Effective suppression of Ih and INa caused by capsazepine, known to be a blocker of TRPV1 receptor.

A synthetic inhibitor of capsaicin-induced TRPV1 channel activation is called capsazepine (CPZ). In this study, we aimed to explore the effects of CPZ on hyperpolarization-activated cationic current (Ih) and voltage-gated Na + current (INa) in pituitary tumor (GH3) cells. Through patch-clamp recordings, we found that CPZ concentration-dependently inhibited Ih amplitude and slowed its activation time course. The IC50 and KD values were 3.1 and 3.16 µM, respectively. CPZ also shifted the steady-state activation curve of Ih towards a more hyperpolarized potential. However, there was no change in the gating charge of the curve. A modified Markovian model predicted the CPZ-induced decrease in the voltage-dependent hysteresis of Ih. CPZ suppressed INa in GH3 cells, without altering its activation or inactivation time course. Additionally, exposure to CPZ reduced spontaneous firing. These findings suggest that CPZ's inhibitory effects on Ih and INa are direct and not dependent on vanilloid receptor binding. This could provide light on an unidentified ionic mechanism influencing the membrane excitability of neurons and endocrine or neuroendocrine cells in vivo.

A systematic review of the use of shockwave therapy for knee osteoarthritis.

Introduction: Previous studies assessed the effect of extracorporeal shockwave therapy (ESWT) for knee osteoarthritis (OA) among different situations. Thus, results from a meta-analysis regarding this topic may not be reliable due to heterogeneity. Methods: A systematic review was conducted on three internet databases, namely Cochrane Library, PubMed, and Embase, gathering pertinent papers from their establishment to March 2024. The search phrases were as follows: "shockwave" OR "shock wave" OR "extracorporeal shockwave" OR "Extracorporeal Shockwave Therapy [MeSH Term]" AND "knee" AND ("osteoarthritis" OR "arthritis" OR "arthritic" OR "osteoarthritis [MeSH term]"). Results: Twenty-four articles (n = 888) were included, with the resulting conclusions demonstrating that ESWT was effective for knee OA compared with sham ESWT; however, ESWT was not effective for patients with severe knee OA. Patients receiving higher energy or higher shock number had significant improvement than those receiving lower energy or less shock number, respectively. Adding ESWT in isokinetic muscular strengthening exercises (IMSE) was more effective than IMSE alone. The efficacy of ESWT was better than other therapies, including intravenously applied prostacyclin and bisphosphonate, corticosteroid injection, kinesiotherapy, hyaluronic acid injection, platelet-rich plasma injection, and physiotherapy. Conclusions: This review demonstrated that ESWT was effective for knee OA. Higher energy and more shock numbers could obtain better efficacy. ESWT could be used as a replacement for some other therapies.

Effects of vitamin D in pregnancy on maternal and offspring health-related outcomes: An umbrella review of systematic review and meta-analyses.

BACKGROUND: Vitamin D deficiency has been linked with several adverse maternal and fetal outcomes. OBJECTIVE: To summarize systematic reviews and meta-analyses evaluating the effects of vitamin D deficiency and of vitamin D supplementation in pregnancy on maternal and offspring health-related outcomes. METHODS: Prior to conducting this umbrella review, we registered the protocol in PROSPERO (CRD42022368003). We conducted searches in PubMed, Embase, and Cochrane Library for systematic reviews and meta-analyses on vitamin D in pregnancy, from database inception to October 2, 2023. All outcomes related to vitamin D in pregnancy obtained from the systematic reviews and meta-analyses were extracted. DATA EXTRACTION: Two reviewers independently chose studies and collected information on health outcomes. The quality of the included articles' methodology was assessed using AMSTAR 2 (A Measurement Tool to Assess Systematic Reviews-2). RESULTS: We identified 16 eligible systematic reviews and meta-analyses, which included 250,569 women. Our results demonstrated that vitamin D deficiency in pregnancy is associated with increased risk of preterm birth, small-for gestational age/low birth weight infants, recurrent miscarriage, bacterial vaginosis and gestational diabetes mellitus. Vitamin D supplementation in pregnancy increases birth weight, and reduces the risk of maternal pre-eclampsia, miscarriage, and vitamin D deficiency, fetal or neonatal mortality, as well as attention-deficit hyperactivity disorder, and autism spectrum disorder in childhood. In women with gestational diabetes mellitus, vitamin D supplementation in pregnancy can reduce the risk of maternal hyperbilirubinemia, polyhydramnios, macrosomia, fetal distress, and neonatal hospitalization. CONCLUSION: Due to the association with adverse maternal and offspring health outcomes, we recommend the vitamin D status in pregnancy should be monitored, particularly in women at high risk of vitamin D deficiency. It is suggested that pregnant women take a dose of >400 IU/day of vitamin D supplementation during pregnancy to prevent certain adverse outcomes.

Efficacy of turmeric in the treatment of oral mucositis in patients with head and neck cancer after radiotherapy or chemoradiotherapy: a systematic review and meta-analysis.

Background: Oral mucositis is a major complication for head and neck cancer (HNC) patients after radiotherapy or chemotherapy. A meta-analysis was performed to assess the efficacy of turmeric in the treatment of oral mucositis in HNC patients. Methods: Randomized controlled trials investigating our topic were included in the meta-analysis. The clinical outcomes considered were the severity of oral mucositis, pain level, and weight loss. Results: A total of eight articles that met our inclusion criteria were included in our meta-analysis. At the 3-week follow-up visit, the turmeric group showed significantly lower grades of oral mucositis compared to the control group (p = 0.03). When compared to the placebo group, a significant difference in the degree of oral mucositis was observed at the 4-(p = 0.03) and 6-week (p < 0.00001) follow-up visits. No significant difference in pain levels was observed between the turmeric and control groups at any of the follow-up visits. However, a significant improvement in pain levels for the turmeric group when compared with the placebo group was observed only at the 6-week follow-up visit (p = 0.006). Interestingly, a significant improvement in pain levels was observed for the turmeric group at the 2-, 4-, 5-, and 6-week follow-up visits (p < 0.05) when compared to the non-placebo group. The turmeric group showed less weight loss than the control group at the final follow-up visit (p = 0.03). conclusion: Our meta-analysis showed that using turmeric may be effective in improving both the severity of oral mucositis and pain levels in HNC patients who have received radiotherapy or radiochemotherapy. In addition, the turmeric group experienced less weight loss.

Extracorporeal shockwave therapy in the management of knee osteoarthritis: A systematic review of dose-response meta-analysis.

Introduction: The aim of the research was to conduct a systematic review of dose-response meta-analysis, examining the correlation between the energy of extracorporeal shockwave therapy (ESWT) and clinical outcomes for patients with knee osteoarthritis (OA). Methods: We conducted a systematic review of three online databases - PubMed, Embase, and Cochrane Library - to collect relevant articles from their inception to May 2023. We included the articles that investigated the efficacy of ESWT in treating knee OA and were designed using randomized controlled trials (RCTs). The main outcomes were measured using the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) for primary outcomes and the Visual Analog Scale (VAS) for secondary outcomes. We conducted a dose-response meta-analysis to examine the correlation between the energy of ESWT and clinical outcomes. Results: Our study included a total of 7 RCTs (comprising 450 subjects) that met the inclusion criteria. We found a negative linear relationship between the doses of ESWT and WOMAC scores at the 1-week (p = 0.0398) and 4-week (p = 0.001) follow-up periods, but not at the 12-week follow-up period (p = 0.202). Furthermore, at the 4-week (p = 0.0477) and 12-week (p < 0.001) follow-up periods, a negative linear connection was found between the ESWT dose and VAS scores, but not at the 1-week follow-up period (p = 0.2268). Conclusions: Our results demonstrate a dose-response connection between the energy of ESWT and clinical outcomes. This suggests that using higher energy levels of ESWT to treat knee OA could lead to greater improvement in clinical outcomes compared to using lower energy levels.

Exploring the Impact of BKCa Channel Function in Cellular Membranes on Cardiac Electrical Activity.

This review paper delves into the current body of evidence, offering a thorough analysis of the impact of large-conductance Ca2+-activated K+ (BKCa or BK) channels on the electrical dynamics of the heart. Alterations in the activity of BKCa channels, responsible for the generation of the overall magnitude of Ca2+-activated K+ current at the whole-cell level, occur through allosteric mechanisms. The collaborative interplay between membrane depolarization and heightened intracellular Ca2+ ion concentrations collectively contribute to the activation of BKCa channels. Although fully developed mammalian cardiac cells do not exhibit functional expression of these ion channels, evidence suggests their presence in cardiac fibroblasts that surround and potentially establish close connections with neighboring cardiac cells. When cardiac cells form close associations with fibroblasts, the high single-ion conductance of these channels, approximately ranging from 150 to 250 pS, can result in the random depolarization of the adjacent cardiac cell membranes. While cardiac fibroblasts are typically electrically non-excitable, their prevalence within heart tissue increases, particularly in the context of aging myocardial infarction or atrial fibrillation. This augmented presence of BKCa channels' conductance holds the potential to amplify the excitability of cardiac cell membranes through effective electrical coupling between fibroblasts and cardiomyocytes. In this scenario, this heightened excitability may contribute to the onset of cardiac arrhythmias. Moreover, it is worth noting that the substances influencing the activity of these BKCa channels might influence cardiac electrical activity as well. Taken together, the BKCa channel activity residing in cardiac fibroblasts may contribute to cardiac electrical function occurring in vivo.

Dose-response technique combined with stable isotope tracing for drug metabolite profiling by using high-resolution mass spectrometry.

Background: Mass spectrometry metabolomics-based data-processing approaches have been developed for drug metabolite profiling. However, existing approaches cannot be used to comprehensively identify drug metabolites with high efficacy. Methods: Herein, we propose a two-stage data-processing approach for effective and comprehensive drug metabolite identification. The approach combines dose-response experiments with stable isotope tracing (SIT). Rosiglitazone (ROS), commonly used to treat type 2 diabetes, was employed as a model drug. Results: In the first stage of data processing, 1,071 features exhibited a dose-response relationship among 22,597 features investigated. In the second stage, these 1,071 features were screened for isotope pairs, and 200 features with isotope pairs were identified. In time-course experiments, a large proportion of the identified features (69.5%: 137 out of 200 features) were confirmed to be possible ROS metabolites. We compared the validated features identified using our approach with those identified using a previously reported approach [the mass defect filter (MDF) combined with SIT] and discovered that most of the validated features (37 out of 42) identified using the MDF-SIT combination were also successfully identified using our approach. Of the 143 validated features identified by both approaches, 74 had a proposed structure of an ROS-structure-related metabolite; the other 34 features that contained a specific fragment of ROS metabolites were considered possible ROS metabolites. Interestingly, numerous ROS-structure-related metabolites were identified in this study, most of which were novel. Conclusion: The results reveal that the proposed approach can effectively and comprehensively identify ROS metabolites.

The Effect of Job Satisfaction on Psychological Well-Being for Taiwanese Home-Care Workers, Mediated by Emotional Labor.

The objective of this study was to investigate the effect of job satisfaction on psychological well-being through emotional labor for Taiwanese home-care workers. A total of 316 home-care workers who worked in Chiayi, Taiwan, were recruited in this study. Most of the participants were Taiwanese (96.5%). The mean age of the participants was 42.05 ± 12.15 years, and the participants were predominantly female (80%). The mean work experience was 5.64 ± 5.13 years. Job satisfaction, emotional labor, and psychological well-being were measured. Partial least squares structural equation modeling was used to examine the direct and indirect effects on job satisfaction, emotional labor, and psychological well-being. The results demonstrated that the internal factors of job satisfaction had indirect effects on psychological well-being through the mediating effects of surface acting and deep acting. However, it was also observed that the external factors of job satisfaction had indirect effects on psychological well-being through the mediating effect of surface acting but not deep acting. The model explained 57.6% of the variance in psychological well-being. The internal factors of job satisfaction are more important than the external factors affecting psychological well-being through the mediating effect of deep acting. Based on our results, we recommend enhancing the deep acting of emotional labor to improve the psychological well-being of Taiwanese home-care workers.

Exposure to bisphenol A associated with multiple health-related outcomes in humans: An umbrella review of systematic reviews with meta-analyses.

Bisphenol A (BPA), a toxic endocrine disruptor, is widely distributed in the environment, and the effects of BPA exposure on human health outcomes are a critical issue. The objective of this study was to perform an umbrella review of published meta-analyses investigating the associations between BPA exposure and human-related health outcomes. The relevant reports were searched from three electronic databases from inception to July 12, 2023 including PubMed, ScienceDirect, and Embase. The reports that were systematic reviews with meta-analyses investigating the associations between BPA exposure and human health outcomes were included in our review. A total of 14 reports were included in our review. Several human health outcomes related to exposure BPA were investigated including maternal prenatal health, infant health, allergic diseases, kidney disease, metabolic syndromes, polycystic ovary syndrome, earlier puberty, inflammation and immune responses, and thyroid function in neonates. Among these health outcomes, BPA exposure was associated with multiple human health outcomes including preterm birth, allergic diseases, kidney disease, polycystic ovarian syndrome, obesity, type 2 diabetes, cardiovascular disease, hypertension, and inflammation and immune responses (C-reactive protein and interleukin-6). These results showed that BPA exposure has seriously affected human health. To protect human health, World Health Organization should develop meaningful regulations on BPA to decrease the environmental contamination.

Characterization of Stimulatory Action on Voltage-Gated Na+ Currents Caused by Omecamtiv Mecarbil, Known to Be a Myosin Activator.

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.

Development of a metabolomics-based data analysis approach for identifying drug metabolites based on high-resolution mass spectrometry.

A metabolomics-based approach to data analysis is required for drug metabolites to be identified quickly. This study developed such an approach based on high-resolution mass spectrometry. Our approach is a two-stage one that combines a time-course experiment with stable isotope tracing. Pioglitazone (PIO) was used to improve glycemic management for type 2 diabetes mellitus. Consequently, PIO was taken as a model drug for identifying metabolites. During Stage I of data analysis, 704 out of 26626 ions exhibited a positive relationship between ion abundance ratio and incubation time in a time-course experiment. During Stage II, 25 isotope pairs were identified among the 704 ions. Among these 25 ions, 18 exhibited a dose-response relationship. Finally, 14 of the 18 ions were verified to be PIO structure-related metabolite ions. Otherwise, orthogonal partial least squares-discriminant analysis (OPLS-DA) was adopted to mine PIO metabolite ions, and 10 PIO structure-related metabolite ions were identified. However, only four ions were identified by both our developed approach and OPLS-DA, indicating that differences in the designs of metabolomics-based approaches to data analysis can result in differences in which metabolites are identified. A total of 20 PIO structure-related metabolites were identified by our developed approach and OPLS-DA, and six metabolites were novel. The results demonstrated that our developed two-stage data analysis approach can be used to effectively mine data on PIO metabolite ions from a relatively complex matrix.

Comparing the effects of water temperature and additives in glucose solution on pregnant women's taste, side effects, and glycemic levels during an oral glucose tolerance test: a randomized controlled trial.

BACKGROUND: The oral glucose tolerance test is a common method of diagnosing gestational diabetes mellitus. This test causes several unpleasant side effects such as nausea, vomiting, abdominal bloating, and headache. OBJECTIVE: This study aimed to assess the effect of liquid temperature and additives on pregnant women's taste perception, side effects, and glycemic levels in an oral glucose tolerance test. STUDY DESIGN: This study was a single-center, randomized, and multi- and open-arm clinical trial. A total of 399 participants receiving the 75-g oral glucose tolerance test for gestational diabetes mellitus diagnosis were included. Solutions for use in the 75-g oral glucose tolerance test were prepared in 8 formulas, with the participants randomly assigned to 1 of the 8 groups: room-temperature water, hot water, cold water, hot water with tea bag, room-temperature water with tea bag, cold water with tea bag, room-temperature soda water, and cold soda water. The main study outcomes were glycemic levels, satisfaction, perceived taste, side effects, and gestational diabetes mellitus. Glycemic levels were measured when fasted and at 1 hour and 2 hours after glucose administration. Satisfaction, taste perception, and side effects were evaluated immediately after the oral glucose tolerance test, and gestational diabetes mellitus was determined on the basis of glycemic levels. RESULTS: The cold soda water solution led to a significantly higher glycemic level at 1 hour after glucose intake compared with room-temperature soda water solution (P=.009). Glucose formula was found to not significantly affect gestational diabetes mellitus incidence (P>.05) or the participants' satisfaction, vomiting, headache, or abdominal bloating (P>.05). However, the formula did significantly affect perceived taste (P=.027) and the degree of nausea (P=.014). CONCLUSION: Several glucose solutions, such as cold glucose solution and any-temperature glucose solution containing a tea bag, led to slightly higher taste scores and a lower degree of nausea compared with the room-temperature water-based glucose solution. However, soda water was found to affect the glycemic level at 1 hour after glucose intake, and is not suggested for use for gestational diabetes mellitus diagnosis.

Inhibition of lncRNA RPPH1 activity decreases tumor proliferation and metastasis through down-regulation of inflammation-related oncogenes.

OBJECTIVE: Ribonuclease P RNA component H1 (RPPH1) is a long non-coding RNA (lncRNA) associated with cancer progression. Higher RPPH1 expression in breast and cervical cancer samples than that in normal tissues were observed through the lncRNASNP2 database; therefore, silencing RPPH1 expression might be a potential strategy for cancer treatments, even though RPPH1 is also an RNA subunit of ribonuclease P involved in processing transfer RNA (tRNA) precursors and the effect of RPPH1 knockdown is not yet fully understood. METHODS: Differentially expressed genes (DEGs) were identified through RNA sequencing in each shRNA-transfected RPPH1 knockdown MDA-MB-231, RPPH1 knockdown HeLa cell, and respective control cells, then the gene ontology enrichment analysis was performed by IPA and MetaCore database according to these DEGs, with further in vitro experiments validating the effect of RPPH1 silencing in MDA-MB-231 and HeLa cells. RESULTS: Hundreds of down-regulated DEGs were identified in RPPH1 knockdown MDA-MB-231 and HeLa cells while bioinformatics analysis revealed that these genes were involved in pathways related to immune response and cancerogenesis. Compared to mock- and vector-transfected cells, the production of mature tRNAs, cell proliferation and migration capacity were inhibited in RPPH1-silenced HeLa and MDA-MB-231 cells. Additionally, RPPH1 knockdown promoted G1 cell cycle arrest mainly through the down-regulation of cyclin D1, although glycolytic pathways were only affected in RPPH1 knockdown HeLa cells but not MDA-MB-231 cells. CONCLUSION: This study demonstrated that knockdown RPPH1 affected tRNA production, cell proliferation and metabolism. Our findings might provide insight into the role of RPPH1 in tumor development.

Young Children with a Bucket-Handle Tear to the Discoid Lateral Meniscus Successfully Treated Using Arthroscopic Saucerization and Repair: Two Case Reports.

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.

Joint hypermobility and preschool-age flexible flatfoot.

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.

Correction: Liu et al. Less Fluctuation in Hemodynamics of the Wide-Awake Local Anesthesia No Tourniquet Technique Than General Anesthesia in Distal Radius Plating Surgery: A Prospective Case-Control Study. J. Clin. Med. 2022, 11, 1123.

In the original publication [...].

Efficacy of Prenatal Yoga in the Treatment of Depression and Anxiety during Pregnancy: A Systematic Review and Meta-Analysis.

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.

Mass defect filter technique combined with stable isotope tracing for drug metabolite identification using high-resolution mass spectrometry.

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.

Effectiveness of a psychological growth camp without internet in the treatment of adolescents at risk of internet addiction: a pilot study.

OBJECTIVE: This study aimed to investigate the effects of a psychological growth camp in the treatment of adolescents at risk of Internet addiction in Taiwan. METHODS: 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. RESULTS: 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. CONCLUSION: The results indicate that the psychological growth camp without Internet might be effective in treating adolescents with Internet addiction.

Syndesmosis Changes before and after Syndesmotic Screw Removal: A Retrospective Radiographic Study.

BACKGROUND AND OBJECTIVES: 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. MATERIALS 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 (2.0 mm) and CS increased (0.8 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 (1.8 mm) and CS increased (0.5 mm) 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. CONCLUSIONS: 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.