Alzheimer disease (AD) diagnosis is confirmed using a medley of modalities, such as the detection of amyloid-β (Aβ) neuritic plaques and neurofibrillary tangles with positron electron tomography (PET) or the appraisal of irregularities in cognitive function with examinations. Although these methods have been efficient in confirming AD pathology, the rising demand for earlier intervention during pathogenesis has led researchers to explore the diagnostic potential of fluid biomarkers in cerebrospinal fluid (CSF) and plasma. Since CSF sample collection is invasive and limited in quantity, biomarker detection in plasma has become more attractive and modern advancements in technology has permitted more efficient and accurate analysis of plasma biomolecules. In this study, we found that a composite of standard factors, Aβ40 and total tau levels in plasma, divided by the variation factor, plasma Aβ42 level, provide better correlation with amyloid neuroimaging and neuropsychological test results than a level comparison between total tau and Aβ42 in plasma. We collected EDTA-treated blood plasma samples of 53 subjects, of randomly selected 27 AD patients and 26 normal cognition (NC) individuals, who received amyloid-PET scans for plaque quantification, and measured plasma levels of Aβ40, Aβ42, and total tau with digital enzyme-linked immunosorbent assay (ELISA) in a blinded manner. There was difficulty distinguishing AD patients from controls when analyzing biomarkers independently. However, significant differentiation was observed between the two groups when comparing individual ratios of total-tau×Aβ40/Aβ42. Our results indicate that collectively comparing fluctuations of these fluid biomarkers could aid in monitoring AD pathogenesis.

Alzheimer disease (AD) diagnosis is confirmed using a medley of modalities, such as the detection of amyloid-β (Aβ) neuritic plaques and neurofibrillary tangles with positron electron tomography (PET) or the appraisal of irregularities in cognitive function with examinations. Although these methods have been efficient in confirming AD pathology, the rising demand for earlier intervention during pathogenesis has led researchers to explore the diagnostic potential of fluid biomarkers in cerebrospinal fluid (CSF) and plasma. Since CSF sample collection is invasive and limited in quantity, biomarker detection in plasma has become more attractive and modern advancements in technology has permitted more efficient and accurate analysis of plasma biomolecules. In this study, we found that a composite of standard factors, Aβ40 and total tau levels in plasma, divided by the variation factor, plasma Aβ42 level, provide better correlation with amyloid neuroimaging and neuropsychological test results than a level comparison between total tau and Aβ42 in plasma. We collected EDTA-treated blood plasma samples of 53 subjects, of randomly selected 27 AD patients and 26 normal cognition (NC) individuals, who received amyloid-PET scans for plaque quantification, and measured plasma levels of Aβ40, Aβ42, and total tau with digital enzyme-linked immunosorbent assay (ELISA) in a blinded manner. There was difficulty distinguishing AD patients from controls when analyzing biomarkers independently. However, significant differentiation was observed between the two groups when comparing individual ratios of total-tau×Aβ40/Aβ42. Our results indicate that collectively comparing fluctuations of these fluid biomarkers could aid in monitoring AD pathogenesis.

Alzheimer disease (AD) diagnosis is confirmed using a medley of modalities, such as the detection of amyloid-β (Aβ) neuritic plaques and neurofibrillary tangles with positron electron tomography (PET) or the appraisal of irregularities in cognitive function with examinations. Although these methods have been efficient in confirming AD pathology, the rising demand for earlier intervention during pathogenesis has led researchers to explore the diagnostic potential of fluid biomarkers in cerebrospinal fluid (CSF) and plasma. Since CSF sample collection is invasive and limited in quantity, biomarker detection in plasma has become more attractive and modern advancements in technology has permitted more efficient and accurate analysis of plasma biomolecules. In this study, we found that a composite of standard factors, Aβ40 and total tau levels in plasma, divided by the variation factor, plasma Aβ42 level, provide better correlation with amyloid neuroimaging and neuropsychological test results than a level comparison between total tau and Aβ42 in plasma. We collected EDTA-treated blood plasma samples of 53 subjects, of randomly selected 27 AD patients and 26 normal cognition (NC) individuals, who received amyloid-PET scans for plaque quantification, and measured plasma levels of Aβ40, Aβ42, and total tau with digital enzyme-linked immunosorbent assay (ELISA) in a blinded manner. There was difficulty distinguishing AD patients from controls when analyzing biomarkers independently. However, significant differentiation was observed between the two groups when comparing individual ratios of total-tau×Aβ40/Aβ42. Our results indicate that collectively comparing fluctuations of these fluid biomarkers could aid in monitoring AD pathogenesis.

Alzheimer disease (AD) diagnosis is confirmed using a medley of modalities, such as the detection of amyloid-β (Aβ) neuritic plaques and neurofibrillary tangles with positron electron tomography (PET) or the appraisal of irregularities in cognitive function with examinations. Although these methods have been efficient in confirming AD pathology, the rising demand for earlier intervention during pathogenesis has led researchers to explore the diagnostic potential of fluid biomarkers in cerebrospinal fluid (CSF) and plasma. Since CSF sample collection is invasive and limited in quantity, biomarker detection in plasma has become more attractive and modern advancements in technology has permitted more efficient and accurate analysis of plasma biomolecules. In this study, we found that a composite of standard factors, Aβ40 and total tau levels in plasma, divided by the variation factor, plasma Aβ42 level, provide better correlation with amyloid neuroimaging and neuropsychological test results than a level comparison between total tau and Aβ42 in plasma. We collected EDTA-treated blood plasma samples of 53 subjects, of randomly selected 27 AD patients and 26 normal cognition (NC) individuals, who received amyloid-PET scans for plaque quantification, and measured plasma levels of Aβ40, Aβ42, and total tau with digital enzyme-linked immunosorbent assay (ELISA) in a blinded manner. There was difficulty distinguishing AD patients from controls when analyzing biomarkers independently. However, significant differentiation was observed between the two groups when comparing individual ratios of total-tau×Aβ40/Aβ42. Our results indicate that collectively comparing fluctuations of these fluid biomarkers could aid in monitoring AD pathogenesis.

A 6-year-old spayed female French Bulldog presented with a left-sided chest wall tumor. Physical examination revealed that the tumor was firmly adhered to the chest wall. A preoperative punch biopsy of the tumor revealed a grade 2 soft tissue sarcoma (STS). On computed tomography, the tumor’s dimensions were assessed as 6.5 × 5.7 × 3.5 cm, and it exhibited invasiveness near the tissue surrounding the ninth rib. The tumor size was large in comparison to the dog’s chest wall area. Hence, if the traditional wide-margin resection surgery were to be performed, primary wound closure seemed impractical and could potentially result in respiratory function complications. Therefore, considering the extent of tumor invasion and grade, deep margins were established to include the removal of the eighth to tenth ribs, and a 1-cm lateral margin was designated to enable primary wound closure. To reconstruct the chest wall, polypropylene mesh was attached to the adjacent ribs and the remaining muscles were sutured and covered over the mesh. The dog exhibited a rapid recovery beginning the day after the operation. Postoperative biopsy confirmed that the tumor was a grade 2 STS, and the surgical margins were evaluated as incomplete. The owner chose to pursue follow-up observation instead of chemotherapy. In this study, the surgical approach was chosen based on the importance of functional recovery after surgery. Recent research indicates that the tumor grade is more critical for postoperative prognosis than the extent of surgical margins when removing an STS.

Alzheimer’s disease (AD) progressively inflicts impairment of synaptic functions with notable deposition of amyloid-β (Aβ) as senile plaques within the extracellular space of the brain. Accordingly, therapeutic directions for AD have focused on clearing Aβ plaques or preventing amyloidogenesis based on the amyloid cascade hypothesis. However, the emerging evidence suggests that Aβ serves biological roles, which include suppressing microbial infections, regulating synaptic plasticity, promoting recovery after brain injury, sealing leaks in the blood-brain barrier, and possibly inhibiting the proliferation of cancer cells. More importantly, these functions were found in in vitro and in vivo investigations in a hormetic manner, that is to be neuroprotective at low concentrations and pathological at high concentrations. We herein summarize the physiological roles of monomeric Aβ and current Aβ-directed therapies in clinical trials. Based on the evidence, we propose that novel therapeutics targeting Aβ should selectively target Aβ in neurotoxic forms such as oligomers while retaining monomeric Aβ in order to preserve the physiological functions of Aβ monomers.

Alzheimer's disease (AD) is pathologically characterized by a long progressive phase of neuronal changes, including accumulation of extracellular amyloid-β (Aβ) and intracellular neurofibrillary tangles, before the onset of observable symptoms. Many efforts have been made to develop a blood-based diagnostic method for AD by incorporating Aβ and tau as plasma biomarkers. As blood tests have the advantages of being highly accessible and low cost, clinical implementation of AD blood tests would provide preventative screening to presymptomatic individuals, facilitating early identification of AD patients and, thus, treatment development in clinical research. However, the low concentration of AD biomarkers in the plasma has posed difficulties for accurate detection, hindering the development of a reliable blood test. In this review, we introduce three AD blood test technologies emerging in South Korea, which have distinctive methods of heightening detection sensitivity of specific plasma biomarkers. We discuss in detail the multimer detection system, the self-standard analysis of Aβ biomarkers quantified by interdigitated microelectrodes, and a biomarker ratio analysis comprising Aβ and tau.

BACKGROUND AND OBJECTIVES: The scent survey for screening (SSS) test is a subjective olfactory questionnaire devised for this study. We demonstrated the correlation of the SSS test with other olfactory tests and the efficacy of the SSS test as an olfactory screening test compared to KVSSII. SUBJECTS AND METHOD: A total of 363 patients who visited our ORL outpatient department underwent the SSS test, VAS, and KVSS I and II. The patients were divided into two groups, a group with normal olfactory function and a group with olfactory dysfunction according to the KVSS II test. In each group, the correlations between the olfactory tests were studied, and the cut-off value of the SSS test as a screening test was investigated. RESULTS: There was positive correlation between CCSIT and KVSS I, II, T, D, and I tests and the SSS test in the total group and in the olfactory dysfunction group (p<0.05). The identification test in the KVSS II showed the highest positive correlation. While the cut-off value of normal olfactory function in the KVSS II is 28, the SSS test showed the highest specificity and sensitivity of 74 under an ROC curve. CONCLUSION: The SSS test showed very high correlation with other olfactory tests, especially in an olfactory dysfunction group. This result indicates that the SSS is appropriate as a screening test to select people with olfactory disorder.
Humans ; Mass Screening* ; Methods ; Olfaction Disorders ; Outpatients ; ROC Curve ; Sensitivity and Specificity

OBJECTIVES: One hypothesis of obstructive sleep apnea syndrome (OSAS) is that long-standing snoring vibrations and hypoxia of the nerves cause a local neuropathy in the upper airway during sleep. The aim of this study was to investigate olfactory function in subjects comprising snorers and untreated subjects with OSAS, and to correlate data with polysomnographic parameters. METHODS: Sixty-nine patients were evaluated for snoring from January 2010 to December 2013. The mild group (apneahypopnea index [AHI]<15) consisted of 19 subjects, and the moderate-severe group (AHI≥15) consisted of 50 subjects. Exclusion criteria were conductive olfactory dysfunction, previous tonsil or soft palatal surgery, central sleep apnea, and medications that are known to affect peripheral nerves. Nocturnal polysomnography and olfactory function test such as Korean version of Sniffin’s stick test I, II (KVSS I, II) were performed. RESULTS: There was a significant difference in body mass index, average oxygen saturation (SaO2), lowest SaO2, average snoring duration, and KVSS I, II between the two groups. AHI was related to odor threshold score, and average SaO2 was related to odor discrimination score. But, odor identification score showed no relation with AHI and average SaO2 except for age. Average SaO2 and AHI were closely related to the function of smell. CONCLUSION: Hypoxia and low nasal airflow caused by OSAS may have an effect on the olfactory function. On comparison between the two groups, patients with a high AHI, especially those with OSAS, had an olfactory dysfunction. Also, low average oxygen is the main risk factor in determining the olfactory function. In people with OSAS, the possibility of olfactory dysfunction should be considered and an olfactory function test should be performed.
Anoxia ; Body Mass Index ; Discrimination (Psychology) ; Humans ; Odors ; Olfaction Disorders ; Oxygen ; Palatine Tonsil ; Peripheral Nerves ; Polysomnography ; Risk Factors ; Sleep Apnea Syndromes* ; Sleep Apnea, Central ; Sleep Apnea, Obstructive ; Smell ; Snoring ; Vibration

Mice deficient in the toll-like receptor (TLR) or the myeloid differentiation factor 88 (MyD88) are resistant to acute liver failure (ALF) with sudden death of hepatocytes. Chalcone derivatives from medicinal plants protect from hepatic damages including ALF, but their mechanisms remain to be clarified. Here, we focused on molecular basis of piperidylmethyloxychalcone (PMOC) in the treatment of TLR/MyD88-associated ALF. C57BL/6J mice were sensitized with D-galactosamine (GalN) and challenged with Escherichia coli lipopolysaccharide (LPS, TLR4 agonist) or oligodeoxynucleotide containing unmethylated CpG motif (CpG ODN, TLR9 agonist) for induction of ALF. Post treatment with PMOC sequentially ameliorated hepatic inflammation, apoptosis of hepatocytes, severe liver injury and shock-mediated death in ALF-induced mice. As a mechanism, PMOC inhibited the catalytic activity of TGF-β-activated kinase 1 (TAK1) in a competitive manner with respect to ATP, displaced fluorescent ATP probe from the complex with TAK1, and docked at the ATP-binding active site on the crystal structure of TAK1. Moreover, PMOC inhibited TAK1 auto-phosphorylation, which is an axis in the activating pathways of nuclear factor-κB (NF-κB) or activating protein 1 (AP1), in the liver with ALF in vivo or in primary liver cells stimulated with TLR agonists in vitro. PMOC consequently suppressed TAK1-inducible NF-κB or AP1 activity in the inflammatory injury, an early pathogenesis leading to ALF. The results suggested that PMOC could contribute to the treatment of TLR/MyD88-associated ALF with the ATP-binding site of TAK1 as a potential therapeutic target.
Adenosine Triphosphate ; Animals ; Apoptosis ; Catalytic Domain ; Chalcone ; Death, Sudden ; Escherichia coli ; Hepatocytes ; In Vitro Techniques ; Inflammation ; Liver ; Liver Failure, Acute* ; Mice ; Myeloid Differentiation Factor 88 ; Phosphotransferases ; Plants, Medicinal ; Toll-Like Receptors