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ABSTRACT Aims/Introduction This prospective cohort study aims to identify the optimal measure of glycated hemoglobin (HbA1c) variability and to explore its relationship with the development of new diabetic sensorimotor polyneuropathy (DSPN) in individuals with type 2 diabetes mellitus, building upon previous cross‐sectional studies that highlighted a significant association between HbA1c visit‐to‐visit variability and DSPN. Materials and Methods In a prospective study, 321 participants diagnosed with type 2 diabetes mellitus underwent comprehensive clinical assessments, neurophysiologic studies, and laboratory evaluations at enrollment and follow‐up. Various indices, including HbA1c standard deviation (HbA1c SD), coefficient of variation (HbA1c CV), HbA1c change score (HbA1c HVS), and average real variability (HbA1c ARV), were employed to calculate the visit‐to‐visit variability HbA1c based on 3 month intervals. The investigation focused on examining the associations between these indices and the development of new DSPN. Results The average follow‐up duration was 16.9 ± 6.9 months. The Cox proportional hazards model identified age (P = 0.001), diabetes duration (P = 0.024), and HbA1C ARV (P = 0.031) as the sole factors associated with the development of new DSPN. Furthermore, the cumulative risk of developing DSPN over 1 year demonstrated a significant association with HbA1C ARV (P = 0.03, log‐rank test). Conclusions Apart from age and diabetes duration, HbA1c variability emerged as a robust predictor for the occurrence of new DSPN. Among the various measures of HbA1c variability evaluated, HbA1c ARV demonstrated the highest potential as a reliable indicator for anticipating the onset of new DSPN.

Background: Diabetes contributes to a spectrum of complications encompassing microvascular and macrovascular disorders. This study aimed to explore the correlation between distal sensorimotor polyneuropathy (DSPN) severity and heightened carotid atherosclerosis among individuals with type 2 diabetes mellitus (T2DM). Method: Participants underwent comprehensive assessments including nerve conduction studies (NCS), Toronto Clinical Neuropathy Score (TCNS) evaluations, assessment of cardiometabolic risk factors, and carotid sonography studies covering dynamic and morphological parameters. The resistance index (RI), pulsatility index (PI), peak systolic velocity (PSV), and end-diastolic velocity (EDV) in both the common carotid artery (CCA) and internal carotid artery (ICA), carotid intima-media thickness (IMT), and carotid plaque score (CPS) were also measured. Peripheral nerve function severity was assessed using composite amplitude scores (CAS) derived from NCS. Results: Individuals with DSPN exhibited lower EDV in the CCA and ICA (p < 0.0001 and p = 0.002), higher PI and RI in both CCA and ICA (all p < 0.0001), and higher CPS (p = 0.002). They also demonstrated a higher prevalence of retinopathy as an underlying condition, higher index HbA1c, and reduced estimated glomerular filtration rate (eGFR) (all p < 0.0001). Multiple linear regression analysis revealed significant associations where eGFR, ICA-PI, index HbA1c, waist circumference, and age were correlated with CAS. Meanwhile, diabetes duration, waist circumference, age, and index HbA1c showed significant associations with TCNS. Conclusions: Our study suggests that individuals with T2DM who exhibit more severe carotid atherosclerosis may not only be at increased risk of developing DSPN but also may experience greater severity of DSPN. PI in both the CCA and ICA, along with the CPS, serve as surrogate biomarkers for DSPN severity.

Educational robotics has been adopted to create interactive and engaging learning environments to develop computational thinking (CT) in K-12 learners. This study systematically examined 22 peer-reviewed empirical research articles on the use of educational robotics to develop CT in young learners (pre-kindergarten to 6th grade) published between 2012 and 2021. The findings revealed that using robotics activities to develop CT has mostly been studied in the formal education settings with the duration of robotics curricular activities ranging from 80 minutes to 24 hours. The five CT skills studied most often include Sequencing, Conditionals, Loops, Debugging, and Algorithmic Thinking. The different versions of LEGO Mindstorms are the most frequently adopted robotic kits in the examined studies. The most frequently adopted learning and instructional strategies in the robotics activities include collaborative learning, project-based learning, and embodied learning. This paper identified and discussed developmentally appropriated CT skills, robotics kits, and pedagogical approaches suitable for supporting CT development in young learners. The findings can guide educators and instructional designers for future robotics activity design and development endeavors. This paper also identified gaps in the current research and recommended directions for advancing research in adopting robotics to develop CT in young learners.

In the present investigation, we compared the radical-scavenging activities and phenolic contents of seven Taiwanese Cirsium species with a spectrophotometric method. We further analyzed their phytochemical profiles with high-performance liquid chromatography–photodiode array detection (HPLC–DAD). We found that the flower part of Cirsium japonicum var. australe (CJF) showed the best radical-scavenging activities against 1,1-diphenyl-2-picrylhydrazyl (DPPH), 2,2′-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid) (ABTS), and the hypochlorite ion, for which the equivalents were 6.44 ± 0.17 mg catechin/g, 54.85 ± 0.66 mmol Trolox/g and 418.69 ± 10.52 mmol Trolox/g respectively. CJF also had the highest contents of total phenolics (5.23 ± 0.20 mg catechin/g) and phenylpropanoids (29.73 ± 0.72 mg verbascoside/g). According to the Pearson’s correlation coefficient, there was a positive correlation between the total phenylpropanoid content and ABTS radical-scavenging activities (r = 0.979). The radical-scavenging activities of the phenylpropanoids are closely related to their reducing power (r = 0.986). HPLC chromatograms obtained in validated HPLC conditions confirm that they have different phytochemical profiles by which they can be distinguished. Only CJF contained silicristin (0.66 ± 0.03 mg/g) and silydianin (9.13 ± 0.30 mg/g). CJF contained the highest contents of apigenin (5.56 ± 0.09 mg/g) and diosmetin (2.82 ± 0.10 mg/g). Among the major constituents, silicristin had the best radical-scavenging activities against DPPH (71.68 ± 0.66 mg catechin/g) and ABTS (3.01 ± 0.01 mmol Trolox/g). However, diosmetin had the best reducing power and radical-scavenging activity against the hypochlorite anion (41.57 ± 1.14 mg mmol Trolox/g). Finally, we found that flavonolignans (especial silicristin and silydianin) and diosmetin acted synergistically in scavenging radicals.

The purpose of this scoping review is to synthesize knowledge of gamified online course design processes and practices extracted from the peer-reviewed research literature. The scoping review followed a systematic process involving five main stages: (a) identifying research questions, (b) identifying relevant studies, (c) study selection, (d) charting the data, and (e) collating, summarizing, and reporting the results. A total of 58 studies, published from 2013 through 2021 were included in this review. Five focus areas of gamified online course design were identified that include gamification elements, activities, tools, frameworks, and user attributes. The well-known ADDIE (Analyze, Design, Develop, Implement, Evaluate) framework was used as a conceptual lens through which gamified online course design processes were considered. This scoping review addresses a gap in the knowledge base by aggregating and interpreting current gamified online course design practices through the common language of a well-known instructional design framework.

Sophora species are used as dietary medicines in aging-associated symptoms. Sophora tomentosa L. (ST) is a native medicinal plant in Southeast Asia; however, there is no pharmacological literature about ST extract. The present study evaluates the antioxidant phytoconstituent contents and radical scavenging capacities of ST extract. The further investigation was to clarify the neuroprotective mechanism of ST extract against 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced Parkinsonism by assaying the activities of the dopaminergic system and antioxidant defenses, glycogen synthase kinase 3β (GSK3-β) phosphorylation, and α-synuclein levels in C57BL/6 mice. The results show that ST extract alleviated the motor deficits in MPTP-induced Parkinsonism with four behavioral tests, including a rearing locomotor, catalepsy test, balance beam walking test, and pole test. ST extract reversed the number of tyrosine hydroxylase (TH)-positive neurons in substantia nigra (SN) that had decreased by MPTP. ST extract also restored the decreased levels of dopamine and the expression of tyrosine hydroxylase (TH) in the striatum. Furthermore, ST extract restored the levels of glutathione (GSH) and the activities of antioxidant enzymes, and decreased the elevated levels of malondialdehyde (MDA) in mouse striatum. ST extract also decreased α-synuclein overexpression and GSK-3β phosphorylation in mouse striatum. In vitro, ST extract exerted higher 2,2′-azino-bis(3-ethylbenzothiazoline-6-sulphonic acid) (ABTS) radical scavenging capacities through its higher phenolic contents, especially protocatechuic acid and epicatechin. These results suggest that ST extract has the potential to counteract MPTP-induced motor deficit. The neuroprotective mechanism of ST extract against MPTP-induced Parkinsonism might be related to decreasing GSK-3β phosphorylation and restoring the activities of striatal antioxidant defenses to restore the nigrostriatal dopaminergic function and decrease α-synuclein accumulation.

The occurrence of tinnitus can be linked to hearing loss in the majority of cases, but there is nevertheless a large degree of unexplained heterogeneity in the relation between hearing loss and tinnitus. Part of the problem might be that hearing loss is usually quantified in terms of increased hearing thresholds, which only provides limited information about the underlying cochlear damage. Moreover, noise exposure that does not cause hearing threshold loss can still lead to hidden hearing loss (HHL), i.e. functional deafferentation of auditory nerve fibres (ANFs) through loss of synaptic ribbons in inner hair cells. Whilst it is known that increased hearing thresholds can trigger increases in spontaneous neural activity in the central auditory system, i.e. a putative neural correlate of tinnitus, the central effects of HHL have not yet been investigated. Here, we exposed mice to octave-band noise at 100 and 105 dB SPL, to generate HHL and permanent increases of hearing thresholds, respectively. Deafferentation of ANFs was confirmed through measurement of auditory brainstem responses and cochlear immunohistochemistry. Acute extracellular recordings from the auditory midbrain (inferior colliculus) demonstrated increases in spontaneous neuronal activity (a putative neural correlate of tinnitus) in both groups. Surprisingly the increase in spontaneous activity was most pronounced in the mice with HHL, suggesting that the relation between hearing loss and neuronal hyperactivity might be more complex than currently understood. Our computational model indicated that these differences in neuronal hyperactivity could arise from different degrees of deafferentation of low-threshold ANFs in the two exposure groups.Our results demonstrate that HHL is sufficient to induce changes in central auditory processing, and they also indicate a non-monotonic relationship between cochlear damage and neuronal hyperactivity, suggesting an explanation for why tinnitus might occur without obvious hearing loss and conversely why hearing loss does not always lead to tinnitus.

Ligustrum (privet) plants are used by Chinese physicians to prevent and cure hepatitis and chronic bronchitis. Three common Ligustrum plant spp., namely Ligustrum lucidum Ait. (LL), L. pricei Hayata (LP) and L. sinensis Lour. (LS) were collected to assess their analgesic/anti-inflammatory properties on chemical-induced nociception and carrageenan-induced inflammation in rodents. The methanol extracts from Ligustrum plants leaves effectively inhibited nociceptive responses induced by 1% acetic acid and 1% formalin. LP and LL reduced the edema induced by 1% carrageenan. LP exhibited the best potency of the Ligustrum plants. Furthermore, LP reduced the abdominal Evan’s blue extravasations caused by lipopolysaccharide, lipoteichoic acid, autocrines and sodium nitroprusside. The triterpenoid content of the three Ligustrum spp. was measured by high performance liquid chromatography using a photodiode array detector. LP contained the highest content of amyrin, betulinic acid and lupeol. LL had the highest content of oleanolic acid and ursolic acid. The various degrees of analgesic/anti-inflammatory effects among three Ligustrum plants may be related to their different triterpenoid contents. LP is a potential analgesic and anti-inflammatory Ligustrum plant. The effects of LP are partially related to the inhibition of cyclooxygenase-2 activity and a decrease in microvascular permeability via the actions of autocrines and kinins.

The medicinal ferns of Polydiaceae and Davalliaceae species are called “Gusuibu” by Chinese physicians and used as antiaging dietary medicines. Our previous report revealed that Drynaria fortunei (Polydiaceae) protected against 6-hydroxydopamine (6-OHDA)-induced oxidative damage via the PI3K/AKT pathway in B35 neuroblastoma cells. The present study compares the antioxidant phytoconstituent contents and radical scavenging capacities of five Davalliaceae species. The further aim was to clarify the protective mechanism of Davallia mariesii (DM) against 6-OHDA-induced oxidative damage and apoptosis in B35 cells. The results show that Araiostegia perdurans (AP) and DM extracts have better radical scavenging capacities against 1,1-diphenyl-2-picryhydrazyl (DPPH) and reactive oxygen species (ROS) than other Davalliaceae species. However, only DM extract inhibited 6-OHDA autoxidation under cell-free systems and increased cell viability, compared to B35 cells solely exposed to 6-OHDA. DM extract decreased apoptosis and restored mitochondrial expression in 6-OHDA-treated B35 cells. Additional data indicated that DM extract decreased intracellular ROS and nitric oxide levels generated by 6-OHDA exposure. DM extract also restored glutathione (GSH) levels and the activities of glutathione peroxidase and reductase, and then decreased the elevated malondialdehyde (MDA) levels. Finally, DM extract regulated the protein expression of the caspase cascade and PI3K/AKT/GSK-3β pathways. These results suggest that the protective mechanism of DM extract against 6-OHDA-induced oxidative damage and apoptosis might be related to its radical scavenging capacity, maintaining the mitochondrial function to inhibit the Bcl-2/caspase cascade pathway and activating intracellular antioxidant defenses (GSH recycling, HO-1 and NQO-1) by modulating the activation of the PI3K/AKT/GSK-3β pathway.

OBJETIVE: To evaluate a sample of patients with persistent facial pain unresponsive to prior treatments. METHODS: Hospital records of 26 patients with persistent facial pain were reviewed (20 female and 6 male). RESULTS: Patients were classified into three groups according to their presenting symptoms: a)Group I, eight patients (30.7%) with severe, diffuse pain at the face, teeth or head; b)Group II, eight patients (30.7%) with chronic non-myofascial pain and; c)Group III, ten patients with chronic myofascial pain (38.4%). We find 11 different diagnoses among the 26 patients: pulpitis(7), leukemia(1), oropharyngeal tumor(1), atypical odontalgia(1), Eagle's syndrome(1), trigeminal neuralgia(4), continuous neuralgia(1), temporomandibular disorders (9), fibromyalgia (2), tension-type headache(1), conversion hysteria(2). After the treatment program all patients had a six-month follow-up period with pain relief, except the patient with tumor. CONCLUSION: The wide variability of orofacial pain diagnosis (benign to life-threatening diseases) indicates the necessity to reevaluate patients presenting recurrent pain that is refractory to the usual treatments.OBJETIVO: Avaliar uma amostra de doentes com dor facial persistente. MÉTODO: Foram revisados 26 prontuários de doentes com dor facial persistente (20 mulheres e 6 homens). RESULTADOS: Classificação dos doentes, após o diagnóstico: a)Grupo I, oito pacientes (30,7%) com dor facial difusa de fortíssima intensidade; b)Grupo II, oito pacientes (30,7%) com dor crônica de natureza não-miofascial e; c)Grupo III, dez pacientes com dor crônica miofascial (38,4%). Foram encontrados 11 diagnósticos diferentes entre os 26 pacientes: pulpites(7), leucemia(1), tumor de orofaringe(1), odontalgia atípica(1), síndrome de Eagle(1), neuralgia idiopática do trigêmeo(4), neuralgia atípica(1), disordens temporomandibular (9), fibromialgia(2) cefaléia tipo-tensão(1), histeria de conversão(2). O acompanhamento dos doentes, após receberem a respectiva terapia, foi de seis meses, com alívio da dor, exceto para o doente com tumor de orofaringe. CONCLUSÃO: A variabilidade das fontes da dor facial inclui doenças benignas e doenças graves, sendo indispensável a reavaliaçâo de doentes que não respondem aos tratamentos convencionais para a dor.

Few studies have investigated the contagion effects of exposure to others' confided suicidal thoughts among adolescents. The aim of this study was to investigate whether recent real-world exposure to confided suicidal thoughts was associated with adolescent self-harm and suicidality within one month, and if so, to determine the related risk and protective factors. A total of 5,879 Taiwanese first-year senior high school students participated in this study and completed on-line questionnaires regarding their experience of exposure to confided suicidal thoughts, self-harm and suicidality, socio-demographic information, Patient Health Questionnaire 9-item, Multi-Dimensional Support Scale, Rosenberg Self-Esteem Scale, and alcohol and cigarette use. Of the enrolled adolescents, 3.4% had been exposed to confided suicidal thoughts (N = 200) within one month. The most common source of exposure was friends (N = 186). After controlling for a large variety of confounders, the adolescents with recent exposure to others' suicidal thoughts were four times more likely to harm themselves within one month (OR = 3.77; 95% CI: 2.26 - 6.30). The risks of suicidal ideation and suicide plans were also markedly increased (both OR = 5.15; 95% CI: 3.48 - 7.64 and 2.78 - 9.52, respectively). The risk ratios were highest if the source of exposure was from parents, and the contagion effects were dose-dependent. Support from parents and teachers could protect the adolescents from the impact of contagion. Our results suggest a contagion effect of exposure to confided suicidal thoughts among adolescents. Parents and school personnel should be aware of this and provide assistance for those in need., Author(s): Hui-Ching Liu [sup.1] , Yu-Hsin Huang [sup.1] [sup.2] , Jin-Jin Tjung [sup.3] , Fang-Ju Sun [sup.4] , Shen-Ing Liu [sup.1] [sup.2] Author Affiliations: (1) grid.413593.9, 0000 0004 0573 007X, [...]