Correlation between visual association memory test and structural changes in patients with Alzheimer's disease and amnestic mild cognitive impairment.

BACKGROUND: Visual association memory test (VAMT) is a brief 6-point cognition test that has been shown to be effective in differentiating Alzheimer's disease (AD) from other types of dementia. This study aimed to investigate the correlation of the VAMT performance with amyloid plaque burden and hippocampal atrophy. METHODS: Fourteen patients with AD, 29 with amnestic mild cognitive impairment (aMCI), and 11 normal cognition (NC) subjects were recruited. Brain magnetic resonance imaging (MRI) and [18F]AV-45 positron emission tomography (PET) were performed to evaluate hippocampal atrophy and amyloid plaque burden. RESULTS: The VAMT median score and interquartile range of the NC, aMCI and AD groups were 6 (6-6), 2 (0-4), and 0 (0-1), respectively (p < 0.001). The hippocampal atrophy was correlated with VAMT results across each group. The VAMT score was correlated with the occipital and parietal cortical [18F]AV-45 uptake in the NC group, and with the frontal, parietal and precuneus uptake in the aMCI group. However, no correlation between VAMT score and [18F]AV-45 uptake was found in the AD group. CONCLUSION: The VAMT can be an adjunctive cognitive test to identify patients with AD, and the early amyloid plaque accumulation is correlated with VAMT scores in patients with aMCI and even NC subjects.

Exploring the multifaceted impact of lanthanides on physiological pathways in human breast cancer cells.

Lanthanum (La) and cerium (Ce), rare earth elements with physical properties similar to calcium (Ca), are generally considered non-toxic when used appropriately. However, their ions possess anti-tumor capabilities. This investigation explores the potential applications and mechanisms of LaCl3 or CeCl3 treatment in triple-negative breast cancer (TNBC) cell lines. TNBC, characterized by the absence of estrogen receptor (ERα), progesterone receptor (PR), and human epidermal growth factor receptor 2 (HER-2) expression, is prone to early metastasis and resistant to hormone therapy. Our results demonstrate that La/Ce treatment reduces cell growth, and when combined with cisplatin, it synergistically inhibits cell growth and the PI3K/AKT pathway. La and Ce induce oxidative stress by disrupting mitochondrial function, leading to protein oxidation. Additionally, they interfere with protein homeostasis and induce nucleolar stress. Furthermore, disturbance in F-actin web formation impairs cell migration. This study delves into the mechanism by which calcium-like elements La and Ce inhibit breast cancer cell growth, shedding light on their interference in mitochondrial function, protein homeostasis, and cytoskeleton assembly.

Toxicity evaluation of neonicotinoids to earthworm (Eisenia fetida) behaviors by a novel locomotion tracking assay.

Pesticides are substances used for controlling, preventing, and repelling pests in agriculture. Among them, neonicotinoids have become the fastest-growing class of insecticides because of their efficiency in targeting pests. They work by strongly binding to nicotinic acetylcholine receptors (nAChRs) in the central nervous system of insects, leading to receptor blockage, paralysis, and death. Despite their selectivity for insects, these substances may be hazardous to non-target creatures, including earthworms. Although earthworms may be invasive in some regions like north America, they contribute to the development of soil structure, water management, nutrient cycling, pollution remediation, and cultural services, positively impacting the environment, particularly in the soil ecosystem. Thus, this study aimed to develop a novel earthworm behavior assay since behavior is a sensitive marker for toxicity assay, and demonstrated its application in evaluating the toxicity of various neonicotinoids. Here, we exposed Eisenia fetida to 1 and 10 ppb of eight neonicotinoids (acetamiprid, clothianidin, dinotefuran, imidacloprid, nitenpyram pestanal, thiacloprid, thiametoxam, and sulfoxaflor) for 3 days to observe their behavior toxicities. Overall, all of the neonicotinoids decreased their locomotion, showed by a reduction of average speed by 24.94-68.63% and increment in freezing time movement ratio by 1.51-4.25 times, and altered their movement orientation and complexity, indicated by the decrement in the fractal dimension value by 24-70%. Moreover, some of the neonicotinoids, which were acetamiprid, dinotefuran, imidacloprid, nitenpyram, and sulfoxaflor, could even alter their exploratory behaviors, which was shown by the increment in the time spent in the center area value by 6.94-12.99 times. Furthermore, based on the PCA and heatmap clustering results, thiametoxam was found as the neonicotinoid that possessed the least pronounced behavior toxicity effects among the tested pesticides since these neonicotinoid-treated groups in both concentrations were grouped in the same major cluster with the control group. Finally, molecular docking was also conducted to examine neonicotinoids' possible binding mechanism to Acetylcholine Binding Protein (AChBP), which is responsible for neurotransmission. The molecular docking result confirmed that each of the neonicotinoids has a relatively high binding energy with AChBP, with the lowest binding energy was possessed by thiametoxam, which consistent with its relatively low behavior toxicities. Thus, these molecular docking results might hint at the possible mechanism behind the observed behavior alterations. To sum up, the present study demonstrated that all of the neonicotinoids altered the earthworm behaviors which might be due to their ability to bind with some specific neurotransmitters and the current findings give insights into the toxicities of neonicotinoids to the environment, especially animals in a soil ecosystem.

Using microfluidic and conventional platforms to evaluate the effects of lanthanides on spheroid formation.

Metastasis contributes to the increased mortality rate of cancer, but the intricate mechanisms remain unclear. Cancer cells from a primary tumor invade nearby tissues and access the lymphatic or circulatory system. If these cells manage to survive and extravasate from the vasculature into distant tissues and ultimately adapt to survive, they will proliferate and facilitate malignant tumor formation. Traditional two-dimensional (2D) cell cultures offer a rapid and convenient method for validating the efficacy of anticancer drugs within a reasonable cost range, but their utility is limited because of tumors' high heterogeneity in vivo and spatial complexities. Three-dimensional (3D) cell cultures that mimic the physiological conditions of cancer cells in vivo have gained considerable interest. In these cultures, cells assemble into spheroids through gravity, magnetic forces, or their low-adhesion to the plates. Although these approaches address some of the limitations of 2D cultures, they often require a considerable amount of time and cost. Therefore, this study aims to enhance the effectiveness of 3D culture techniques by using microfluidic systems to provide a high-throughput and sensitive pipeline for drug screening. Using these systems, we studied the effects of lanthanide elements, which have garnered interest in cancer treatment, on spheroid formation and cell spreading. Our findings suggest that these elements alter the compactness of cell spheroids and decrease cell mobility.

Gallium maltolate shows synergism with cisplatin and activates nucleolar stress and ferroptosis in human breast carcinoma cells.

PURPOSE: Breast cancer is the most common cancer in women. Triple-negative breast cancer (TNBC) is an aggressive disease with poor outcomes. TNBC lacks effective targeted treatments, and the development of drug resistance limits the effectiveness of chemotherapy. It is crucial to identify new drugs that can enhance the efficacy of traditional chemotherapy to reduce drug resistance and side effects. METHODS: TNBC cell lines, MDA-MB-231 and Hs 578T, and a normal cell line, MCF-10 A, were included in this study. The cells were treated with gallium maltolate (GaM), and their transcriptome was analyzed. Ferroptosis and nucleolar stress markers were detected by qPCR, western blotting, fluorescence microscopy, and flow cytometry. The impairment of ribosome synthesis was evaluated by northern blotting and sucrose gradients. RESULTS: GaM triggered cell death via apoptosis and ferroptosis. In addition, GaM impaired translation and activated nucleolar stress. Cisplatin (DDP) is a chemotherapeutic agent for advanced breast cancer. While single treatment with GaM or DDP at low concentrations did not impact cell growth, co-administration enhanced cell death in TNBC but not in normal breast cells. The enhancement of ferroptosis and nucleolar stress could be observed in TNBC cell lines after co-treatment. CONCLUSIONS: These results suggest that GaM synergizes with cisplatin via activation of nucleolar stress and ferroptosis in human breast carcinoma cells. GaM is marginally toxic to normal cells but impairs the growth of TNBC cell lines. Thus, GaM has the potential to be used as a therapeutic agent against TNBC.

5 days of time-restricted feeding increases fat oxidation rate but not affect postprandial lipemia: a crossover trial.

Studies have revealed that time-restricted feeding affects the fat oxidation rate; however, its effects on the fat oxidation rate and hyperlipidemia following high-fat meals are unclear. This study investigated the effects of 5-day time-restricted feeding on the fat oxidation rate and postprandial lipemia following high fat meals. In this random crossover experimental study, eight healthy male adults were included each in the 5-day time-restricted feeding trial and the control trial. The meals of the time-restricted feeding trial were provided at 12:00, 16:00, and 20:00. The meals of the control trial were provided at 08:00, 14:00, and 20:00. The contents of the meals of both trials were the same, and the calories of the meals met the 24-h energy requirement of the participants. After 5 days of the intervention, the participants consumed high-fat meals on the sixth day, and their physiological changes were determined. The fasting fat oxidation rate (p < 0.001) and postprandial fat oxidation rate (p = 0.019) of the time-restricted feeding trial were significantly higher than those of the control trial. The 24-h energy consumption and postprandial triglyceride, blood glucose, insulin, glycerol, and free fatty acid concentrations of the two trials showed no significant differences (p > 0.05). The results revealed that 5 days of time-restricted feeding effectively increased the fasting and postprandial fat oxidation rate, but it did not affect postprandial lipemia.

Nociceptor neurons promote IgE class switch in B cells.

Nociceptors, the high-threshold primary sensory neurons that trigger pain, interact with immune cells in the periphery to modulate innate immune responses. Whether they also participate in adaptive and humoral immunity is, however, not known. In this study, we probed if nociceptors have a role in distinct airway and skin models of allergic inflammation. In both models, the genetic ablation and pharmacological silencing of nociceptors substantially reduced inflammatory cell infiltration to the affected tissue. Moreover, we also found a profound and specific deficit in IgE production in these models of allergic inflammation. Mechanistically, we discovered that the nociceptor-released neuropeptide substance P helped trigger the formation of antibody-secreting cells and their release of IgE. Our findings suggest that nociceptors, in addition to their contributions to innate immunity, play a key role in modulating the adaptive immune response, particularly B cell antibody class switching to IgE.

Association of apolipoproteins e4 and c1 with onset age and memory: a study of sporadic Alzheimer disease in Taiwan.

OBJECTIVE: To identify clinical manifestations and neuropsychological effects of Alzheimer disease (AD) in apolipoprotein (ApoE) e4 carriers and to investigate the relationships between ApoE HhaI polymorphism and apolipoprotein C1 (APOC1) HpaI polymorphism in Taiwanese patients with AD. PARTICIPANTS AND METHODS: A total of 127 patients with AD and 191 elderly individuals were screened for ApoE and APOC1 polymorphism. All patients underwent neuropsychological testing, including a Mini-Mental Status Examination (MMSE), Clinical Dementia Rating (CDR), and/or the Visual Association Memory Test (VAMT) with Cognitive Abilities Screening Instrument. RESULTS: The frequencies of the e4 and A alleles were significantly higher in the AD group. In the patients with AD, the e4 and A allele effects on those with an age-of-onset of 60 to 79 years were stronger than those with an age-of-onset of 80 years or higher. Visual Association Memory Test performance was significantly worse in e4-allele carriers but not in A-allele carriers, in the early AD, particularly in those affected with AD for less than 2 years. Although there was no statistically significant difference in genotypic frequency between patients and controls, the 2 genes were linked. In addition, the presence of the AA genotype concomitant with the e4 allele may be better associated with AD diagnosis than either factor alone. CONCLUSION: We conclude that the e4 allele affects neuropsychological performance and illness morbidity. Concomitantly, ApoE e4 and APOC1 A alleles have a better association with AD than ApoE e4 alone. In addition, APOC1 may partially contribute to the pathogenesis of AD, but the nature of its relationship with e4 requires further investigation.

Sequence and phylogenetic analysis of the thrombospondin-related adhesive protein (TRAP) gene of Babesia gibsoni isolates from dogs in Taiwan.

The genetic diversity of Babesia gibsoni strains worldwide is currently poorly defined. The aim of the present study was to characterize B. gibsoni strains in naturally infected dogs in Taiwan using a combination of polymerase chain reaction (PCR) and sequence analysis of both 18S rDNA and the gene encoding thrombospondin-related adhesive protein (TRAP). Genomic DNA was extracted from 29 parasitemic dogs, and the target genes were separately amplified, sequenced and aligned with corresponding sequences available in GenBank. All 18S rDNA sequences (1,262 bp) amplified from the Taiwanese isolates were identical to each other and had very high similarity (99.9-100%) with previously reported B. gibsoni sequences. These results provide the first molecular evidence showing infection of dogs with B. gibsoni from Taiwan. On the other hand, a phylogenetic analysis based on the deduced amino acid sequence of the TRAP gene demonstrated that the Taiwanese isolates were closely related to strains previously identified from Okinawa Island, Japan, but genetically distinct from strains found on Honshu in Japan and Jeju Island in South Korea. The divergence of TRAP among the geographically dispersed strains examined in this study and others supports the conclusion that this gene is useful for molecular genotyping of B. gibsoni strains.

Remyelination alters the pattern of myelin in the cerebral cortex.

Destruction of oligodendrocytes and myelin sheaths in cortical gray matter profoundly alters neural activity and is associated with cognitive disability in multiple sclerosis (MS). Myelin can be restored by regenerating oligodendrocytes from resident progenitors; however, it is not known whether regeneration restores the complex myelination patterns in cortical circuits. Here, we performed time lapse in vivo two photon imaging in somatosensory cortex of adult mice to define the kinetics and specificity of myelin regeneration after acute oligodendrocyte ablation. These longitudinal studies revealed that the pattern of myelination in cortex changed dramatically after regeneration, as new oligodendrocytes were formed in different locations and new sheaths were often established along axon segments previously lacking myelin. Despite the dramatic increase in axonal territory available, oligodendrogenesis was persistently impaired in deeper cortical layers that experienced higher gliosis. Repeated reorganization of myelin patterns in MS may alter circuit function and contribute to cognitive decline.

Fabrication of Hydrophilic Surface on Rigid Gas Permeable Contact Lenses to Enhance the Wettability Using Ultraviolet Laser System.

The widely used rigid gas permeable (RGP) contact lenses provide higher oxygen permeability and tear exchange rate than do soft contact lenses. However, their wettability warrants improvement to enhance the wearing comfort. This study used UV laser (wavelength = 355 nm) to modify the surface properties of RGP contact lenses with materials of Boston XO® (Bausch & Lomb Incorporated). Briefly, the mesh pattern was fabricated on the RGP contact lens surface by using the laser and smoothed by using oxygen plasma; the enhanced hydrophilic efficiency was analyzed using contact angle measurement. The experiment results indicated that the contact angle of the lens material decreased by approximately 10°-20° when the pitch of mesh pattern was <50 µm under a 500-mm/s scanning speed. The oxygen plasma enhanced surface wettability with a decreased contact angle (40°). The hydrophilic characteristic of the UV laser and oxygen plasma-treated surface was twice that of oxygen plasma-treated and untreated surfaces. In the future, RGP contact lens edges could be treated with UV laser and oxygen plasma to enhance the tear wettability and wearing comfort.

Clinical evaluation of the eBsensor hand-held blood glucose monitoring system.

BACKGROUND: Home glucose monitoring system is increasingly recognized as an important tool for glycemic control. We evaluated the clinical performance of the eBsensor glucose monitoring system. METHODS: Fingertip capillary blood glucose concentrations from 282 subjects were measured using eBsensor glucose monitoring system and compared against predicate devices and the Yellow Springs Instruments (YSI) 2300 blood glucose analyzer. Accuracy and precision of the eBsensor glucose monitoring system were assessed using several methods. The comparative study between the eBsensor and 2 currently marketed monitoring systems was performed. RESULTS: The 282 eBsensor readings covered a wide range from 2.6 to 24.4 mmol/l. Deming regression and Pearson correlation analyses showed a linear relationship between the eBsensor readings and the YSI reference method (eBsensor=0.9496 YSI+0.4127 mmol/l; r=0.98). Error Grid analysis demonstrated that 100% of the eBsensor readings in clinically acceptable zones A and B. The CVs for the 6 lots of strips were within the satisfactory interval (<6%). The comparative study showed that the eBsensor readings correlated well with the OneTouch Ultra values (r=0.97) and the Glucocard II values (r=0.97). CONCLUSIONS: eBsensor is a reliable glucose monitoring system which provides high accurate and precise glucose readings over a wide range of glucose concentrations.

Carbon disulfide encephalopathy: cerebral microangiopathy.

To understand cerebral blood circulation after long-term exposure to carbon disulfide (CS2), four patients with encephalopathy and polyneuropathy, who had worked in a viscose rayon plant, were studied. Clinical and laboratory examinations, including brain magnetic resonance images (MRI), computed tomography (CT), CT perfusion, and CT angiography, were carried out. Brain CT and MRI disclosed mild cortical atrophy in all four patients, and multiple lesions in the subcortical white matter, and basal ganglia in three patients. Brain CT angiography and perfusion revealed a statistically significant decrease of cerebral blood flow (CBF) in the total brain parenchyma and basal ganglia, and a decrease of the cerebral blood volume (CBV) in the basal ganglia and a prolonged mean transit time (MTT) in the total brain parenchyma, and the territories of the internal carotid artery (ICA), basal ganglia and occipital lobe. In conclusion, the decrease of CBV and CBF, and the prolonged MTT in the total brain parenchyma, ICA, basal ganglia and occipital lobes, indicated a microangiopathy in patients with CS2 encephalopathy.

Visual association memory test in differentiating early stage of Alzheimer's disease from vascular dementia.

We studied the results of the Visual Association Memory Test (VAMT) in differentiating Alzheimer's disease (AD) and vascular dementia (VaD). In addition, other basic neuropsychological tests, including the Mini-Mental State Examination (MMSE) and the Clinical Dementia Rating (CDR) were also used. Generally, with the VAMT, AD patients had a worse performance than VaD patients. Particularly among patients with a CDR = 0.5, the AD patients had statistically significantly lower VAMT scores (score less than 3) (p = 0.026) compared to those of VaD patients. However, the VAMT could not predict clinical severity or disease progression. The VAMT, as revealed in this study, is a brief, simply administered, and less biased test, and may offer a diagnostic adjunct to differentiate AD from VaD especially in an early dementia state.

Brain magnetic resonance image changes in a family with congenital and classic myotonic dystrophy.

We present the clinical manifestations, brain magnetic resonance images (MRI), and genetic analysis of a family with 2 siblings with congenital myotonic dystrophy type 1 (DM1) and 4 patients with classic DM1. These 2 patients with congenital DM1 had severe mental retardation and a characteristic feature of hyperintensity of white matter at the posterior-superior trigone (HWMPST), in addition to ventricular dilatation in T2-weighted images (T2WI) of brain MRI. In 2 of the 4 classic DM1 patients, brain T2WI MRI showed hyperintensity lesions in the bilateral frontal and/or temporal regions, which were absent in congenital DM1. In conclusion, we suggest that the HWMPST in brain MRI is a characteristic finding in congenital DM1, and that the severe cognitive impairments are not only attributable to the subcortical white matter lesions. In congenital DM1, the cognitive function is a diffuse impairment, which is different from that in classic DM1.

Multiple analytical approaches demonstrate a complex relationship of genetic and nongenetic factors with cisplatin- and carboplatin-induced nephrotoxicity in lung cancer patients.

BACKGROUND: Cisplatin and carboplatin cause nephrotoxicity by forming platinum-DNA adducts and lead to cell death. METHODS: One-hundred and sixteen Taiwanese lung cancer patients who received cisplatin or carboplatin more than twice were recruited, and their genotypes were determined. The risk of renal dysfunction, injury to the kidney, failure of kidney function, loss of kidney function, and end-stage kidney disease (RIFLE) criteria were used to evaluate the occurrence of nephrotoxicity. A logistic regression, multiple regression with a classification and regression tree (CART), and the Framingham study risk score were used to analyze interactions between genetic and nongenetic factors in producing platinum-induced nephrotoxicity. RESULTS: ERCC1 118C and TP53 72Arg polymorphisms were associated with increased risks of platinum-induced nephrotoxicity. Other risk factors found included the platinum type, baseline serum creatinine (Scr), coadministration of vinorelbine, and the number of chemotherapy cycles. The overall prediction rate of the CART was 82.7%, with a sensitivity of 0.630 and specificity of 0.896. The Framingham study risk prediction model contained 7 factors. Its prediction rate was 84.5%, with a sensitivity of 0.643 and specificity of 0.909. CONCLUSIONS: Genetic polymorphisms of ERCC1 and TP53 are risk factors for nephrotoxicity. The CART analysis may provide a clinically applicable model to predict the risk of cisplatin- and carboplatin-induced nephrotoxicity.

Sequence and phylogenetic analysis of the gp200 protein of Ehrlichia canis from dogs in Taiwan.

Ehrlichia (E.) canis is a Gram-negative obligate intracellular bacterium responsible for canine monocytic ehrlichiosis. Currently, the genetic diversity of E. canis strains worldwide is poorly defined. In the present study, sequence analysis of the nearly full-length 16S rDNA (1,620 bp) and the complete coding region (4,269 bp) of the gp200 gene, which encodes the largest major immunoreactive protein in E. canis, from 17 Taiwanese samples was conducted. The resultant 16S rDNA sequences were found to be identical to each other and have very high homology (99.4~100%) with previously reported E. canis sequences. Additionally, phylogenetic analysis of gp200 demonstrated that the E. canis Taiwanese genotype was genetically distinct from other reported isolates obtained from the United States, Brazil, and Israel, and that it formed a separate clade. Remarkable variations unique to the Taiwanese genotype were found throughout the deduced amino acid sequence of gp200, including 15 substitutions occurring in two of five known species-specific epitopes. The gp200 amino acid sequences of the Taiwanese genotype bore 94.4~94.6 identities with those of the isolates from the United States and Brazil, and 93.7% homology with that of the Israeli isolate. Taken together, these results suggest that the Taiwanese genotype represents a novel strain of E. canis that has not yet been characterized.

Detection and characterization of four novel genotypes of Ehrlichia canis from dogs.

The genetic diversity of Ehrlichia canis strains worldwide is currently poorly defined. The present study aimed to characterize E. canis strains in naturally infected dogs in Taiwan, using a combination of PCR and sequence analysis of the 16S rDNA and two antigen-encoding genes, gp19 and gp36. Genomic DNA was extracted from 34 parasitemic dogs and the genes of the pathogen were separately amplified, sequenced, and aligned with corresponding sequences available in GenBank. All 16S rDNA sequences (1623 bp) amplified from the Taiwanese isolates were identical and had very high similarity (99.4-100%) with previously reported E. canis sequences. Nevertheless, most of the gp19 gene sequences (414 bp) from the Taiwanese isolates had three specific nucleotide substitutions at positions 9, 323 and 371 that resulted in three amino acid changes. The gp36 gene of the Taiwanese isolates consists of three regions: a 5' end pre-repeat region (426 bp), a tandem repeat region with variable numbers of the 27-bp repeat unit depending on the isolate, and a 3' end region (87 bp). The nucleotide sequences of the 5' end region of gp36 from Taiwanese isolates were identical to each other, but unexpectedly, quite distinct from the sequences of eleven other E. canis strains previously published, with 86.7-87.2% identities only. A phylogenetic tree of E. canis strains based on the gp36 amino acid sequences showed that the Taiwanese isolates fell into a separate clade, indicating the presence of a novel strain that had not yet been characterized.

Subtle Changes in Cutaneous Nerves and Sural Nerve Biopsy in a Patient With Fabry's Disease.

We report the clinical manifestations, and sural nerve and skin biopsy findings in a patient with Fabry's disease who had normal renal function. The patient had a typically painful neuropathy with an increase of sensory thresholds in quantitative sensory tests and a low level of serum alpha-galactosidase. Although the sural nerve biopsy revealed electron-dense bodies in the perineurial cells, normal axon and myelin structures and even the fiber density of large and small myelinated fibers were noted. However, the cutaneous nerve biopsy study showed early changes in the small-fiber neuropathy. The data indicate that a cutaneous nerve biopsy study can be an adjuvant diagnostic tool in some patients with Fabry's disease and a normal renal function.