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Background: Glecaprevir/pibrentasvir (G/P; 300 mg/120 mg) is a new direct-acting antiviral (DAA) that exhibits anti-hepatitis C virus (HCV) pan-genotype (GT) activity for 8, 12, or 16 weeks. However, the U.S. Food and Drug Administration have received reports that using G/P causes moderate to severe liver impairment. In some cases, isolated hyperbilirubinemia and jaundice have been reported without concomitant evidence of increased transaminase levels or other hepatic decompensation events. Objective: This study aimed to analyze the incidence of drug-induced liver injury of G/P for chronic hepatitis C virus. Materials and methods: We searched databases from the inception of each database until March 2021. Data were pooled using a random-effects model. The Cochrane Risk of Bias Tool (RoB 2.0) and the OpenMeta [Analyst] software were performed for quality assessment and quantitative studies, respectively. The primary outcome was grade 3 level of drug-induced liver injury (DILI). Results: The nine studies included in the meta-analysis involved a total of 7,650 participants, and the overall sustained virologic response rate was above 95%. The most frequent drug-related laboratory abnormalities in DILI involved total bilirubin, alanine aminotransferase, aspartate aminotransferase, and hemoglobin, but these abnormalities were minimal. The cirrhosis–without cirrhosis incidence risk ratio (IRR) was 2.724 (95% confidence interval: 1.182–6.276) in the grade 3 hyperbilirubinemia subgroup analysis. No significant differences were found within the other subgroups, in HCV GTs, and in treatment duration. Conclusions: DILI was found to occur frequently with G/P treatment. Hyperbilirubinemia occurred most frequently, especially, in patients with cirrhosis. However, G/P is still the primary therapy of choice for CKD and end-stage renal disease (ESRD) patients due to a superior safety rate.

This study aimed to investigate the effects of a psychological growth camp in the treatment of adolescents at risk of Internet addiction in Taiwan. We designed a psychological growth camp to treat adolescents at risk of Internet addiction. The CIAS (Chen Internet Addiction Scale) was used to assess the severity of Internet addiction at baseline, immediately after the camp, and at 1-month and 2-month follow-up visits. A total of 16 participants were recruited, including 10 at risk of Internet addiction and 6 without the risk of Internet addiction. The results indicated that the participants not in a 2-parent family had significantly higher CIAS scores than those in a 2-parent family (p = .034). The participants at risk of Internet addiction exhibited significant improvements in total CIAS score at the time immediately after the camp (p = .033) and at 1-month (p = .001) and 2-month (p = .003) follow-up visits. Moreover, the incidence of possible Internet addiction was not significantly decreased immediately after the camp (p = .056) but was significantly decreased at 1- and 2-month follow-up visits (p < .05) compared with the baseline level. Otherwise, no significant improvements in total CIAS score or subscales were observed at the follow-up visits (p > .05) for the participants not at risk of Internet addiction. The results indicate that the psychological growth camp without Internet might be effective in treating adolescents with Internet addiction.

Sterile water injections (SWIs) as a non-pharmacologic and cost-effective method have been adopted to relieve low back labor pain (LBLP).To compare the efficacy of intradermal and subdermal SWIs in the treatment of LBLP.Three databases (PubMed, Cochrane Library, and ScienceDirect) were searched to find relevant articles using two terms, "labor" and "sterile water".Studies reporting women with LBLP treated by intradermal or subdermal SWIs in the low back area were included.Mean differences with 95% confidence interval (CI) and relative risk with 95% CI were used to estimate VAS score and cesarean section rate, respectively.Except for 10 min, the patients in the intradermal or subdermal SWI group experienced considerable pain reduction compared with the control group for 30-45, 60, and 90 min. Directly comparing intradermal and subdermal SWI groups, the subdermal injection group had significantly better pain relief than the intradermal injection group only at 10 min after treatment.Both intradermal and subdermal SWIs could reduce LBLP at 30-90 min. The subdermal SWI had significantly better LBLP relief than the intradermal injection only at 10 min after treatment.

Aims Interleukin (IL)-1β is one of the major pathogenic regulators during the pathological development of intervertebral disc degeneration (IDD). However, effective treatment options for IDD are limited. Suramin is used to treat African sleeping sickness. This study aimed to investigate the pharmacological effects of suramin on mitigating IDD and to characterize the underlying mechanism. Methods Porcine nucleus pulposus (NP) cells were treated with vehicle, 10 ng/ml IL-1β, 10 μM suramin, or 10 μM suramin plus IL-1β. The expression levels of catabolic and anabolic proteins, proinflammatory cytokines, mitogen-activated protein kinase (MAPK), and nuclear factor (NF)-κB-related signalling molecules were assessed by Western blotting, quantitative real-time polymerase chain reaction (qRT-PCR), and immunofluorescence analysis. Flow cytometry was applied to detect apoptotic cells. The ex vivo effects of suramin were examined using IDD organ culture and differentiation was analyzed by Safranin O-Fast green and Alcian blue staining. Results Suramin inhibited IL-1β-induced apoptosis, downregulated matrix metalloproteinase (MMP)-3, MMP-13, a disintegrin and metalloproteinase with thrombospondin motifs (ADAMTS)-4, and ADAMTS-5, and upregulated collagen 2A (Col2a1) and aggrecan in IL-1β-treated NP cells. IL-1β-induced inflammation, assessed by IL-1β, IL-8, and tumour necrosis factor α (TNF-α) upregulation, was alleviated by suramin treatment. Suramin suppressed IL-1β-mediated proteoglycan depletion and the induction of MMP-3, ADAMTS-4, and pro-inflammatory gene expression in ex vivo experiments. Conclusion Suramin administration represents a novel and effectively therapeutic approach, which could potentially alleviate IDD by reducing extracellular matrix (ECM) deposition and inhibiting apoptosis and inflammatory responses in the NP cells. Cite this article: Bone Joint Res 2021;10(8):498–513.

Objective Shockwave application is a potential treatment for osteoarthritis (OA), but the underlying mechanism remains unknown. Oxidative stress and a counterbalancing antioxidant system might be the key to understanding this mechanism. We hypothesized that reactive oxygen species (ROS) and the transcription factor nuclear factor erythroid 2-related factor 2 (Nrf2),which is an important regulator of cellular redox homeostasis, are plausible elements. Design Porcine chondrocytes were cultured in a 3-dimensional pellet model and subjected to shockwaves. The effects of shockwaves with various energy-flux densities on optimal extracellular matrix (ECM) synthesis were assessed. ROS, mitogen-activated protein kinase (MAPK) signaling, and the redox activity of Nrf2 were measured. To investigate the signaling mechanism involved in the shockwave treatment in chondrocytes, specific inhibitors of ROS, MAPK signaling, and Nrf2 activity were targeted. Results Shockwaves increased ECM synthesis without affecting cell viability or proliferation. Furthermore, they induced transient ROS production mainly through xanthine oxidase. The phosphorylation of ERK1/2 and p38 and the nuclear translocation of Nrf2 were activated by shockwaves. By contrast, suppression of ROS signaling mitigated shockwave-induced MAPK phosphorylation, Nrf2 nuclear translocation, and ECM synthesis. Pretreatment of chondrocytes with the specific inhibitors of MEK1/2 and p38, respectively, mitigated the shockwave-induced nuclear translocation of Nrf2 and ECM synthesis. Nrf2 inhibition by both small hairpin RNA knockdown and brusatol reduced the shockwave-enhanced ECM synthesis. Conclusions Shockwaves activated Nrf2 activity through the induction of transient ROS signaling and subsequently enhanced ECM synthesis in chondrocytes. This study provided fundamental evidence confirming the potential of shockwaves for OA management.

Observations of a symptomatic discoid lateral meniscus in young children are infrequent. The objective of this report was to demonstrate the use of arthroscopic saucerization and repair for treating a bucket-handle tear of a lateral discoid meniscus in two young children. Two young children (a 28-month-old girl and a 5-year-old boy) presented with a bucket-handle tear of the complete type lateral discoid meniscus. Both patients received arthroscopic saucerization and repair. A full knee extension under a long leg cast was applied for one month after surgery. The two patients were able to achieve a full range of motion of their operated knees without limping or presenting an antalgic gait at the third month after surgery. Both patients and their parents felt satisfied with the treatment at the 2- and 3-year follow-ups, respectively. Our results demonstrated that arthroscopic saucerization and repair seems to be an effective treatment for bucket-handle tears of the lateral discoid meniscus in young children-even those younger than 3 years old. We reported the youngest case (a 28-month-old girl) in comparison with the findings from a literature review.

Omecamtiv mecarbil (OM, CK-1827452) is recognized as an activator of myosin and has been demonstrated to be beneficial for the treatment of systolic heart failure. However, the mechanisms by which this compound interacts with ionic currents in electrically excitable cells remain largely unknown. The objective of this study was to investigate the effects of OM on ionic currents in GH3 pituitary cells and Neuro-2a neuroblastoma cells. In GH3 cells, whole-cell current recordings showed that the addition of OM had different potencies in stimulating the transient (INa(T)) and late components (INa(L)) of the voltage-gated Na+ current (INa) with different potencies in GH3 cells. The EC50 value required to observe the stimulatory effect of this compound on INa(T) or INa(L) in GH3 cells was found to be 15.8 and 2.3 µM, respectively. Exposure to OM did not affect the current versus voltage relationship of INa(T). However, the steady-state inactivation curve of the current was observed to shift towards a depolarized potential of approximately 11 mV, with no changes in the slope factor of the curve. The addition of OM resulted in an increase in the decaying time constant during the cumulative inhibition of INa(T) in response to pulse-train depolarizing stimuli. Furthermore, the presence of OM led to a shortening of the recovery time constant in the slow inactivation of INa(T). Adding OM also resulted in an augmentation of the strength of the window Na+ current, which was evoked by a short ascending ramp voltage. However, the OM exposure had little to no effect on the magnitude of L-type Ca2+ currents in GH3 cells. On the other hand, the delayed-rectifier K+ currents in GH3 cells were observed to be mildly suppressed in its presence. Neuro-2a cells also showed a susceptibility to the differential stimulation of INa(T) or INa(L) upon the addition of OM. Molecular analysis revealed potential interactions between the OM molecule and hNaV1.7 channels. Overall, the direct stimulation of INa(T) and INa(L) by OM is assumed to not be mediated by an interaction with myosin, and this has potential implications for its pharmacological or therapeutic actions occurring in vivo.

This prospective case-control study aimed to compare the intraoperative hemodynamic changes between the wide-awake local anesthesia no tourniquet (WALANT) technique and general anesthesia (GA) in patients undergoing distal radius plating surgery. Forty adults with distal radius fractures underwent plating surgery via the WALANT technique (20 patients) or GA (20 patients). Mean arterial pressure (MAP) and heart rate were recorded. Intraoperative pain intensity was measured using the visual analog scale (VAS) for pain in the WALANT group. The measures of hemodynamics and VAS were recorded at seven-time points perioperatively. The VAS score decreased significantly compared with the preoperative status in the WALANT group for most of the intraoperative period except during injections of local anesthetics and fracture reduction. The intraoperative MAP in the WALANT group showed no significant change during the perioperative period. In addition, the WALANT group showed fewer perioperative MAP fluctuations than the GA group (p < 0.05). The reduction and plating quality were similar between the two groups. WALANT provided a feasible technique with less fluctuation in hemodynamic status. With gentle manipulation of the fracture reduction, distal radius plating surgery using the WALANT technique is a well-tolerated surgical procedure and shows similar reduction and plating quality to GA.

Background and purpose: In patients with ankle fractures complicated by syndesmotic injuries, no consensus has been reached on the best method of syndesmosis fixation using syndesmotic screws. One previous study revealed no difference in the tibiofibular overlap between two groups with or without syndesmotic screw removal. Other studies have indicated that distal tibiofibular diastasis exists after the removal of syndesmotic screws. In this study, we aimed to confirm the effect of syndesmotic screw removal on diastasis occurrence. We further analyzed the risk factors that may contribute to the widening of the tibiofibular syndesmosis.Patients and methods: This retrospective study involved a review of the records of 63 patients with ankle fractures accompanied by syndesmosis injuries that required syndesmotic screw fixation. Anteroposterior radiographs were analyzed for each patient at various time points, from syndesmotic screw fixation to outpatient department follow-ups after screw removal. The changes in tibia–fibula overlap (OL), tibia–fibula clear space (CS), and medial clear space (MCS) were analyzed. Further analysis was performed to reveal potential factors that may have contributed to radiographic differences.Results: Compared with the postoperation radiographs following syndesmotic screw fixation, OL decreased (2.006 mm) and CS increased (0.821 mm) in the anteroposterior radiographs from outpatient department follow-ups. No significant changes were noted in OL or CS after syndesmotic screw removal. However, OL decreased (1.782 mm) and CS increased (0.492mm) before syndesmotic screw removal. No significant change in MCS occurred during the whole observation period. Linear regression analysis did not reveal any significant correlations between potentially related factors and radiographic changes. Conclusion: Marked diastasis had occurred at final follow-up. Notably, the diastasis occurred before rather than after screw removal. This implies that screw removal does not significantly influence the radiographic outcomes of rotational ankle fractures.

Ankle arthrodesis (AA) and total ankle arthroplasty (TAA) are the 2 primary surgical treatments for patients with end-stage ankle arthritis. The comparative outcomes between AA and TAA using modern techniques remain unclear. A systematic search to identify all relevant articles comparing AA with TAA was conducted through 3 online databases. The clinical outcomes were extracted for meta-analysis, including AOFAS (American Orthopaedic Foot & Ankle Society) score, VAS (visual analog scale), AOS (Ankle Osteoarthritis Scale), gait analysis, ROM (range of motion), satisfaction, complication, and reoperation. Our meta-analysis shows no heterogeneity in any subgroup analyses. There were no significant differences in AOFAS total, pain, and alignment scores between the AA and TAA groups. The TAA group had significant improvement in AOFAS function score compared with the AA group. There was no significant difference in VAS and AOS total scores between the 2 groups. No significant differences in gait analysis were observed between the 2 groups. The TAA group had significant improvement in both ROM and change in ROM compared with the AA group. There was no significant difference in satisfaction rate between the 2 groups. The TAA group had significantly higher complication and reoperation rates compared with the AA group. Our meta-analysis provides updated evidence on clinical outcomes comparing AA with TAA using third-generation implants. The TAA group had better improvement in AOFAS function and ROM than the AA group. No significant differences in pain relief, gait analysis, or patient satisfaction were observed between the 2 groups.

Objective: To compare the efficacy of various strategies in the treatment of trigger finger. Data sources: A systematic literature search for randomized controlled trials to compare treatments for trigger finger was conducted through three online databases, Pubmed, Embase and Cochrane Library, from their inception dates to 22 May 2020. Methods: Relative risk (RR) with 95% confidence interval (CI) was used to evaluate the effect sizes in success rate for included articles. Results: Sixteen articles ( n = 1185) were included in our meta-analysis. The results showed that the efficacy of steroid injection was significantly better than the placebo group at short-term follow-ups (RR = 19.00, 95% CI = 1.17–309.77 for one-week; RR = 3.70, 95% CI = 3.70, 95% CI = 1.61–8.53 for one-month), and then became non-significant at four months (RR = 3.21, 95% CI = 0.88–11.79). There was no significant difference in success rate between steroid injection and nonsteroidal anti-inflammatory drug injection, and between open surgery and percutaneous release at all the follow-ups. Only surgical treatment had significantly better efficacy in success rate than steroid injection at all follow-ups (RR = 0.48, 95% CI = 0.34–0.66 for one-month; RR = 0.87, 95% CI = 0.80–0.96 for three-month; RR = 0.58, 95% CI = 0.48–0.68 for six-month; RR = 0.38, 95% CI = 0.20–0.72 for 12-month). Conclusion: There were no differences in efficacy between steroid injection and shockwave or nonsteroidal anti-inflammatory drug injection. The surgical treatments had the best efficacy among these treatments.

Study Design: This was a single-center, retrospective study. Objective: The objective of this study was to assess the risk factors for deformity progression after scoliosis correction surgery in spinal muscular atrophy (SMA) patients. Summary of Background Data: Moderate residual postoperative scoliosis curve is common in SMA populations; however, the acceptable postoperative scoliosis curve for preventing deformity progression remains uncertain. Materials and Methods: Twenty-nine SMA patients undergoing scoliosis correction surgery were included. Scoliosis progression was defined as an increase of 10 degrees in the major curve of Cobb angle (MCCA); pelvic obliquity (PO) or concave-side hip progression was arbitrarily defined as an increase of ≥1 grade after surgery. Risk factors for deformity progression were examined using Cox proportional hazard models. The cumulative incidence rate of deformity progression was performed by the Kaplan-Meier survival analysis Results: The mean age at surgery was 13.3 years (range: 8–25 y) and the mean follow-up time was 7 years (range: 2–22.9 y). The mean MCCA was corrected from 69 to 34.6 degrees at initial follow-up and 42.2 degrees at the final follow-up. Postoperative MCCA (P=0.002) and PO (P=0.004) at initial follow-up were the risk factors for scoliosis progression. Postoperative MCCA at initial follow-up (P=0.007) and age at the time of surgery (P=0.017) were the risk factors for PO progression. Different cutoff points of postoperative MCCA at initial follow-up were compared for predicting deformity progression. We found the patient with postoperative MCCA of

Observations of a symptomatic discoid lateral meniscus in young children are infrequent. The objective of this report was to demonstrate the use of arthroscopic saucerization and repair for treating a bucket-handle tear of a lateral discoid meniscus in two young children. Two young children (a 28-month-old girl and a 5-year-old boy) presented with a bucket-handle tear of the complete type lateral discoid meniscus. Both patients received arthroscopic saucerization and repair. A full knee extension under a long leg cast was applied for one month after surgery. The two patients were able to achieve a full range of motion of their operated knees without limping or presenting an antalgic gait at the third month after surgery. Both patients and their parents felt satisfied with the treatment at the 2- and 3-year follow-ups, respectively. Our results demonstrated that arthroscopic saucerization and repair seems to be an effective treatment for bucket-handle tears of the lateral discoid meniscus in young children—even those younger than 3 years old. We reported the youngest case (a 28-month-old girl) in comparison with the findings from a literature review.

Background: Diagnosing intervertebral instability is crucial for the treatment of degenerative lumbar spondylolisthesis (DLS). Disabling back pain will reduce spinal mobility which leads to an underestimate of the incidence of intervertebral instability. We hypothesized that adequate analgesia could alter the flexion/extension exam performance, and thus increase the diagnostic accuracy of segmental instability. Materials and methods: One hundred patients with low-grade DLS were prospectively enrolled in the before–after cohort study. Standing lateral flexion/extension radiographs of lumbar spines were examined and analyzed before and after intramuscular injections of 30 mg ketorolac. Results: Pain score decreased significantly after analgesic injections (p &lt, 0.001). Dynamic slip (DS), dynamic segmental angle (DA), dynamic lumbar lordosis, and slip percentage (SP) were significantly increased after pain reduction (all p &lt, 0.001). According to the diagnostic criteria for segmental instability (DS &gt, 4.5 mm, DA &gt, 15°, or SP &gt, 15%), there were 4%, 4%, and 0.7% of total motion segments fulfilling the criteria which markedly increased to 42%, 32%, and 16.7% after analgesia was administered. The incidence of instability also increased from 6% to 38% after analgesia. Conclusions: The diagnosis rate of intervertebral instability is commonly underestimated in the presence of low back pain. This short-term pain relief facilitates reliable functional imaging adding to the diagnosis of intervertebral instability.

Radiofrequency ablation (RFA) was first introduced for treating knee osteoarthritis (OA) in 2010 and has emerged as a minimally invasive treatment option. Three RFA techniques have been adopted for treating knee OA, including conventional, pulsed, and cooled RFA. However, the efficacy among different RFA techniques in the treatment of knee OA is still unclear. Three electronic databases were systematically searched for relevant articles, including PubMed, Embase, and Cochrane Library. A meta-analysis of articles that investigated the use of RFA techniques in the treatment of knee OA was conducted to pool the effect size in pain before and after treatment. A total of 20 eligible articles (including 605 patients) were included for our meta-analysis. After treatment, the patients had significant improvements in pain for all three RFA techniques when compared with the baseline level for the 1, 3-, and 6-month follow-ups (p &lt, 0.00001). However, there were no significant differences in the efficacy among the three RFA techniques for all follow-up visits (p &gt, 0.05). The three RFA techniques demonstrated a significant improvement in pain for up to 6 months after treatment. Comparing the efficacy of the three RFA techniques in the treatment of knee OA, our results showed that no significant differences in pain relief among the three RFA techniques were observed at the 1-, 3-, 6, and 12-month follow-up visits.

Flexible flatfoot is the most common condition seen in pediatric orthopedic practice and generalized joint hypermobility is widely regarded as one of the predisposing factors. However, in previous studies, the flatfoot was defined by observers' subjective evaluation of the eversion of the bare foot in the standing position; and the joint hypermobility was defined by the Beighton score. The objective of this study is to evaluate the correlation between preschool-age flexible flatfoot and joint hypermobility in preschool-age children objectively. Footprints were measured on a Harris and Beath footprint mat. Flatfoot flexibility was assessed by Staheli Plantar Arch Index (PAI). Other than the Beighton score, 2 new measurement methods, the thumb-to-forearm test and the thumb-thrust test were developed to evaluate joint hypermobility. Of the 291 preschool children from 4 different kindergarten schools included in this study, 156 were boys and 135 were girls. The mean age was 64.18 ± 9.33 months (range 35-88 months). Pearson correlation analysis demonstrated PAI was not associated with the Beighton score (R = 0.020, P = .735), thumb-to-forearm grade (R = 0.109, P = .066), and thumb-thrust grade (R = 0.027, P = .642). Two-sample t-test results showed that the normal and flatfoot groups did not differ significantly in the Beighton score (P = .404), thumb-to-forearm grade (P = .063), and thumb-thrust grade (P = .449). The results demonstrated no correlation between joint hypermobility and preschool-age flexible flatfoot when flatfoot was defined with Staheli PAI and joint hypermobility with the Beighton score. Even with 2 new methods, the thumb-to-forearm test and thumb-thrust test, to define joint hypermobility, we still found no correlation between preschool-age flexible flatfoot and joint hypermobility.

Background This study aimed to compare the efficacy and safety of intra-articular hyaluronic acid (HA) injection with different molecular weights (MWs) for treating hip osteoarthritis (OA). Methods A systematic literature search for relevant studies was conducted in 3 electronic databases, including PubMed, BMJ Journals, and Cochrane Library, from inception to April 2020. Extracted outcomes included visual analogue scale (VAS) (1, 3, and 6 months), Lequesne index (3 and 6 months), and adverse effects. HAs were classified into low-molecular-weight (LMW), moderate-molecular-weight (MMW), high-molecular-weight (HMW), and ultra-high-molecular-weight (UHMW) groups. Meta-analysis was performed using Review Manager 5.3. Results A total of 15 studies with 614 patients were included. Our meta-analysis showed that the HMW HA group had the best improvement in VAS and Lequesne index compared with other HA groups for all the follow-up visits. Moreover, the HMW group demonstrated significantly better improvement than the other groups in VAS at 6-month follow-up and in Lequesne index at 3- and 6-month follow-ups. Analysis for adverse effects revealed low rates of systemic adverse effects (≤0.6%) in all groups and similar rate of local adverse effects (around 10%) among the groups except for UHMW HA group (37.5%). Conclusion Among different MWs of HA for treating hip OA, HMW HA injection demonstrated the best efficacy for up to 6 months after treatment without increased risk of adverse effects. Further studies with more comprehensive data and a higher level of evidence are required to prove our results.

Di-(2-propylheptyl) phthalate (DPHP) is an alternative plasticizer that can replace other phthalates currently being scrutinized, and its use and production volumes are increasing. This study aimed to develop a high-resolution mass spectrometry (HRMS)-based metabolomics strategy to comprehensively screen urinary biomarkers of DPHP exposure and filter out potentially useful DPHP exposure markers for human exposure assessments. This strategy included three stages: screening of biomarkers, verification of dose-response relationships in laboratory animals, and application in human subjects. The multivariate data analysis method known as orthogonal partial least-squares discriminant analysis (OPLS-DA) was used to screen and find meaningful signals in an MS dataset generated from urine samples collected from DPHP-administered rats. Thirty-six MS signals were verified as exposure marker candidates by assessing dose-response relationships in an animal feeding study. A biotransformation product of DPHP, mono-(2-propyl-7-dihydroxy-heptyl) phthalate, was suggested as a DPHP exposure marker for general human exposure assessments after the human application study and chemical structure identification. Three previously oxidized DPHP biotransformation products might be suitable for human exposure assessments in high-level exposure groups but not in the general population due to their low sensitivity. Keywords: Phthalate, Di-(2-propylheptyl)phthalate, Biomarker, Metabolomics, Exposure assessment

Di-(2-propylheptyl) phthalate (DPHP) is a plasticizer and has been suggested to be a subchronic toxicant in rats. DPHP has been approved to be used in food containers and handling by the U.S. Food and Drug Administration. The use of DPHP is still increasing, and the risk of human exposure to DPHP via food may be high. Exposure markers measured in human samples are commonly used to monitor human exposure levels. Ultra-performance liquid chromatography-mass spectrometry (UPLC-MS) and a rat model were used to discover tentative DPHP exposure markers. DPHP and mono-(2-propylheptyl) phthalate (MPHP) were used as the precursors for calculating metabolite candidates using biotransformation mass changes of known enzymatic reactions. A rat model was designed to validate these metabolite candidates as tentative exposure markers. A total of 28 signals show dose–response relationships and these signals contain a few isomers. The chemical structures of 15 tentative exposure marker signals were speculated based on the product ion mass spectra from MS/MS analysis. These 15 signals included 7 chemical structures and some of them may be isomers. The different arrangement of the atoms in space of these isomers should be validated by standard compounds in the future studies. Among the 7 speculated chemical structures, 2 structures were novel tentative DPHP metabolites, and 5 structures have been previously reported in the literature. The results indicate that using UPLC-MS and a rat model can be used to identify tentative toxicant exposure markers. Keywords: Biotransformation mass changes, Di-(2-propylheptyl) phthalate, Ultra-performance liquid chromatography-mass spectrometry

In the original publication [...]

To examine the efficacy of extracorporeal shock wave therapy (ESWT) and injection therapies by synthesizing direct and indirect evidence for all pairs of competing therapies for lateral epicondylitis.PubMed, EMBASE, and Web of Science databases were searched for all appropriate randomized controlled trials (RCTs), assessing the effect of ESWT or injection therapies. The primary outcome was short-term (≤3 months) and medium-term (3 months but ≤12 months) pain, while the secondary outcomes were grip strength and patient-reported outcome measures. All outcomes were assessed using standardized mean differences (SMDs) with 95% confidence intervals (CIs) and were ranked using surface under the cumulative ranking curve (SUCRA) probabilities to determine a hierarchy of treatments. Sensitivity analysis was performed to eliminate potential therapeutic effects of normal saline (NS) and exclude trials that included patients with acute lateral epicondylitis (LE).40 RCTs were included to evaluate ESWT and five different injection therapies, including corticosteroids (CSs), autologous whole blood, platelet-rich plasma (PRP), botulinum toxin A (BoNT-A), and dextrose prolotherapy (DPT). DPT (-.78 [-1.34 to -.21]), ESWT (.57 [-.89 to -.25]), PRP (-.48 [-.85 to -.11]), and BoNT-A (-.43 [-.84 to -.02]) outperformed placebo for short-term pain relief; ESWT (-.44 [-.85 to -.04]) outperformed placebo for medium-term pain relief. DPT was ranked as the most optimal short-term and medium-term pain reliever (SUCRA, 87.3% and 98.6%, respectively). ESWT was ranked as the most optimal short-term and medium-term grip strength recovery (SUCRA; 79.4% and 86.4%, respectively).DPT and ESWT were the best two treatment options for pain control and ESWT was the best treatment option for grip strength recovery. CSs were not recommended for the treatment of LE. More evidence is required to confirm the superiority in pain control of DPT among all these treatment options on LE.Level I, meta-analysis of Level I randomized controlled trials.

Metabolism studies are one of the important steps in pharmaceutical research. LC-MS combined with metabolomics data-processing approaches have been developed for rapid screening of drug metabolites. Mass defect filter (MDF) is one of the LC/MS-based metabolomics data processing approaches and has been applied to screen drug metabolites. Although MDF can remove most interference ions from an incubation sample, the true positive rate of the retaining ions is relatively low (approximately 10%). To improve the efficacy of MDF, we developed a two-stage data-processing approach by combining MDF and stable isotope tracing (SIT) for metabolite identification. Pioglitazone (PIO), which is an antidiabetic drug used to treat type 2 diabetes mellitus, was taken as an example drug. Our results demonstrated that this new approach could substantially increase the validated rate from about 10% to 74%. Most of these validated metabolite signals (13/14) could be verified as PIO structure-related metabolites. In addition, we applied this approach to identify uncommon metabolite signals (a mass change beyond the window of 50 Da around its parent drug, MDF1). SIT could remove most interference ions (approximately 98%) identified by MDF1, and four out of five validated metabolite signals could be verified as PIO structure-related metabolites. Interestingly, a lot of the verified metabolites (10/17) were novel PIO metabolites. Among these novel metabolites, nine were thiazolidinedione ring-opening signals that might be related to the toxicity of PIO. Our developed approach could significantly improve the efficacy in drug metabolite identification compared with that of MDF.

Women commonly suffer from depression during pregnancy. For reducing depression, yoga seems to be more suitable for pregnant women than other physical activities because of its low exercise intensity. The objective of this study was to assess the efficacy of prenatal yoga on the treatment of depression during pregnancy. Three electronic databases were searched for relevant articles from their inception to May 2021, including PubMed, Cochrane Library, and ScienceDirect. Pre- and post-test outcomes were adopted to estimate standardized mean difference with a 95% confidence interval for assessing the efficacy of yoga. Heterogeneity among articles was detected using I2 value. A total of 13 articles that contained 379 subjects were included for meta-analysis. No significant improvement in depression scores after practicing yoga was observed for women without depression (p = 0.09) but significant improvement was observed for women with depression (p = 0.001). Although significant improvement in anxiety scores after yoga was observed for women without depression (p = 0.02), the results of the sensitivity analysis were not consistent, while significant improvement in anxiety scores after yoga was also observed for women with depression (p < 0.00001). The current evidence has suggested that yoga had significant improvement in depression and anxiety scores in pregnant women with depression. However, the level of evidence of this study was not high. More articles with high levels of evidence should be conducted to confirm our conclusion in the future.

Several studies have reported that Hemoglobin A1c (HbA1c) levels increase with age for people without diabetes. However, HbA1c levels associated with age and gender have not been well investigated for Taiwanese adults. The objective of this study was to investigate the sex-specific association between HbA1c levels and age for Taiwanese adults without diabetes. The data were collected from the Taiwan Biobank database with inclusive criteria being participants without diabetes. The association between HbA1c values and age was conducted by linear regression analysis, HbA1c values between sexes were compared by two-sample t-test, and HbA1c levels among age groups were compared using one-way ANOVA. The results showed that HbA1c levels were positively correlated with age, and the levels for males were significantly higher than for females among all participants. However, there was no significantly positive correlation between HbA1c levels and age in males for age group of 50–70 years. The levels of males were significantly higher than females for age groups of 30–39 and 40–49 years. There were significant differences in HbA1c levels among age groups for all participants, males, and females except for the two age groups of 50–59 and 60–70 years in males. Age and gender were important factors affecting HbA1c levels. Our results suggested that the HbA1c cut-point levels for the diagnosis of diabetes should vary by age and gender.

Aim: Taiwan’s response to the coronavirus disease 2019 (COVID-19) differed in that it successfully prevented the spread without having to shutdown or overburden medical services. Patients’ fear regarding the pandemic would be the only reason to reduce surgeries, so Taiwan could be the most suitable place for research on the influence of psychological factors. This study aimed to assess the impact of patients’ fear on orthopedic surgeries in Taiwan amid the peak period of the COVID-19 pandemic. Patients and Methods: The investigation period included the COVID-19 pandemic (March 2020 to April 2020) and the corresponding period in the previous year. The following data on patients with orthopedic diseases were collected: outpatient visits, hospital admission, and surgical modalities. Results: The COVID-19 pandemic led to a 22%–29% and 20%–26% reduction in outpatients, 22%–27% and 25%–37% reduction in admissions, and 26%–35% and 18%–34% reduction in surgeries, respectively, at both hospitals. The weekly mean number of patients was significantly smaller during the COVID-19 pandemic for all types of surgery and elective surgeries at the university hospital, and for all types of surgery, elective surgeries, and total knee arthroplasties at the community hospital. Further, patients visiting the community hospital during the pandemic were significantly younger, for all types of surgery, elective surgeries, and total knee arthroplasties. Conclusions: The reduction in orthopedic surgeries in Taiwan’s hospitals during COVID-19 could be attributed to patients’ fear. Even without restriction, the pandemic inevitably led to a reduction of about 20%–30% of the operation volume.

The purpose of this study was to build on existing qualitative to quantitative approaches to develop a new quantitative method for evaluating pelvic and trunk rotational pitching mechanics. Thirty pitchers were divided into two groups (&ldquo, Pattern1&rdquo, closed &ldquo, hip-to-shoulder separation&rdquo, &ldquo, Pattern2&rdquo, open &ldquo, ). Several parameters were analyzed. Higher ball speeds were found in group of Pattern1, four key characteristics of which were identified. Based on the results, a new evaluation method was developed. Pelvic and trunk rotational mechanics were classified into four types. Type1 (proper mechanics) enabled significantly higher ball speed than the other three types and was thought to involve proper energy transfer from the stride foot to the throwing upper limb. Types 2&ndash, 4, however, were regarded as &ldquo, improper mechanics&rdquo, which could result in slower ball speeds and less efficient energy transfer. A qualitative approach, based on &ldquo, expert opinion&rdquo, can specify optimal pelvis and trunk rotational mechanics. However, quantitative analysis is more precise in identifying three improper types of pelvis and trunk rotational mechanics. Furthermore, special programs, such as core strengthening and flexibility training, can be developed for various improper practices in order to improve pitching mechanics.

AIMS This study aimed to compare the efficacy of different numbered sets of injections of platelet-rich plasma (PRP) in the treatment of mild-moderate knee osteoarthritis (OA). METHODS A comprehensive search in three databases of Cochrane Library, Embase, and PubMed was conducted to find relevant articles that investigated the efficacy of PRP injection therapies in the treatment of mild-moderate knee OA through August 2020. The Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) pain and function scores were the primary outcomes and visual analogue scale (VAS) was the secondary outcome. The pooled improvements amongst different injection therapies were compared. RESULTS No significant differences in the improvement of WOMAC pain were observed amongst 1-, 2-, and 3-injection therapies at 3- (P = .26) and 6-month (P = .13) follow-ups. For a 12-month follow-up, the difference amongst different therapies reached borderline significance (P = .05) in which 3-injection therapy had a significantly better improvement than 2-injection therapy (P = .02) and reached borderline significance compared with 1-injection (P = .07). However, no significant differences in the improvement of VAS scores were observed amongst three injection therapies for all the follow-up visits (P > .05). For WOMAC function score, 3-injection therapy performed significantly better than 1-injection (P

Background Distal radius fracture (DRF) is the most common upper extremity fracture that requires surgery. Operative treatment with a volar locking plate has proved to be the treatment of choice for unstable fractures. However, no consensus has been reached about the benefits of pronator quadratus (PQ) repair after volar plate fixation of DRF in terms of patient-reported outcome measures, pronation strength, and wrist mobility. Methods We searched the PubMed, Embase, Cochrane Central, and China National Knowledge Infrastructure (CNKI) databases up to March 13, 2020, and included randomized-controlled, non-randomized controlled, or case-control cohort studies that compared cases with and without PQ repair after volar plate fixation of DRF. We used a random-effects model to pool effect sizes, which were expressed as standardized mean differences (SMDs) and 95% confidence intervals. The primary outcomes included Disabilities of the Arm, Shoulder, and Hand scores and pronation strength. The secondary outcomes included the SMDs in pain scale score, wrist mobility, and grip strength. The outcomes measured were assessed for publication bias by using a funnel plot and the Egger regression test. Results Five randomized controlled studies and six retrospective case-control studies were included in the meta-analysis. We found no significant difference in primary and secondary outcomes at a minimum of 6-month follow-up. In a subgroup analysis, the pronation strength in the PQ repair group for AO type B DRFs (SMD = − 0.94; 95% CI, − 1.54 to − 0.34; p < 0.01) favored PQ repair, whereas that in the PQ repair group for non-AO type B DRFs (SMD = 0.39; 95% CI, 0.07–0.70; p = 0.02) favored no PQ repair. Discussion We found no functional benefit of PQ repair after volar plate fixation of DRF on the basis of the present evidence. However, PQ muscle repair showed different effects on pronation strength in different groups of DRFs. Future studies are needed to confirm the relationship between PQ repair and pronation strength among different patterns of DRF. Registration This study was registered in the PROSPERO registry under registration ID No. CRD42020188343. Level of evidence Therapeutic III

Background: Wide-awake local anesthesia no tourniquet (WALANT) is a promising technique for bony procedure in recent years. During distal radius surgery via WALANT technique, surgeons may concern about intraoperative pain. This prospective case-control study was aimed to compare the intraoperative hemodynamic changes between WALANT technique and general anesthesia (GA) in patients undergoing distal radius plating surgery.Methods: We recruited 40 adults with distal radius fracture underwent plating using the WALANT technique (group A) or general anesthesia (group B). Each group comprised 20 patients with similar demographics. Mean arterial pressure (MAP) and heart rate were recorded in both groups. Intraoperative pain intensity was measured by numeric rating scale (NRS) for pain in group A.Results: The NRS decreased significantly compared with preoperative status in group A for most of the intraoperative period. The intraoperative MAP in group A showed no significant change among each peri-operatively period. In addition, group A showed less peri-operative MAP fluctuation than group B (p< 0.05). The intraoperative changes in HR showed significant changes between group A and B during reduction, plating and skin closure. The reduction and plating quality were similar between each group.Conclusions: Patients undergoing distal radius plating surgery via WALANT technique has a lower MAP changes. Distal radius plating surgery using the WALANT technique is a well-tolerated surgical procedure and showing the similar reduction and plating quality to through GA.

Background: Shockwaves are acoustic pulses that have been widely used in the management of musculoskeletal disease. In current study, we investigated the biological effect of shockwaves on articular chondrocytes and clarified the mechanism by which chondrocytes sense and respond to the mechanical stimulation of shockwave treatment. Methods: Porcine articular chondrocytes and human osteoarthritis (OA) chondrocytes were cultured in a three-dimensional pellet culture model and subjected to shockwaves. Then alamarBlue assay, Hoechest DNA assay, fluorescence-activated cell sorter, real-time polymerase chain reaction immunofluorescence staining, and western blotting were used to determine biological function and signaling transduction of chondrocytes after shockwaves.Results: Shockwaves increased the sulfated glycosaminoglycan (GAG), Col2a1, and Acan production of chondrocytes without affecting cell viability and proliferation. Furthermore, shockwaves increased transient reactive oxygen species (ROS) production primarily through the action of xanthine oxidase and subsequently through phosphorylation of Erk1/2 and p38. Shockwaves also activated the nuclear translocation of Nrf2 and the Nrf2-related downstream gene expression of Ho-1 and Nqo-1. We suppressed the xanthine oxidase activity by allopurinol or specific siRNA, which significantly abrogated shockwave-induced mitogen-activated protein kinase (MAPK) phosphorylation, Nrf2 nuclear translocation, and extracellular matrix (ECM) synthesis. U0126 and SB203580, the specific inhibitors of MAPKs MEK1/2 and p38, respectively, significantly abolished shockwave-induced Nrf2 nuclear translocation and ECM synthesis. Inhibition of Nrf2 by both shRNA knockdown and brusatol reduced the shockwave-increased GAG, Col2a1, and Acan production. Conclusions: Maintaining the homeostasis of the ECM of the articular cartilage is crucial for preventing the development OA. Our data indicate that shockwaves enhanced the ECM synthesis of chondrocytes through the activation of the ROS/MAPK/Nrf2 signaling axis. This study demonstrates that shockwaves holds promising therapeutic potential for OA and provides fundamental evidence for developing an optimal therapeutic strategy.

Background: Low back pain may inhibit patients’ spinal range of motion during radiography. Little is known about the dynamic changes of measurement variables and diagnosis of unstable segments in flexion/extension radiographs before and after analgesic injections. We hypothesise that pain control with intramuscular (IM) ketorolac could reveal more radiographic instability segments currently masked by low back pain. Methods: One hundred patients with symptomatic spondylolisthesis from outpatient clinics were recruited. Standing flexion-extension radiographs before and after analgesic injections (IM ketorolac 30 mg) were examined. The visual analog scale (VAS) score and the parameters of segmental instability, including dynamic lumbar lordosis (º; DL), dynamic segmental angulation (º; DA), dynamic segmental translation (mm; DT), and slip percentage (dynamic translation divided with vertebral body width; SP) (%), before and after ketorolac injection were measured. In addition, newly diagnosed unstable segments by different instability criteria were recorded. Pre-post changes between the two groups were analysed using paired t-tests.Results: The VAS score decreased significantly after analgesic injections (66.9 ± 0.97 vs. 32.2 ± 13.1 mm, P < 0.001). DL, DA, DT, and SP were significantly increased (P < 0.001) after providing analgesia compared to pre-analgesia. More unstable segments were found from radiography after ketorolac injection.Conclusion: Ketorolac 30 mg injections provided effective analgesia. The radiographic change and diagnosis of instability segments, which might be masked by back pain, significantly changed after IM Ketorolac in patients with symptomatic spondylolisthesis.

Objective To compare the efficacy of different radiofrequency techniques (thermal, pulsed, and cooled radiofrequency) for treating lumbar facet joint (LFJ) or sacroiliac joint (SIJ) pain. Patients and methods The inclusion criteria were as follows: (1) age > 18 years; (2) patients suffering from LFJ or SIJ pain; and (3) patients receiving radiofrequency treatments. Four electronic databases, including Pubmed, Embase, Cochrane Library, and ISI Web of Knowledge were systematically searched from inception until December 2019 for relevant articles. The search was conducted on 2 January 2020. When the outcomes among articles showed heterogeneity, then a random-effects model was adopted to calculate the effect size; otherwise, a fixed-effects model was adopted. Results All the three techniques showed significant improvements in LFJ or SIJ pain for up to 12 months compared with the baseline level. However, no significant differences among the three techniques were observed at any follow-up visits except for possibly a trend for variance in efficacy. For treating LFJ pain, cooled radiofrequency was the most effective, followed by thermal radiofrequency and then pulsed radiofrequency as the least respectively for the follow-up visit at 6 months. No serious complications were reported after receiving treatment using the three techniques. Conclusion Sequentially, cooled radiofrequency followed by thermal radiofrequency and then pulsed radiofrequency for treating LFJ pain were identified as most to least effective at the 6-month follow-up.

Background A small sample size (n < 30 for each treatment group) is usually enrolled to investigate the differences in efficacy between treatments for knee osteoarthritis (OA). The objective of this study was to use simulation for comparing the power of four statistical methods for analysis of small sample size for detecting the differences in efficacy between two treatments for knee OA. Methods A total of 10,000 replicates of 5 sample sizes (n=10, 15, 20, 25, and 30 for each group) were generated based on the previous reported measures of treatment efficacy. Four statistical methods were used to compare the differences in efficacy between treatments, including the two-sample t-test (t-test), the Mann-Whitney U-test (M-W test), the Kolmogorov-Smirnov test (K-S test), and the permutation test (perm-test). Results The bias of simulated parameter means showed a decreased trend with sample size but the CV% of simulated parameter means varied with sample sizes for all parameters. For the largest sample size (n=30), the CV% could achieve a small level (Conclusion The perm-test is suggested for analysis of small sample size to compare the differences in efficacy between two treatments for knee OA.

Additional file 1:. Search query

Supplemental material, Supplyment_material_revision3 for Comparative effectiveness of various treatment strategies for trigger finger by pairwise meta-analysis by Po-Chih Shen, Shih-Hsiang Chou, Cheng-Chang Lu, Yin-Chih Fu, Chun-Kuan Lu, Wen-Chih Liu, Peng-Ju Huang, Yin-Chun Tien and Chia-Lung Shih in Clinical Rehabilitation

Objective The objective of this study was to assess the efficacy and safety of extracorporeal shockwave therapy (ESWT) for treatment of knee osteoarthritis (OA) using a systemic review and meta-analysis. Methods An extensive search of relevant articles from electronic databases Pubmed, Embase, and Cochrane Library from inception to March 2019 was conducted. The treatment outcomes (visual analog scale [VAS] and the Western Ontario and McMaster Universities Arthritis Index [WOMAC]) of the included articles were pooled to calculate effect sizes. The assessment of heterogeneity among articles was evaluated using I2. Statistical analyses were conducted using RevMan software. Results The results showed that the ESWT group had significant improvement in pain relief compared with the control group through 12 months based on WOMAC and VAS scores. Compared with the baseline level, the patients had significant improvement in pain relief at most follow-up points (one week to 12 months) based on WOMAC and VAS scores. The patients showed significant improvement in physical function at six- and 12-month follow-up when compared with the control group and for all follow-up (one to 12 months) when compared with the baseline level. Additionally, only minor complications were observed after ESWT treatment. Conclusions The use of ESWT for treatment of knee OA had a beneficial effect on pain relief and physical function improvement for up to 12 months, and only minor complications occurred after ESWT treatment. However, there remains a lack of clarity regarding the frequency and dosage levels of ESWT required to achieve the maximum improvement.

The full characterization of nonbiological complex drugs (NBCDs) is not possible, but analytical approaches are of urgent need to evaluate the similarity between different lots and compare with their follow-up versions. Here, we propose a hypothesis testing-based approach to assess the similarity/difference between random amino acid copolymer drugs using liquid chromatography mass spectrometry (LC-MS) analysis. Two glatiramer acetate (GA) drugs, commercially available Copaxone and in-house synthesized SPT, and a negative control were digested by Lys-C and followed by HILIC-MS analysis. After retention time alignment and feature identification, 1627 features matched to m/z values in an elemental composition database were considered as derived from active drug ingredients. A hypothesis testing approach, the sum of squared deviations test, was developed to process high-dimensional data derived from LC-MS spectra. The feasibility of this approach was first demonstrated by testing 5 versus 5 lots of Copaxone and Copaxone versus SPT, which suggested a significant similarity by obtaining the estimated 95th percentile of the distribution of the estimator (ρ(95%)) at 0.0056 (p-value = 0.0026) and 0.0026 (p-value < 0.0001), respectively. In contrast, the ρ was 0.036 (p-value = 1.00), while comparing Copaxone and the negative control, implying a lack of similarity. We further synthesized nine stable isotope-labeled peptides to validate the proposed amino acid sequences in the database, demonstrating the correctness in sequence identification. The quantitation variations in our analytical procedures were determined to be 6.8-7.7%. This approach was found to have a great potential for evaluating the similarity between generic NBCDs and listed reference drugs, as well as to monitor the lot-to-lot variation.

Di(isononyl)cyclohexane-1,2-dicarboxylate (DINCH) is a plasticizer used in polyvinyl chloride (PVC) products, such as toys and food packaging. Because the use of DINCH is on the rise, the risk of human exposure to this chemical may likewise increase. Discovering markers for assessing human chemical exposure is difficult because the metabolism of chemicals within humans is complex. In this study, two mass spectrometry (MS)-based metabolite profiling data processing methods, the mass defect filter (MDF) method and the signal mining algorithm with isotope tracing (SMAIT) method, were used for DINCH metabolite discovery, and 110 and 18 potential DINCH metabolite signal candidates were discovered, respectively, from in vitro DINCH incubation samples. Of these, the 21 signals were validated as tentative exposure marker signals in a rat model. Interestingly, the two methods generated rather different sets of DINCH exposure markers. Five of the 21 tentative exposure marker signals were verified as the probable DINCH structure-related metabolite signals based on their MS/MS product ion profiles. These five signals were detected in at least one human urine sample. Of the five probable DINCH structure-related metabolite signals, two novel signals might be suitable exposure markers that should be further investigated for their application in human DINCH exposure assessments. These observations indicate that the MDF and SMAIT methods may be used to discover a relatively different set of potential DINCH exposure markers.

Di-(2-propylheptyl) phthalate (DPHP) is a plasticizer used in polyvinyl chloride and vinyl chloride copolymer that has been suggested to be a toxicant in rats and may affect human health. Because the use of DPHP is increasing, the general German population is being exposed to DPHP. Toxicant metabolism is important for human toxicant exposure assessments. To date, the knowledge regarding DPHP metabolism has been limited, and only four metabolites have been identified in human urine. Ultra-performance liquid chromatography was coupled with Orbitrap high-resolution mass spectrometry (MS) and two data-screening approaches-the signal mining algorithm with isotope tracing (SMAIT) and the mass defect filter (MDF)-for DPHP metabolite candidate discovery. In total, 13 and 104 metabolite candidates were identified by the two approaches, respectively, in in vitro DPHP incubation samples. Of these candidates, 17 were validated as tentative exposure biomarkers using a rat model, 13 of which have not been reported in the literature. The two approaches generated rather different tentative DPHP exposure biomarkers, indicating that these approaches are complementary for discovering exposure biomarkers. Compared with the four previously reported DPHP metabolites, the three tentative novel biomarkers had higher peak intensity ratios, and two were confirmed as DPHP hydroxyl metabolites based on their MS/MS product ion profiles. These three tentative novel biomarkers should be further investigated for potential application in human exposure assessment.

Pediatric humeral medial condyle fracture (HMCF) is a rare condition and is difficult to detect, especially in young children. The management of late presentation of HMCF is challenging and lacks consensus. Herein, we reported four cases of HMCF nonunion received open reduction and internal fixation (ORIF) or supracondyle osteotomy from our institution. In addition, 12 cases of ORIF and 4 cases of osteotomy reported in the previous studies were also reviewed. The HMCF nonunion can heal after ORIF, but the indication and the optimal techniques need to be clarified. Supracondylar osteotomy alone is an effective and safe treatment option to improve the functional and cosmetic outcomes of HMCF nonunion.

Urine and hair are used for assessing human exposure to toxicants. Urine tests can show acute toxicant exposure. Hair analysis can be used to determine chronic toxicant exposure after months to years; however, compared to urine, hair analysis in exposure assessments is much less frequently investigated. Urine and hair are different matrices, and their mechanisms of toxicant metabolite incorporation are different. The toxicant metabolites present in urine and hair may also be different. To clarify this issue, a procedure was developed to identify toxicant metabolites in rat samples using a mass spectrometry-based metabolomic data processing method. Di-(2-propylheptyl) phthalate (DPHP), an industrial plasticizer, was used as the model toxicant. The developed procedure identified not only known DPHP metabolites (mono-(propyl-6-oxo-heptyl) phthalate, mono-(propyl-6-hydroxyheptyl) phthalate, and mono-(propyl-6-carboxyhexyl) phthalate) but also novel metabolites that were structurally related to DPHP in the rat samples, indicating that the developed procedure successfully identified toxicant metabolites in in vivo samples. Among the 62 tentative metabolites identified from the 7th-day urine and the 28th-day hair samples, 33 were detected in only the urine samples, 19 were detected in only the hair samples, and 10 were identified in both the urine and hair samples. A total of 15 out of the 62 metabolites were confirmed as DPHP structure-related metabolites based on MS/MS analysis. Among the 15 DPHP structure-related metabolites, only 2 metabolites were present in both the urine and hair samples. These results suggested that the metabolites identified in urine could not be applied to exposure assessments based on hair analysis.

This study compared the dosage and different medication-taking habits of glucosamine sulfate (GS) for osteoarthritis patients and evaluated the influence of the National Health Insurance (NHI) prescription guidelines. The subjects were collected from the Taiwan NHI Research Database from 1 January 2004, to 31 December 2008, and 10,501 osteoarthritis patients were included. Then, 271 patients who continuously used nonsteroidal anti-inflammatory drug (NSAIDs) and started to receive glucosamine for the first time since 2005 (no glucosamine use in 2004) were compared with 593 age-matched patients who continuously used NSAIDs but never received any glucosamine drugs from 2004 to 2008. The mean treatment duration of the glucosamine-treated and NSAID-treated groups was 40.38 &plusmn, 7.89 and 45.82 &plusmn, 3.89 months, respectively. The most common medication-taking habit was 250 mg 3 times a day for 3 months and discontinued for 3 months. It was as indicated and covered by the NHI. Only 0.7% of patients used the recommended daily dosage of 1500 mg. Patients using GS surprisingly had a higher incidence rate of joint replacement surgery than those who did not use GS. The NHI prescription guidelines may cause patient selection bias, which decreases the efficacy of GS. Moreover, patients tend to have an altered medication-taking habit, with a daily dosage of 750 mg, which is lower than the recommended therapeutic dose.

Heroin dependent patients have a high incidence of HIV infection. In contrast to the gene expression method, we developed a systemic correlation analysis method built upon the results of pharmacogenomics study in a methadone maintenance treatment (MMT) cohort consisting of 344 Taiwanese heroin dependent patients. We identified genetic variants and their encoding proteins that may be involved with HIV infection and MMT treatment outcome. Cadherin 2 (CDH2) genetic determinants were identified through the genome-wide pharmacogenomic study. We found significant correlations among HIV infection status, plasma levels of CDH2, cytokine IL-7, ADAM10, and the treatment responses to methadone. Two single nucleotide polymorphisms located within CDH2 gene showed associations with blood pressure and plasma CDH2 concentration. Plasma concentration of CDH2 showed correlations with the level of cytokine IL-7, status of HIV infection, and urine morphine test result. Plasma level of IL-7 was correlated with corrected QT interval (QTc) and gooseflesh skin withdrawal symptom score, while level of ADAM10 was correlated with plasma concentrations of vitamin D metabolite, nicotine metabolite, and R-methadone. The results suggest a novel network involving HIV infection and methadone treatment outcome.

This study first attempts to investigate the age and growth of yellowfin tuna in the Indian Ocean and clarifies its sex-specific growth using sectioned otoliths. The results indicate that the assumption of annual opaque zones may be reliable and fish age at the first opaque zone formation is about 0.75 years. The age estimates cover a large range of lifespans (age estimates range from 0.75 to 10.50 years) in which the maximum age estimate shows that males (9.50 years) are older than females (6.50 years). The estimated von Bertalanffy growth curves are shown to be significantly different between sexes, while the von Bertalanffy growth parameters (L∞, k and t0) are 123.6 cm, 0.846 year−1 and −0.449 years for females and 162.9 cm, 0.244 year−1 and −2.139 years for males. The growth curves of both sexes are similar before 4 years, after which males start to grow larger than females. Sexual size dimorphism in growth curves occurs after mature age.

The objective of this study was to assess the efficacy of different energy levels used in extracorporeal shockwave therapy (ESWT) in the treatment of plantar fasciitis using a systematic review and meta-analysis. We searched PubMed, Embase, and Cochrane library, from inception to March 2019 for randomized controlled trials that compared ESWT with placebo in patients with plantar fasciitis. The risk of bias for selected articles was assessed based on the Cochrane Handbook Systematic Review of Interventions. The pooled data were estimated by the mean difference or odds ratio. The meta-analysis showed that the high-energy ESWT group had a better success rate than the control group only at a three-month follow-up, but no significant difference between groups was observed for the other follow-up visits (1 and 12 months). In addition, no significant differences in visual analog scale (VAS) scores between groups were observed for all the follow-up visits (one-month and three-month). On the contrary, the medium-energy ESWT group had significantly better success rates than the control group for all the follow-up visits (3, 6, and 12 months). In addition, the medium-energy ESWT group had significant improvement in VAS scores compared with the control group for all the follow-up visits (1, 3, 6, and 12 months) after removing the extreme values. The low-energy ESWT group had significant improvement in VAS scores compared with the control group for all the follow-up visits (3 and 12 months). Otherwise, focused ESWT seems to be more effective than radial ESWT when compared with the control group. Use of local anesthesia can reduce the efficacy of low- and high-energy ESWTs. Our meta-analysis suggested that medium-energy ESWT in the treatment of plantar fasciitis was more effective than the control group. A limited number of trials related to low- and high-energy ESWTs were included in our meta-analysis. More research is required to confirm the efficacy of low- and high-energy ESWTs in future studies.

Phthalates are chemicals widely used in industry and the consequences on human health caused by exposure to these agents are of significant interest currently. The urinary metabolites of phthalates can be measured and used as exposure markers for the assessment of the actual internal contamination of phthalates coming from different sources and absorbed by various ways. The purpose of this paper is to review the markers for exposure and risk assessment of phthalates such as di-methyl phthalate (DMP), di-ethyl phthalate (DEP), di-butyl phthalate (DBP), benzylbutyl phthalate (BBP), di-(2-ethylhexyl)phthalate (DEHP), di-(2-propylheptyl)phthalate (DPHP), di-iso-nonyl phthalate (DINP), di-n-octyl phthalate (DnOP) and di-iso-decyl phthalate (DIDP), and introduction of the analytical approach of three metabolomics data processing approaches that can be used for chemical exposure marker discovery in urine with high-resolution mass spectrometry (HRMS) data.

The present study investigates how sample size, length interval size, recruitment variation, and mortality over time influence total mortality, which is estimated by applying the length-converted catch method to the bigeye tuna (Thunnus obesus) population. Given the assumption of fish dynamics under an equilibrium state, an increasing sample size and decreasing length interval size can raise the accuracy of total mortality estimates, with a sample size of 3000 individuals and length class interval of 5 cm generally producing the most accurate estimates. When fish dynamics follow a non-equilibrium state, randomly varied recruitment does not affect the estimation of total mortality. However, recruitment that varies with increasing or decreasing trends would affect total mortality remarkably. Therefore, total mortality that varies by time influences estimated total mortality, and in this situation, fish stocks that undergo stable total mortality for four successive years could produce an accurate total mortality figure. Finally, we suggest that the non-equilibrium state of fish dynamics should be considered before applying the length-converted catch method to estimate Z.