algorithms were trained to predict remission. Ten single-nucleotide polymorphisms were investigated. Univariate and multivariable analyses were performed to evaluate associations between genetic polymorphisms and the efficacy of TNF-α inhibitors. A random forest-based classification approach was used to assess the importance of different variables associated with the efficacy of TNF-α inhibitors. Various machine learning methods were used for finding vital factors and prediction of remission. The eight most significant features included in the multivariable analysis were sex, age, hypertension, sulfasalazine, rs1862513, rs3219178, rs3219177, and rs3745369. T-allele carriers of rs3219177 and males showed approximately 6.0- and 3.6-fold higher remission rates compared to those with the CC genotype and females, respectively. The elastic net algorithm was the best machine-learning method for predicting remission of patients with RA treated with TNF-α inhibitors. On the basis of the results of this study, it may be possible to design individually tailored treatment regimens to predict the efficacy of TNF-α inhibitors.

Incidence, risk factors, and prediction of acute kidney injury after off-pump coronary artery bypass grafting.

BACKGROUND: Acute kidney injury (AKI) is a serious complication after coronary artery bypass grafting and is closely associated with high mortality. The objective of the present study was to identify the incidence and risk factors for AKI after off-pump coronary artery bypass grafting (OPCAB) and to construct a risk model for prediction of AKI after OPCAB. METHODS: We retrospectively studied 448 adult patients who underwent isolated OPCAB between April 2006 and July 2007. AKI was defined as an increase in serum creatinine of 0.3 mg/dL or 50% within 48 h after surgery. Multivariate analysis was used to evaluate risk factors for AKI after OPCAB and a risk model was developed with a weighted score based on the odds ratio. RESULTS: The incidence of AKI was 7.6% (n = 34). Most patients (97%) had mild AKI. Independent preoperative risk factors of postoperative AKI were identified as high systolic blood pressure, decreased glomerular filtration rate, and coronary angiography (CAG) less than 7 days prior to OPCAB. The incidence of AKI across each increasing score level increased from 2.2% to 60%. CONCLUSION: AKI after OPCAB was common. High systolic blood pressure, renal dysfunction, and CAG less than 7 days prior to cardiac surgery were associated with AKI after OPCAB. Our risk model may provide information to clinicians and patients about the risk of postoperative AKI.

A Critical Appraisal: Development and Use of Perceived Stress Scale in U.S. Immigrants.

Few studies have critically appraised Perceived Stress Scale (PSS) in immigrants. The purpose of the article is to determine if PSS is adequately developed and properly used with U.S. immigrants. Searching via PubMed and PsycINFO databases resulted in 10 research papers published between 2009 and 2019 that met the selection criteria and were integrated for this review. Most of the studies do not have adequate theoretical models and do not have proper consideration of socio-cultural factors. Five studies used the PSS translated into different languages but only one study validated the translated version. Six studies reported the reliability of the PSS. The PSS-14 and PSS-10 may be appropriately used in immigrants to measure psychological stress. Some issues, such as the PSS's reliability and validity, need to be addressed in future use in immigrants.

Inosine 5'-Monophosphate to Raise Serum Uric Acid Level in Multiple System Atrophy (IMPROVE-MSA study).

The aim of this trial was to investigate the safety, tolerability, and capability of serum uric acid (UA) elevation of inosine 5'-monophosphate (IMP) in multiple system atrophy (MSA). The IMPROVE-MSA trial was a randomized, double-blind, placebo-controlled trial in patients with MSA with no history of hyperuricemia-related disorders. The participants were assigned to placebo (n = 25) or IMP (n = 30) in a 1 to 1 ratio, and then followed up for 24 weeks. The primary end points included safety, tolerability, and alteration of the serum UA level during the follow-up period. The secondary end points were changes in scores of the unified MSA rating scale (UMSARS) and the Mini-Mental Status Examination (MMSE) and Montreal Cognitive Assessment (MoCA). The total number of adverse events (AEs) and serious AEs was comparable between the active and placebo groups. Serum UA level (mg/dL) was significantly increased from baseline (active vs. placebo, 4.57 vs. 4.58; P = 0.98) to study end point (6.96 vs. 4.43; P < 0.001) in the active group compared with the placebo group (time × group interaction; P < 0.001). The change in UMSARS scores did not differ between the active and placebo groups. However, the active group showed better alterations in MoCA scores with nominal significance (P < 0.001) and tendency for better alterations in MMSE scores (P = 0.09) than the placebo group. Our data demonstrated that IMP treatment was generally safe and well-tolerated in patients with MSA. A further trial with a long-term follow-up is required to examine whether UA elevation will slow clinical progression in early MSA.

Interactions between polystyrene particles with diameters of several tens to hundreds of micrometers at the oil-water interface.

HYPOTHESIS: The charged spherical colloidal particles at the fluid-fluid interface experience considerably strong and long-ranged electrostatic and capillary interactions. The contribution of capillary force becomes more significant as the particle size increases beyond a certain limit. The relative strengths of the two competing interactions between the spherical polystyrene particles at the oil-water interface are quantified depending on their size. EXPERIMENTS: The studied particles, obtained using the microfluidic method, have diameters of tens to hundreds of micrometers. The scaling behaviors of the commercially available colloidal particles with diameters of ~3 µm are also compared. An optical laser tweezer apparatus is used to directly or indirectly measure the interparticle force. Subsequently, the capillary force that can be attributed to the gravity-induced interface deformation and contact line undulation is calculated and compared with the measured interaction force. FINDINGS: Regardless of the particle diameter (~3-330 µm), the measured force is observed to decay as r-4, where r denotes the center-to-center separation, demonstrating that the dipolar electrostatic interaction is important and that the gravity-induced capillary interaction is negligible. Furthermore, numerical calculations with respect to the undulated meniscus confirm that the magnitude of capillary interaction is significantly smaller than that of the measured electrostatic interaction.

Correction of Internal Astigmatism Using Toric Scleral Contact Lens after Implantable Collamer Lens Surgery

Purpose@#We present a case of internal astigmatism correction using a toric scleral contact lens in a patient with high myopia after implantable collamer lens (ICL) surgery.Case summary: A 45-year-old man presented with a significant decrease in visual acuity despite previous ICL surgery. Initial attempts to fit a corneal rigid gas permeable contact lens to the left eye were unsuccessful due to fitting challenges. Subsequently, the use of a spherical scleral contact lens effectively corrected corneal astigmatism but failed to address internal astigmatism, thereby limiting improvement in visual acuity. Postoperative corneal ectasia and ICL rotation were suspected to be the underlying causes of this astigmatism. The introduction of a front toric scleral lens resulted in a significant improvement in visual acuity and sustained comfort throughout the 3-month follow-up period. @*Conclusions@#The use of toric scleral lenses can significantly improve visual acuity and provide exceptional comfort in cases where corneal morphology and lens position change after ICL surgery. This modality presents a promising alternative for future consideration.

Cytokines, Vascular Endothelial Growth Factors, and PlGF in Autoimmunity:Insights From Rheumatoid Arthritis to Multiple Sclerosis

In this review, we will explore the intricate roles of cytokines and vascular endothelial growth factors in autoimmune diseases (ADs), with a particular focus on rheumatoid arthritis (RA) and multiple sclerosis (MS). AD is characterized by self-destructive immune responses due to auto-reactive T lymphocytes and Abs. Among various types of ADs, RA and MS possess inflammation as a central role but in different sites of the patients. Other common aspects among these two ADs are their chronicity and relapsing-remitting symptoms requiring continuous management. First factor inducing these ADs are cytokines, such as IL-6, TNF-α, and IL-17, which play significant roles in the pathogenesis by contributing to inflammation, immune cell activation, and tissue damage. Secondly, vascular endothelial growth factors, including VEGF and angiopoietins, are crucial in promoting angiogenesis and inflammation in these two ADs. Finally, placental growth factor (PlGF), an emerging factor with bi-directional roles in angiogenesis and T cell differentiation, as we introduce as an "angio-lymphokine" is another key factor in ADs. Thus, while angiogenesis recruits more inflammatory cells into the peripheral sites, cytokines secreted by effector cells play critical roles in the pathogenesis of ADs. Various therapeutic interventions targeting these soluble molecules have shown promise in managing autoimmune pathogenic conditions. However, delicate interplay between cytokines, angiogenic factors, and PlGF has more to be studied when considering their complementary role in actual pathogenic conditions. Understanding the complex interactions among these factors provides valuable insights for the development of innovative therapies for RA and MS, offering hope for improved patient outcomes.

Intake of energy and macronutrients according to household income among elementary, middle, and high school students before and during the COVID-19 pandemic: a cross-sectional study / 대한지역사회영양학회지

Objectives@#This study examined the intake of energy and macronutrients among elementary, middle, and high school students according to household income before the COVID-19 pandemic (2016–2019), during the social distancing period (2020–2021), and after the social distancing measures were lifted (2022). @*Methods@#We included 5,217 students aged 5–18 from the Korea National Health and Nutrition Examination Survey (KNHANES) conducted between 2016 and 2022. Dietary intake was assessed using one-day 24-hour dietary recalls. We estimated the least squares means (LS-means) of intake according to household income for each period using a weighted linear regression model, adjusted for age and sex. Differences in LS-means between the periods were analyzed using the t-test. @*Results@#During the social distancing period, the LS-means of energy intake among students decreased significantly by 143.2 kcal/day compared to pre-pandemic levels (P < 0.001). Students from low-income households experienced a more pronounced decrease in energy intake (−379.1 kcal/day, P < 0.001) and macronutrient intake compared to those from other income groups. Energy intake at school significantly declined for all income groups during the social distancing period compared to before the pandemic. No significant changes in home energy intake were observed among low-income students, whereas there was an increase for students from higher-income groups. Before the pandemic, 8.5% of students from low-income households reported insufficient food due to economic difficulties; this figure rose to 21.3% during the pandemic. @*Conclusions@#During the pandemic, students from low-income families experienced significantly lower intake of energy and macronutrients compared to pre-pandemic levels.The most substantial reductions were noted among low-income students, largely due to the lack of compensation for decreased school-based intake with increased intake at home.

Positive Predictive Values of Abnormality Scores From a Commercial Artificial Intelligence-Based Computer-Aided Diagnosis for Mammography

Objective@#Artificial intelligence-based computer-aided diagnosis (AI-CAD) is increasingly used in mammography. While the continuous scores of AI-CAD have been related to malignancy risk, the understanding of how to interpret and apply these scores remains limited. We investigated the positive predictive values (PPVs) of the abnormality scores generated by a deep learning-based commercial AI-CAD system and analyzed them in relation to clinical and radiological findings. @*Materials and Methods@#From March 2020 to May 2022, 656 breasts from 599 women (mean age 52.6 ± 11.5 years, including 0.6% [4/599] high-risk women) who underwent mammography and received positive AI-CAD results (Lunit Insight MMG, abnormality score ≥ 10) were retrospectively included in this study. Univariable and multivariable analyses were performed to evaluate the associations between the AI-CAD abnormality scores and clinical and radiological factors. The breasts were subdivided according to the abnormality scores into groups 1 (10–49), 2 (50–69), 3 (70–89), and 4 (90–100) using the optimal binning method. The PPVs were calculated for all breasts and subgroups. @*Results@#Diagnostic indications and positive imaging findings by radiologists were associated with higher abnormality scores in the multivariable regression analysis. The overall PPV of AI-CAD was 32.5% (213/656) for all breasts, including 213 breast cancers, 129 breasts with benign biopsy results, and 314 breasts with benign outcomes in the follow-up or diagnostic studies. In the screening mammography subgroup, the PPVs were 18.6% (58/312) overall and 5.1% (12/235), 29.0% (9/31), 57.9% (11/19), and 96.3% (26/27) for score groups 1, 2, 3, and 4, respectively. The PPVs were significantly higher in women with diagnostic indications (45.1% [155/344]), palpability (51.9% [149/287]), fatty breasts (61.2% [60/98]), and certain imaging findings (masses with or without calcifications and distortion). @*Conclusion@#PPV increased with increasing AI-CAD abnormality scores. The PPVs of AI-CAD satisfied the acceptable PPV range according to Breast Imaging-Reporting and Data System for screening mammography and were higher for diagnostic mammography.