Pathophysiology of Neuropathic Pain in Type 2 Diabetes: Skin denervation and contact heat–evoked potentials

OBJECTIVE: Neuropathic pain due to small-fiber sensory neuropathy in type 2 diabetes can be diagnosed by skin biopsy with quantification of intra- epidermal nerve fiber ( IENF) density. There is, however, a lack of noninvasive physiological assessment. Contact heat-evoked potential ( CHEP ) is a newly developed approach to record cerebral responses of A fiber- mediated thermonociceptive stimuli. We investigated the diagnostic role of CHEP. RESEARCH DESIGN AND METHODS: From 2006 to 2009, there were 32 type 2 diabetic patients (20 males and 12 females, aged 51.63 10.93 years) with skin denervation and neuropathic pain. CHEPs were recorded with heat stimulations at the distal leg, where skin biopsy was performed. RESULTS: CHEP amplitude was reduced in patients compared with age- and sex-matched control subjects (14.8 15.6 vs. 33.7 10.1 V, P < 0.001). Abnormal CHEP patterns ( reduced amplitude or prolonged latency) were noted in 81.3 % of these patients. The CHEP amplitude was the most significant parameter correlated with IENF density (P = 0. 003) and pain perception to contact heat stimuli (P = 0.019) on multiple linear regression models. An excitability index was derived by calculating the ratio of the CHEP amplitude over the IENF density. This excitability index was higher in diabetic patients than in control subjects (P = 0.023), indicating enhanced brain activities in neuropathic pain. Among different neuropathic pain symptoms, the subgroup with evoked pain had higher CHEP amplitudes than the subgroup without evoked pain (P = 0.011). CONCLUSIONS: CHEP offers a noninvasive approach to evaluate the degeneration of thermonociceptive nerves in diabetic neuropathy by providing physiological correlates of skin denervation and neuropathic pain

The relations between 3-year changes in physical fitness and academic performance in nationally representative sample of junior high school students

Abstract The objective of the current study was to examine the relationship between different components of physical fitness across 3 years of junior high school with academic performance assessed at the end of the period. Two nationwide representative datasets were used. The first was the physical fitness profile assessed at the beginning of each of the three school years. The second contained the scores on a standardized test administered at the end of the third year. All data were standardized by calculating percentile rank (PR). Students were classified as “High-fit” if their fitness scores ≧ top 25% PR on the age- and sex-adjusted norms. All other students were classified as “not high-fit”. The relationships between fitness and exam performance were tested adjusting for sex, body mass index, and level of urbanization. Students who were in the high-fit group in both years 1 and 3 academically outperformed those who were outside this classification during both assessments. The degree of outperformance was greatest for those who were aerobically fit, followed by those who were high-fit in terms of muscular endurance, muscular strength, and flexibility, respectively. It is therefore concluded that the relationship between physical fitness and academic performance in Taiwanese junior high school students is strongest in the case of aerobic fitness

A High-Accuracy Detection System: Based on Transfer Learning for Apical Lesions on Periapical Radiograph

Apical Lesions, one of the most common oral diseases, can be effectively detected in daily dental examinations by a periapical radiograph (PA). In the current popular endodontic treatment, most dentists spend a lot of time manually marking the lesion area. In order to reduce the burden on dentists, this paper proposes a convolutional neural network (CNN)-based regional analysis model for spical lesions for periapical radiographs. In this study, the database was provided by dentists with more than three years of practical experience, meeting the criteria for clinical practical application. The contributions of this work are (1) an advanced adaptive threshold preprocessing technique for image segmentation, which can achieve an accuracy rate of more than 96%; (2) a better and more intuitive apical lesions symptom enhancement technique; and (3) a model for apical lesions detection with an accuracy as high as 96.21%. Compared with existing state-of-the-art technology, the proposed model has improved the accuracy by more than 5%. The proposed model has successfully improved the automatic diagnosis of apical lesions. With the help of automation, dentists can focus more on technical and medical diagnoses, such as treatment, tooth cleaning, or medical communication. This proposal has been certified by the Institutional Review Board (IRB) with the certification number 202002030B0

Improvement of Statistical Typhoon Rainfall Forecasting with ANN-Based Southwest Monsoon Enhancement

Typhoon Morakot 2009, with significant southwest monsoon flow, produced a record-breaking rainfall of 2361 mm in 48 hours. This study hopes to improve a statistical typhoon rainfall forecasting method used over the mountain region of Taiwan via an artificial neural network based southwest monsoon enhancement (ANNSME) model. Rainfall data collected at two mountain weather stations, ALiShan and YuShan, are analyzed to establish the relation to the southwest monsoon moisture flux which is calculated at a designated sea area southwest of Taiwan. The results show that the moisture flux, with southwest monsoon flow, transported water vapor during the landfall periods of Typhoons Mindulle, Bilis, Fungwong, Kalmaegi, Haitaing and Morakot. Based on the moisture flux, a linear regression is used to identify an effective value of moisture flux as the threshold flux which can enhance mountain rainfall in southwestern Taiwan. In particular, a feedforward neural network (FNN) is applied to estimate the residuals from the linear model to the differences between simulated rainfalls by a typhoon rainfall climatology model (TRCM) and observations. Consequently, the ANNSME model integrates the effective moisture flux, linear rainfall model and the FNN for residuals. Even with very limited training cases, our results indicate that the ANNSME model is robust and suitable for improvement of TRCM rainfall prediction. The improved prediction of the total rainfall and of the multiple rainfall peaks is important for emergency operation

Efficacy of concurrent radiotherapy in patients with locally advanced rectal cancer and synchronous metastasis receiving systemic therapy

BackgroundNeoadjuvant chemoradiotherapy followed by total mesorectal excision is the standard treatment for patients with nonmetastatic locally advanced rectal cancer (LARC). However, for patients with LARC and synchronous metastasis, the optimal treatment strategy and sequence remain inconclusive. In the present study, we evaluated the efficacy and safety of concurrent radiotherapy in patients with de novo metastatic rectal cancer who received chemotherapy and targeted therapy.MethodsWe retrospectively reviewed the data of 63 patients with LARC and synchronous metastasis who received intensive therapy at the study hospital between April 2015 and November 2018. The included patients were divided into two groups: RT-CT, those who received systemic chemotherapy with targeted therapy and concurrent radiotherapy (for primary rectal cancer), and CT, those who received only systemic chemotherapy with targeted therapy.ResultsTreatment response was better in the RT-CT group than in the CT group. The rate of primary tumor resection (PTR) was higher in the RT-CT group than in the CT group (71.4% and 42.9%, respectively; P = .0286). The RT-CT group exhibited considerably longer local recurrence-free survival (P = .0453) and progression-free survival (PFS; from 13.3 to 22.5 months) than did the CT group (P = .0091); however, the groups did not differ in terms of overall survival (OS; P = .49). Adverse events were almost similar between the groups, except frequent diarrhea, the prevalence of which was higher in the RT-CT group than in the CT group (59.5% and 23.8%, respectively; P = .0075).ConclusionsIn the era of biologics, radiotherapy may increase the resectability of primary rectal tumors, reducing the risk of locoregional failure and prolonging PFS. Concurrent pelvic radiotherapy may not substantially improve OS, which is indicated by metastasis. Hence, the resection of the distant metastases may be essential for improving long-term OS. To further determine the efficacy of concurrent radiotherapy, additional prospective, randomized studies must combine preoperative pelvic radiotherapy with PTR and metastectomy to treat patients with stage IV LARC

Anti-Cancer Effects of Radix Angelica Sinensis (Danggui) and N-Butylidenephthalide on Gastric Cancer: Implications for REDD1 Activation and mTOR Inhibition

Background/Aims: Radix Angelica Sinensis (danggui in Chinese) is widely used in traditional chinese medicine (TCM). N-butylidenephthalide (BP), a bioactive compound in danggui, is a potential antitumor agent for various cancer types. However, its clinical effect and mechanism in the treatment of gastric cancer remain undetermined. Methods: The in vivo protective effect of danggui in patients with gastric cancer were validated using data from Taiwan’s National Health Insurance Research Database (NHIRD). The genes induced by BP-treatment were analyzed by whole transcriptome RNA sequencing (RNA-seq) and validated by real-time PCR, western blot and siRNA transfection. The effect of BP on AGS cell migration and invasion was evaluated in transwell assays. The antitumor effects of BP were evaluated in vivo in an AGS xenograft animal model. Results: Danggui users were found to have an increased survival rate when compared with danggui nonusers (log-rank test p = 0.002) . The use of danggui highly associated with decreased mortality (the adjusted hazard ratio (HR) of danggui user was 0.72 [95 % CI, 0.57-0.92] (p = 0.009). The in vitro results showed that BP inhibited gastric cancer cell proliferation, and triggered cellular apoptosis depending on the activation of mitochondrial apoptotic pathway. Using RNA-seq analysis we found that REDD1 was the highest transcript induced by BP in gastric cancer cells. BP induce an increase of REDD1 expression that inhibits mTOR signaling, thus inhibiting gastric cancer growth. We used RNA interference to demonstrate that the knock-down of REDD1 attenuated the BP-induced mTORC1 activation and growth inhibition. BP suppressed the growth of AGS xenografts tumor in vivo. Conclusion: Danggui can prolong the survival rate of gastric cancer patients in Taiwan. BP caused gastric cancer cell death through the activation of mitochondria-intrinsic pathway and induced the REDD1 expression leading to mTOR signal pathway inhibition in gastric cancer cells. BP inhibited the in vivo growth of AGS xenograft tumors. These results may provide the basis for a new therapeutic approach toward the treatment of gastric cancer progression

High-resolution spatial and genomic characterization of coral-associated microbial aggregates in the coral Stylophora pistillata

Bacteria commonly form aggregates in a range of coral species [termed coral-associated microbial aggregates (CAMAs)], although these structures remain poorly characterized despite extensive efforts studying the coral microbiome. Here, we comprehensively characterize CAMAs associated with Stylophora pistillata and quantify their cell abundance. Our analysis reveals that multiple Endozoicomonas phylotypes coexist inside a single CAMA. Nanoscale secondary ion mass spectrometry imaging revealed that the Endozoicomonas cells were enriched with phosphorus, with the elemental compositions of CAMAs different from coral tissues and endosymbiotic Symbiodiniaceae, highlighting a role in sequestering and cycling phosphate between coral holobiont partners. Consensus metagenome--assembled genomes of the two dominant Endozoicomonas phylotypes confirmed their metabolic potential for polyphosphate accumulation along with genomic signatures including type VI secretion systems allowing host association. Our findings provide unprecedented insights into Endozoicomonas-dominated CAMAs and the first direct physiological and genomic linked evidence of their biological role in the coral holobiont