How to achieve adequate quenching for DBP analysis in drinking water?

Quenching is an important step to terminate disinfection during preparation of disinfected water samples for the analysis of disinfection byproducts (DBPs). However, an incomplete quenching might result in continued reactions of residual chlorine, whereas an excessive quenching might decompose target DBPs. Therefore, an adequate quenching to achieve simultaneous disinfection termination and DBP preservation is of particular importance. In this study, the two-stage reaction kinetics of chlorine and three commonly used quenching agents (i.e., ascorbic acid, sodium thiosulfate, and sodium sulfite) were determined. Stopping quenching during the first stage prevented interactions of residual chlorine with natural organic matter. Complete quenching was achieved by minimizing the quenching time for ascorbic acid and sodium sulfite, while limiting the quenching time to less than 3 min for sodium thiosulfate. At the optimized quenching times, the molar ratios (MRs) of quenching agent to chlorine were 1.05, 1.10, and 0.75 for ascorbic acid, sodium sulfite, and sodium thiosulfate, respectively. The destructive effects of the three quenching agents on total organic halogen (TOX) followed the rank order of ascorbic acid (33.7-64.8 %) < sodium sulfite (41.6-72.8 %) < sodium thiosulfate (43.3-73.2 %), and the destructive effects on aliphatic DBPs also followed the rank order of ascorbic acid (29.5-44.5 %) < sodium sulfite (34.9-51.9 %) < sodium thiosulfate (46.9-53.2 %). For total organic chlorine (TOCl) and aliphatic DBPs, the quenching behavior itself had more significant destructive effect than the quenching agent type/dose and quenching time, but for total organic bromine (TOBr), the destructive effect caused by quenching agent type/dose and quenching time was more significant. High-dose, long-duration quenching enhanced the reduction of TOX, but had little effect on aliphatic DBPs. Additionally, the three quenching agents reduced the levels of halophenols (except for tribromophenol), while maintained or increased the levels of tribromophenol, halobenzoic/salicylic acids, and halobenzaldehydes/salicylaldehydes. To achieve adequate quenching for overall DBP analysis in chlorinated water samples, it is recommended to use ascorbic acid at a quenching agent-to-chlorine MR of 1.0 for a quenching time of < 0.5 h.

Disrupted topological properties of structural brain networks present a glutamatergic neuropathophysiology in people with narcolepsy.

STUDY OBJECTIVES: Growing evidences have documented various abnormalities of the white matter bundles in people with narcolepsy. We sought to evaluate topological properties of brain structural networks, and their association with symptoms and neuropathophysiological features in people with narcolepsy. METHODS: Diffusion tensor imaging was conducted for people with narcolepsy (n = 30) and matched healthy controls as well as symptoms assessment. Structural connectivity for each participant was generated to analyze global and regional topological properties and their correlations with narcoleptic features. Further human brain transcriptome was extracted and spatially registered for connectivity vulnerability. Genetic functional enrichment analysis was performed and further clarified using in vivo emission computed tomography data. RESULTS: A wide and dramatic decrease in structural connectivities was observed in people with narcolepsy, with descending network degree and global efficiency. These metrics were not only correlated with sleep latency and awakening features, but also reflected alterations of sleep macrostructure in people with narcolepsy. Network-based statistics identified a small hyperenhanced subnetwork of cingulate gyrus that was closely related to rapid eye movement sleep behavior disorder (RBD) in narcolepsy. Further imaging genetics analysis suggested glutamatergic signatures were responsible for the preferential vulnerability of connectivity alterations in people with narcolepsy, while additional PET/SPECT data verified that structural alteration was significantly correlated with metabotropic glutamate receptor 5 (mGlutR5) and N-methyl-D-aspartate receptor (NMDA). CONCLUSIONS: People with narcolepsy endured a remarkable decrease in the structural architecture, which was not only closely related to narcolepsy symptoms but also glutamatergic signatures.

ADHD in narcolepsy: A closer look at prevalence and ties.

The reported prevalence of attention deficit hyperactivity disorder (ADHD) in narcolepsy varies considerably, while the associated factors remain inadequately established. A systematic search of studies published in PubMed, EMBASE, and the Cochrane Library was performed from inception to March 2023. Ten studies with 839 patients with narcolepsy were included in the study. Utilizing a random effects model, the pooled prevalence of ADHD in narcolepsy was 25% (95% CI, 14-38%). Notably, patients with narcolepsy type 2 showed a significantly higher prevalence of ADHD than that of narcolepsy type 1 (46% vs. 20%, p = 0.045). Furthermore, the rate of ADHD was notably elevated in narcolepsy compared with the healthy controls (odds ratio 9.59, 95% CI, 4.06-22.63, p < 0.001). Several factors such as excessive daytime sleepiness (EDS), fatigue, insomnia severity, and the quality of life were significantly associated with ADHD in narcolepsy (all ps < 0.05). These findings highlight the importance of monitoring and managing ADHD in narcolepsy, and provide a clue to help reducing ADHD by intervening in these associated factors.

Case report: Overlapping anti-AMPAR encephalitis with anti-IgLON5 disease post herpes simplex virus encephalitis.

Autoimmune encephalitis (AE) is the result of an autoimmune process that occurs as a rapidly advancing encephalopathy. Autoimmune encephalitis was commonly linked to herpes simplex virus 1 (HSV-1) as the most frequently identified virus. The main areas affected by this invasion are the temporal lobe, frontal lobe, and limbic system. Limbic encephalitis is a highly uncommon occurrence involving anti-alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor (AMPAR) encephalitis and anti-IgLON family member 5 (IgLON5) disease, both belonging to the rare category. As far as we know, this is the first report showing that a patient diagnosed with AMPAR encephalitis overlapped with anti-IgLON5 disease post herpes simplex virus encephalitis (HSE), which helps to broaden the range of this uncommon autoimmune disease. We recommend autoantibody testing in all patients with HSE, particularly those involving neurological relapses or progression.

A nuclease-mimetic platinum nanozyme induces concurrent DNA platination and oxidative cleavage to overcome cancer drug resistance.

Platinum (Pt) resistance in cancer almost inevitably occurs during clinical Pt-based chemotherapy. The spontaneous nucleotide-excision repair of cancer cells is a representative process that leads to Pt resistance, which involves the local DNA bending to facilitate the recruitment of nucleotide-excision repair proteins and subsequent elimination of Pt-DNA adducts. By exploiting the structural vulnerability of this process, we herein report a nuclease-mimetic Pt nanozyme that can target cancer cell nuclei and induce concurrent DNA platination and oxidative cleavage to overcome Pt drug resistance. We show that the Pt nanozyme, unlike cisplatin and conventional Pt nanoparticles, specifically induces the nanozyme-catalyzed cleavage of the formed Pt-DNA adducts by generating in situ reactive oxygen species, which impairs the damage recognition factors-induced DNA bending prerequisite for nucleotide-excision repair. The recruitment of downstream effectors of nucleotide-excision repair to DNA lesion sites, including xeroderma pigmentosum groups A and F, is disrupted by the Pt nanozyme in cisplatin-resistant cancer cells, allowing excessive accumulation of the Pt-DNA adducts for highly efficient cancer therapy. Our study highlights the potential benefits of applying enzymatic activities to the use of the Pt nanomedicines, providing a paradigm shift in DNA damaging chemotherapy.

Densely granulated adenoma pattern is associated with an increased risk of obstructive sleep apnea in patients with acromegaly.

OBJECTIVES: To explore the prevalence of obstructive sleep apnea (OSA) and the association between the adenoma granulation patterns and OSA in patients with acromegaly. METHODS: An overnight polysomnography (PSG) assessment was carried out on participants with acromegaly. Results classified participants into a non-OSA group, mild to moderate OSA group, and severe OSA group. Morphological and biochemical analyses were performed. Demographic, clinical, biochemical, and polysomnographic data were compared among the three groups. Using logistic regression models, the risk of OSA in acromegalic subjects was estimated. RESULTS: OSA was reported in 36 of 49 patients (74%) with acromegaly. Contrasted with the non-OSA group, OSA patients had a larger proportion of the densely granulated (DG) pattern. The OSA groups with DG acromegaly had a smaller maximum tumor diameter and Vol/2 than those with the sparsely granulated (SG) pattern. Furthermore, a higher growth hormone (GH) level (45.0 ± 36.9 vs 18.6 ± 15.8, P = 0.047) and GH index (28.4 ± 13.8 vs 6.6 ± 8.2, P = 0.003) were found in DG acromegaly patients with severe OSA. Additionally, there was a trend toward higher standardized insulin-like growth factor 1 (IGF-1) in patients with DG acromegaly than in those with SG acromegaly in the severe OSA group. After adjusting for potential confounding variables, the DG pattern was correlated with the risk of OSA (OR = 14.84, 95%CI 1.36-162.20, P = 0.027) in patients with acromegaly. CONCLUSIONS: The findings indicate that a high prevalence of OSA exists in patients with acromegaly, and the DG pattern may be a risk factor for OSA in acromegaly.

Characteristics of Objective Sleep and Its Related Risk Factors Among Parkinson's Disease Patients With and Without Restless Legs Syndrome.

Objective: This study aimed to investigate the objective sleep characteristics and their related risk factors among Parkinson's disease (PD) patients with and without restless legs syndrome (RLS). Methods: A total of 125 patients with PD who underwent overnight polysomnography (PSG) were recruited consecutively. Eighty-one patients, including 27 PD with RLS (PD-RLS) and 54 PD without RLS (PD-NRLS), were included in the final analysis after 1:2 propensity score matching. Demographic, clinical, and polysomnographic data were compared between PD patients with and without RLS. The risk factors for sleep quality were examined using a multiple linear regression model. Results: The prevalence of RLS among PD patients was 28.0% (35/125). The PD-RLS group exhibited a higher score for the Unified Parkinson Disease Rating Scale (UPDRS) III than the PD-NRLS group. Also, the PD-RLS patients displayed significantly shorter total sleep times, worse sleep quality, decreased stage 3 duration, a longer wake time after sleep onset, and a higher arousal index than those without RLS (all p < 0.05). In the multiple linear regression model, PD duration (ß = -0.363, 95% CI: -0.652 to -0.074; p = 0.016), UPDRS-III (ß = -0.356, 95% CI: -0.641 to -0.071; p = 0.016), and periodic limb movement index (PLMI) (ß = -0.472, 95% CI: -0.757 to -0.187; p = 0.002) were determined to be the risk factors influencing sleep quality in PD-RLS patients. The UPDRS-III (ß = -0.347, 95% CI: -0.590 to -0.104; p = 0.006) and HAMD scores (ß = -0.343, 95% CI: -0.586 to -0.100; p = 0.007) were significantly associated with sleep quality after adjusting for confounding factors in PD-NRLS patients, respectively. Conclusions: PD-RLS patients exhibited more disturbed and fragmented sleep in objective sleep architecture than PD-NRLS patients. The severity of motor symptoms in PD was significantly associated with poor sleep quality in both PD-RLS and PD-NRLS patients. Notably, our findings indicated that periodic limb movements during sleep (PLMS) was the risk factor that influenced the objective sleep quality in PD patients with RLS.

Rapid eye movement sleep and slow wave sleep rebounded and related factors during positive airway pressure therapy.

This study aimed to investigate the clinical characteristics and predictors of increased rapid eye movement (REM) sleep or slow wave sleep (SWS) in patients with obstructive sleep apnea (OSA) following positive airway pressure (PAP) therapy. The study retrospectively analyzed data from patients with OSA who underwent both diagnostic polysomnography (PSG) and pressure titration PSG at the Tangdu Hospital Sleep Medicine Center from 2011-2016. Paired diagnostic PSG and pressure titration studies from 501 patients were included. REM rebound was predicted by a higher oxygen desaturation index, lower REM proportion, higher arousal index, lower mean pulse oxygen saturation (SpO2), higher Epworth sleepiness score and younger age (adjusted R2 = 0.482). The SWS rebound was predicted by a longer total duration of apneas and hypopneas, lower N3 duration, lower SpO2 nadir, lower REM proportion in diagnostic PSG and younger age (adjusted R2 = 0.286). Patients without REM rebound or SWS rebound had a high probability of comorbidities with insomnia and mood complaints. Some parameters (subjective and objective insomnia, excessive daytime sleepiness, age and OSA severity) indicate changes in REM sleep and SWS between diagnostic and titration PSG tests. Treatment of insomnia and mood disorders in patients with OSA may helpful to improve the use PAP.

A Tauopathy-Homing and Autophagy-Activating Nanoassembly for Specific Clearance of Pathogenic Tau in Alzheimer's Disease.

The hyperphosphorylated and aggregated tau accumulation represents a significant pathological hallmark of tauopathies including Alzheimer's disease (AD), which is highly associated with defective autophagy in neuronal cells. Autophagy-activating strategies demonstrate the therapeutic potential for AD in many studies; however, further development is limited by their low efficacy and serious side effects that result from a lack of selectivity for diseased cells. Herein, we report a tauopathy-homing nanoassembly (THN) with autophagy-activating capacity for AD treatment. Specifically, the THN can bind to hyperphosphorylated and/or aggregated tau and selectively accumulate in cells undergoing tauopathy. The THN further promotes the clearance of pathogenic tau accumulation by stimulating autophagic flux, consequently rescuing neuron viability and cognitive functions in AD rats. This study presents a promising nanotechnology-based strategy for tauopathy-homing and autophagy-mediated specific removal of pathogenic tau in AD.

Catalytic activity tunable ceria nanoparticles prevent chemotherapy-induced acute kidney injury without interference with chemotherapeutics.

Acute kidney injury (AKI) is a prevalent and lethal adverse event that severely affects cancer patients receiving chemotherapy. It is correlated with the collateral damage to renal cells caused by reactive oxygen species (ROS). Currently, ROS management is a practical strategy that can reduce the risk of chemotherapy-related AKI, but at the cost of chemotherapeutic efficacy. Herein, we report catalytic activity tunable ceria nanoparticles (CNPs) that can prevent chemotherapy-induced AKI without interference with chemotherapeutic agents. Specifically, in the renal cortex, CNPs exhibit catalytic activity that decomposes hydrogen peroxide, and subsequently regulate the ROS-involved genes by activating the Nrf2/Keap1 signaling pathway. These restore the redox homeostasis for the protection of kidney tubules. Under an acidic tumor microenvironment, CNPs become inert due to the excessive H+ that disrupts the re-exposure of active catalytic sites, allowing a buildup of chemotherapy-mediated ROS generation to kill cancer cells. As ROS-modulating agents, CNPs incorporated with context-dependent catalytic activity, hold a great potential for clinical prevention and treatment of AKI in cancer patients.

Effects of transcranial direct current stimulation on performance and recovery sleep during acute sleep deprivation: a pilot study.

BACKGROUND: Previous studies claimed that transcranial direct current stimulation (tDCS) over the left dorsolateral prefrontal cortex (DLPFC) improves cognition in neuropsychiatric patients with cognitive impairment, schizophrenia, organic hypersomnia, etc, but few studies evaluated the effects of tDCS on cognitive improvement following sleep deprivation. The objective of this study was to determine whether tDCS (anode on the left DLPFC and cathode on the right DLPFC with a 2-mA current for 30 min) improves cognition following sleep deprivation. METHODS: Seven participants received active tDCS and eight participants received sham tDCS when their cognition declined during at least 30 h of sleep deprivation. All participants completed the psychomotor vigilance task, Trail Making Tests A and B, digit cancellation test, Stroop color word test, the Brief Visuospatial Memory Test-Revised and a procedural game every 2 h during the sleep deprivation and after recovery sleep. RESULTS: Compared to the sham stimulation, active tDCS (anode on the left DLPFC and cathode on the right DLPFC at a 2-mA current for 30 min) had beneficial effects on attention, memory, executive function, processing speed, and the ability to inhibit cognitive interference, and improved in subjective drowsiness and fatigue following sleep deprivation. The lasting effect of a single tDCS on cognition during sleep deprivation was greater than 2 h. In all participants, tDCS did not disturb recovery sleep, and cognitive performance recovered to the baseline levels after recovery sleep. CONCLUSIONS: The study results indicate that tDCS can improve cognition following sleep deprivation and does not disturb recovery sleep or cognitive performance after recovery sleep. The possible pathophysiological mechanisms might be related to the modulation of the corticothalamic pathway. We believe that tDCS can be applied in the treatment of sleep disorders involving sleepiness. TRIAL REGISTRATION NUMBER: ChiCTR2000029420. DATE OF REGISTRATION: 2020-1-31.

Association between leg motor restlessness and depression among Chinese males living at high-altitude: the mediating role of insomnia.

OBJECTIVE: Previous research has documented an association between insomnia and depression among patients with restless legs syndrome (RLS)/Willis-Ekbom disease. Given that leg motor restlessness (LMR) is closely related to RLS, the purpose of this study was to investigate the prevalence of insomnia and depression among individuals with LMR. In addition, we examined the associations among LMR, insomnia, and depression in a sample of young Chinese men living in high-altitude areas. METHODS: Chinese military personnel working on the Qinghai Tibet Plateau (Lhasa, an altitude of 3600 m) were recruited in 2019 to complete a series of questionnaires. Participants having the urge to move their legs but not meeting the diagnostic criteria for RLS were classified as having LMR. Hierarchical linear regressions and mediational analyses using the SPSS PROCESS macro in SPSS were conducted to examine the associations among LMR, insomnia, and depression. RESULTS: Of 196 participants, 36 (18%) had LMR. Only 1 participant was diagnosed with RLS. The proportions of participants suffering from insomnia who had LMR and did not have LMR were 44% and 22%, respectively. For depression, the proportions were 47% and 28%, respectively. Results of the hierarchical linear regressions showed that both LMR and depression were associated with increased insomnia symptoms. In addition, results from the mediational analyses indicated that the indirect effect of LMR on depression was significant and accounted for 52% of the total effect. CONCLUSIONS: Participants with LMR had a higher prevalence of insomnia and depression compared with those without LMR. In addition, LMR was correlated with depression, and insomnia played a significant role in this co-occurrence.

[Electroacupuncture improves inflammatory reaction and insulin sensitivity in insulin-resistant obese rats].

OBJECTIVE: To observe the effect of electroacupuncture (EA) on inflammatory reaction and insulin sensitivity in insulin-resistant obese (OIR) rats. METHODS: Thirteen male Wistar rats were randomly selected as the control group and fed with common diet. The other 39 rats were fed with high-fat diet for 8 weeks to establish OIR model and then randomized into model, EA and sham EA groups. EA (2 Hz, 1 mA) was applied to unilateral "Zusanli" (ST36), "Fenglong" (ST40), "Zhongwan" (CV12) and "Guanyuan" (CV4) for 15 min, once every other day for 8 weeks, and sham EA was applied to unilateral 4 control spots about 5 mm lateral to the aforementioned 4 acupoints after shallowly inserting acupuncture needles, but without electric current output. After 8 weeks' intervention, the body weight was recorded and the glucose infusion rate (GIR) measured using hyperinsulinemic-euglycemic clamp technique. At the 6th week of intervention, glucose contents of intraperitoneal glucose tolerance test (IPGTT) and intraperitoneal insulin tole-rance test (IPITT) were measured. The levels of serum insulin (INS) and inflammatory factors as C-reactive protein (CRP), IL-6 and TNF-α were measured by using ELISA at the end of the treatment. The expression levels of IL-6, TNF-α, monocyte chemoattractant protein-1(MCP-1), IL-10 and IL-1ß proteins and mRNAs in the abdominal adipose tissues were detected by Western blot and quantitative real time-PCR, separately. The CD68 expression (displaying infiltration of macrophages) of adipose tissue was detected using immunohistochemistry. RESULTS: After modeling, the contents of glucose of IPGTT at 30, 60 and 120 min and those of IPITT at 15, 30, 60 and 120 min, serum INS, CRP, IL-6 and TNF-α, as well as the expression levels of IL-6, TNF-α, IL-1ß and MCP-1 proteins and mRNAs and CD68 protein were significantly increased (P<0.01, P<0.05), while the levels of GIR and IL-10 protein and mRNA were obviously decreased in the model group in comparison with those of the control group (P<0.01), suggesting an increase of inflammation and a decline of INS sensitivity. Following the interventions, the increased contents of glucose of IPGTT and IPITT, serum INS, CRP, IL-6 and TNF-α, expression levels of IL-6, TNF-α, IL-1ß and MCP-1 proteins and mRNAs and CD68 protein, and the decreased levels of GIR and IL-10 protein and mRNA were evidently reversed in the EA group compared with the model group (P<0.01, P<0.05) rather than those in the sham EA group (P>0.05). CONCLUSION: EA can reduce the level of inflammation and improve insulin sensitivity in OIR rats.