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1.
Internet resource in Portuguese | LIS -Health Information Locator | ID: lis-48779

ABSTRACT

Dores que se espalham por várias partes do corpo, fadiga, distúrbios do sono, ansiedade e alterações de memória e de atenção podem ser sintomas de fibromialgia, doença mais comum entre as mulheres


Subject(s)
Fibromyalgia , Fatigue Syndrome, Chronic/diagnosis , Quality of Life , Early Diagnosis
2.
Internet resource in Portuguese | LIS -Health Information Locator | ID: lis-48781

ABSTRACT

As talassemias são um grupo de doenças hereditárias crônicas que se caracterizam pela redução ou ausência de hemoglobina – substância dos glóbulos vermelhos do sangue responsável pelo transporte de oxigênio para todo o corpo


Subject(s)
Thalassemia/diagnosis , Early Diagnosis , Anemia/diagnosis
3.
BMC Oral Health ; 22(1): 164, 2022 05 06.
Article in English | MEDLINE | ID: mdl-35524204

ABSTRACT

BACKGROUND: This study aimed to develop and validate five machine learning models designed to predict actinomycotic osteomyelitis of the jaw. Furthermore, this study determined the relative importance of the predictive variables for actinomycotic osteomyelitis of the jaw, which are crucial for clinical decision-making. METHODS: A total of 222 patients with osteomyelitis of the jaw were analyzed, and Actinomyces were identified in 70 cases (31.5%). Logistic regression, random forest, support vector machine, artificial neural network, and extreme gradient boosting machine learning methods were used to train the models. The models were subsequently validated using testing datasets. These models were compared with each other and also with single predictors, such as age, using area under the receiver operating characteristic (ROC) curve (AUC). RESULTS: The AUC of the machine learning models ranged from 0.81 to 0.88. The performance of the machine learning models, such as random forest, support vector machine and extreme gradient boosting was significantly superior to that of single predictors. Presumed causes, antiresorptive agents, age, malignancy, hypertension, and rheumatoid arthritis were the six features that were identified as relevant predictors. CONCLUSIONS: This prediction model would improve the overall patient care by enhancing prognosis counseling and informing treatment decisions for high-risk groups of actinomycotic osteomyelitis of the jaw.


Subject(s)
Machine Learning , Osteomyelitis , Early Diagnosis , Humans , Logistic Models , Osteomyelitis/diagnosis , ROC Curve
4.
Arch Soc Esp Oftalmol (Engl Ed) ; 97(5): 290-294, 2022 May.
Article in English | MEDLINE | ID: mdl-35526953

ABSTRACT

A 38-year-old man who attended the emergency department with headache, accompanied by vomiting, bradypsychia and gait instability, for which he was admitted to Neurology for study. During his admission, he began to present bilateral hearing loss and blurred vision in the left eye, with areas of arterial occlusion and hyperfluorescence of the arterial wall being observed in the ophthalmological examination. As a result, he was diagnosed with Susac syndrome. He was treated with systemic corticosteroids, as well as with rituximab and subsequently, with intravenous immunoglobulins and mycophenolate mofetil. The patient managed to preserve visual acuity, with gait instability and bilateral hearing loss as sequelae. Early diagnosis of Susac syndrome is important, because a delay in the start of treatment can lead to irreversible sequelae such as deafness, blindness or neurological involvement.


Subject(s)
Susac Syndrome , Adult , Early Diagnosis , Hearing Loss, Bilateral/complications , Humans , Magnetic Resonance Imaging , Male , Susac Syndrome/diagnostic imaging , Susac Syndrome/drug therapy , Vision Disorders/etiology
5.
J Med Case Rep ; 16(1): 185, 2022 May 09.
Article in English | MEDLINE | ID: mdl-35527279

ABSTRACT

BACKGROUND: Elderly and frail patients who are unable to call for help in case of vital distress can develop complications during their hospitalization. As a supplement to clinical monitoring by the nursing staff, these patients can also be monitored in real time, with the Sensium E-health technology. An application notifies clinical staff of any change in their vital signs (heart rate, respiratory rate, temperature) outside of normal ranges, suggestive of physiological decline. Nurses and physicians are notified of these abnormal changes by email and also via mobile application (iPhone or iPad), allowing early intervention to prevent further deterioration. CASE PRESENTATION: An 86-year-old Caucasian female, with chronic kidney disease, was hospitalized in our medical unit for pyelonephritis associated with a moderate deterioration of serum creatinine. Remote continuous monitoring allowed us to diagnose clinical deterioration early and adjust her treatment. The treatment improved her clinical condition and amended the secondary sepsis with circulation failure in 2 days. CONCLUSIONS: The prognosis for patients with acute complicated pyelonephritis is much worse than for those with uncomplicated pyelonephritis. Remote continuous monitoring might be helpful to early diagnose urosepsis. This technology leads to improved prognosis of patients without initial vital distress, allowing early treatment and admission to intensive care unit.


Subject(s)
Pyelonephritis , Sepsis , Telemedicine , Aged , Aged, 80 and over , Early Diagnosis , Female , Humans , Intensive Care Units , Male , Pyelonephritis/diagnosis , Pyelonephritis/therapy , Sepsis/diagnosis , Sepsis/therapy
6.
Int J Mol Sci ; 23(9)2022 Apr 21.
Article in English | MEDLINE | ID: mdl-35563001

ABSTRACT

The degeneration and dysfunction of neurons are key features of neurodegenerative diseases (NDs). Currently, one of the main challenges facing researchers and clinicians is the ability to obtain reliable diagnostic tools that will allow for the diagnosis of NDs as early as possible and the detection of neuronal dysfunction, preferably in the presymptomatic stage. Additionally, better tools for assessing disease progression in this group of disorders are also being sought. The ideal biomarker must have high sensitivity and specificity, be easy to measure, give reproducible results, and reflect the disease progression. Molecular biomarkers include miRNAs and extracellular microvesicles known as exosomes. They may be measured in two extracellular fluids of the highest importance in NDs, i.e., cerebrospinal fluid (CSF) and blood. The aim of the current review is to summarize the pathophysiology of the four most frequent NDs-i.e., Alzheimer's disease (AD), Parkinson's disease (PD), amyotrophic lateral sclerosis (ALS), and multiple sclerosis (MS)-as well as current progress in the research into miRNAs as biomarkers in these major neurodegenerative diseases. In addition, we discuss the possibility of using miRNA-based therapies in the treatment of neurodegenerative diseases, and present the limitations of this type of therapy.


Subject(s)
Exosomes , MicroRNAs , Neurodegenerative Diseases , Amyotrophic Lateral Sclerosis/diagnosis , Biomarkers , Disease Progression , Early Diagnosis , Exosomes/genetics , Humans , MicroRNAs/genetics , Neurodegenerative Diseases/diagnosis , Neurodegenerative Diseases/genetics
7.
BMC Infect Dis ; 22(1): 430, 2022 May 04.
Article in English | MEDLINE | ID: mdl-35509042

ABSTRACT

BACKGROUND: Brucellosis is an endemic systemic infectious disease, the most common complication is bone and joint involvement. Sacroiliac joint and spinal joint are the most frequently involved sites in adults, but knee joint infection is rare, and acute infectious knee arthritis complicated by acute osteomyelitis is even extremely uncommon in adults. Here, we report two cases of acute septic knee arthritis complicated by acute osteomyelitis caused by Brucella melitensis (B. melitensis). CASE PRESENTATION: Both patients had a history of traveling in animal husbandry areas within three months. On clinical examination, their right knee joint was tender, swollen, had limited movement and an effusion was present. Imaging examination showed effusion and synovial thickening of the right knee joint, as well as subchondral bone edema of the distal femur and proximal tibia. Laboratory examination showed that the serum agglutination test (SAT) in both patients were positive (1: 640 and 1: 320) without leukocytosis, although the proportion of lymphocytes, erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP) significantly increased. Both patients underwent knee joint aspiration. Real-time polymerase chain reaction (Real-time PCR) analysis of synovial fluid showed that there was B. melitensis, and blood bacterial culture was negative. We determined that two patients had acute brucellosis knee arthritis complicated by acute osteomyelitis. Antibiotic treatment was given during hospitalization consisting of doxycycline (0.1 g po bid) and rifampicin (0.6 g po qd) for six weeks, and the changes of inflammatory indexes were closely monitored. At discharge, the symptoms had completely resolved, imaging abnormalities disappeared, and inflammatory indexes returned to normal. There was no recurrence of the disease at 1-year follow-up. CONCLUSION: Acute brucellosis knee arthritis complicated by acute osteomyelitis is a rare but serious complication of brucellosis in adults. There is no obvious specificity of clinical manifestation and imaging examination. Early diagnosis and treatment can prevent the occurrence of knee joint deformity and even pathological fracture. Clinicians should fully consider the possibility of brucellosis where the travel or occupational history is suggestive.


Subject(s)
Arthritis, Infectious , Brucellosis , Osteomyelitis , Acute Disease , Animals , Arthritis, Infectious/complications , Arthritis, Infectious/diagnosis , Arthritis, Infectious/drug therapy , Brucellosis/complications , Brucellosis/diagnosis , Brucellosis/drug therapy , Early Diagnosis , Humans , Knee Joint/microbiology , Osteomyelitis/diagnosis , Osteomyelitis/therapy
8.
Curr Med Res Opin ; 38(5): 743-747, 2022 May.
Article in English | MEDLINE | ID: mdl-35380092

ABSTRACT

BACKGROUND: The aim of this study was to estimate primary care costs of prodromal signs/symptoms of Alzheimer disease (AD), during a 10-year or longer period preceding AD diagnosis, in relation to costs cumulated in the general population for the same reasons. METHODS: Nested case-control study involving 1889 AD cases and 18,890 controls aged 60+ from the Italian primary care Health Search Database (HSD). AD incident cases were through the International Classification of Diseases, 9th edition. Costs related to drugs, diagnostic tests and specialist referrals triggered by prodromal AD signs and/or symptoms were quantified and compared with costs cumulated by non-AD counterparts. RESULTS: During the pre-diagnosis 10-year or longer period, prodromal signs and symptoms trigger diagnostic and therapeutic costs 55% higher than those cumulated in general population for the same clinical reasons. After accounting for patients' comorbidity and regional differences, the mean cost related to diagnostic and therapeutic procedures, and those related to specialist referrals, amounted to 854.1 €(SD: 630.6 €) in AD incident cases vs. 527.3 €(SD: 446.2) cumulated in patients not developing AD. CONCLUSION: Prodromal AD manifestations are associated with primary care costs that resulted higher than those cumulated in the general population aged 60+. It remains to be elucidated if earlier dementia diagnoses would be associated with reduced costs triggered by the same clinical signs and symptoms.


Subject(s)
Alzheimer Disease , Alzheimer Disease/diagnosis , Alzheimer Disease/epidemiology , Alzheimer Disease/therapy , Case-Control Studies , Comorbidity , Early Diagnosis , Humans , Primary Health Care
9.
Comput Intell Neurosci ; 2022: 9005278, 2022.
Article in English | MEDLINE | ID: mdl-35479597

ABSTRACT

As a result of technology improvements, various features have been collected for heart disease diagnosis. Large data sets have several drawbacks, including limited storage capacity and long access and processing times. For medical therapy, early diagnosis of heart problems is crucial. Disease of heart is a devastating human disease that is quickly increasing in developed and also developing countries, resulting in death. In this type of disease, the heart normally fails to provide enough blood to different body parts in order to allow them to perform their regular functions. Early, as well as, proper diagnosis of this condition is very critical for averting further damage and also to save patients' lives. In this work, machine learning (ML) is utilized to find out whether a person has cardiac disease or not. Both the types of ensemble classifiers, namely, homogeneous as well as heterogeneous classifiers (formed by combining two separate classifiers), have been implemented in this work. The data mining preprocessing using Synthetic Minority Oversampling Technique (SMOTE) has been employed to cope with the imbalance problem of the class as well as noise. The proposed work has two steps. SMOTE is used in the initial phase to reduce the impact of data imbalance and the second phase is classifying data using Naive Bayes (NB), decision tree (DT) algorithms, and their ensembles. The experimental results demonstrate that the AdaBoost-Random Forest classifier provides 95.47% accuracy in the early detection of heart disease.


Subject(s)
Algorithms , Heart Diseases , Bayes Theorem , Early Diagnosis , Heart Diseases/diagnosis , Humans , Research Design
11.
Ulus Travma Acil Cerrahi Derg ; 28(4): 403-410, 2022 Apr.
Article in English | MEDLINE | ID: mdl-35485506

ABSTRACT

BACKGROUND: Acute mesenteric ischemia (AMI) is a rarely observed acute abdominal disease that may be mortal and is difficult to diagnose early. The aim of our study is to assess the role of Thiol-Disulphide Haemostasis (TDH), a new method for AMI which still has no specific biochemical markers for early diagnosis, and to assess it together with Ischemia-Modified Albumin (IMA) which has previously proven reliability for AMI. METHODS: The study included 32 Wistar albino rats in four groups. The 1st group (n=8) was the control group, 2nd group (n=8) was the sham group, 3rd group (n=8) had 3 h of arterial mesentery ischemia and the 4th group (n=8) had 6 h of arterial mesentery ischemia. TDH, IMA, and serum lactate values were measured at h 0, 1, 3, and 6. RESULTS: In the 3rd and 6th h, serum total thiol and native thiol values significantly reduced (p<0.001), while serum disulfide, IMA, and lactate values clearly increased (p<0.001). Serum thiol values were observed to reduce from the 1st h. CONCLUSION: TDH changes in the early period of AMI. The TDH parameters can be used with IMA as diagnostic parameters for patients with suspected AMI in the early period.


Subject(s)
Disulfides , Mesenteric Ischemia , Biomarkers , Early Diagnosis , Hemostasis , Humans , Lactates , Mesenteric Ischemia/diagnosis , Mesentery , Oxidative Stress , Reproducibility of Results , Serum Albumin , Sulfhydryl Compounds
12.
Rheum Dis Clin North Am ; 48(2): 537-547, 2022 May.
Article in English | MEDLINE | ID: mdl-35400377

ABSTRACT

Rheumatoid arthritis (RA) is a chronic, progressive inflammatory disorder that manifests as a symmetric polyarthritis of small and large joints that may lead to joint and periarticular structural damage and the consequences of systemic inflammation. This overview of early RA examines the unmet needs and challenges in RA, how to best diagnose RA, and pitfalls in early diagnosis and treatment. The rules for referral to a rheumatologist are reviewed. Primary care physicians are at the front line of early diagnosis and need to start disease-modifying therapy as soon as a diagnosis of RA is established.


Subject(s)
Antirheumatic Agents , Arthritis, Rheumatoid , Antirheumatic Agents/therapeutic use , Arthritis, Rheumatoid/diagnosis , Arthritis, Rheumatoid/drug therapy , Early Diagnosis , Humans , Inflammation , Referral and Consultation , Rheumatologists
13.
Front Public Health ; 10: 850191, 2022.
Article in English | MEDLINE | ID: mdl-35387184

ABSTRACT

Objective: To investigate whether first-trimester fasting plasma glucose (FPG), blood coagulation function and lipid metabolism could predict gestational diabetes mellitus (GDM) risk. Methods: From October 2020 to May 2021, a total of 584 pregnant women who took prenatal care in Shanghai Jiaotong University Affiliated Sixth People's Hospital were chosen as the observation subjects. The clinical information and serum samples of all pregnant women were collected at 10-13 weeks of gestation and the blood coagulation function, fasting blood glucose and lipid profiles of the pregnant women were detected. A 75 g oral glucose tolerance test was performed up to 24-28 weeks of gestation. One hundred forty-two pregnant women with GDM and 442 pregnant women without GDM were detected. Data were expressed by x ± s or median (interquartile range) and were analyzed using student's t-test, Wilcoxon rank sum test and Logistic regression analysis. The area under the curve (AUC) was calculated by receiver operating characteristic curve (ROC) to analyze the predictive values. Results: Compared with non-GDM group, age, pre-pregnancy BMI, FPG, FIB, D-Dimer, FDP, FPG, TC, TG, LDL-C, sdLDL-C, APOB and APOE in GDM group were significantly higher than those in non-GDM group, while PT, INR, APTT and TT were significantly lower than those in non-GDM group. Univariate logistic regression analysis was used to explore the risk factors of GDM. Gestational age, pre-pregnancy BMI, FPG, PT, INR, APTT, FIB, TT, D-Dimer, TC, TG, LDL-C, sdLDL-C, APOB and APOE were all independent predictors of GDM. Multivariatelogistic regression showed that pre-pregnancy BMI, FPG, APTT, TT, TG, LDL-C, sdLDL-C and APOB were risk factors for GDM. The AUC of the established GDM risk prediction model was 0.892 (0.858-0.927), and the sensitivity and specificity were 80.71 and 86.85%, respectively; which were greater than that of pre-pregnancy BMI, FPG, APTT, TT,TG, LDL-C, sdLDL-C, APOB alone, and the difffference was statistically signifificant (P < 0.05). Conclusions: FPG, APTT, TT, TG, LDL-C, sdLDL-C, APOB and pre-pregnancy BMI in early pregnancy has important clinical value for the prediction of GDM, We combined these laboratory indicators and established a GDM risk prediction model, which is conducive to the early identification, intervention and treatment of GDM, so as to reduce the morbidity of maternal and infant complications.


Subject(s)
Diabetes, Gestational , Apolipoproteins B/metabolism , Apolipoproteins E/metabolism , Blood Coagulation , Blood Glucose/analysis , Blood Glucose/metabolism , Body Mass Index , Cholesterol, LDL/metabolism , Diabetes, Gestational/diagnosis , Early Diagnosis , Female , Glycolipids , Humans , Lipid Metabolism , Pregnancy
14.
BMC Pediatr ; 22(1): 176, 2022 04 04.
Article in English | MEDLINE | ID: mdl-35379203

ABSTRACT

BACKGROUND: Invasive bacterial infections (IBI) in children present a difficult clinical challenge. They are often life-threatening, however in the early stages they can be hard to differentiate from benign viral infections. This leaves clinicians with the risk of missing a serious IBI diagnosis or inappropriately using antimicrobials in a child with a viral infection- contributing to the ongoing development of increased antimicrobial resistance. Hence, biomarkers which could aid in early detection of IBI and differentiation from viral infections are desirable. Mid-Regional pro-Adrenomedullin (MR-proADM) is a biomarker which has been associated with IBI. The aim of this systematic review was to determine its diagnostic accuracy in identifying children with IBI. METHODS: A strategy was devised to search online databases MEDLINE, Embase, Web of Science and Scopus for human clinical trials reporting the accuracy of MR-proADM in children. Against predesigned inclusion and exclusion criteria full texts were selected for inclusion and data extraction. True positives, false positives, true negatives and false negatives were extracted from each included study to fill 2 × 2 tables. Using the Quality Assessment of Diagnostic Accuracy Studies (QUADAS-2) tool methodological quality of each study was assessed. RESULTS: A total of 501 articles were initially identified. After the removal of duplicates and abstract screening 11 texts were fully reviewed and four texts (totaling 1404 patients) were included in the systematic analysis. Only one study was of a high quality and that study accounted for the vast majority of patients. A single study reported the diagnostic accuracy of MR-proADM for invasive bacterial infection reporting an Area under the Curve of 0.69. The paucity of available studies made meta-analysis and studies of heterogeneity impossible. CONCLUSION: There is a paucity of research regarding the diagnostic accuracy of MR-proADM in the diagnosis of invasive bacterial infections in children. Initial results would suggest that MR-proADM testing alone is poor at identifying IBI in young children. It remains unclear if MR-proADM performs differently in older children or in children with signs and symptoms of IBI. TRIAL REGISTRATION: PROSPERO CRD42018096295 .


Subject(s)
Anti-Infective Agents , Bacterial Infections , Adrenomedullin , Bacterial Infections/diagnosis , Bacterial Infections/drug therapy , Biomarkers , Child , Child, Preschool , Early Diagnosis , Humans
15.
Anal Chem ; 94(15): 5805-5813, 2022 04 19.
Article in English | MEDLINE | ID: mdl-35380780

ABSTRACT

Early diagnosis of rheumatoid arthritis (RA) is crucial to prevent deterioration and improve the prognosis of disease outcome. However, current clinical diagnostic methods are unable to achieve accurate and early detection of RA. In this work, we designed an activatable organic nanoprobe (ONP-CySe) capable of specific and real-time imaging of ClO- in early RA. ONP-CySe comprises a near-infrared fluorescent selenomorpholine-caged cyanine dye as the sensing component and an amphiphilic triblock copolymer triphenyl phosphine derivative for mitochondria targeting. Our results showed that ONP-CySe successfully detected elevated levels of ClO- in the mitochondria of macrophages with high selectivity, low limit of detection (31.5 nM), excellent photostability, and good biocompatibility. Furthermore, ONP-CySe can also be used to monitor anti-inflammatory responses and efficacies of RA therapeutics, such as selenocysteine and methotrexate, in BALB/c mouse models. Therefore, our research proposes a universal molecular design strategy for the detection of ClO-, which holds potential for early diagnosis and drug screening for RA.


Subject(s)
Arthritis, Rheumatoid , Hypochlorous Acid , Animals , Arthritis, Rheumatoid/diagnostic imaging , Early Diagnosis , Fluorescent Dyes , Mice , Mice, Inbred BALB C
17.
Bol Med Hosp Infant Mex ; 79(2): 129-134, 2022.
Article in English | MEDLINE | ID: mdl-35468122

ABSTRACT

BACKGROUND: Megalencephalic leukoencephalopathy with subcortical cysts is a rare type of leukodystrophy associated with mutations in the MLC1 and GlialCAM genes. The classic form is characterized by macrocephaly, early or delayed normal neurodevelopment followed by a period of slow motor skill loss, with cerebellar ataxia and spasticity; some patients develop movement disorders and seizures. Magnetic resonance imaging shows widespread diffuse white matter involvement with edema and subcortical cysts. CASE REPORT: We describe the case of two sisters aged 6 and 10 years, consanguineous parents, with a history of psychomotor delay and macrocephaly. The older sister presented with seizures at the age of 4 years and spasticity without loss of gait; the younger sister had a similar clinical picture. Magnetic resonance imaging showed diffuse alteration of the white matter and subcortical cysts in the temporal lobes. Electroencephalogram detected focal epileptiform activity. Seizure control was achieved upon initiation of carbamazepine treatment. By sequencing, a homozygous variant of the MLC1 gene was found in exon 3: c.255T>G (p.Cys85Trp). CONCLUSIONS: Leukodystrophies are rare diseases that represent a diagnostic challenge. Clinical, radiological, and molecular findings allow diagnostic certainty, the appropriate direction of interventions, and adjustment to the prognosis of each entity. The c.255T>G mutation was previously described in a South American patients, suggesting that it is a specific variant to Latin populations.


INTRODUCCIÓN: La leucoencefalopatía megalencefálica con quistes subcorticales es una leucodistrofia poco frecuente, asociada con mutaciones en los genes MLC1 y GlialCAM. La forma clásica se caracteriza por macrocefalia, neurodesarrollo temprano normal o con retraso seguido por un periodo de pérdida lenta de habilidades motoras, con ataxia cerebelosa y espasticidad; algunos pacientes desarrollan trastornos del movimiento y crisis convulsivas. La resonancia magnética muestra afección difusa generalizada de la sustancia blanca con edema y quistes subcorticales. CASO CLÍNICO: Se presenta el caso de dos hermanas de 6 y 10 años con historia de retraso psicomotor y macrocefalia, hijas de padres consanguíneos. La mayor inició con crisis convulsivas a los 4 años y espasticidad sin pérdida de la marcha autónoma; la menor presentó un cuadro clínico similar. La resonancia magnética mostró una alteración difusa de la sustancia blanca y quistes subcorticales en los lóbulos temporales. El electroencefalograma detectó actividad epileptiforme focal. Se logró el control de las crisis convulsivas al iniciar el tratamiento con carbamazepina. Por secuenciación, se encontró una variante homocigota del gen MLC1 en el exón 3: c.255T>G (p.Cys85Trp). CONCLUSIONES: Las leucodistrofias son enfermedades raras que representan un desafío para su diagnóstico. Los hallazgos clínicos, radiológicos y moleculares permiten la certeza del diagnóstico, la dirección adecuada de las intervenciones y el ajuste al pronóstico de cada una. La mutación c.255T>G fue descrita previamente en pacientes sudamericanos, lo que sugiere que podría tratarse de una variante específica de poblaciones latinas.


Subject(s)
Cysts , Megalencephaly , Cysts/complications , Cysts/diagnosis , Cysts/genetics , Early Diagnosis , Hereditary Central Nervous System Demyelinating Diseases , Humans , Megalencephaly/complications , Membrane Proteins/genetics , Seizures/complications
20.
Theranostics ; 12(6): 2549-2559, 2022.
Article in English | MEDLINE | ID: mdl-35401818

ABSTRACT

Background: Imaging amyloid-beta (Aß) deposits with high fidelity in naturally aging brains is crucial for the early diagnosis of Alzheimer's disease (AD). However, this is impeded by the lack of highly sensitive probes. Methods: By conducting computational modelling to quantitatively fine-tune the twisted intramolecular charge transfer (TICT) tendency of Thioflavin T (ThT) analogues, we developed an ultrasensitive probe AH-2. AH-2 retained the binding affinity and binding mode of ThT towards Aß deposits, and exhibited ca 10-fold less background fluorescence and 5-10 folds of improved signal-to-background contrast upon binding Aß deposits. These desirable features endowed AH-2 the sensitivity to detect Aß deposition in naturally aging wild-type mice. Results: AH-2 imaging revealed that Aß puncta signals appeared near the nuclei in young mice and spread through the intracellular and extracellular compartments in older mice. Moreover, Aß deposits were observed to emerge earlier in mice cerebral cortex than in the hippocampus region. Given this desirable sensitivity and good spatiotemporal resolution, AH-2 was successfully applied in the preclinical evaluation of Aß-targeted treatment by melatonin. Conclusions: We expect that AH-2 is promising for early diagnosis of AD and will serve as a sensitive tool for studying Aß-related AD pathology.


Subject(s)
Alzheimer Disease , Alzheimer Disease/diagnostic imaging , Alzheimer Disease/drug therapy , Amyloid beta-Peptides/metabolism , Animals , Early Diagnosis , Fluorescent Dyes/chemistry , Mice , Mice, Transgenic , Optical Imaging/methods
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