Two novel compound heterozygous loss-of-function mutations cause fetal IRAK-4 deficiency presenting with Pseudomonas Aeruginosa sepsis.

PURPOSE: To report a case of a five-month-old Chinese infant who died of interleukin-1 receptor-associated kinase-4 (IRAK-4) deficiency presenting with rapid and progressive Pseudomonas aeruginosa sepsis. METHODS: The genetic etiology of IRAK-4 deficiency was confirmed through trio-whole exome sequencing and Sanger sequencing. Functional consequences were invested using an in vitro minigene splicing assay. RESULTS: Trio-whole exome sequencing of genomic DNA identified two novel compound heterozygous mutations, IRAK-4 (NM_016123.3): c.942-1G > A and c.644_651+ 6delTTGCAGCAGTAAGT in the proband, which originated from his symptom-free parents. These mutations were predicted to cause frameshifts and generate three truncated proteins without enzyme activity. CONCLUSIONS: Our findings expand the range of IRAK-4 mutations and provide functional support for the pathogenic effects of splice-site mutations. Additionally, this case highlights the importance of considering the underlying genetic defects of immunity when dealing with unusually overwhelming infections in previously healthy children and emphasizes the necessity for timely treatment with wide-spectrum antimicrobials.

Corrigendum to "Effects of Motor Training on Accuracy and Precision of Jaw and Finger Movements".

[This corrects the article DOI: 10.1155/2019/9593464.].

[Application of chromosomal microarray analysis in prenatal diagnosis of pregnant women with advanced age].

OBJECTIVE: To assess the value of chromosomal microarray analysis (CMA) for the detection of fetal anomalies among pregnant women with advanced age. METHODS: CMA results of 562 cases, in addition with the outcome of pregnancy and neonatal follow-up were reviewed. RESULTS: Among the 562 amniotic fluid samples, 73 cases (12.99%) of fetal chromosomal abnormalities were detected, which included 21 cases (3.73%) of chromosomal aneuploidies and 52 cases (9.25%) of copy number variations (CNVs). The latters included 27 cases of pathological CNVs (4.80%), 4 cases of possible pathogenic CNVs (0.71%) and 42 cases of variants with unknown clinical significance (7.47%). Compared with those under 35, the detection rate of fetal chromosomal aneuploidies for women with advanced age was higher under the indications of voluntary test, abnormal ultrasonic structures, abnormal ultrasonic soft index and risks indicated by non-invasive prenatal testing (NIPT). No significant difference was found in the detection rate of CNVs between those ≥35 and <35 and between those with age factor only and with additional indications (P> 0.05). 552 cases (98.22%) of pregnant women have completed the followed up. Among 31 women with pathological and possible pathogenic fetal CNVs detected by CMA, 25 had terminated the pregnancy, 6 (19.35%) have delivered without obvious abnormality. 41 pregnant women with fetal CNVs of unknown clinical significance have completed the follow up, among whom 3 had terminated the pregnancy, 1 newborn was found with malformation after birth, which yielded an abnormal pregnancy rate of 9.76%. 480 pregnant women with negative CMA results have completed the follow up, among whom 5 (1.04%) had abnormal pregnancy or delivered a child with birth defect. CONCLUSION: There is a certain difference between the outcome of pregnancy predicted by CMA testing and the actual outcome. The pregnancies with fetal CNVs with unknown clinical significance detected by CMA have a high adverse rate, which should attract clinical attention. CMA testing should be recommended for pregnant women with advanced age regardless of whether they have other symptoms. CMA combined with other detection methods is the trend for prenatal diagnosis.

Somatosensory profiling of patients with plaque-induced gingivitis: a case-control study.

OBJECTIVES: This study aimed to assess the mechanical and thermal sensory thresholds of the gingiva in patients with plaque-induced gingivitis compared with a control group to help characterize effects of an inflammatory condition in the oral mucosa on somatosensory function. MATERIALS AND METHODS: Quantitative sensory testing (QST) was used in 22 patients (men 10, women 12, age 20-30 years) with plaque-induced gingivitis at the lower lateral incisors and in 22 age- and gender-matched healthy volunteers as a control group. One lower lateral incisor (32 or 42) was randomly identified for each included subject. Cold detection threshold (CDT), warm detection threshold (WDT), cold pain threshold (CPT), and heat pain threshold (HPT) of the attached gingiva at the identified lower lateral incisors were assessed in both groups. Pressure pain threshold (PPT) at the teeth was also tested from vertical and lateral directions and analyzed. One-way ANOVA was used to compare the mean values of the identified lower lateral incisors between the two groups. RESULTS: The results showed that the CDT (P = 0.027), WDT (P = 0.021), and HPT (P = 0.005) at the gingiva and PPT (P < 0.001) at the identified lower lateral incisors from the vertical direction were significantly less sensitive, whereas the PPT (P = 0.016) at the gingiva of the identified lateral incisors were significantly more sensitive in the gingivitis group compared to the control group. Plaque-induced gingivitis and the inflammatory response appear to be associated with significant changes in somatosensory sensitivity at the gingiva and periodontal tissue in a bidirectional mode, i.e., both increased and decreased sensitivity to different types of stimuli. CONCLUSIONS: Inflammatory reactions in the gingiva seem to be associated with demonstrable changes in somatosensory function including both hypo- and hyperesthesia. CLINICAL RELEVANCE: These findings may have significance for general oral health and well-being in patients with even plaque-induced gingivitis.

Effect of transcutaneous electrical nerve stimulation on jaw movement-evoked pain in patients with TMJ disc displacement without reduction and healthy controls.

Objective: Transcutaneous electrical nerve stimulation (TENS) may serve as non-invasive intervention for painful temporomandibular disorders (TMD) to improve jaw motor function, but its efficacy is still debated. This parallel study evaluated the effect of TENS on pain and movement patterns after repeated jaw movements in patients with painful temporomandibular joints (TMJ) and disc displacement without reduction (DDwoR), and compared with healthy controls.Material and Methods: 20 patients with TMJ pain and DDwoR and 20 age- and gender-matched healthy volunteers were randomly assigned to TENS/sham TENS (sTENS) intervention groups in a block design (10 in each group). Participants performed 20 repeated jaw movements (4 x 5 sessions), and reported pain intensity on a 0-10 Numerical Rating Scale (NRS) subsequently both before and after the intervention. Data were tested by repeated measures analysis of variance (ANOVA).Results: Significant increase of pain intensity and reduction of opening range were shown within repeated jaw movements in TMJ pain patients in contrast to healthy participants (p ≤ .001). Pain was significantly reduced during repeated open-close (p = .007), fast open-close (p = .016) and horizontal movements (p = .023), accompanied with increased opening range (p = .033) and open-close velocity (p = .019) with TENS intervention when compared with sTENS group (p > .05) in TMJ pain patients.Conclusions: This study indicated that movement-evoked pain was reduced either spontaneously or by sTENS in TMJ pain patients with DDwoR, and interestingly, that TENS could attenuate movement-evoked pain and improve jaw motor function during repeated jaw movements. The findings may have implications for TENS treatment in TMJ pain patients with DDwoR.

Human tissue inhibitor of metalloproteinases-1 improved wound healing in diabetes through its anti-apoptotic effect.

Impaired wound healing accompanies severe cell apoptosis in diabetic patients. Tissue inhibitor of metalloproteinases-1 (TIMP-1) was known to have effects on promoting growth and anti-apoptosis for cells. We aimed to determine the actual levels of TIMP-1 and cell apoptosis in: (i) the biopsies of diabetic and non-diabetic foot tissue and (ii) the human fibroblasts with or without treatments of advanced glycation end-products (AGEs). Next, we aimed to determine the improved levels of cell apoptosis and wound healing after the treatments of either active protein of TIMP-1 or in vivo expression of gene therapy vector-mediated TIMP-1 in both the human fibroblasts and the animal model of diabetic rats. The levels of TIMP-1 were significantly reduced in diabetic skin tissues and in AGEs-treated fibroblasts. Both AGEs-treated cells were effectively protected from apoptosis by active protein of TIMP-1 at appropriate dose level. So did the induced in vivo TIMP-1 expression after gene delivery. Similar effects were also found on the significant improvement of impaired wound healing in diabetic rats. We concluded that TIMP-1 improved wound healing through its anti-apoptotic effect. Treatments with either active protein TIMP-1 or TIMP-1 gene therapy delivered in local wound sites may be used as a strategy for accelerating diabetic wound healing.

Effects of Motor Training on Accuracy and Precision of Jaw and Finger Movements.

Objective: To compare the effects of training of jaw and finger movements with and without visual feedback on precision and accuracy. Method: Twenty healthy participants (10 men and 10 women; mean age 24.6 ± 0.8 years) performed two tasks: a jaw open-close movement and a finger lifting task with and without visual feedback before and after 3-day training. Individually determined target positions for the jaw corresponded to 50% of the maximal jaw opening position, and a fixed target position of 20 mm was set for the finger. Movements were repeated 10 times each. The variability in the amplitude of the movements was expressed as percentage in relation to the target position (D accu-accuracy) and as coefficient of variation (CVprec-precision). Result: D accu and CVprec were significantly influenced by visual feedback (P = 0.001 and P < 0.001, respectively) and reduced after training jaw and finger movements (P < 0.001). D accu (P = 0.004) and CVprec (P = 0.019) were significantly different between jaw and finger movements. The relative changes in D accu (P = 0.017) and CVprec (P = 0.027) were different from pretraining to posttraining between jaw and finger movements. Conclusion: The accuracy and precision of standardized jaw and finger movements are dependent on visual feedback and appears to improve more by training in the trigeminal system possibly reflecting significant neuroplasticity in motor control mechanisms.

Quantitative sensory testing for assessment of somatosensory function in human oral mucosa: a review.

OBJECTIVE: This narrative review provides an overview of the quantitative sensory testing (QST) to assess somatosensory function in human oral mucosa. MATERIAL AND METHODS: A literature search was conducted in the PubMed database to identify studies in vivo on human oral mucosa using QST methods. A list of 149 articles was obtained and screened. A total of 36 relevant articles remained and were read in full text. Manual search of the reference lists identified eight additional relevant studies. A total of 44 articles were included for final assessment. RESULTS: The included studies were divided into six categories according to the study content and objective. In each category, there was a great variety of aims, methods, participants and outcome measures. The application of QST has nevertheless helped to monitor somatosensory function in experimental models of intraoral pain, effects of local anesthesia, after oral and maxillofacial surgery and after prosthodontic and orthodontic treatment. CONCLUSIONS: QST has been proved to be sufficiently stable and reliable, and valuable information has been obtained regarding somatosensory function in healthy volunteers, special populations and orofacial pain patients. However, as most of the studies were highly heterogeneous, the results are difficult to compare quantitatively. A standardized intraoral QST protocol is recommended and expected to help advance a mechanism-based assessment of neuropathies and other intraoral pain conditions.

Quantitative sensory testing (QST) in the orofacial region of healthy Chinese: influence of site, gender and age.

OBJECTIVE: To establish a preliminary thermal and mechanical somatosensory profile using a standardized quantitative sensory testing (QST) to investigate site, gender and age differences in healthy Chinese. MATERIALS AND METHODS: Twenty younger (age: 20-40 years, 10 men, 10 women) and twenty older (age: 41-61 years, 10 men, 10 women) healthy participants completed the study. Cold detection threshold (CDT), warm detection threshold (WDT), cold pain threshold (CPT), heat pain threshold (HPT), mechanical detection threshold (MDT) and mechanical pain threshold (MPT) were measured at five sites: Left hand, bilaterally at the mental area, tip of tongue and the lower lip mucosa. Mixed model ANOVAs with repeated measures were used to analyze the data. RESULTS: MDT(p < .001) and MPT (p < .05) were significantly higher on the hand compared to the mental areas. The CDT ( p = .006) was significantly higher and WDT (p < .001) was significantly lower at the tongue compared to lip mucosa and CDT (p < .001) was higher at the tongue mucosa than at the mental areas. WDT (p < .001) and HPT (p < .05) were significantly higher at the tip of the tongue and the lower lip mucosa compared to the mental areas. Significantly lower sensitivity for WDT (p < .001) and CDT (p = .004) were found in the older group compared to the younger group. Significant gender differences were found with less sensitivity for WDT (p = .024) and MDT (p = .003) in men compared to women. CONCLUSIONS: Application of standardized QST can provide valuable information of orofacial somatosensory phenotypes in a Chinese population. Age, gender and site are mandatory to control for.

Analysis of the Literature and Patents on Solid Dispersions from 1980 to 2015.

Background: Solid dispersions are an effective formulation technique to improve the solubility, dissolution rate, and bioavailability of water-insoluble drugs for oral delivery. In the last 15 years, increased attention was focused on this technology. There were 23 marketed drugs prepared by solid dispersion techniques. Objective: This study aimed to report the big picture of solid dispersion research from 1980 to 2015. Method: Scientific knowledge mapping tools were used for the qualitative and the quantitative analysis of patents and literature from the time and space dimensions. Results: Western Europe and North America were the major research areas in this field with frequent international cooperation. Moreover, there was a close collaboration between universities and industries, while research collaboration in Asia mainly existed between universities. The model drugs, main excipients, preparation technologies, characterization approaches and the mechanism involved in the formulation of solid dispersions were analyzed via the keyword burst and co-citation cluster techniques. Integrated experimental, theoretical and computational tools were useful techniques for in silico formulation design of the solid dispersions. Conclusions: Our research provided the qualitative and the quantitative analysis of patents and literature of solid dispersions in the last three decades.

α-ketoglutarate is associated with delayed wound healing in diabetes.

AIM: A high level of matrix metalloproteinase 9 (MMP-9) is a predictor of poor wound healing in diabetic foot ulcers. In skin keratinocytes, site-specific DNA demethylation plays an important role in MMP-9 expression. Ten-eleven translocation enzyme 2 (TET2) protein, one member of TET family, could rely on α-ketoglutarate (α-KG) as cosubstrate to exhibit catalytic activity of DNA demethylation. Here, we aimed to explore the changes of α-KG and its relationship with MMP-9 and TET2 during diabetic wound healing. METHODS: Seventy-one cases of patients with diabetic foot ulcers and 53 cases of nondiabetic ulcers were enrolled. Serum, urine and wound fluids were collected for measurement of α-KG levels and MMP-9 expression. Skin tissues were collected for the measurement of TET2 and MMP-9 expression. Clinical parameters were collected, and transcutaneous oxygen pressure (TcPO2) levels of feet were detected. RESULTS: The levels of α-KG, TET2 and MMP-9 were significantly increased in diabetic wound compared with nondiabetic wound (P = 0·010, 0·016 and 0·025). There was a significant correlation between a low TcPO2 and a high α-KG level of wound fluids (r = -0·395, P = 0·002). Further analysis showed that α-KG concentration had a positive correlation with both haemoglobin A1c (HbA1C) and 2 h postprandial blood glucose (PBG) (r = 0·393, P = 0·005; r = 0·320, P = 0·025, respectively). CONCLUSIONS: The levels of α-KG, TET2 and MMP-9 were significantly increased in diabetic wound compared with nondiabetic wound. Elevated α-KG was related to local hypoxia ischaemia status and systematic poor glycaemic control.

AGE-induced keratinocyte MMP-9 expression is linked to TET2-mediated CpG demethylation.

Studies have documented that unusually high expression of matrix metalloproteinase-9 (MMP-9) suppresses wound healing during the late stages of diabetic foot ulcers. Recently, it has been reported that the presence of advanced glycation end products-bovine serum albumin (AGE-BSA) resulted in a higher expression of MMP-9 in skin primary keratinocytes. The aim of the present study was to elucidate the molecular machinery that is responsible for the inappropriately high AGE-BSA-induced expression of MMP-9. It has been demonstrated that site-specific DNA demethylation played an important role in MMP-9 expression in AGE-BSA-stimulated keratinocytes. Ten-eleven translocation-2 (TET2) was up-regulated, whereas the percentage of methylation in the MMP-9 promoter was reduced. Furthermore, TET2 directly bound to a fragment surrounding the transcriptional start site in the MMP-9 promoter region, contributing to the regulation of MMP-9 expression. In addition, evidence indicated that TET2 affected the migration and proliferation in vitro of cultured skin primary keratinocytes. These findings indicated that TET2 directly interacted with the promoter region of MMP-9 in diabetic tissues and may be a novel master regulator of wound healing.

Test-retest reliability of a new technique with pressure algometry applied to teeth in healthy Chinese individuals.

Pressure pain thresholds (PPTs) have been shown to be useful measures of mechanical pain sensitivity in deep tissues. However, clinical methods for measuring mechanical allodynia or hyperalgesia in teeth have not been reported. The aim of this study was to assess the reliability of PPTs in periodontal ligament of healthy Chinese participants. Twenty healthy young adults participated. Pressure pain thresholds were measured at six teeth and in two directions. The tests included three consecutive trials, in two separate sessions, which were performed on the first day by one examiner. After 1-3 wk, an identical protocol was carried out by two examiners, also in two separate sessions. There were no significant differences between repeated measures for all teeth. The PPTs had excellent reliability with high intraclass coefficients (ICCs) across different sessions (ICC: 0.871-0.956), days (ICC: 0.879-0.951), and examiners (ICC: 0.845-0.950). Pressure pain thresholds applied to the teeth have excellent intra- and inter-examiner agreement in healthy participants. This method may be proposed as an easy and reliable technique to assess mechanical pain sensitivity (e.g. mechanical allodynia and hyperalgesia) in the periodontal ligament, which is associated with endodontic or periodontal conditions.

Fixed orthodontic appliances cause pain and disturbance in somatosensory function.

This study aimed to assess the short-term effects of orthodontic pain on quantitative sensory testing (QST) in subjects receiving fixed orthodontic treatment. Twenty patients and 12 healthy volunteers (as controls) participated. All 20 patients had bonded AO self-ligating brackets, with a 0.014 super elastic nickel-titanium arch wire placed in the brackets. Pain [self-reported on a visual analog scale (VAS)], and thermal and mechanical thresholds, were tested at six time points--before (baseline), and 2 h, 24 h, 7 d, 14 d, and 30 d after, force application--in the treatment group. The attached gingiva adjacent to the left upper central incisor (21 gingiva) was hypersensitive to cold stimuli (i.e. increased cold detection thresholds were detected) in the treatment group. The pressure pain thresholds of the left upper central incisor (21) and 21 gingiva were significantly reduced. Our results suggest clear signs of sensitization of the trigeminal nociceptive system up to 1 month after force application and orthodontic pain. Quantitative assessment of somatosensory function may help to provide a better understanding and profiling of the underlying neurobiological mechanisms related to orthodontic pain.

Sleep bruxism: an updated review of an old problem.

Objective To provide an update on what is known about bruxism and some of the major clinical highlights derived from new insights into this old problem in dentistry. Materials and methods A selective, non-systematic but critical review of the available scientific literature was performed. Results There are two main different types of bruxism, which are related to different circadian periods (sleep and awake bruxism) that may differ in terms of pathophysiology, but they share some common signs and symptoms. Approximately one out of 10 adult individuals may suffer from bruxism, but not all bruxers may need treatment. Bruxism is complicated to diagnose in the clinic and self-report of bruxism may not necessarily reflect the true presence of jaw muscle activity. Better understanding has been acquired of bruxism relationships with sleep stages, arousal responses and autonomic function with the help of polysomnography and controlled sleep studies. Meanwhile, there is still much more to learn about awake bruxism. With the available scientific knowledge it is possible to systematically assess the effects of bruxism and its potential risk factors for oral and general health. Moreover, we can be aware of the realistic possibilities to manage/treat the patient suffering from bruxism. Conclusion Bruxism is a parafunctional activity involving the masticatory muscles and probably it is as old as human mankind. Different ways have been proposed to define, diagnose, assess the impact and consequences, understand the pathophysiology and treat or manage bruxism. Despite the vast research efforts made in this field, there are still significant gaps in our knowledge.

Cilostazol Can Increase Skin Oxygen Supply Assessed by Transcutaneous Oxygen Pressure Measurement in Type 2 Diabetes With Lower Limb Ischemic Disease: A Randomized Trial.

PURPOSE: The purpose of this study was to compare the efficacy and safety of cilostazol versus acetylsalicylic acid (ASA) for amelioration of lower limb ischemia in type 2 diabetes. DESIGN: Prospective, randomized positive-controlled open clinical trial. SUBJECTS AND SETTING: Eighty-nine patients with type 2 diabetes mellitus and symptoms of lower limb ischemia (perceptions of coldness of the lower limbs, numbness, intermittent claudication, or pain at rest) present for 6 months or more that had not significantly changed within the past 3 months participated in the study. All subjects had an initial transcutaneous oxygen pressure (TcpO2) of less than 40 mm Hg in the foot when measured in the supine position. Subjects included 46 males and 43 females; their ages ranged from 35 to 80 years. METHODS: Participants were randomly allocated to 2 groups, one was treated with cilostazol 100 mg taken twice daily (n = 48), and a second group took 100 mg of ASA daily (n = 41) for 8 weeks. Clinical assessment included measurement of transcutaneous oxygenation, and symptoms associated with lower limb ischemia. Blood analyses included a full blood panel, coagulation screen, renal function tests, hepatic function tests, and lipid profiles. All tests were performed at baseline and repeated at 8 weeks. RESULTS: Age, duration of diabetes, diabetic complications, lower limb ischemic symptoms, TcpO2, and smoking status did not differ between the 2 groups. In contrast, TcpO2 significantly improved from 37.1 ± 11.9 mm Hg to 42.0 ± 9.7 mm Hg in the cilostazol-treated group (P < .05), whereas no significant change was observed in the ASA-treated group (P > .05). Ischemic symptoms such as intermittent claudication (P = .009), perception of limb coldness (P = .008), and pain at rest (P = .017) showed greater improvement in the cilostazol-treated group when compared to subjects treated with ASA. Approximately 10% of patients treated with cilostazol experienced adverse side effects (palpitations, headache, diarrhea). Cilostazol was not found to have significant detrimental effects in hematologic or biochemical indices, including renal, hepatic, and blood coagulant function tests. CONCLUSIONS: We found that 8 weeks of treatment with cilostazol 100 mg daily was safe and well tolerated for the treatment of type 2 diabetes with lower limb ischemic disease.

Thermal and mechanical quantitative sensory testing in Chinese patients with burning mouth syndrome--a probable neuropathic pain condition?

BACKGROUND: To explore the hypothesis that burning mouth syndrome (BMS) probably is a neuropathic pain condition, thermal and mechanical sensory and pain thresholds were tested and compared with age- and gender-matched control participants using a standardized battery of psychophysical techniques. METHODS: Twenty-five BMS patients (men: 8, women: 17, age: 49.5 ± 11.4 years) and 19 age- and gender-matched healthy control participants were included. The cold detection threshold (CDT), warm detection threshold (WDT), cold pain threshold (CPT), heat pain threshold (HPT), mechanical detection threshold (MDT) and mechanical pain threshold (MPT), in accordance with the German Network of Neuropathic Pain guidelines, were measured at the following four sites: the dorsum of the left hand (hand), the skin at the mental foramen (chin), on the tip of the tongue (tongue), and the mucosa of the lower lip (lip). Statistical analysis was performed using ANOVA with repeated measures to compare the means within and between groups. Furthermore, Z-score profiles were generated, and exploratory correlation analyses between QST and clinical variables were performed. Two-tailed tests with a significance level of 5 % were used throughout. RESULTS: CDTs (P < 0.02) were significantly lower (less sensitivity) and HPTs (P < 0.001) were significantly higher (less sensitivity) at the tongue and lip in BMS patients compared to control participants. WDT (P = 0.007) was also significantly higher at the tongue in BMS patients compared to control subjects . There were no significant differences in MDT and MPT between the BMS patients and healthy subjects at any of the four test sites. Z-scores showed that significant loss of function can be identified for CDT (Z-scores = -0.9±1.1) and HPT (Z-scores = 1.5±0.4). There were no significant correlations between QST and clinical variables (pain intensity, duration, depressions scores). CONCLUSION: BMS patients had a significant loss of thermal function but not mechanical function, supporting the hypothesis that BMS may be a probable neuropathic pain condition. Further studies including e.g. electrophysiological or imaging techniques are needed to clarify the underlying mechanisms of BMS.

Reliability study of thermal quantitative sensory testing in healthy Chinese.

BACKGROUND: Test-retest reliability is important to establish for any diagnostic tool. The reliability of quantitative sensory testing (QST) in the trigeminal region has recently been described in Caucasians as well as differences in absolute thresholds and responses between Caucasians and Chinese. However, the test-retest reliability has not been determined in a Chinese population. OBJECTIVE: To provide novel information on the test-retest reliability of thermal QST in the trigeminal and spinal system in healthy Chinese. METHODS: Twenty healthy volunteers (10 women and 10 men) participated. Cold detection threshold (CDT), warm detection threshold (WDT), cold pain threshold (CPT), and heat pain threshold (HPT) were measured at two sites: the surface of the left hand and the left masseter. The testing was performed over three consecutive stimuli trials, three sessions conducted on one day and repeated one week later. Data were analyzed with intra-tester reliability test and four-way analysis of variance (ANOVA) for repeated measures. RESULTS: There was a tendency for the first trial in CDT (p = 0.005), CPT (p = 0.02), and HPT (p < 0.001) to reflect higher sensitivity than the subsequent two trials. Most variables showed acceptable to excellent reliability and non-significant difference across different trials (ICC: 0.912-0.989), sessions (ICC: 0.791-0.977), and days (ICC: 0.415-0.837). Between-site differences were significant for CDT (p = 0.003) and HPT (p = 0.045) with higher sensitivity at the masseter muscle. There were significant gender differences with higher sensitivity in women for CPT (p = 0.001) and HPT (p = 0.001). CONCLUSION: Test site and gender affect thermal thresholds substantially. The test-retest reliability of most thermal threshold measures were acceptable for assessing somatosensory function, however, innocuous thresholds appear to be associated with larger variability than noxious thresholds in a Chinese population.

Self-knowledge distillation for surgical phase recognition.

PURPOSE: Advances in surgical phase recognition are generally led by training deeper networks. Rather than going further with a more complex solution, we believe that current models can be exploited better. We propose a self-knowledge distillation framework that can be integrated into current state-of-the-art (SOTA) models without requiring any extra complexity to the models or annotations. METHODS: Knowledge distillation is a framework for network regularization where knowledge is distilled from a teacher network to a student network. In self-knowledge distillation, the student model becomes the teacher such that the network learns from itself. Most phase recognition models follow an encoder-decoder framework. Our framework utilizes self-knowledge distillation in both stages. The teacher model guides the training process of the student model to extract enhanced feature representations from the encoder and build a more robust temporal decoder to tackle the over-segmentation problem. RESULTS: We validate our proposed framework on the public dataset Cholec80. Our framework is embedded on top of four popular SOTA approaches and consistently improves their performance. Specifically, our best GRU model boosts performance by [Formula: see text] accuracy and [Formula: see text] F1-score over the same baseline model. CONCLUSION: We embed a self-knowledge distillation framework for the first time in the surgical phase recognition training pipeline. Experimental results demonstrate that our simple yet powerful framework can improve performance of existing phase recognition models. Moreover, our extensive experiments show that even with 75% of the training set we still achieve performance on par with the same baseline model trained on the full set.

How provider payment methods affect health expenditure of depressive patients? Empirical study from national claims data in China from 2013 to 2017.

BACKGROUND: This study aimed to investigate the associations between provider payment methods and expenditure of depressive patients, stratified by service types and hospital levels. METHODS: We used a 5 % random sample of urban claims data in China (2013-2017), collected by China Health Insurance Research Association. Provider payment methods (fee-for-services, global budget, capitation, case-based and per-diem payments) were the explanatory variables. A generalized linear model was fitted for the associations between provider payment methods and expenditure. All analyses were adjusted for patient"cioeconomic and health-related characteristics. RESULTS: In total, 64,615 depressive patient visits were included, 59,459 for outpatients and 5156 for inpatients. Female patients accounted for 63.00 %. The total and out-of-pocket (OOP) expenditure significantly differentiated by provider payments. Among outpatient services, when comparing with fee-for-services, capitation payment was associated with substantial marginal reduction in total and OOP expenditure (-$34.18, -$9.71) in primary institutes, yet increases ($27.26, $24.11) in secondary hospitals. Similarly, global budget was associated with lower total and OOP expenditure (-$13.51, -$1.61) in secondary hospitals, while higher total and OOP expenditure ($7.43, $32.27) in tertiary hospitals than fee-for-services. For inpatients, total and OOP expenditures under per-diem (-$857.65, -$283.48) and case-based payments (-$997.93, -$137.56) were remarkably smaller than those under fee-for-services in primary and secondary hospitals, respectively. Besides, case-base payment was only linked with the largest reduction in OOP expense (-$239.39) in inpatient services of tertiary hospitals. LIMITATION: Only urban claims data was included in this study, and investigations for rural population still warrant. And updated data are needed for future studies. CONCLUSIONS: There were varying correlations between provider payment methods and expenditure, which differed by service types and hospital levels. These findings provided empirical evidence for optimizing the mixed payment methods for depression in China.