Discovery of a Highly Potent Lysine Methyltransferases G9a/NSD2 Dual Inhibitor to Treat Solid Tumors.

Both G9a and NSD2 have been recognized as promising therapeutic targets for cancer treatment. However, G9a inhibitors only showed moderate inhibitory activity against solid tumors and NSD2 inhibitors were limited to the treatment of hematological malignancies. Inspired by the advantages of dual-target inhibitors that show great potential in enhancing efficiency, we developed a series of highly potent G9a/NSD2 dual inhibitors to treat solid tumors. The candidate 16 demonstrated much enhanced antiproliferative activity compared to the selective G9a inhibitor 3 and NSD2 inhibitor 15. In addition, it exhibited superior potency in inhibiting colony formation, inducing cell apoptosis, and blocking cancer cell metastasis. Furthermore, it effectively inhibited the catalytic functions of both G9a and NSD2 in cells and exhibited significant antitumor efficacy in the PANC-1 xenograft model with good safety. Therefore, compound 16 as a highly potent G9a/NSD2 dual inhibitor presents an attractive anticancer drug candidate for the treatment of solid tumors.

Oral fecal transplantation enriches Lachnospiraceae and butyrate to mitigate acute liver injury.

While fecal microbiota transplantation (FMT) shows promise in treating human diseases, oral capsule FMT is more accepted and accessible to patients. However, microbe selection in the upper gastrointestinal tract (UGIT) through oral administration remains unclear. Here, we demonstrate that short-term oral fecal gavage (OFG) alleviates acetaminophen-induced acute liver injury (AILI) in mice, regardless of the divergent effects of commensal gut microbes. Pasteurized fecal gavage yields similar therapeutic effects. OFG enriches gut Lachnospiraceae and butyrate compared to donor feces. Butyrate mitigates AILI-induced ferroptosis via AMPK-ULK1-p62 signaling to simultaneously induce mitophagy and Nrf2 antioxidant responses. Combined N-acetylcysteine and butyrate administration significantly improves AILI mouse survival rates. These observations indicate the significance of the UGIT in modulating the implanted fecal microbes through oral administration and its potential biological and clinical impacts. Our findings also highlight a possible strategy for applying microbial metabolites to treat acute liver injury.

Melatonin-loaded self-healing hydrogel targets mitochondrial energy metabolism and promotes annulus fibrosus regeneration.

Intervertebral disc (IVD) herniation is a major cause of chronic low back pain and disability. The current nucleus pulposus (NP) discectomy effectively relieves pain symptoms, but the annulus fibrosus (AF) defects are left unrepaired. Tissue engineering approaches show promise in treating AF injury and IVD degeneration; however, the presence of an inflammatory milieu at the injury site hinders the mitochondrial energy metabolism of AF cells, resulting in a lack of AF regeneration. In this study, we fabricated a dynamic self-healing hydrogel loaded with melatonin (an endocrine hormone well-known for its antioxidant and anti-inflammatory properties) and investigate whether melatonin-loaded hydrogel could promote AF defect repair by rescuing the matrix synthesis and energy metabolism of AF cells. The protective effects of melatonin on matrix components (e.g. type I and II collagen and aggrecan) in AF cells were observed in the presence of interleukin (IL)-1ß. Additionally, melatonin was found to activate the nuclear factor erythroid 2-related factor signaling pathway, thereby safeguarding the mitochondrial function of AF cells from IL-1ß, as evidenced by the increased level of adenosine triphosphate, mitochondrial membrane potential, and respiratory chain factor expression. The incorporation of melatonin into a self-healing hydrogel based on thiolated gelatin and ß-cyclodextrin was proposed as a means of promoting AF regeneration. The successful implantation of melatonin-loaded hydrogel has been shown to facilitate in situ regeneration of AF tissue, thereby impeding IVD degeneration by preserving the hydration of nucleus pulposus in a rat box-cut IVD defect model. These findings offer compelling evidence that the development of a melatonin-loaded dynamic self-healing hydrogel can promote the mitochondrial functions of AF cells and represents a promising strategy for IVD regeneration.

Fucoidan-functionalized gelatin methacryloyl microspheres ameliorate intervertebral disc degeneration by restoring redox and matrix homeostasis of nucleus pulposus.

Loss of extracellular matrix (ECM) and dehydration of the nucleus pulposus (NP) are major pathological characteristics of intervertebral disc degeneration (IVDD), the leading cause of low back pain. Excessive reactive oxygen species (ROS) induced by proinflammatory cytokines substantially contribute to IVDD pathogenesis. This study aimed to examine the potential of fucoidan in protecting the matrix metabolism of NP cells and its therapeutic efficacy in the prevention of IVDD. In an inflammatory environment induced by interleukin (IL)-1ß, fucoidan treatments demonstrated a dose-dependent enhancement of ECM production in NP cells, while concurrently reducing the expression of matrix degradation enzymes. The protective effect of fucoidan was mediated through the activation of nuclear factor erythroid 2-related factor 2 (NRF2) and subsequent induction of antioxidant enzymes, whereas silencing Nrf2 abrogated the protection of fucoidan on NP cells against IL-1ß-induced oxidative stress. Moreover, a novel fucoidan-functionalized gelatin methacryloyl microsphere (Fu@GelMA-MS) was synthesized. The in vivo application of Fu@GelMA-MS via in situ injection in a rat caudal IVD model effectively conserved the ECM components and maintained the hydration of the NP tissue, thereby preventing IVDD caused by puncture. Collectively, fucoidan-functionalized hydrogel microspheres represent a promising strategy for the regeneration of NP and the treatment of IVDD.

Structure-Based Design and Characterization of the Highly Potent and Selective Covalent Inhibitors Targeting the Lysine Methyltransferases G9a/GLP.

Protein lysine methyltransferases G9a and GLP, which catalyze mono- and di-methylation of histone H3K9 and nonhistone proteins, play important roles in diverse cellular processes. Overexpression or dysregulation of G9a and GLP has been identified in various types of cancer. Here, we report the discovery of a highly potent and selective covalent inhibitor 27 of G9a/GLP via the structure-based drug design approach following structure-activity relationship exploration and cellular potency optimization. Mass spectrometry assays and washout experiments confirmed its covalent inhibition mechanism. Compound 27 displayed improved potency in inhibiting the proliferation and colony formation of PANC-1 and MDA-MB-231 cell lines and exhibited enhanced potency in reducing the levels of H3K9me2 in cells compared to noncovalent inhibitor 26. In vivo, 27 showed significant antitumor efficacy in the PANC-1 xenograft model with good safety. These results clearly indicate that 27 is a highly potent and selective covalent inhibitor of G9a/GLP.

Lower Limb Biomechanics during the Golf Downswing in Individuals with and without a History of Knee Joint Injury.

Although prevention is better than treatment, after a knee injury occurs, the adjustment of the movement technique back to the posture before the injury and the restoration of accuracy is very important for professional and amateur players. This study aimed to compare the differences in lower limb mechanics during the golf downswing between those with and without a history of knee joint injury. A total of 20 professional golfers with single-digit handicaps were recruited for this study, 10 of whom had a knee injury history (KIH+), while another 10 players were without a knee injury history (KIH-). From the 3D analysis, selected kinematic and kinetic parameters during the downswing were analyzed using an independent samples t-test with a significance level of α = 0.05. During the downswing, individuals with KIH+ exhibited a smaller hip flexion angle, smaller ankle abduction angle, and larger ankle adduction/abduction range of motion (ROM). Moreover, there was no significant difference found in the knee joint moment. Athletes with a history of knee injury can adjust the motion angles of their hip and ankle joints (e.g., by avoiding excessive forward leaning of the trunk and maintaining stable foot posture without inward or outward rotation) to minimize the impact of changes in their movement patterns resulting from the injury.

Exploring Nursing Undergraduates' Experiences with a Redesigned Blended Learning Course: A Descriptive Qualitative Study.

AIM: To explore the experience of nursing undergraduates with a blended course, that was redesigned using the Community of Inquiry framework. DESIGN: The Obstetrics and Gynaecology Nursing Course was redesigned using blended learning pedagogy, which starts from the creation of teaching presence, plays the intermediary role of social presence and aims at realizing cognitive presence. METHODS: After the course completion, we conducted a qualitative descriptive study and collected data using focus group interviews and field notes. RESULTS: The findings comprised three main themes including role promotion, passive and selective learning and recommendations. Teachers and peers reportedly played the supervisors, facilitators and coordinators in learning promotion. Some students experienced difficulties in adapting to the blended learning environment due to passive learning habits, character flaws and academic pressure. However, a majority of them supported the application of the model.

Upper Extremity Muscle Activation during Drive Volley and Groundstroke for Two-Handed Backhand of Female Tennis Players.

Drive volley is one of the essential backhand stroke technique trends seen in recent women's tennis competitions. Although movements of the drive volley and groundstroke are similar, activation of the internal muscles vary due to different incoming ball conditions. Most previous studies only focused on the groundstroke, however. The current study investigates the different muscle activation patterns in the upper extremity muscle during the two-handed backhand drive volley as well as the groundstroke for female tennis players. Ten elite female tennis players were measured in the muscle activation of the flexor carpi radialis (FCR), extensor carpi radialis (ECR), biceps brachii (BB), and triceps brachii (TB) from both upper extremities. Racket-head speed at impact, swing duration of each phase, and racket-head average velocity in both strokes were also recorded. Significant differences were found between the drive volley and groundstroke in the velocity profile of racket tip, swing duration of each phase (preparation, early follow-through, and late follow-through), activation patterns of upper extremity muscles, and flexor/ extensor ratios of wrist and elbow in both upper extremities. Different racket trajectory strategies were also observed between the two strokes, with greater horizontal racket velocity recorded in the groundstroke but greater vertical velocity in the drive volley. ECR and TB muscle activation during the drive volley preparation phase was greater than the groundstroke when completing a quicker backswing. In the early acceleration phase, the greater FCR leading arm activation in the drive volley assisted wrist stabilization in preparation for impact. In the late follow-through phase, less TB leading arm activity and higher ECR trailing arm activity in the drive volley showed more forward compression movement in racket contact with the ball. As it is essential for the drive volley to complete a quicker backswing and to increase shot efficiency at the end of the forward movement, coaches should consider the two strokes' muscle activation and technique differences to enhance specific techniques and fitness training programs.

Genetic Disruption of KLF1 K74 SUMOylation in Hematopoietic System Promotes Healthy Longevity in Mice.

The quest for rejuvenation and prolonged lifespan through transfusion of young blood has been studied for decades with the hope of unlocking the mystery of the key substance(s) that exists in the circulating blood of juvenile organisms. However, a pivotal mediator has yet been identified. Here, atypical findings are presented that are observed in a knockin mouse model carrying a lysine to arginine substitution at residue 74 of Krüppel-like factor 1 (KLF1/EKLF), the SUMOylation-deficient Klf1K74R/K74R mouse, that displayed significant improvement in geriatric disorders and lifespan extension. Klf1K74R/K74R mice exhibit a marked delay in age-related physical performance decline and disease progression as evidenced by physiological and pathological examinations. Furthermore, the KLF1(K74R) knockin affects a subset of lymphoid lineage cells; the abundance of tumor infiltrating effector CD8+ T cells and NKT cells is increased resulting in antitumor immune enhancement in response to tumor cell administration. Significantly, infusion of hematopoietic stem cells (HSCs) from Klf1K74R/K74R mice extends the lifespan of the wild-type mice. The Klf1K74R/K74R mice appear to be an ideal animal model system for further understanding of the molecular/cellular basis of aging and development of new strategies for antiaging and prevention/treatment of age-related diseases thus extending the healthspan as well as lifespan.

Alkaloid from Alstonia yunnanensis diels root against gastrointestinal cancer: Acetoxytabernosine inhibits apoptosis in hepatocellular carcinoma cells.

Liver cancer belongs to Gastrointestinal (GI) malignancies which is a common clinical disease, a thorny public health problem, and one of the major diseases that endanger human health. Molecules from natural products (NPs) or their derivatives play an increasingly important role in various chronic diseases such as GI cancers. The chemical composition of the Alstonia yunnanensis Diels roots was studied using silica column chromatography, gel chromatography, recrystallization, and HPLC, and the compounds were structurally identified by modern spectral analysis using mass spectrometry (MS) and nuclear magnetic resonance (1H-, 13C-, HMQC-, HMBC-, and 1H-1HCOSY-NMR), ultraviolet and visible spectrum (UV), and electronic Circular Dichroism (ECD). Acetoxytabernosine (AC), an indole alkaloid with antitumor activity, was isolated from Alstonia yunnanensis Diels root. The current study aimed to investigate the influence of AC on the cell proliferation of BEL-7402 and SMMC7721 and to elucidate the underlying mechanism. The absolute configuration of AC was calculated by ECD (electronic circular dichroism). The effects of AC on the viability of different tumor cell lines were studied by the SRB method. The death mode of human hepatoma cells caused by AC was studied by TUNEL cell apoptosis detection and AnnexinV-FITC/PI double staining image. Mitochondrial membrane potential was detected by JC-1. The effects of AC on the expression of apoptosis-related proteins (Caspase9, Caspase3, and Parp-1) in SMMC7721 and BEL-7402 cells were detected by western blot. It was found that the absolute configuration of AC is 19(s), 20(s)-Acetoxytabernosine. AC could induce apoptosis of SMMC7721 and BEL-7402, and block the replication of DNA in the G1 phase. Under the treatment of AC, the total protein expression of apoptosis-related proteins (Caspase9, Caspase3, and Parp-1) significantly decreased in SMMC7721 and BEL-7402. The results suggested that AC induced apoptosis through a caspase-dependent intrinsic pathway in SMMC7721 and BEL-7402, and natural product-based drug development is an important direction in antitumor drug discovery and research.

Exploring Shank Circumference by Stretching after Training among Volleyball Players.

This preliminary study examined the effects of a stretching intervention after training and its duration (15 vs. 30 min) on participants' shank circumference (SC) reduction and subjective discomfort score. Ten male volleyball players underwent a routine 3 h training. A two-way analysis of variance revealed that the stretching intervention had significant effects on SC reduction (p < 0.01) and subjective discomfort scores (p < 0.001). Stretching after training could help eliminate shank strain, and a slighter discomfort in shanks when stretching was also seen (score, 20.1/100). An independent-samples t test revealed a significantly higher SC reduction (p < 0.01) with 30 min of stretching (5.6 mm) than with 15 min of stretching (2.7 mm); both stretching durations reduced SC significantly more than the no-stretching condition did. The findings of this study can serve as a reference for volleyball players to alleviate shank strain after daily routine training.

Antitumor effects of 3-bromoascochlorin on small cell lung cancer via inhibiting MAPK pathway.

Small cell lung cancer (SCLC) was defined as a recalcitrant cancer, and novel therapies are urgently needed. Marine natural products (MNPs) may bring continuing hope for treatment of SCLC. In this study, 3-bromoascochlorin (BAS), an MNP isolated from the coral-derived fungus Acremonium sclerotigenum GXIMD 02501, was primarily screened out with antiproliferative activity towards SCLC cell lines. Then western blot analysis (WB) and flow cytometry were conducted, and we found BAS could induce the apoptosis of H446 and H69AR cells. Besides, BAS could suppress the invasion and migration of H446. In an SCLC xenograft mice model, BAS inhibited the growth of tumor without affecting the body weight of mice. Finally, the underlying mechanisms were preliminarily explored. According to the results of RNA-seq, reverse transcription-quantitative polymerase chain reaction, and WB, our results revealed that BAS exerted antitumor activity via inhibiting mitogen-activated protein kinase (MAPK)/extracellular signal-regulated kinases (ERK) pathway. Collectively, these results indicated that BAS can be used as a promising compound for the treatment of human SCLC.

Comorbidity of Narcolepsy and Psychotic Disorders: A Nationwide Population-Based Study in Taiwan.

BACKGROUND: Narcolepsy is a chronic sleep disorder that is likely to have neuropsychiatric comorbidities. Psychotic disorders are characterized by delusion, hallucination, and reality impairments. This study investigates the relationship between narcolepsy and psychotic disorders. DESIGN AND METHODS: This study involves patients who were diagnosed with narcolepsy between January 2002 and December 2011 (n = 258) and age- and gender-matched controls (n = 2580) from Taiwan's National Health Insurance database. Both the patients and the controls were monitored from January 1, 2002 to December 31, 2011 to identify any occurrence of a psychotic disorder. Drugs that have been approved for treating narcolepsy: immediate-release methylphenidate (IR-MPH), osmotic controlled-release formulations of methylphenidate (OROS-MPH), and modafinil, were analyzed. A multivariate logistic regression model was used to evaluate the potential comorbidity of narcolepsy with psychotic disorders. RESULTS: During the study period, 8.1% of the narcoleptic patients exhibited comorbidity with a psychotic disorder, whereas only 1.5% of the control subjects (1.5%) had psychotic disorders (aOR, 4.07; 95% CI, 2.21-7.47). Of the narcolepsy patients, 41.5, 5.4, and 13.2% were treated with MPH-IR, MPH-OROS, and modafinil, accordingly. Pharmacotherapy for narcolepsy did not significantly affect the risk of exhibiting a psychotic disorder. CONCLUSIONS: This nationwide study revealed that narcolepsy and psychotic disorders commonly co-occur. Pharmacotherapy for narcolepsy was not associated with the risk of psychotic disorders. Our findings serve as a reminder that clinicians must consider the comorbidity of narcolepsy and psychosis.

Ultra Sensitivity Silicon-Based Photonic Crystal Microcavity Biosensors for Plasma Protein Detection in Patients with Pancreatic Cancer.

Defect-engineered photonic crystal (PC) microcavities were fabricated by UV photolithography and their corresponding sensitivities to biomarkers in patient plasma samples were compared for different resonant microcavity characteristics of quality factor Q and biomarker fill fraction. Three different biomarkers in plasma from pancreatic cancer patients were experimentally detected by conventional L13 defect-engineered microcavities without nanoholes and higher sensitivity L13 PC microcavities with nanoholes. 8.8 femto-molar (0.334 pg/mL) concentration of pancreatic cancer biomarker in patient plasma samples was experimentally detected which are 50 times dilution than ELISA in a PC microcavity with high quality factor and high analyte fill fraction.

Spexin as an anxiety regulator in mouse hippocampus: Mechanisms for transcriptional regulation of spexin gene expression by corticotropin releasing factor.

Spexin (SPX) acts as a neuropeptide with pleiotropic functions that can participate in anxiety regulation. Corticotropin releasing factor (CRF) is widely expressed in brain tissues and associated with depression and anxiety and addiction. With the anxious mice under chronic unpredictable stress, we found SPX mRNA expression level in the hippocampus of the brain was significantly reduced, while local CRF mRNA expression level was increased. Furthermore, CRF injection in the hippocampus could also decrease SPX mRNA expression levels in hippocampus and other brain tissues, including pituitary and hypothalamus. With the primary mouse hippocampal cell model, CRF treatment could decrease SPX mRNA expression at hippocampal cell level and this inhibitory effect was mediated only by corticotropin releasing factor receptor 2 (CRFR2) but not corticotropin releasing factor receptor 1 (CRFR1). In HEK293 cells with CRFR2 over-expression, CRF could also inhibit SPX promoter activity coupling with AC/cAMP/PKA and MEK1/2/Erk1/2 cascades. In addition, Epac was also involved with the CRF-repressed SPX promoter activity and cross-talked with MEK1/2/Erk1/2 pathway. CRF could inhibit SPX gene expression in mouse hippocampus via transcriptional activation at the promoter level with coupling of AC/cAMP and MEK1/2/Erk1/2 signaling, which will be relevant to the anxiety response mediated by SPX in central nervous system.

Optimization of double-vortex-assisted matrix solid-phase dispersion for the rapid determination of paraben preservative residues in leafy vegetables.

The extensive use of preservatives during the growth, transport and storage of vegetables has been a concern because of their known or suspected toxicity that jeopardizes human health. This paper reports the development of a technique that rapidly determines the presence of five paraben preservative residues in leafy vegetables using double-vortex-assisted matrix solid-phase dispersion (DVA-MSPD) and UHPLC-electrospray ionization(-)-quadrupole time-of-flight mass spectrometry detection. We simplified the original MSPD technique by eliminating the use of mortar/pestle and SPE-column procedures. The DVA-MSPD factors were screened by a multilevel categorical design, and then optimized by Box-Behnken Design plus response surface methodology. The limits of quantification were 1.2-1.8 ng g-1 (dry weight). The satisfactory average recoveries were 85-104% with RSDs less than 10%. The developed method was successfully employed for the rapid determination of selected paraben residues at trace-level in leafy vegetable samples.

Testicular Function After Long-Term Methylphenidate Treatment in Boys with Attention-Deficit/Hyperactivity Disorder.

Objective: Treating attention-deficit/hyperactivity disorder (ADHD) with methylphenidate (MPH) has become increasingly common, while both animal studies and case reports have previously suggested that MPH may exert adverse effects on the reproductive system or gonadal hormones. This study aims to investigate whether long-term MPH treatment of boys with ADHD can induce testicular dysfunction (TD). Methods: A nationwide cohort that included 59,746 boys diagnosed with ADHD and 52,008 healthy subjects retrieved from the National Health Insurance database in Taiwan was also observed between 1999 and 2011. TD was defined by the International Classification of Diseases, 9th revision, Clinical Modifications codes (257.0, 257.1, 257.2, 257.8, or 257.9). Cumulative time of MPH use was categorized into nonuse, short-term use (1-365 days), and long-term use (>365 days). We compared the rate of TD diagnosis between ADHD patients and controls and analyzed the risk of developing a TD after MPH treatment. Results: Compared with the control group (0.06%), the ADHD group had a higher comorbidity rate of TD (0.14%) (adjusted odds ratio [aOR] = 1.95, 95% confidence interval [95% CI]: 1.26-3.04, p = 0.003). However, MPH did not significantly influence the risk of developing TD (adjusted hazard ratio = 1.40, 95% CI: 0.77-2.54, p = 0.272). Compared with ADHD boys without MPH treatment, patients who were prescribed short-term MPH (aOR = 0.96, 95% CI: 0.51-1.82, p = 0.900) and long-term MPH (aOR = 1.40, 95% CI: 0.69-2.83, p = 0.351) showed no significance associated with an increased risk of developing TD. Conclusions: Our nationwide cohort showed that long-term treatment with MPH has no harmful effect on the testosterone function of ADHD patients. However, due to the increased comorbidity rate of ADHD and TD, early recognition and detection of TD in ADHD children have the potential to change the trajectory of TD morbidity later in life.

Correlation between attention-deficit/hyperactivity disorder, its pharmacotherapy and thyroid dysfunction: A nationwide population-based study in Taiwan.

OBJECTIVE: The aim of this study was to examine the comorbid rates of thyroid dysfunction among patients with attention-deficit/hyperactivity disorder (ADHD) and the general population. We further examined whether pharmacotherapy affects ADHD patients' risk of developing thyroid dysfunction. DESIGN AND MEASUREMENT: We recruited 75 247 newly diagnosed ADHD patient and 75 247 healthy controls between January 1999 and December 2011 from the National Health Insurance database in Taiwan. We compared hyperthyroidism, hypothyroidism and other common paediatric psychiatric diseases between ADHD patients and controls. We carried out logistic regression analysis to identify an independent factor for predicting thyroid dysfunction. Furthermore, we analysed the time sequence of the diagnosis and the risk of developing a thyroid disorder after receiving pharmacotherapy. RESULTS: Compared to the control group, the ADHD group had higher comorbidity rates of both hyperthyroidism (1.1% of ADHD vs 0.7% of controls, aOR: 1.72, P < 0.001) and hypothyroidism (0.6% of ADHD vs 0.2% of controls, aOR: 2.23, P < 0.001). Of the ADHD patients with comorbid thyroid dysfunction, about two-thirds and half of patients were diagnosed with ADHD prior to their diagnosis of hyperthyroidism and hypothyroidism, respectively. Furthermore, pharmacotherapy had no significant influence on the risk of developing hyperthyroidism (aHR: 1.09, P = 0.363) or hypothyroidism (aHR: 0.95, P = 0.719) among ADHD patients. CONCLUSION: Patients with ADHD had greater comorbid rates with thyroid dysfunction than the control subjects, but pharmacotherapy for treating ADHD did not affect thyroid dysfunction later in life. However, these findings should be further verified using a clinical cohort with comprehensive laboratory assessment in future.

Serum Glutamine Levels as a Potential Diagnostic Biomarker in Sepsis following Surgery for Peritonitis.

Few diagnostic biomarkers for sepsis after emergency peritonitis surgery are available to clinicians, and, thus, it is important to develop new biomarkers for patients undergoing this procedure. We investigated whether serum glutamine and selenium levels could be diagnostic biomarkers of sepsis in individuals recovering from emergency peritonitis surgery. From February 2012 to March 2013, patients who had peritonitis diagnosed at the emergency department and underwent emergency surgery were screened for eligibility. Serum glutamine and selenium levels were obtained at pre-operative, post-operative and recovery time points. The average level of pre-operation serum glutamine was significantly different from that on the recovery day (0.317 ± 0.168 vs. 0.532 ± 0.155 mM, P < 0.001); moreover, serum glutamine levels were unaffected by surgery. Selenium levels were significantly lower on the day of surgery than they were at recovery (106.6 ± 36.39 vs. 130.68 ± 56.98 ng/mL, P = 0.013); no significant difference was found between pre-operation and recovery selenium levels. Unlike selenium, glutamine could be a sepsis biomarker for individuals with peritonitis. We recommend including glutamine as a biomarker for sepsis severity assessment in addition to the commonly used clinical indicators.

Comorbidity of narcolepsy and depressive disorders: a nationwide population-based study in Taiwan.

OBJECTIVE: Narcolepsy is a chronic sleep disorder that is likely to have neuropsychiatric comorbidities. Depression is a serious mood disorder that affects individuals' daily activities and functions. The current study aimed to investigate the relationship between narcolepsy and depressive disorders. METHODS: The study consisted of patients diagnosed with narcolepsy between January 2002, and December 2011 (n = 258), and age-matched and gender-matched controls (n = 2580) from Taiwan's National Health Insurance database. Both the patients and the controls were monitored through December 31, 2011, to identify the occurrence of a depressive disorder. A multivariate logistic regression model was used to assess the narcolepsy's potential influence on the comorbidity of a depressive disorder. RESULTS: During the study period, 32.7%, 24.8%, and 10.9% of the narcoleptic patients were comorbid with any depressive disorder, dysthymic disorder, and major depressive disorder, respectively. When compared to the control subjects, the patients with narcolepsy were at greater risks of having any depressive disorder (aOR 6.77; 95% CI 4.90-9.37), dysthymic disorder (aOR 6.62; 95% CI 4.61-9.57), and major depressive disorder (aOR 6.83; 95% CI 4.06-11.48). Of the narcoleptic patients that were comorbid with depression, >50% had been diagnosed with depression prior to being diagnosed with narcolepsy. CONCLUSIONS: This nationwide data study revealed that narcolepsy and depression commonly co-occurred. Since some symptoms of narcolepsy overlapped with those of depressive disorders, the findings serve as a reminder that clinicians must pay attention to the comorbidity of narcolepsy and depression.