[Lights and Shadows of Lecanemab: Post-diagnosis Support for People with Dementia Receiving Early Diagnosis].

The advent of lecanemab is a hope not only for people with dementia and their families but also for society as a whole. However, the effectiveness of lecanemab is limited, and the need to inform patients of their dementia may emphasize negative aspects more than ever as "early diagnosis leads to early despair." In this situation, it is important to provide post-diagnostic support to make the "time spent living with dementia," which is prolonged by lecanemab, as meaningful as possible. In this review, the authors introduce the "Peer Support Activities for people with mild dementia and their families," a post-diagnosis support program for those diagnosed early in the course of the disease.

[Prevalence of diabetic retinopathy assessed using two-field mydriatic fundus photography]. / Otsenka rasprostranennosti diabeticheskoi retinopatii s pomoshch'yu dvukhpol'nogo midriaticheskogo fundus-fotografirovaniya.

Early detection of diabetic retinopathy (DR) is an urgent ophthalmological problem in Russia and globally. PURPOSE: This study assesses the prevalence of asymptomatic retinopathy and attempts to identify risk groups for its development in patients with type 1 and 2 diabetes mellitus (T1DM and T2DM). MATERIAL AND METHODS: The study involved clinics from 5 cities in the Russian Federation and it included 367 patients with DM, 34.88% men and 65.12% women, aged 50.88±20.55 years. 34.88% of patients suffered from T1DM, 65.12% suffered from T2DM, the average duration of the disease was 9.02±7.22 years. 58.31% of patients had a history of arterial hypertension, 13.08% had a history of smoking. The primary endpoint was the frequency of detection of diabetic changes in the eye fundus of patients with T1DM and T2DM in general; the secondary endpoint - same but separately, and for T2DM patients depending on the duration of the disease. The exploratory endpoint was the assessment of the influence of various factors on the development of DR. The patients underwent visometry (modified ETDRS table), biomicroscopy, mydriatic fundus photography according to the «2 fields¼ protocol. RESULTS: The average detection rate of DR was 12.26%, primarily observed in patients with T2DM (13.81%), women (9.26%), in both eyes (8.17%). Among patients with DR, 26 (19.55%) had glycated hemoglobin (HbA1c) level exceeding 7.5% (p=0.002), indicating a direct relationship between this indicator and the incidence of DR. Logistic regression analysis showed that the duration of diabetes of more than 10 years has a statistically significant effect on the development of DR. In the modified model for odds estimation, the likelihood of developing DR is increased by the duration of DM for more than 10 years; increased blood pressure; HbA1c level >7.5%. CONCLUSION: The obtained results, some of which will be presented in subsequent publications, highlight the effectiveness of using two-field mydriatic fundus photography as a screening for DR.

Early detection of perinatal depression in couples: a single-center prospective study.

OBJECTIVE: This prospective study aimed to assess couples' psychological status during the perinatal period to identify those at risk for postpartum depression. METHODS: Conducted at Lyon University Hospital from March to July 2022, the study enrolled pregnant women without progressive psychiatric disorders or obstetric risk factors, and their partners. Participants completed the Edinburgh Postnatal Depression Scale (EPDS) at three points: during the 9th month of pregnancy, immediate postpartum, and 6-8 weeks after delivery. A score ≥10 on the EPDS indicated depression risk. A score ≥10 on the EPDS indicate depression risk. The primary endpoint was EPDS scores throughout the perinatal period. RESULTS: Ninety-five couples participated; 96% of patients and 68% of partners completed pre-delivery questionnaires, 81% and 71% during maternity stay, and 64% and 46% postpartum, respectively. Overall, 15% of patients and 1% of partners had EPDS scores >10 in the postpartum period. Psychiatric history and emergency cesarean sections were associated with higher immediate postpartum EPDS scores in patients [Beta 3.7 points, 95% CI 0.91; 6.4 and Beta 5.2 points, 2.2; 8.1, respectively]. Episiotomy was associated with higher EPDS scores in partners. No significant association between the different factors studied and the EPDS score was found at 6-8 weeks postpartum in patients nor their partners. CONCLUSIONS: While specific risk factors for persistent perinatal depression in couples were not identified, a notable proportion of patients exhibited high EPDS scores. Screening all couples during prepartum and postpartum periods is crucial, regardless of identified risk factors.

The assessment of structural and functional test results for early detection of hydroxychloroquine macular toxicity.

PURPOSE: To assess structural (optical coherence tomography, fundus autofluorescence) and functional (contrast sensitivity and visual field) test results which were used for detecting early retinal changes in patients using oral hydroxychloroquine. METHODS: Patients using oral hydroxychloroquine for at least one year were divided into two groups according to the duration of drug use. Groups 1 and 2 consisted of patients with drug use for more than 5 years and 1-5 years, respectively. The drug-using groups were compared with the control group. The mean retinal nerve fiber layer (RNFL), central macular thickness (CMT), ganglion cell-inner plexiform layer (GC-IPL), static 10-2 visual field, fundus autofluorescence (FAF) imaging, and contrast sensitivity tests were performed and statistically compared between groups. RESULTS: Median and temporal quadrant RNFL thicknesses were found to be statistically significantly lower in the drug groups. In the drug groups, the GC-IPL sectoral and mean thicknesses were found to be statistically lower in all quadrants. Central macular thickness was also found to be similar in all three groups. There was no significant difference between the groups in visual field parameters. Macular FAF images were significantly higher in the drug users, but there was no significant difference between the three groups in foveal FAF images. Contrast sensitivity measurements were significantly lower in the drug groups than in the control group at all spatial frequencies except 6 and 18 cycles/degree. CONCLUSIONS: The combined use of structural and functional tests in patients using hydroxychloroquine provides useful information in detecting early retinal changes.

[Research progress on the application of artificial intelligence in the early diagnosis and treatment of burn diseases].

Artificial intelligence (AI) technology is advancing rapidly, constantly presenting its application value and broad prospects in the medical field. Especially in the early intervention of burn diseases, the new developments, applications, and challenges of AI technology have a significant impact on the clinical outcomes of burn patients. Based on this, this article reviews the concept, classification, learning style, and application of AI in the early diagnosis and treatment of burn diseases, with a focus on discussing the challenges and suggestions of the application of AI technology in the medical field, in order to provide reference and suggestions for the better application of AI in the early diagnosis and treatment of burn diseases.

Global data monitoring systems and early identification for kidney diseases.

BACKGROUND: Data monitoring and surveillance systems are the cornerstone for governance and regulation, planning, and policy development for chronic disease care. Our study aims to evaluate health systems capacity for data monitoring and surveillance for kidney care. METHODS: We leveraged data from the third iteration of the International Society of Nephrology Global Kidney Health Atlas (ISN-GKHA), an international survey of stakeholders (clinicians, policymakers and patient advocates) from 167 countries conducted between July and September 2022. ISN-GKHA contains data on availability and types of kidney registries, the spectrum of their coverage, as well as data on national policies for kidney disease identification. RESULTS: Overall, 167 countries responded to the survey, representing 97.4% of the global population. Information systems in forms of registries for dialysis care were available in 63% (n = 102/162) of countries, followed by kidney transplant registries (58%; n = 94/162), and registries for non-dialysis chronic kidney disease (19%; n = 31/162) and acute kidney injury (9%; n = 14/162). Participation in dialysis registries was mandatory in 57% (n = 58) of countries; however, in more than half of countries in Africa (58%; n = 7), Eastern and Central Europe (67%; n = 10), and South Asia (100%; n = 2), participation was voluntary. The least-reported performance measures in dialysis registries were hospitalization (36%; n = 37) and quality of life (24%; n = 24). CONCLUSIONS: The variability of health information systems and early identification systems for kidney disease across countries and world regions warrants a global framework for prioritizing the development of these systems.

Early screening for chronic liver disease: impact of a FIB-4 first integrated care pathway to identify patients with significant fibrosis.

Liver fibrosis is often undetected whereas it is the determinant of liver-related mortality. We evaluate a pathway based on the systematic calculation of FIB-4 to screen for advanced hepatic fibrosis. Systematic calculation of FIB-4 was implemented in the centralized laboratory of a French University Hospital in 4 pilot departments. If ≥ 2.67, the FIB-4 result was returned to the prescribers, for patients between 18 and 70 years of age, with an incentive to measure liver stiffness by vibration controlled transient elastography. During a 2-years period, a FIB-4 was calculated in 2963 patients and 135 were ≥ 2.67 (4.6%). After exclusion of patients with a known cause of elevated FIB-4, 47 patients (34.8%) were eligible for elastography. Forty patients underwent elastography, but only 15% (7/47) at the spontaneous request of the referring physician. Fifteen patients were identified with significant fibrosis, among which 8 attended the scheduled specialist consultation, all with a confirmed diagnosis of cirrhosis. A sequential pathway based on the systematic calculation of FIB-4 enables the identification of patients with significant unknown liver fibrosis, allowing to refer them to specialized care. Raising awareness is essential to improve the care pathway.

Predictors of Mothers Living with HIV Uptake of HIV Early Infant Diagnosis Services in Iringa District, Tanzania.

BACKGROUND: Uptake of HIV early infant diagnosis (HEID) among HIV-exposed infants is the key to timely initiation of Antiretroviral Treatment (ART). However, despite the availability of HEID services in Tanzania, its uptake is low. We aimed to determine predictors of mothers living with HIV' with HIV-exposed infants' uptake of HEID services in Iringa District, Tanzania. METHODS: A health facility-based cross-sectional study was conducted in Iringa District from May to June 2023. Mothers with HIV-exposed infants were recruited in the study through a multistage sampling technique and interviewed using pre-tested structured questions. Logistic regression analysis was employed to determine potential predictors of HEID uptake. RESULTS: A total of 309 mothers with HIV-exposed infants participated in the study. About 78.3% of the HIV-exposed infants had initial DNA PCR for HEID within 6 weeks of age and 86.1% within 8 weeks. Most mothers had high perceived benefits on uptake of HEID with a mean score of 4.3, high perceived self-efficacy with a mean score of 3.8 and 2.7 perceived risk of HIV infection on their HIV-exposed infants on the 5 scale Likert scale with 5 showing the highest perceived benefit, self-efficacy and risk. High perceived self-efficacy and being a businesswoman were the predictors of uptake of HEID. The odds of self-efficacy on the uptake of HEID by 2.4 times (aOR 2.4 95% CI 1.6-3.2) within 6 weeks of age and 1.9 (aOR 1.9 95% CI 1.3-2.7) within 8 weeks. The odds of being a businesswoman were 0.4 for 6 weeks and 0.3 for 8 weeks (aOR 0.4 95% CI 0.2-0.8) and (aOR 0.3 95% CI 0.1-0.8) respectively. CONCLUSION: Over three-quarters of the HIV-exposed infants had initial DNA PCR for HEID testing as recommended. Perceived self-efficacy was the main factor influencing HEID uptake. These findings highlight the need for strengthening HIV-positive mother's self-efficacy for improved uptake of HEID services.

Predictors of mothers living with HIV' uptake of HIV early infant diagnosis services in Iringa District, TanzaniaThis study aimed to find out the factors associated with the uptake of HIV early infant diagnosis (HEID) services among mothers living with HIV in Iringa District, Tanzania. The uptake of HEID in Tanzania is still below the 95% national and global target of ending AIDS as a public health by 2030 We employed a cross-sectional study design and collected data from May to June 2023 to determine predictors of mothers with HIV-exposed infants' uptake of HEID in Iringa District, Tanzania. The analysis was done by descriptive statistics and logistic regression analysis. A total of 309 mothers with HIV-exposed infants participated in the study. About 78.3% of the HIV-exposed infants had initial DNA PCR for HEID within 6 weeks of age and 86.1% within 8 weeks. Most mothers had high perceived benefits on uptake of HEID with a mean score of 4.3, high perceived self-efficacy with a mean score of 3.8 and 2.7 perceived risk of HIV infection on their HIV-exposed infants. High perceived self-efficacy was positively associated These findings highlight the need for strengthening HIV-positive mother's self-efficacy for improved uptake of HEID services.

Ultrasound as a tool for the diagnosis of spondylarthritis in women.

OBJECTIVE: The journey to a diagnosis of spondyloarthritis (SpA) can be difficult for women, who often experience delays in receiving the correct diagnosis as their symptoms are frequently misinterpreted due to other conditions like osteoarthritis, fibromyalgia, or other psychosomatic disorders. The purpose of this article is to examine the challenges in the diagnosis of SpA in women and the possible role of musculoskeletal ultrasound in early diagnosis and in avoiding misdiagnosis. METHODS: We have performed a narrative review of the currently available literature on the subject. RESULTS: The complexity of diagnosing SpA in women is compounded by the misconception that the disease predominantly affects men. To facilitate early diagnosis and prevent misdiagnosis, it is crucial not to overlook gender differences in the clinical presentation of SpA. Since women have more peripheral and enthesitic involvement, performing an ultrasound of entheses, tendons, and joints in women with musculoskeletal symptoms that could refer to SpA may help both in the early and differential diagnosis. CONCLUSIONS: There is a need to increase awareness among physicians of the existence of a different clinical presentation of SpA between men and women. The use of musculoskeletal ultrasound, which allows the detection of even subclinical inflammation and structural damage since early disease at the level of joints, tendons, and entheses can help make an early diagnosis and avoid misdiagnosis. Early diagnosis and timely treatment of SpA are crucial to reducing irreversible damage.

ERCC1 which affects lipids metabolism and actin dynamics in coal workers' pneumoconiosis is a candidate biomarker for early warning and diagnosis.

The single-nucleotide polymorphisms of genes related to DNA damage repair and inflammasomes and mutated gene expression in coal workers' pneumoconiosis (CWP) were analysed to identify the risk factors of CWP and potential biomarkers for early warning and diagnosis. Further, mutated gene pathways were analysed based on proteome and metabolome. Han Chinese male subjects were randomly selected and divided into 4 or 5 groups according to the process of CWP. MassARRAY was used to sequence single-nucleotide polymorphism genotypes. Mutated gene expression in plasma was tested using enzyme-linked immunosorbent assay (ELISA). Odds ratios (ORs) and receiver operating characteristic curves (ROC) were calculated. The serum different proteins and metabolites were identified by Ultra Performance Liquid Chromatography Quadrupole time of flight/Mass Spectrum (UPLC-Q-TOF/MS) and analysed using bioinformation software. As CWP progressed, the CC and CA genotypes of ERCC1 rs3212986 decreased and increased significantly, respectively. AA (OR = 3.016) and CA (OR = 2.130) genotypes were identified as risk factors for stage II. ERCC1 significantly decreased in processing of CWP. The cutoff value of ERCC1 was 5.265 pg/ml, with a sensitivity of 90.0% and specificity of 86.7%. ERCC1 had an indirect interaction with activator protein-1 and insulin and its pathways were mainly made with molecules related to lipid metabolism and actin dynamics. ERCC1 is a candidate biomarker for detection and precise intervention in CWP. If it reaches the threshold, workers will change other jobs in time and will not develop and diagnose as pneumoconiosis and will help the employers spend less money. Meanwhile, the signal molecules of ERCC1 pathway could be as a candidate target for drug discovery.

[Early identification of acute kidney injury in children with primary nephrotic syndrome]. / å„¿ç«¥åŽŸå‘æ€§è‚¾ç— ç»¼åˆå¾å¹¶å‘æ€¥æ€§è‚¾æŸä¼¤çš„æ—©æœŸè¯†åˆ«.

OBJECTIVES: To investigate the incidence and risk factors for acute kidney injury (AKI) in children with primary nephrotic syndrome (PNS), as well as the role of neutrophil gelatinase-associated lipocalin (NGAL) and kidney injury molecule-1 (KIM-1) in the early identification of AKI in these children. METHODS: A prospective collection of clinical data from children hospitalized with PNS at the Children's Hospital of the Capital Institute of Pediatrics from January 2021 to October 2022 was conducted. The children were divided into two groups based on the presence of AKI: the AKI group (47 cases) and the non-AKI group (169 cases). The risk factors for AKI in children with PNS were identified by multivariate logistic regression analysis. Urinary KIM-1 and NGAL levels were compared between the AKI and non-AKI groups, as well as among the different stages of AKI. RESULTS: The incidence of AKI in children with PNS was 21.8%. Multivariate logistic regression analysis revealed that steroid-resistant nephrotic syndrome, gastrointestinal infections, and heavy proteinuria were independent risk factors for AKI in these children with PNS (P<0.05). Urinary KIM-1 and NGAL levels were higher in the AKI group compared to the non-AKI group (P<0.05), and the urinary NGAL and KIM-1 levels in the AKI stage 2 and stage 3 subgroups were higher than those in the AKI stage 1 subgroup (P<0.017). CONCLUSIONS: KIM-1 and NGAL can serve as biomarkers for the early diagnosis of AKI in children with PNS. Identifying high-risk populations for AKI in children with PNS and strengthening the monitoring of related risk factors is of significant importance.

Motor unit number index in Bell's palsy: A potential electrophysiological biomarker for early evaluation.

INTRODUCTION: Reliable, noninvasive early diagnostics of neuromuscular function in Bell's palsy, which causes facial paralysis and reduced quality of life, remain to be established. Here, we aimed to evaluate the utility of the motor unit number index (MUNIX) for the quantitative electrophysiological assessment of early-stage Bell's palsy, its correlation with clinical assessments, changes following treatment, and association with clinical prognosis. METHODS: MUNIX measures were recorded from the bilateral zygomaticus, orbicularis oculi, and orbicularis oris muscles of 10 healthy individuals and 64 patients with Bell's palsy. The patients were assessed by two specialist neurologists using the House-Brackmann and Sunnybrook Facial Grading Systems. Repeat assessments were performed on 20 patients with Bell's palsy who received treatment. Additionally, the 64 patients were reassessed using clinical scales after a 1-month interval. RESULTS: The MUNIX values of the main affected muscles on the affected side were lower than those on the healthy side in patients with Bell's palsy (p < .05). The MUNIX measurements significantly correlated with the clinical facial nerve palsy scale scores (p < .05). Significant improvements were observed in the MUNIX values on repeat testing following treatment (p < .05). The baseline motor unit size index (the compound muscle action potential amplitude divided by MUNIX) was positively associated with improved clinical presentation after 1 month (p < .05). CONCLUSION: MUNIX can be used as an electrophysiological biomarker for the quantitative assessment of facial nerve palsy and treatment response, and as a prognostic biomarker, in patients with early Bell's palsy, and is recommended as a complement to conventional neurophysiological examinations.

Blood-based HYAL2 methylation as a potential marker for the preclinical detection of coronary heart disease and stroke.

BACKGROUND: Coronary heart disease (CHD) and stroke have become the leading cause of premature mortality and morbidity worldwide. Therefore, sensitive and accurate biomarkers for early detection of CHD and stroke are urgently needed for effective prevention and treatment. We aim to investigate the association between blood-based HYAL2 methylation and the risk of CHD and stroke in Chinese population. METHODS: In a prospective nested case-control study comprising 171 CHD cases, 139 stroke cases, who developed the diseases after recruitment and 356 controls who remained healthy during the 2.5 years of follow-up time, the methylation level of HYAL2 in the peripheral blood was quantified using mass spectrometry, and the association was calculated by logistic regression adjusted for covariant. RESULTS: Significant association between HYAL2 methylation in the peripheral blood and increased risk of preclinical CHD and stroke were identified [odds ratios (ORs) per - 10% methylation: 1.35-1.64, p ≤ 0.045 for HYAL2_CpG_1, HYAL2_CpG_2 and HYAL2_CpG_3 in CHD; ORs per - 10% methylation: 0.76-1.64, p ≤ 0.033 for HYAL2_CpG_2 and HYAL2_CpG_4 in stroke]. The association in CHD was further enhanced by female gender, younger age (< 70 years old), without the history of hypertension and cancer. The combination of four HYAL2 methylation sites showed an effective discrimination of CHD and stroke cases without hypertension from controls [area under curve (AUC) = 0.78 and 0.75, respectively]. CONCLUSIONS: This study presents a strong association of altered HYAL2 methylation in peripheral blood with preclinical CHD and stroke, providing a novel biomarker for risk assessment and early detection of cardiovascular diseases.

Early Intervention in the Treatment of Psychosis.

This article aims to: (1) describe the evolution of first episode of psychosis (FEP) approaches; (2) define a model of multidisciplinary care; (3) identify challenges and limitations; (4) discuss the unique challenges for those first experiencing psychosis; (5) identify strategies to expand early psychosis interventions. The authors take the medical standpoint and use the differential diagnosis and initial medical work-up as a context for assessment. The remainder of the article will be focused on treatment of FEP in those with schizophrenia-spectrum disorders.

[Chinese guideline for clinical application of fluid biomarkers for Alzheimer's disease(2024 edition)].

Alzheimer's disease is the most prevalent neurodegenerative disorder leading to cognitive impairment, but its progression is subtle and the early recognition is difficult. With advancements in disease-modifying therapies, the need for precise early diagnosis of Alzheimer's disease is increasingly pressing. Fluid biomarkers of Alzheimer's disease, detectable in bodily fluid samples, are intricately associated with the disease.It can be used for screening, diagnosis, staging, prediction of disease progression, and clinical trials, playing an increasingly critical role in clinical practice.. This guideline systematically reviews and evaluates the spectrum of fluid biomarkers for Alzheimer's disease, propose standardized protocols for sample collection and processing, and delineates the application standards of fluid biomarkers in disease screening, diagnosis, staging, prognosis of disease progression, and clinical trials. A total of 24 recommendations have been formulated. The publication of this guideline aims to standardize the application of fluid biomarkers in clinical practice, thereby advancing research in Alzheimer's disease fluid biomarkers.

Early Detection of Vascular Obstruction in Microvascular Flaps using Thermographic Camera.

OBJECTIVE: To evaluate the early detection of vascular obstruction in microvascular flaps using a thermographic camera. STUDY DESIGN: A cross-sectional study. Place and Duration of the Study: Department of Plastic Surgery, Jinnah Burn and Reconstructive Surgery Centre, Lahore, Pakistan, from July to December 2023. METHODOLOGY: Microvascular flaps with cutaneous islands were monitored postoperatively with a thermographic camera in addition to conventional clinical methods. The decision to re-explore was based on conventional methods, and confirmation was achieved through intraoperative findings of vascular obstruction during re-exploration. RESULTS: Thirty-one patients who underwent microvascular surgery were monitored postoperatively with a thermographic camera. There were 20 (64.5%) anterolateral thigh flaps, 4 (12.9%) radial forearm flaps, 3 (9.7%) scapular-parascapular flaps, 1 (3.2%) medial plantar flap, 1 (3.2%) myocutaneous gracilis flap, 1 (3.2%) latissimus dorsi (LD) flap, and 1 (3.2%) chimeric adductor longus and gracilis flap. Three (9.7%) flaps developed postoperative vascular obstruction. The thermographic camera detected complications two to four hours earlier than conventional methods, with a statistically significant difference (p >0.109). CONCLUSION: A thermographic camera is a valuable, non-invasive, and simple tool for monitoring microvascular flaps. It can detect complications several hours earlier and has the potential to be a practice-changing modality. KEY WORDS: Microvascular flaps, Thermographic camera, Vascular obstruction.

Calprotectin, a Promising Serological Biomarker for the Early Diagnosis of Superinfections with Multidrug-Resistant Bacteria in Patients with COVID-19.

Bacterial and fungal superinfections are common in COVID-19, and early diagnosis can enable timely intervention. Serum calprotectin levels increase with bacterial, fungal, and viral infections. This study evaluated serum calprotectin as a diagnostic and prognostic tool for microbial superinfections in COVID-19. Serum samples from adult patients with moderate and severe COVID-19 were collected during hospitalization from 2020 to 2024. Calprotectin levels were measured using an enzyme-linked immunosorbent assay in 63 patients with moderate COVID-19, 60 patients with severe COVID-19, and 34 healthy individuals. Calprotectin serum levels were elevated in patients with moderate COVID-19 compared with controls, and these levels were further increased in the severe cases. Patients with severe COVID-19 and vancomycin-resistant enterococci (VRE) bacteremia had elevated calprotectin levels, but their C-reactive protein and procalcitonin levels were not increased. Fungal superinfections and herpes simplex virus reactivation did not change the calprotectin levels. A calprotectin concentration of 31.29 µg/mL can be used to diagnose VRE bloodstream infection with 60% sensitivity and 96% specificity. These data suggest that serum calprotectin may be a promising biomarker for the early detection of VRE bloodstream infections in patients with COVID-19.

Preclinical Detection of Early Glomerular Injury in Children with Kidney Diseases-Independently of Usual Markers of Kidney Impairment and Inflammation.

Glomerular kidney diseases typically begin insidiously and can progress to end stage kidney failure. Early onset of therapy can slow down disease progression. Early diagnosis is required to ensure such timely therapy. The goal of our study was to evaluate protein biomarkers (BMs) for common nephropathies that have been described for children with Alport syndrome. Nineteen candidate BMs were determined by commercial ELISA in children with congenital anomalies of the kidneys and urogenital tract, inflammatory kidney injury, or diabetes mellitus. It is particularly essential to search for kidney disease BMs in children because they are a crucial target group that likely exhibits early disease stages and in which misleading diseases unrelated to the kidney are rare. Only minor differences in blood between affected individuals and controls were found. However, in urine, several biomarker candidates alone or in combination seemed to be promising indicators of renal injury in early disease stages. The BMs of highest sensitivity and specificity were collagen type XIII, hyaluronan-binding protein 2, and complement C4-binding protein. These proteins are unrelated to inflammation markers or to risk factors for and signs of renal failure. In conclusion, our study evaluated several strong candidates for screening for early stages of kidney diseases and can help to establish early nephroprotective regimens.

A New Strategy for Ultrasensitive Detection Based on Target microRNA-Triggered Rolling Circle Amplification in the Early Diagnosis of Alzheimer's Disease.

There is an urgent need to accurately quantify microRNA (miRNA)-based Alzheimer's disease (AD) biomarkers, which have emerged as promising diagnostic biomarkers. In this study, we present a rapid and universal approach to establishing a target miRNA-triggered rolling circle amplification (RCA) detection strategy, which achieves ultrasensitive detection of several targets, including miR-let7a-5p, miR-34a-5p, miR-206-3p, miR-9-5p, miR-132-3p, miR-146a-5p, and miR-21-5p. Herein, the padlock probe contains three repeated signal strand binding regions and a target miRNA-specific region. The target miRNA-specific region captures miRNA, and then the padlock probe is circularized with the addition of T4 DNA ligase. Subsequently, an RCA reaction is triggered, and RCA products containing multiple signal strand binding regions are generated to trap abundant fluorescein-labeled signal strands. The addition of exonuclease III (Exo III) causes signal strand digestion and leads to RCA product recycling and liberation of fluorescein. Ultimately, graphene oxide (GO) does not absorb the liberated fluorescein because of poor mutual interaction. This method exhibited high specificity, sensitivity, repeatability, and stability toward let-7a, with a detection limit of 19.35 fM and a linear range of 50 fM to 5 nM. Moreover, it showed excellent applicability for recovering miRNAs in normal human serum. Our strategy was applied to detect miRNAs in the plasma of APP/PS1 mice, demonstrating its potential in the diagnosis of miRNA-associated disease and biochemical research.