Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease that leads to progressive weakness of the respiratory and limb muscles. Consequently, most patients with ALS exhibit progressive ...hypoventilation, which worsens during sleep. The aim of this study was to evaluate the relationship between nocturnal hypoxia and cognitive dysfunction and to assess the pattern of nocturnal hypoxia in patients with ALS.
Twenty-five patients with definite or probable ALS underwent neuropsychologic testing, nocturnal pulse oximetry, and capnography. Patients were grouped according to the presence of nocturnal hypoxia (SpO2<95% for ≥10% of the night) and their clinical characteristics and cognitive function were compared.
Compared to patients without nocturnal hypoxia, those with nocturnal hypoxia (n = 10, 40%) had poor memory retention (p = 0.039) and retrieval efficiency (p = 0.045). A cluster-of-desaturation pattern was identified in 7 patients (70%) in the Hypoxia Group.
These results suggest that nocturnal hypoxia can be related to cognitive dysfunction in ALS. In addition, a considerable number of patients with ALS may be exposed to repeated episodes of deoxygenation-reoxygenation (a cluster-of-desaturation pattern) during sleep, which could be associated with the generation of reactive oxygen species. Further studies are required to define the exact causal relationships between these phenomena, the exact manifestations of nocturnal cluster-of-desaturation patterns, and the effect of clusters of desaturation on ALS progression.
Thermoreception is an important cutaneous sense, which plays a role in the maintenance of our body temperature and in the detection of potential noxious heat stimulation. In this study, we ...investigated event‐related fields (ERFs) and neural oscillatory activities, which were modulated by warmth stimulation. We developed a warmth stimulator that could elicit a warmth sensation, without pain or tactile sensation, by using a deep‐penetrating 980‐nm diode laser. The index finger of each participant (n = 24) was irradiated with the laser warmth stimulus, and the cortical responses were measured using magnetoencephalography (MEG). The ERFs and oscillatory responses had late latencies (∼1.3 s and 1.0–1.5 s for ERFs and oscillatory responses, respectively), which could be explained by a slow conduction velocity of warmth‐specific C‐fibers. Cortical sources of warmth‐related ERFs were seen in the bilateral primary and secondary somatosensory cortices (SI and SII), posterior part of the anterior cingulate cortex (pACC), ipsilateral primary motor, and premotor cortex. Thus, we suggested that SI, SII, and pACC play a role in processing the warmth sensation. Time–frequency analysis demonstrated the suppression of the alpha (8–13 Hz) and beta (18–23 Hz) band power in the bilateral sensorimotor cortex. We proposed that the suppressions in alpha and beta band power are involved in the automatic response to the input of warmth stimulation and sensorimotor interactions. The delta band power (1–4 Hz) increased in the frontal, temporal, and cingulate cortices. The power changes in delta band might be related with the attentional processes during the warmth stimulation.
Rapidly reconfigurable, adaptive materials are essential for the realization of "smart", highly engineered technologies sought by aerospace, medicine, and other application areas. Shape memory ...observed in metal alloys and polymers (SMPs) is a primary example of shape change (adaptation). To date, nearly all shape adaptations in SMPs have been thermally triggered. A desire for isothermal, remotely cued shape adaptations of SMP has motivated examinations of other stimuli, such as light. Only a few reports document so-called light-activated SMP, in both cases exploiting photoinduced adjustments to the crosslink density of a polymer matrix with UV light of 365 nm (crosslinking) and 260 nm (decrosslinking). This work presents a distinctive approach to generating light-activated SMP by employing a glassy liquid crystal polymer network (LCN) material that is capable of rapid photo-fixing with short exposures (5 min) of eye-safe 442 nm light. Here, linearly polarized 442 nm light is used to photo-fix temporary states in both cantilever and free-standing geometries which are then thermally or optically restored to the permanent shape. The combination of thermal and photo-fixable shape memory presented here yields substantial functionality in a single adaptive material that could reduce part count in applications. As a demonstration of the opportunities afforded by this functional material, the glassy, photoresponsive LCN is thermally fixed as a catapult and subsequently used to transduce light energy into mechanical work, demonstrated here in the "photo-fueled" launching of an object at a rate of 0.3 m s-1.
The aim of this study was to examine whether integration accuracy increases upon removing artifacts from the registration area when integrating maxillofacial cone beam computed tomography (CBCT) ...scans and intraoral scans.
Three methods were implemented according to the region of interest (ROI): R0, all teeth included as the registration area (artifacts included); R1, anterior teeth included as the registration area (artifacts in premolars and molars not included); and R2, anterior teeth and second molars included as the registration area (artifacts in premolars and first molars not included). Discrepancies between the 2 images were evaluated by using color-mapping methods. The average surface distance was calculated by measuring the shell/shell deviations for overall discrepancies and 3-dimensional distances between the surface points on the 2 images for registration discrepancies.
The R1 method showed more discrepancies between the CBCT and intraoral scans compared with the other 2 methods. The R2 method showed smaller overall discrepancy values compared with the R1 method. Most CBCT artifacts were located in the posterior area. Registration discrepancies were greatest in the x-dimension.
The results suggest that intraoral and CBCT scans might be integrated by using a registration method that involves exclusion of artifacts and inclusion of the second molar on both sides.
Colposcopy is widely used to detect cervical cancers, but experienced physicians who are needed for an accurate diagnosis are lacking in developing countries. Artificial intelligence (AI) has been ...recently used in computer-aided diagnosis showing remarkable promise. In this study, we developed and validated deep learning models to automatically classify cervical neoplasms on colposcopic photographs. Pre-trained convolutional neural networks were fine-tuned for two grading systems: the cervical intraepithelial neoplasia (CIN) system and the lower anogenital squamous terminology (LAST) system. The multi-class classification accuracies of the networks for the CIN system in the test dataset were 48.6 ± 1.3% by Inception-Resnet-v2 and 51.7 ± 5.2% by Resnet-152. The accuracies for the LAST system were 71.8 ± 1.8% and 74.7 ± 1.8%, respectively. The area under the curve (AUC) for discriminating high-risk lesions from low-risk lesions by Resnet-152 was 0.781 ± 0.020 for the CIN system and 0.708 ± 0.024 for the LAST system. The lesions requiring biopsy were also detected efficiently (AUC, 0.947 ± 0.030 by Resnet-152), and presented meaningfully on attention maps. These results may indicate the potential of the application of AI for automated reading of colposcopic photographs.
Nanoplastics (NPs) exposure to humans can occur through various routes, including the food chain, drinking water, skin contact, and respiration. NPs are plastics with a diameter of less than 100 nm ...and have the potential to accumulate in tissues, leading to toxic effects. This study aimed to investigate the neurotoxicity of polystyrene NPs on neural progenitor cells (NPCs) and hippocampal neurogenesis in a rodent model. Toxicity screening of polystyrene NPs based on their charge revealed that cationic amine-modified polystyrene (PS–NH3+) exhibited cytotoxicity, while anionic carboxylate-modified polystyrene (PS–COO-) and neutral NPs (PS) did not. NPCs treated with PS-NH3+ showed a significant reduction in growth rate due to G1 cell cycle arrest. PS-NH3+ increased the expression of cell cycle arrest markers p21 and p27, while decreasing cyclin D expression in NPCs. Interestingly, PS-NH3+ accumulated in mitochondria, leading to mitochondrial dysfunction and energy depletion, which caused G1 cell cycle arrest. Prolonged exposure to PS-NH3+ in C17.2 NPCs increased the expression of p16 and senescence-associated secretory phenotype factors, indicating cellular senescence. In vivo studies using C57BL/6 mice demonstrated impaired hippocampal neurogenesis and memory retention after 10 days of PS-NH3+ administration. This study suggests that NPs could deplete neural stem cell pools in the brain by mitochondrial dysfunction, thereby adversely affecting hippocampal neurogenesis and neurocognitive functions.
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•Positively charged polystyrene NP (PS–NH3+) is toxic to NPCs.•PS-NH3+ induces p53-independent cell cycle arrest at the G1 phase in NPCs.•PS-NH3+ accumulates in mitochondria, causing mitochondrial dysfunction in NPCs.•Long-term exposure to PS-NH3+ induces senescence in NPCs.•The exposure to PS-NH3+ impairs hippocampal neurogenesis and mememory retention in young mice.
Abstract
Energy-based computing is a promising approach for addressing the rising demand for solving NP-hard problems across diverse domains, including logistics, artificial intelligence, ...cryptography, and optimization. Probabilistic computing utilizing pbits, which can be manufactured using the semiconductor process and seamlessly integrated with conventional processing units, stands out as an efficient candidate to meet these demands. Here, we propose a novel pbit unit using an NbO
x
volatile memristor-based oscillator capable of generating probabilistic bits in a self-clocking manner. The noise-induced metal-insulator transition causes the probabilistic behavior, which can be effectively modeled using a multi-noise-induced stochastic process around the metal-insulator transition temperature. We demonstrate a memristive Boltzmann machine based on our proposed pbit and validate its feasibility by solving NP-hard problems. Furthermore, we propose a streamlined operation methodology that considers the autocorrelation of individual bits, enabling energy-efficient and high-performance probabilistic computing.
Mutations in the X-linked methyl-CpG-binding protein 2 (MECP2) gene were first described as a cause of Rett syndrome. MECP2 duplication can cause intellectual disability, developmental delay, severe ...feeding difficulties, and recurrent infections. Here, we report a Korean family with MECP2 duplication syndrome, which was previously misdiagnosed as cerebral palsy. A man in his early 30 s visited our clinic with intellectual disability, speech impairment, epilepsy, and progressive spasticity. He had been previously misdiagnosed with cerebral palsy, and had received orthopedic surgeries such as musculotendinous lengthening and derotational osteotomy. After the surgeries, he received comprehensive rehabilitation. Upon carefully checking his family history, we noted that his younger brother had similar symptoms. Next-generation sequencing revealed whole exon duplication in MECP2 in both the patient and his brother; their mother also had this genetic mutation but was asymptomatic. Early diagnosis is essential for improving the success of MECP2 duplication syndrome treatment. Individuals with MECP2 duplication syndrome should be referred to specialists to manage multidisciplinary symptoms and to regularly check for complications that are common in this syndrome.
This study aimed to evaluate the association between the dietary intake of vitamin B complex (thiamine, riboflavin, and niacin) and cervical cancer in Korea.
The data from the Korean National Health ...and Nutrition Examination Survey (KNHANES) from 2010 to 2021 were analyzed, which included 28,306 participants who were categorized into non-cervical cancer and cervical cancer groups. The following dietary intake threshold levels of thiamine, riboflavin, and niacin were identified based on the recommended daily allowances (RDAs): thiamine, 1.1 mg/day; riboflavin, 1.2 mg/day; and niacin, 14 mg/day.
Among 28,306 participants, 27,976 were in the non-cervical cancer group and 330 were in the cervical cancer group. Riboflavin intakes of more than 1.2 mg/day but less than 2.4 mg/day were associated with a significantly reduced risk of cervical cancer, whereas intakes of above 2.4 mg/day were not associated with cervical cancer. Thiamine and niacin intakes were not significantly related to the risk of cervical cancer.
The results of this study suggest that an intake of riboflavin of 1.2-2.4 mg/day may contribute to a lower risk of cervical cancer.
Patients with ALS may be exposed to variable degrees of chronic intermittent hypoxia. However, all previous experimental studies on the effects of hypoxia in ALS have only used a sustained hypoxia ...model and it is possible that chronic intermittent hypoxia exerts effects via a different molecular mechanism from that of sustained hypoxia. No study has yet shown that hypoxia (either chronic intermittent or sustained) can affect the loss of motor neurons or cognitive function in an in vivo model of ALS.
To evaluate the effects of chronic intermittent hypoxia on motor and cognitive function in ALS mice.
Sixteen ALS mice and 16 wild-type mice were divided into 2 groups and subjected to either chronic intermittent hypoxia or normoxia for 2 weeks. The effects of chronic intermittent hypoxia on ALS mice were evaluated using the rotarod, Y-maze, and wire-hanging tests. In addition, numbers of motor neurons in the ventral horn of the spinal cord were counted and western blot analyses were performed for markers of oxidative stress and inflammatory pathway activation.
Compared to ALS mice kept in normoxic conditions, ALS mice that experienced chronic intermittent hypoxia had poorer motor learning on the rotarod test, poorer spatial memory on the Y-maze test, shorter wire hanging time, and fewer motor neurons in the ventral spinal cord. Compared to ALS-normoxic and wild-type mice, ALS mice that experienced chronic intermittent hypoxia had higher levels of oxidative stress and inflammation.
Chronic intermittent hypoxia can aggravate motor neuronal death, neuromuscular weakness, and probably cognitive dysfunction in ALS mice. The generation of oxidative stress with activation of inflammatory pathways may be associated with this mechanism. Our study will provide insight into the association of hypoxia with disease progression, and in turn, the rationale for an early non-invasive ventilation treatment in patients with ALS.
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