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.

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.

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.

SIG-Former: monocular surgical instruction generation with transformers.

PURPOSE: Automatic surgical instruction generation is a crucial part for intra-operative surgical assistance. However, understanding and translating surgical activities into human-like sentences are particularly challenging due to the complexity of surgical environment and the modal gap between images and natural languages. To this end, we introduce SIG-Former, a transformer-backboned generation network to predict surgical instructions from monocular RGB images. METHODS: Taking a surgical image as input, we first extract its visual attentive feature map with a fine-tuned ResNet-101 model, followed by transformer attention blocks to correspondingly model its visual representation, text embedding and visual-textual relational feature. To tackle the loss-metric inconsistency between training and inference in sequence generation, we additionally apply a self-critical reinforcement learning approach to directly optimize the CIDEr score after regular training. RESULTS: We validate our proposed method on DAISI dataset, which contains 290 clinical procedures from diverse medical subjects. Extensive experiments demonstrate that our method outperforms the baselines and achieves promising performance on both quantitative and qualitative evaluations. CONCLUSION: Our experiments demonstrate that SIG-Former is capable of mapping dependencies between visual feature and textual information. Besides, surgical instruction generation is still at its preliminary stage. Future works include collecting large clinical dataset, annotating more reference instructions and preparing pre-trained models on medical images.

SD-Net: joint surgical gesture recognition and skill assessment.

PURPOSE: Surgical gesture recognition has been an essential task for providing intraoperative context-aware assistance and scheduling clinical resources. However, previous methods present limitations in catching long-range temporal information, and many of them require additional sensors. To address these challenges, we propose a symmetric dilated network, namely SD-Net, to jointly recognize surgical gestures and assess surgical skill levels only using RGB surgical video sequences. METHODS: We utilize symmetric 1D temporal dilated convolution layers to hierarchically capture gesture clues under different receptive fields such that features in different time span can be aggregated. In addition, a self-attention network is bridged in the middle to calculate the global frame-to-frame relativity. RESULTS: We evaluate our method on a robotic suturing task from the JIGSAWS dataset. The gesture recognition task largely outperforms the state of the arts on the frame-wise accuracy up to [Formula: see text] 6 points and the F1@50 score [Formula: see text] 8 points. We also keep the 100% predicted accuracy for the skill assessment task using LOSO validation scheme. CONCLUSION: The results indicate that our architecture is able to obtain representative surgical video features by extensively considering the spatial, temporal and relational context from raw video input. Furthermore, the better performance in multi-task learning implies that surgical skill assessment has a complementary effects to gesture recognition task.

Sensory recovery and oral health-related quality of life following tongue reconstruction using non-innervated radial forearm free flaps.

OBJECTIVES: This study aimed to monitor the recovery of somatosensory function and oral health-related quality of life after tongue reconstruction using a non-innervated radial forearm free flap (RFFF). METHODS: Twenty patients (9 men, age: 42-67 years) underwent tongue reconstruction with non-innervated RFFFs, and twenty age- and sex-matched controls were included in this study. Quantitative sensory testing (QST), including cold, warm, and mechanical detection thresholds (CDT, WDT, MDT); cold, heat, and mechanical pain thresholds (CPT, HPT, MPT); and static two-point, sharp/blunt, and direction discrimination (S2-PD, S/BD, DD) were determined 9 months and 18 months after surgery on the surgical (9 M, 18 M) and contralateral sides (9Mc, 18Mc). Oral Health Impact Profile-49 (OHIP-49) was used to determine the oral-related quality of life of participants. RESULTS: All parameters showed significantly lower sensitivity at 9 M and 18 M (p < 0.001) compared to those for the controls and the contralateral side, except for DD (p = 0.101). In addition, the parameters showed a significant decrease in sensitivity for 9Mc and 18Mc (p ≤ 0.043) compared to those for the controls, except for MPT, HPT, S/SD, and DD (p ≥ 0.453). Findings on WDT, MPT, S2-PD, and DD (p ≤ 0.046) indicated significantly higher somatosensory function at 18 M than that at 9 M. MDT and MPT (p ≤ 0.038) showed significantly higher sensitivity at 18Mc than at 9Mc. Scores for all dimensions of OHIP-49 were significantly higher in patients (decrease in quality of life, p ≤ 0.002) than in controls, except for physical discomfort (p = 0.51). However, the scores were significantly higher at 18 M than at 9 M (p ≤ 0.011), except for handicap (p = 0.36). Postoperative chemotherapy was significantly correlated with impaired thermal sensitivity of the flaps (WDT, p = 0.049). CONCLUSION: The present findings showed significant impairment in somatosensory function on both the surgical and contralateral sides of patients with RFFFs. However, a significant increase in somatosensory function was observed on both sides over time. Somatosensory disturbances observed after surgery were associated with poor oral health-related quality of life.

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

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

Dentists have a high occupational risk of neck disorders with impact on somatosensory function and neck mobility.

OBJECTIVES: Musculoskeletal disorders (MSDs) in the neck and shoulder region may be associated with significant impairment of quality of life and well-being. The study was to determine the prevalence of painful MSDs in Chinese dentists and evaluate somatosensory function and neck mobility compared with non-dental professional controls. METHODS: One hundred dentists (age: 36.5 ± 9.8 years) and 102 controls (age: 36.2 ± 10.0 years) were recruited between September 2019 and December 2020. The Medical Outcome Study 36-item short-form health survey questionnaire and information of MSDs history were recorded. The cervical range of motion (CROM) with and without pain, and the pressure pain thresholds (PPTs) of the facial and neck muscles were tested. Chi-square test, Mann-Whitney U test and multiple linear regression analysis were used to analyze the data. The factors in the multiple linear regression analysis were occupation, working age, and gender. RESULTS: The prevalence rate of neck pain was significantly higher in dentists (73.0%) compared with the controls (52.0%) (P = .002). The regression models of cervical range of posterior extension, lateral flexion and rotation were statistically significant (P ≤ .001). The regression models of PPTs of the tested facial and neck muscles were statistically significant (P < .001). CONCLUSION: Dentists are at higher risk of neck pain. The bigger cervical range of left rotation of dentists could be related to the working posture. The lower PPTs in dentists may reflect a hypersensitivity in the facial and neck muscles. Preventive measures are needed to reduce occupational hazards in dentists.

Mental health is correlated with lipoprotein(a) levels in male patients with premature coronary heart disease.

BACKGROUND: High levels of lipoprotein(a) (Lp(a)) is an independent risk factor for premature coronary heart disease (PCHD). It is also considered a residual risk for controlled low density lipoprotein cholesterol (LDL-C). Dietary control, exercise, and drugs have limited effects on the levels of Lp(a). Recently, mental health was found to be associated with lipid levels and increased risk of PCHD. However, the relationship between mental health and Lp(a) is still unknown. This study explored the association between mental health and Lp(a) levels in men with PCHD. METHODS: A retrospective, observational study was conducted. A total of 226 male patients with PCHD, aged 49.65±3.68 years, was included in this study. The control group consisted of 230 age-matched healthy male volunteers. Serum Lp(a) levels ≥30 mg/dL, as measured by the immunoturbidimetry method, were considered high. All participants received health related quality of life (HRQoL) scores using the self-assessed 36-Item Short Form Health Survey (SF-36). The HRQoL includes both a physical component summary (PCS) and a mental component summary (MCS). RESULTS: Patients with PCHD were found to have higher levels of Lp(a) (51.61±33.39 vs. 26.42±21.93, P<0.001), and lower MCS (35.83±4.21 vs. 39.85±4.12) and PCS scores (38.02±3.73 vs. 39.63±3.21) compared to healthy volunteers. The MCS score was negatively correlated with Lp(a) levels in the PCHD group (R=-0.295, P<0.001), but no correlation was detected in the control group. There was no relationship between the PCS score and Lp(a) levels in neither the PCHD group nor the healthy control group. Multivariate logistic regression analysis indicated that the MCS and PCS scores were negatively correlated with the risk of PCHD. CONCLUSIONS: These findings suggested that poor mental health may be associated with high levels of Lp(a) and increased risk of PCHD in men. Therefore, improving the mental state in men with PCHD may be crucial.

Effect of photobiomodulation therapy on painful temporomandibular disorders.

To evaluate the effect of photobiomodulation therapy (PBMT) on painful temporomandibular disorders (TMD) patients in a randomized, double-blinded, placebo-controlled manner. Participants were divided into a masseter myalgia group (n = 88) and a temporomandibular joint (TMJ) arthralgia group (n = 87) according to the Diagnostic Criteria for Temporomandibular Disorders (DC/TMD). Both groups randomly received PBMT or placebo treatment once a day for 7 consecutive days, one session. The PBMT was applied with a gallium-aluminum-arsenide (GaAlAs) laser (wavelength = 810 nm) at pre-determined points in the masseter muscle (6 J/cm2, 3 regions, 60 s) or TMJ region (6 J/cm2, 5 points, 30 s) according to their most painful site. Pain intensity was rated on a 0-10 numerical rating scale (NRS) and pressure pain thresholds (PPT) and mechanical sensitivity mapping were recorded before and after the treatment on day 1 and day 7. Jaw function was assessed by pain free jaw opening, maximum unassisted jaw opening, maximum assisted jaw opening, maximum protrusion and right and left excursion. Data were analyzed with a mixed model analysis of variance (ANOVA). Pain intensity in arthralgia patients decreased over time (P < 0.001) for both types of interventions, however, PBMT caused greater reduction in pain scores than placebo (P = 0.014). For myalgia patients, pain intensity decreased over time (P < 0.001) but without difference between interventions (P = 0.074). PPTs increased in both myalgia (P < 0.001) and TMJ arthralgia patients over time (P < 0.001) but without difference between interventions (P ≥ 0.614). Overall, PBMT was associated with marginally better improvements in range of motion compared to placebo in both myalgia and arthralgia patients. Pain intensity, sensory function and jaw movements improve after both PBMT and placebo treatments in myalgia and arthralgia patients indicating a substantial non-specific effect of PBMT.

[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.

Comparison of Pain-Generated Functional Outcomes in Experimental Models of Delayed-Onset Muscle Soreness and Nerve Growth Factor Injection of the Masticatory Muscles.

AIMS: To compare two pain models of myalgic TMD, delayed-onset muscle soreness (DOMS) and injections of nerve growth factor (NGF), in terms of pain-related and motor function outcomes, as well as activity-related temporal summation. METHODS: Fifty age- and gender-matched healthy participants were recruited and randomized into one of three groups: to a repeated eccentric contraction task to cause DOMS (n = 20), to receive NGF injections into the masseter muscle (n = 20), or to a control group (n = 10). Mechanical sensitivity of masticatory muscles, chewing parameters, jaw function limitation, maximum bite force, and activity-related temporal summation were assessed at baseline and at days 1, 2, and 7 following the intervention. RESULTS: Compared to baseline, both model groups showed increased mechanical sensitivity, jaw function limitation, pain on chewing, and decreased chewing efficiency, lasting longer in the NGF group than in the DOMS group (P < .05). Furthermore, also compared to baseline, the NGF group showed increased pain on maximum bite and decreased pain-free maximum opening (P < .05). No increases in activity-related temporal summation were shown for any of the model groups when compared to baseline or the control group (P > .05). CONCLUSION: Both models produced similar pain-related outcomes, with the NGF model having a longer effect. Furthermore, the NGF model showed a more substantial effect on motor function, which was not seen for the DOMS model. Finally, neither of the models were able to provoke activity-related temporal summation of pain.

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.

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.

miR-96-5p promotes the proliferation and migration of ovarian cancer cells by suppressing Caveolae1.

BACKGROUND: Ovarian cancer (OC) is the second most common gynaecological malignancy. MicroRNAs (miRNAs) have been found to be aberrantly expressed in OC tissue and have been proposed as biomarkers and therapeutic targets for OC. RESULTS: In this study, we found that miR-96-5p was up-regulated in OC tissues and OC cells compared to normal ovarian tissues and epithelial cell line. And, miR-96-5p was also up-regulated in the serum samples from OC patients compared to health participants. In addition, there was a positive correlation of miR-96-5p levels between OC tissues and serum samples. At the cellular level, overexpression of miR-96-5p promoted cell proliferation and migration in OC cells. Moreover, we further validated Caveolae1 (CAV1) as the direct target of miR-96-5p in OC cells through luciferase activity assays and western blot. CAV1 was obvious low expression in OC tissues. The overexpression of CAV1 abrogated the promotion of miR-96-5p on the OC cells proliferation and migration. Finally, we found that AKT signaling pathway was involved in this process. MiR-96-5p inhibited the phosphorylation of AKT and expression of down-stream proteins Cyclin D1 and P70 by targeting CAV1. CONCLUSIONS: The above findings suggested that targeting miR-96-5p may be a promising strategy for OC treatment.

Temporal Summation of Painful Heat Stimulation Is Facilitated in Trigeminal and Extratrigeminal Regions in Painful Myofascial Temporomandibular Disorders: Evidence from a Case-Control Study.

AIMS: To determine whether patients with painful myofascial temporomandibular disorders (TMD) demonstrate facilitated temporal summation (TS) responses to painful heat stimuli applied to the painful trigeminal and extratrigeminal regions and whether there is a side difference in the trigeminal region for myofascial TMD pain patients compared to healthy controls. METHODS: Twenty female Chinese myofascial TMD pain patients and 20 age-matched female volunteers participated in this case-control study. Thermal detection thresholds, thermal pain thresholds, and TS of 20 repetitive noxious thermal stimuli were measured on the skin above the masseter muscle on both sides and the thenar eminence of the less painful side/dominant hand. Numeric rating scale (NRS) scores of pain were provided after the 1st, 5th, 10th, 15th, and 20th stimuli, and TS was calculated as the highest NRS score minus the first NRS score in each test. RESULTS: Evidence of TS was found in the trigeminal and extratrigeminal regions for both groups, but with facilitated TS responses in myofascial TMD pain patients (P < .001). Within the myofascial TMD group and control group, there were no side-to-side differences (P > .289). Interestingly, the repetition of the TS test was associated with facilitated responses in myofascial TMD pain patients (P < .001). CONCLUSION: The current findings suggest TS of painful heat stimulation is facilitated in myofascial TMD pain patients with no side difference in the trigeminal region.

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.

Reliability of Mechanical Sensitivity Mapping in the Orofacial Region of Healthy Chinese Individuals: Towards Standardized Assessment of Somatosensory Function.

AIMS: To investigate the test-retest reliability of mechanical sensitivity mapping in the masseter and temporomandibular joint (TMJ) regions between sessions, days, and examiners with a fixed and standardized pressure stimulus, as well as to compare mechanical sensitivity between sides and sites. METHODS: A total of 20 healthy young volunteers participated. Pressure stimulation was applied to 15 sites in the masseter region with a Palpeter device of 1.0-kg force and to 9 sites in the TMJ region with a Palpeter of 0.5-kg force. All participants were tested twice in two separate sessions on the same day by Examiner 1 with an interval of 3 hours between tests. After 1 week, the protocol was repeated in the same manner in two separate sessions by Examiner 1 and Examiner 2 (one session each). RESULTS: Analysis of variance (ANOVA) of numeric rating scale (NRS) scores and center of gravity (COG) values in both regions showed no significant main effects of examiner, day, or session (P ≥ .167). The test-retest reliability of data implied excellent agreement (intra-class correlation coefficients all > 0.75) between different examiners, days, and sessions. In addition, the ANOVA of the mean NRS scores in both regions showed significant main effects of site (P = .001). CONCLUSION: This feasible and reliable technique may provide a new tool for comprehensive evaluation of mechanical allodynia and hyperalgesia in the orofacial region, which are common features related to temporomandibular disorders and other chronic craniofacial pain conditions.

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.