Mendelian randomization studies of depression: evidence, opportunities, and challenges.

BACKGROUND: Major depressive disorder (MDD) poses a significant social and economic burden worldwide. Identifying exposures, risk factors, and biological mechanisms that are causally connected to MDD can help build a scientific basis for disease prevention and development of novel therapeutic approaches. METHODS: In this systematic review, we assessed the evidence for causal relationships between putative causal risk factors and MDD from Mendelian randomization (MR) studies, following PRISMA. We assessed methodological quality based on key elements of the MR design: use of a full instrumental variable analysis and validation of the three key MR assumptions. RESULTS: We included methodological details and results from 52 articles. A causal link between lifestyle, metabolic, inflammatory biomarkers, particular pathological states and MDD is supported by MR investigations, although results for each category varied substantially. CONCLUSIONS: While this review shows how MR can offer useful information for examining prospective treatment targets and better understanding the pathophysiology of MDD, some methodological flaws in the existing literature limit reliability of results and probably underlie their heterogeneity. We highlight perspectives and recommendations for future works on MR in psychiatry.

Prognostic factors in transnasal endoscopic surgery for paediatric patients with ossifying fibroma of the paranasal sinuses and skull base.

BACKGROUND: Ossifying fibroma of the paranasal sinuses and skull base in paediatric patients is difficult to operate and can recur easily after surgery. This study aimed to analyse factors associated with recurrence after transnasal endoscopic resection of ossifying fibroma in paediatric patients. METHODS: This retrospective observational study included 34 patients under 17 years of age who underwent transnasal endoscopic resection of ossifying fibroma of the paranasal sinuses and skull base from 2005 to 2021 at a single tertiary medical centre. Clinical indicators such as age; surgical history; pathological type; intraoperative bleeding; and orbit, anterior skull base, sphenoid bone, sella turcica, clivus, or frontal sinus involvement were subjected to univariate analysis using the χ2 test, to investigate whether any of these factors affected recurrence. RESULTS: All 34 patients underwent transnasal endoscopic resection. The follow-up period was 6-120 months (mean: 48.0 months). Five patients experienced local recurrence during the follow-up period (14.7%). Results of χ2 tests indicated that a history of previous surgery, the amount of intraoperative bleeding, and sphenoid and/or sella turcica and clivus involvement were significantly associated with recurrence (P < 0.05). Age; pathological stage; and orbit, anterior skull base, and frontal sinus involvement were not associated with recurrence (P > 0.05). CONCLUSIONS: The increased risk of recurrence after transnasal endoscopic resection of nasal-skull base ossifying fibroma should be considered during endoscopic surgery in paediatric patients with a history of previous surgery, intraoperative bleeding tendency, and sphenoid and/or sella turcica and clivus involvement. These patients require careful postoperative follow-up.

An advanced LC-MS/MS protocol for simultaneous detection of pharmaceuticals and personal care products in the environment.

RATIONALE: The development of appropriate analytical screening techniques for pharmaceuticals and personal care products (PPCPs) is the basis for studying the distribution and environmental impact of emerging contaminants (ECs). Mass spectrometry-based screening methods vary with the complexity of the target compounds. It is challenging to balance both positive and negative ion quantification with a low detection limit. To establish a set of experimental methods including extraction, chromatography-separation and mass spectrometry screening is one of the most important topics in PPCP research. This paper describes a universal and efficient qualification and quantification protocol for the simultaneous detection of 34 PPCPs in different environmental samples in a single analytical data acquisition run. METHODS: Thirty-four representative PPCPs, which are widely distributed in the environment with high ecological toxicity and complex chemical structures, were selected as representative target ECs. The extraction of the target PPCPs was achieved using only one solid-phase extraction cartridge without the need to adjust the pH of samples. The enriched samples were detected by LC-MS/MS in both positive and negative ion modes simultaneously. The protocol was evaluated based on the accuracy, precision, detection limits and matrix effects. RESULTS: This method achieved simultaneous detection of PPCPs in both positive and negative ion modes, with a single analytical cycle of 12 min. The observed SPE recoveries were between 40% and 115%. The instrumental detection limits (IDL) varied from 0.01 to 1 pg, and the method detection limits (MDL) were between 0.002 and 3.323 ng/l in different matrices. Most of the PPCPs were subjected to matrix suppression below 30%. The method was successfully applied for quantitative analysis of the PPCPs in different environmental samples, including river samples, wastewater treatment plant (WWTP) samples and soil samples. CONCLUSIONS: This protocol developed a rapid and efficient detection method to simultaneous qualitative and quantitative 34 representative PPCPs in the environment. The IDL ranged from 0.01 to 1 pg and the MDL ranged from 0.002 to 3.323 ng/l in different matrices. The detection limit was one order of magnitude lower compared to previous studies. The protocol also provided a wide application range for different environmental matrices, which permitted the migration and transformation of PPCPs to be explored.

Neuroprotective Effects of Quercetin on Ischemic Stroke: A Literature Review.

Ischemic stroke (IS) is characterized by high recurrence and disability; however, its therapies are very limited. As one of the effective methods of treating acute attacks of IS, intravenous thrombolysis has a clear time window. Quercetin, a flavonoid widely found in vegetables and fruits, inhibits immune cells from secreting inflammatory cytokines, thereby reducing platelet aggregation and limiting inflammatory thrombosis. In pre-clinical studies, it has been shown to exhibit neuroprotective effects in patients with ischemic brain injury. However, its specific mechanism of action remains unknown. Therefore, this review aims to use published data to elucidate the potential value of quercetin in patients with ischemic brain injury. This article also reviews the plant sources, pharmacological effects, and metabolic processes of quercetin in vivo, thus focusing on its mechanism in inhibiting immune cell activation and inflammatory thrombosis as well as promoting neuroprotection against ischemic brain injury.

TiO2/CdS composite photocathode improves the performance and degradation of wastewater in microbial fuel cells.

Optimization of dye decolourization for wastewater and power production are explored in dual-chamber microbial fuel cells (MFCs) with TiO2/CdS photocathodes. The rapid reduction of azo dye methylene blue (MB) and power production were enhanced with TiO2/CdS photocathode under illumination. The analysis of electrochemical impedance spectra indicated that the photocatalysis of TiO2/CdS accelerated the electron transfer process of photoelectrode reduction. Moreover, the UV-visible light spectrophotometer showed that the maximum degradation of the MFCs was 98.25%, which illustrated that MB may be cleaved by photoelectrons generated by light irradiation on the illuminated TiO2/CdS photocathode. Finally, the power production of MFCs in this work promoted reductive decolourization of the dye MB solution.

Cell-envelope proteinases from lactic acid bacteria: Biochemical features and biotechnological applications.

Proteins displayed on the cell surface of lactic acid bacteria (LAB) perform diverse and important biochemical roles. Among these, the cell-envelope proteinases (CEPs) are one of the most widely studied and most exploited for biotechnological applications. CEPs are important players in the proteolytic system of LAB, because they are required by LAB to degrade proteins in the growth media into peptides and/or amino acids required for the nitrogen nutrition of LAB. The most important area of application of CEPs is therefore in protein hydrolysis, especially in dairy products. Also, the physical location of CEPs (i.e., being cell-envelope anchored) allows for relatively easy downstream processing (e.g., extraction) of CEPs. This review describes the biochemical features and organization of CEPs and how this fits them for the purpose of protein hydrolysis. It begins with a focus on the genetic organization and expression of CEPs. The catalytic behavior and cleavage specificities of CEPs from various LAB are also discussed. Following this, the extraction and purification of most CEPs reported to date is described. The industrial applications of CEPs in food technology, health promotion, as well as in the growing area of water purification are discussed. Techniques for improving the production and catalytic efficiency of CEPs are also given an important place in this review.

Enhanced performance and degradation of wastewater in microbial fuel cells using titanium dioxide nanowire photocathodes.

This paper explores the decolorization of dye wastewaters and electricity generation using dual-chamber microbial fuel cells (MFCs) with titanium dioxide nanowire (TiO2 NW) photocathodes. TiO2 NW cathodes under ultraviolet light are observed to enhance the reduction of azo dye Active Red 30 (AR 30) and electricity generation. The analysis of electrochemical impedance spectra (EIS) indicates acceleration of the electron transfer processes of photoelectrode reduction by the photocatalysis of TiO2 NWs, with polarization resistance of the photocathode being 10.45 Ω under light irradiation from 294 Ω in the dark. Ultraviolet-visible light spectroscopy shows that the maximum degradation of the MFCs is 78.1%; the azo bond of AR 30 may be cleaved by photoelectrons generated by light irradiation of the illuminated TiO2 NW photocathode. The electricity produced by microbial fuel cells (MFCs) is expected to enhance the reductive decolorization of the azo dye AR 30 solution.

[The impact of endoscopic sinus surgery on sinonasal microbiome of chronic rhinosinusitis with nasal polyps].

Objective:To compare the sinonasal microbiome of patients with chronic rhinosinusitis with nasal polyps （CRSwNP） and healthy subjects, and to prospectively observe the effect of surgery-centered comprehensive treatment on microbiome. Method:A case-control and prospective self-controlled study was conducted, recruiting the CRSwNP patients who were surgically treated, and collecting swab samples from the middle meatus. They were followed up for three months at an interval of one month. And we recruited healthy volunteers' samples as well. All specimens were analyzed by the second-generation high-throughput sequencing, collecting subjective and objective data, and analyzed the relationship between them. Result:①There was no significant difference of α diversity between the two groups（Shannon index were 4.41 vs. 3.89）. However, there was a dynamic change of the α diversity in the CRSwNP group, and the Shannon index for 1, 2, 3 months follow-up were 2.33, 2.89, 4.24 respectively, which showed an increase followed a descend. The ß diversity showed that the MRA of cyanobacteria was higher in the CRSwNP group than the control group before the operation（P<0.05）, but significantly decreased（P<0.05） to be close to the control group at 3 months postoperatively. ②Comparing the microbiome with clinical factors and prognosis, we found that both the Lund-Kennedy scores and the history of asthma were positively correlated with the MRA of pseudomonas（r=0.397, P=0.012; r=0.420, P=0.008）. Campylobacter was negatively correlated with improvement of SNOT-22 scores（r=-0.63, P=0.038）, and enterococcus was negatively correlated with improvement of Lund-Kennedy scores（r=-0.77, P=0.005）. Conclusion:The surgery-centered comprehensive treatment played an important role in the reconstruction of sinonasal microbiome. Pseudomonas may aggravate sinusitis and increase the risk of combined asthma. Campylobacter and enterococcus may affect the prognosis of surgery.

[Efficacy and safety of pulmicort repulas-impregnated nasal dressing following endoscopic sinus surgery: a randomized, single-blind, placebo-controlled study].

Objective:To investigate the efficacy and safety of pulmicort respulas immerse with nasopore as nasal packing after nasal endoscopic surgery on patients with chronic rhinosinusitis with nasal polyps. Method:This single-blind, randomized study recruit 33 patients diagnosed as chronic rhinosinusitis with polyposis. All of them underwent bilateral endoscopic sinus surgery and randomized to receive pulmicort respulas immersed nasopore in one nasal cavity and saline immersed nasopore contralaterally. Both groups were followed up at 2, 4, 8, 12, 24 weeks after operation. Subjective （VAS score） and objective （Lund-Kennedy score） scores are collected at each time point from both sides of nasal cavity. Result:There are 30 enrolled patients in the study completed the 24-week trial. Both the subjective and objective scores of two groups shows a significant reduction after the ESS operation. The VAS score of the two groups remains roughly unchanged during week 2 to week 24. A statistically significant difference of the Lund-Kennedy score can be detected between the groups from week 2 to week 24. Though the serum cortisol reduced （5.97±4.10） mmol/L vs （12.48±4.33） mmol/L after the surgery, neither group shows any clinical symptoms related with the hypothalamic-pituitary-adrenal axis suppression. Conclusion:This study demonstrated a significant improvement in postoperative healing in nasal cavities receiving pulmicort respulas immersed nasopore as nasal packing following ESS. This method of using budesonide is generally safe for patients with chronic rhinosinusitis with polyposis.

Maximal Medical Therapy for Chronic Rhinosinusitis: A Survey of Chinese Otolaryngologists.

The aim of the present study was to evaluate the clinical practice patterns in maximal medical therapy (MMT) before endoscopic sinus surgery for chronic rhinosinusitis (CRS) by Chinese otolaryngologists. An anonymous web-based survey of MMT was performed. This survey assessed types of therapies, the frequency of use, duration of use, and demographic data of respondents. A total of 134 (26.8%) questionnaires were completed and returned. The majority (62.69%) of respondents would consider surgery less than 3 months after commencing MMT, 33.58% would wait 3 to 6 months. Intranasal corticosteroid sprays, saline irrigation, oral antibiotics, oral mucolytics, and oral Chinese herbals were the most commonly used therapies and listed as "often (>70%)". Macrolides were most commonly antibiotics prescribed among the clinicians surveyed (51.49%). Intranasal corticosteroid sprays, oral antibiotics, oral mucolytics, nasal saline irrigations, and oral Chinese herbals are most commonly prescribed by the majority of Chinese otolaryngologists as MMT for CRS. Current practice patterns of MMT among Chinese otolaryngologists are not uniformly based on evidence-based guidelines.

Transnasal endoscopic resection of orbital cavernous hemangiomas: our experience with 23 cases.

BACKGROUND: The aim of this work was to present our single-center experience on orbital cavernous hemangiomas managed using an endonasal endoscopic approach. METHODS: The study design used was one-institutional retrospective review. Twenty-three cases of orbital cavernous hemangioma were analyzed and followed up. RESULTS: There were 10 males and 13 females, with an average age of 46.1 years, included in our study. Seven cases were extraconal, 16 cases were intraconal, and in 10 of the patients the optic nerve was involved and compressed. Total resection of the tumor was achieved in 16 cases; of the remaining 7 cases, partial tumor resection and orbital decompression were conducted, orbital decompression was conducted in 2 cases, and orbital decompression and optic nerve decompression were conducted in 3 cases. Visual acuity in 9 patients improved significantly, as 16 of the 20 patients with a preoperative visual field defect had a smaller defect after surgery. CONCLUSION: This study adds to the literature showing that endoscopic transnasal surgery is likely a reasonable option for patients with the orbital cavernous hemangiomas medial of the optic nerve. With greater experience, skilled surgical technique, and careful operation, better clinical efficacy can be achieved.

Bioabsorbable steroid-eluting sinus stents for patients with refractory frontal diseases undergoing a revision Draf 3 procedure: a case series.

Background: Bioabsorbable steroid-eluting sinus stents are safe and effective in maintaining the patency of the frontal sinus ostium. Aims/objectives: To assess the efficacy of steroid-eluting sinus stents in improving postoperative outcomes following revision and re-revision Draf 3 procedures in patients with frontal diseases. Material and methods: Patients with recalcitrant chronic frontal rhinosinusitis (FRS) and mucocele who underwent revision and re-revision Draf 3 procedures from 2015 to 2017 were included. Preoperative disease parameters, demographics, and endoscopic and radiographic images were recorded. Results: Seven patients undergoing the Draf 3 procedure for recalcitrant chronic FRS (43%) and mucocele after complete resection of benign tumours in the frontal sinus (57%) were followed up for a mean of 16.5 months. At the end of follow-up, seven (100%) patients were asymptomatic and all patients (100%) had patent neo-ostia. Conclusions and significance: The use of bioabsorbable steroid-eluting sinus stents had no unanticipated consequences, and the drainage pathways of the frontal neo-ostium remained patent. Steroid-eluting sinus stents may decrease recurrence rates in revision cases where patients have extensive scarring or neo-osteogenesis of the operative field from prior Draf 2 or 3 procedures. Further follow-up of the current cases and studies with larger cohorts are needed.

Transnasal endoscopic resection of pediatric orbital cyst: "How I do it".

BACKGROUND: An orbital cystic lesion is a common orbital disease and has classically been approached via external incision. The introduction of endoscopic surgery has revolutionized the management of sinus and skull base disorders. Similarly, endoscopic techniques have been increasingly used to access intraorbital lesions with excellent outcomes, especially in pediatric patients. OBJECTIVE: We described, in detail, the surgical technique of the endoscopic approach to treat a pediatric orbital cyst. RESULTS: The cyst was completely resected, and the patient quickly recovered without any complication. CONCLUSION: The transnasal endoscopic surgical approach can be safe and effective for pediatric patients with orbital lesions. Use of this approach is based on the surgeon's experience and progressive instrumentation.

Consensus of Hybrid Multi-Agent Systems.

In this brief, we consider the consensus problem of hybrid multiagent systems. First, the hybrid multiagent system is proposed, which is composed of continuous-time and discrete-time dynamic agents. Then, three kinds of consensus protocols are presented for the hybrid multiagent system. The analysis tool developed in this brief is based on the matrix theory and graph theory. With different restrictions of the sampling period, some necessary and sufficient conditions are established for solving the consensus of the hybrid multiagent system. The consensus states are also obtained under different protocols. Finally, simulation examples are provided to demonstrate the effectiveness of our theoretical results.

Endoscopic transnasal repair of cerebrospinal fluid leaks with and without an encephalocele in pediatric patients: from infants to children.

PURPOSE: The diagnosis and management of pediatric cerebrospinal fluid (CSF) leak and encephalocele are challenging. The current study aimed to identify patient characteristics, review operative techniques, and evaluate the efficacy and safety of endoscopic endonasal repair in a pediatric population. METHODS: We retrospectively reviewed the records of pediatric patients who underwent transnasal endoscopic repair of CSF leak with or without a meningocele or an encephalocele at Beijing Tongren Hospital, Capital Medical University, between July 2003 and May 2014. All patients had preoperative radiological evaluations and underwent endoscopic endonasal repair of their skull base defects. RESULTS: Altogether, 23 children (mean age 7.0 years) underwent the procedures. Sixteen cases were congenital, and 7 patients had trauma history. The herniations or defects included meningoencephaloceles in 15 cases, meningoceles in 4 cases, and CSF leak in 4 cases (2 patients had bilateral leaks). The leak or herniation sites were ethmoid roof in 10 patients (one was bilateral), cribriform plate in 5, lateral to the foramen cecum in 3, posterior wall of the frontal sinus in 1, sphenoid sinus in 2, lateral recess of the sphenoid sinus in 1, and sella turcica base in 2. All subjects had favorable clinical outcomes without recurrence during a follow-up of 6-123 months (mean 61.1 months). CONCLUSIONS: The endoscopic endonasal approach was the preferred method for repairing CSF leaks with or without an encephalocele in pediatric patients. Compared to traditional operations, this endoscopic procedure is minimally invasive, efficient, and safe.

PI3Kγ kinase activity is required for optimal T-cell activation and differentiation.

Phosphatidylinositol-3-kinase gamma (PI3Kγ) is a leukocyte-specific lipid kinase with signaling function downstream of G protein-coupled receptors to regulate cell trafficking, but its role in T cells remains unclear. To investigate the requirement of PI3Kγ kinase activity in T-cell function, we studied T cells from PI3Kγ kinase-dead knock-in (PI3Kγ(KD/KD)) mice expressing the kinase-inactive PI3Kγ protein. We show that CD4(+) and CD8(+) T cells from PI3Kγ(KD/KD) mice exhibit impaired TCR/CD28-mediated activation that could not be rescued by exogenous IL-2. The defects in proliferation and cytokine production were also evident in naïve and memory T cells. Analysis of signaling events in activated PI3Kγ(KD/KD) T cells revealed a reduction in phosphorylation of protein kinase B (AKT) and ERK1/2, a decrease in lipid raft formation, and a delay in cell cycle progression. Furthermore, PI3Kγ(KD/KD) CD4(+) T cells displayed compromised differentiation toward Th1, Th2, Th17, and induced Treg cells. PI3Kγ(KD/KD) mice also exhibited an impaired response to immunization and a reduced delayed-type hypersensitivity to Ag challenge. These findings indicate that PI3Kγ kinase activity is required for optimal T-cell activation and differentiation, as well as for mounting an efficient T cell-mediated immune response. The results suggest that PI3Kγ kinase inhibitors could be beneficial in reducing the undesirable immune response in autoimmune diseases.

Application of ionic liquids in organic pollutants control.

For their unique properties and good solubility for many different materials, ionic liquids (ILs) have been applied in several fields, such as separation process, synthesis, catalysis and electrochemistry. This paper focuses on applications of ILs in organic pollutants control. An overview of separation, recycling and control of organic pollutants with ILs is present, for example, phenolic compounds, polycyclic aromatic hydrocarbon (PAHs) and dyes from wastewater, dioxins from waste gas, polyamides from solid wastes, chlorophenothane (DDT) and dieldrin from contaminated soils. Furthermore, the problems and challenges of ILs in organic pollutants control are discussed.

Application of multiwalled carbon nanotubes/ionic liquid modified electrode for amperometric determination of sulfadiazine.

A highly sensitive amperometric sulfadiazine sensor based on coating multiwalled carbon nanotubes (MWCNTs) and N-octyl-pyridinium-hexafluorophosphate (OPPF(6)) ionic liquid composite on a glassy carbon (GC) electrode is described. The MWCNTs/OPPF(6) composite contributed new properties to electrochemical sensors by combining the advantages of both ionic liquids and MWCNTs. Compared with bare GC electrode, the electrocatalytic activity of MWCNTs/OPPF(6) generated a greatly improved electrochemical detection of sulfadiazine including low oxidation potential, high current responses, and good anti-fouling performance. The oxidation peak currents of sulfadiazine obtained on the MWCNTs/OPPF(6) coated GC electrode were proportional to the concentration of sulfadiazine within the range of 3.3-35.4 µM with a detection limit of 0.21 µM.