Intraoperative transcutaneous electroacupoint stimulation on early postoperative fatigue in patients with Parkinson's disease undergoing deep brain stimulation surgery.

Background: In this clinical trial, we evaluated the effects of transcutaneous electroacupoint stimulation (TEAS) on postoperative fatigue (POF) in Parkinson disease (PD) patients undergoing deep brain stimulation (DBS) surgery. Methods: A total 60 PD patients undergoing DBS surgery were enrolled. They were randomized to receive either electrical stimulation [alternative frequency 2/10 Hz, dense and disperse, intensity adjusted to the maximum tolerated by the participants (6-15 mAmp)] via surface electrodes (TEAS group) or surface electrodes only without electrical stimulation (Con group) at bilateral Zusanli and Sanyinjiao acupuncture points. All participants received their assigned intervention (TEAS or Con) during the 1st stage of surgery [(except during microelectrode recording (MER)] and the entire 2nd stage of surgery. Intraoperative anesthetic requirements were adjusted based on bispectral index (BIS) monitor. POF was assessed by Christensen fatigue scales (ChrFS), along with Quality of Recovery-15 (QoR-15) and mini-mental state examination (MMSE) postoperatively over a 7-day-period. We recorded the usage of rescue analgesics and anti-emetics. Results: Fifty-nine patients' datasets were included for final analyses. Fewer patients in TEAS experienced severe POF (defined as ChrFS ≥6) at T3 than those in the Con group (TEAS vs. Con: 7 vs. 22, p < 0.001). During the 1st stage of surgery, more patients in Con group required dexmedetomidine infusion (TEAS vs. Con: 2 vs. 6; P < 0.01). Total dosages of propofol and remifanil during the 2nd stage of surgery were TEAS vs. Con: 374.7 ± 61.2 vs 421.5 ± 81.9; p < 0.001 and 572.3 ± 82.0 vs. 662 ± 148.2; P < 0.001, respectively. Postoperative rescue analgesics (TEAS vs. Con: 2 vs. 6; P < 0.001) were used less in the TEAS group. TEAS patients reported better POF, MMSE and QoR15 scores than those in the Con group during most of the assessment period. Conclusions: Intraoperative TEAS decreased the severity of POF, reduced intraoperative anesthetic requirements and facilitated post-DBS recovery in this group of PD patients.

Quantification and characterization of microplastics in farmland soils of Jiangsu Province, East China.

The soil ecosystem plays a significant role in the dynamics of microplastics. Qualitative and quantitative analyses of microplastics in six farmland plots from the cities of Nanjing, Suzhou, and Xuzhou were conducted by using laser infrared imaging system (LDIR). The results showed that the abundance of microplastics in farmland soils in Jiangsu Province ranged from 667-9333 items/kg, and the difference between the abundance of microplastics in soils from open-field cultivation and greenhouse farming was not significant. The vertical distribution characteristics showed that the abundance of microplastic decreased significantly with the increase of soil depth. However, there was no significant difference in particle size between top soil (0-5 cm) and deep soil (10-20 cm). Fragments were the most common microplastic form in soil samples (94.6%), with polyvinyl chloride (PVC) being the main polymer type, followed by polyethylene terephthalate (PET). Compared with previous studies conducted in China, the abundance of microplastics in farmland soils in Jiangsu Province was at moderate level but was notably higher than other places within the Yangtze River Delta region. The conclusions drawn from this paper provided important reference data for future assessment of microplastic pollution in agricultural fields. Furthermore, they establish a fundamental groundwork for understanding the migration patterns of MPs in soil environments.

Comparison of glial fibrillary acidic protein-immunoglobulin G-associated myelitis with myelin oligodendrocyte glycoprotein-immunoglobulin G-associated myelitis.

Objective: Glial fibrillary acidic protein-immunoglobulin G (GFAP-IgG)-associated myelitis and myelin oligodendrocyte glycoprotein-IgG (MOG-IgG)-associated myelitis have rarely been compared. Therefore, this study aimed to explore the clinical, laboratory, and imaging features of them to identify the differences. Methods: Overall, 14 and 24 patients with GFAP-IgG-and MOG-IgG-associated myelitis, respectively, were retrospectively screened and included in the study. Results: Among the 14 patients with GFAP-IgG-associated myelitis, the condition was more common in males (71.4%), with a median age of onset of 36.5 years, and more common in adults than in children (35.7%). In contrast, among the 24 patients with MOG-IgG-associated myelitis, the condition was equally divided between males and females, with a median age of onset of 9.5 years and more in children (66.7%) than in adults. The median age of onset of GFAP-IgG-associated myelitis was later than that of the MOG-IgG group. Isolated myelitis was rare in both groups. Elevated cerebrospinal fluid (CSF) protein levels were more prevalent in patients with GFAP-IgG-associated myelitis (64.3%) than in those with MOG-IgG-associated myelitis (16.7%) (p < 0.05), whereas patchy gadolinium enhancement of the cerebral lesion site was less common in patients with GFAP-IgG-associated myelitis than in those with MOG-IgG associated myelitis (p < 0.05). Six patients had a combination of other neurological autoantibodies, the specific mechanism of the overlapping antibodies remains unclear. Conclusion: Cerebrospinal fluid analysis and gadolinium enhanced MRI examination may help to distinguish the two kinds of myelitis.

Enhancing physical and chemical stability of hygroscopic hydroxytyrosol by cocrystal formation.

Hydroxytyrosol (HT) is a natural phenolic compound with potent antioxidant activity extracted from olive trees. It is generally a slightly hydrated viscous liquid at ambient conditions, and it is highly susceptible to oxygen due to the presence of catechol moiety. Although encapsulation technique provides HT in powder form, it does not improve its chemical stability. Herein, we propose an efficient solution to the high hygroscopicity and poor stability of HT. Four cocrystals were first reported, and their intermolecular interactions were analyzed in detail. After cocrystallization, the melting point is increased and the hygroscopicity is significantly decreased. HT cocrystals are thus solid at room temperature. Moreover, hydroxytyrosol cocrystals with betaine (HT-BET) and nicotinamide (HT-NIC) demonstrate superior chemical stability than pure HT, olive extract, and HT encapsulation material. Therefore, cocrystallization can be considered as a promising approach to overcome the application obstacles of HT.

Effect of different irrigation methods on the toxicity and bioavailability of microcystin-LR to lettuce and carrot.

The use of cyanobacteria-polluted water for irrigation has become an increasing concern due to the potential contamination of microcystins (MCs). However, the effects of MCs on plant performance and food safety under different irrigation methods are not well understood. In this study, we investigated the effects of microcystin-LR (MC-LR) on the growth, food quality, and safety of lettuce and carrot using four irrigation methods (spray irrigation and three types of drip irrigation with different distances from the plant stem). Our results showed that exposure to 10 µg L-1 MC-LR negatively affected plant growth and food quality in treatments with spray irrigation (TS) and drip irrigation directly to the stem (TD0), but not in treatments with drip irrigation away from the plant stem (TD10 and TD20). Using soil as a filtration system, the bioavailability of MC-LR in soil was reduced in TD10 and TD20, resulting in less bioaccumulation in plant edible tissues. The estimated daily intake (EDI) values of TS and TD0 in both lettuce and carrot cultivation exceeded the tolerable daily intake (TDI) limit proposed by WHO, whereas the EDI values of TD10 and TD20 could be effectively reduced below the TDI limit. This study highlights the importance of drip irrigation away from the plant stem as a practical measure to mitigate the effects of cyanobacteria-polluted water in agricultural production.

Clinical, imaging features and outcomes of patients with anti-GFAP antibodies: a retrospective study.

Objective: To evaluate and compare the clinical features, imaging, overlapping antibodies, and prognosis of pediatric and adult patients with anti-GFAP antibodies. Methods: This study included 59 patients with anti-GFAP antibodies (28 females and 31 males) who were admitted between December 2019 and September 2022. Results: Out of 59 patients, 18 were children (under 18 years old), and 31 were adults. The overall cohort's median age at onset was 32 years old, 7 for children, and 42 for adults. There were 23 (41.1%) patients with prodromic infection, 1 (1.7%) patient with a tumor, 29 (53.7%) patients with other non-neurological autoimmune diseases, and 17 (22.8%) patients with hyponatremia. Fourteen (23.7%) patients had multiple neural autoantibodies, with the AQP4 antibody being the most common. Encephalitis (30.5%) was the most common phenotypic syndrome. Common clinical symptoms included fever (59.3%), headache (47.5%), nausea and vomiting (35.6%), limb weakness (35.6%), and disturbance of consciousness (33.9%). Brain MRI lesions were primarily located in the cortex/subcortex (37.3%), brainstem (27.1%), thalamus (23.7%), and basal ganglia (22.0%). Spinal cord MRI lesions often involved the cervical and thoracic spinal cord. There was no statistically significant difference in the MRI lesion site between children and adults. Out of 58 patients, 47 (81.0%) had a monophasic course, and 4 died. The last follow-up showed that 41/58 (80.7%) patients had an improved functional outcome (mRS <3), and children were more likely than adults to have no residual disability symptoms (p = 0.001). Conclusion: There was no statistically significant difference in clinical symptoms and imaging findings between children and adult patients with anti-GFAP antibodies; Patients with anti-GFAP antibodies may present with normal MRI findings or delayed MRI abnormalities, and patients with overlapping antibodies were common. Most patients had monophasic courses, and those with overlapping antibodies were more likely to relapse. Children were more likely than adults to have no disability. Finally, we hypothesize that the presence of anti-GFAP antibodies is a non-specific witness of inflammation.

A data-driven group emergency decision-making method based on interval-valued intuitionistic hesitant fuzzy sets and its application in COVID-19 pandemic.

The outbreak of Corona Virus Disease 2019 (COVID-19) makes people more concerned about the validity and timeliness of emergency decision making. When an emergency occurs, it is difficult for decision makers (DMs) to give accurate assessment information in the early stage due to the urgency of time, the incompleteness of information, and the limitations of DMs' cognition and knowledge. Hence, we use interval-valued intuitionistic hesitant fuzzy sets rather than exact numbers to better characterize the fuzziness and uncertainty of emergencies. In addition, the Internet has become a major platform for the public to express their opinions or concerns, so we can collect the user-generated content on social media to help DMs determine appropriate emergency decision-making criteria which are the premise and basis of scientific decisions. However, there is likely to be some correlation between the obtained criteria. To this end, we first extend the Bonferroni mean (BM) operator to the interval-valued intuitionistic hesitant fuzzy environment, and propose three interval-valued intuitionistic hesitant fuzzy BM operators to capture the interrelation of fuzzy input variables, including an interval-valued intuitionistic hesitant fuzzy BM operator, a simplified interval-valued intuitionistic hesitant fuzzy BM operator, and a simplified interval-valued intuitionistic hesitant fuzzy weighted BM (SIVIHFWBM) operator. Then, a new group emergency decision-making method based on the SIVIHFWBM operator and social media data is proposed, and the specific steps of ranking all emergency plans are put forward. Moreover, our method is applied to evaluate emergency plans for the prevention and control of COVID-19. Finally, the effectiveness and feasibility of the method are verified by the sensitivity analysis, validity test, and comparative analysis.

Rucaparib cocrystal: Improved solubility and bioavailability over camsylate.

Rucaparib (Ruc) is a drug used to treat advanced ovarian cancer associated with deleterious BRCA mutations. Its commercial form, the camsylate salt (Ruc-Cam), suffers from poor aqueous solubility and thus causes low and erratic oral bioavailability. In this work, we aimed to improve the oral exposure of Ruc through cocrystallization. Liquid-assisted grinding, slurry, and solvent evaporation methods were employed to prepare new solid forms of Ruc. Cocrystals of rucaparib-theophylline monohydrate (Ruc-Thp MH), rucaparib-maltol (Ruc-Mal), and rucaparib-ethyl maltol (Ruc-Emal) were obtained. Powder X-ray diffraction, Fourier transform infrared spectroscopy, thermogravimetric analysis, differential scanning calorimetry, and dynamic vapor sorption were utilized to characterize these multi-component systems. All cocrystals dissolve faster than Ruc-Cam at pH 2.0 and 4.5, and Ruc-Thp MH displays the highest apparent solubility in pH 4.5 and 6.8 buffers. Pharmacokinetic studies in rats show that Ruc-Thp MH exhibits 2.4 times the Cmax and 1.4 times the AUC0-24h at a single dose compared with Ruc-Cam. The enhanced solubility and bioavailability of Ruc-Thp MH showcase the power of cocrystallization in addressing absorption issues in drug development.

Behavior and fate of microcystin-LR in soils amended with biochar and peat.

Activities such as irrigation with cyanobacteria-polluted water can lead to microcystins (MCs) migration from soil surface to the deeper layers, which could pose a potential risk to ground drinking water safety. The present study evaluated the sorption, degradation and leaching behavior of microcystin-LR (MC-LR) in two different soils amended with biochar and peat. Results showed that both biochar and peat could significantly increase MC-LR sorption in both soils. The Freundlich unit capacity coefficient (Kf) of 2% biochar treatment were 2-3 times higher than those of the control treatment. Amendment of 2% peat greatly boosted the biodegradation of MC-LR, whereas amendment of 2% biochar significantly reduced the biodegradation of MC-LR in both soils. The half-lives of MC-LR were 4.99 d (Control), 5.59 d (2% Biochar) and 3.50 d (2% Peat) in soil A and 6.66 d (Control), 6.93 d (2% Biochar) and 5.13 d (2% Peat) in soil B, respectively. All the amendments, except treatment 1% Peat, could significantly reduce the recovery rates of MC-LR in the leachate of columns with both soils. Amendment of 2% biochar and 2% peat reduced the recovery rates of MC-LR by 15.87% and 8.6% in soil A and 18.4% and 10.3% in soil B, compared with the controls. This work provides a better understanding of the environmental behavior of MC-LR in soils with different amendments, which is also meaningful for groundwater protection in cyanobacterial-polluted areas.

NR4A1 agonist cytosporone B attenuates neuroinflammation in a mouse model of multiple sclerosis.

Nuclear receptor subfamily 4 group A1 (NR4A1) is an orphan nuclear receptor, which is expressed in the majority of cells. NR4A1 expression in peripheral blood mononuclear cells is low during the preclinical stage of multiple sclerosis. Knockout of the Nr4a1 gene in mice can aggravate the symptoms of experimental autoimmune encephalomyelitis (EAE), which is an animal model of multiple sclerosis. In this study, we intragastrically administered the NR4A1 agonist cytosporone B (Csn-B) to mice after inducing EAE. After treatment with Csn-B, the clinical symptoms in the EAE mice were substantially attenuated compared with that in PBS-treated control mice. The percentages of CD4+ T cells and F4/80+ cells in the central nervous system were decreased. In addition, interferon-γ and interleukin-17 production by proinflammatory Th1/Th17 cells in the central nervous system and interferon-γ levels in splenocytes were decreased after Csn-B treatment. These findings suggest that the NR4A1 agonist Csn-B can alleviate nerve injury after EAE induction, and, therefore, may be useful as a potential treatment for multiple sclerosis.

Improving the dissolution behaviors and bioavailability of abiraterone acetate via multicomponent crystal forms.

Abiraterone acetate (ABA), the first-line drug for the treatment of metastatic castration resistant prostate cancer (mCRPC), is administered at a high daily dosage of 1000 mg due to its poor solubility, and its fasted absolute oral bioavailability is estimated to be less than 10%. In this work we have focused on developing multicomponent forms with improved dissolution behaviors and bioavailability. Two salts of ABA with malonic acid (ABA-MA) and saccharin (ABA-SAC), and five cocrystals with trans-aconitic acid (ABA-TAA), 1-hydroxy-2-naphthoic acid (ABA-1HNA), pyrocatechol (ABA-PCA), resorcinol (ABA-RES) and hydroquinone (ABA-HDE) were successfully obtained. Their crystal structures were elucidated by single crystal X-ray diffraction, and these multicomponent forms were fully characterized by powder X-ray diffraction, thermal analysis and Fourier Transform Infrared spectra. Among them, ABA-TAA cocrystal shows substantial enhancements both in the solubility and intrinsic dissolution rates in different buffer solutions. In the meantime, we unexpectedly found the gelation of ABA-MA salt and ABA-SAC salt in pH 2.0 buffer solution. The gel-like materials generated on the surface of drug will suppress the release of ABA. Moreover, in vivo pharmacokinetic study on beagle dogs was conducted for ABA-TAA cocrystal preparation and ABA commercial product, and ABA-TAA cocrystal preparation shows enhanced absorption. These advantages in dissolution behaviors and bioavailability demonstrate the potential of ABA-TAA cocrystal to be a better candidate for the treatment of mCRPC compared with ABA.

Surveillance and control of meningococcal disease in the COVID-19 era: A Global Meningococcal Initiative review.

This review article incorporates information from the 4th Global Meningococcal Initiative summit meeting. Since the introduction of stringent COVID-19 infection control and lockdown measures globally in 2020, there has been an impact on IMD prevalence, surveillance, and vaccination compliance. Incidence rates and associated mortality fell across various regions during 2020. A reduction in vaccine uptake during 2020 remains a concern globally. In addition, several Neisseria meningitidis clonal complexes, particularly CC4821 and CC11, continue to exhibit resistance to antibiotics, with resistance to ciprofloxacin or beta-lactams mainly linked to modifications of gyrA or penA alleles, respectively. Beta-lactamase acquisition was also reported through horizontal gene transfer (blaROB-1) involving other bacterial species. Despite the challenges over the past year, progress has also been made on meningococcal vaccine development, with several pentavalent (serogroups ABCWY and ACWYX) vaccines currently being studied in late-stage clinical trial programmes.

Privacy-Preserved Electronic Medical Record Exchanging and Sharing: A Blockchain-Based Smart Healthcare System.

The digitization of Electronic Medical Record (EMR) provides potential access to a wealth of medical information, but also presents new challenges in privacy-preserved EMR exchanging and sharing. In this paper, we propose a blockchain-based smart healthcare system with fine-grained privacy protection for reliable data exchanging and sharing among different users. We design a blockchain-enabled dynamic access control framework combined with Local Differential Privacy (LDP) strategies to provide the attribute-based privacy protection in transaction workflow. We design four types of smart contracts in the framework to meet the requirements of anonymous transaction, dynamic access control, beneficial matching decision, and evaluation of published data in an open network. To satisfy fine-grained privacy protection, we classify sensitive attributes of EMRs into different levels and set differential privacy budgets to randomize attributes before data publishing. Also, we design data quality function to depict the disturbance incurred by LDP-based privacy preferences at the requester view, and present appropriate many-to-many matching decisions among participants for beneficial transactions. Finally, we develop a prototype system and test our approach using 200,000 real-world EMRs. Experimental results show that the proposed privacy-preserved scheme can make stable and reliable transactions between EMR publishers and requesters. The prototype system achieves individual-centric privacy configuration at the patient site, while providing error-guaranteed statistics at the requester site. Additionally, the access control policies, logs of anonymous transaction are kept in the blockchain to provide system-level traceability.

Identification of a potentially novel LncRNA-miRNA-mRNA competing endogenous RNA network in pulmonary arterial hypertension via integrated bioinformatic analysis.

AIMS: Pulmonary arterial hypertension (PAH) is a fatal cardiovascular disease with a cancer-like phenotype. Competing endogenous RNA (ceRNA) networks extensively involve in its pathological processes. But rare ceRNA networks and profound molecular mechanisms have been revealed in PAH. The aim of this study was to illuminate the ceRNA networks in PAH. MATERIALS AND METHODS: In this work, we have chosen the idiopathic PAH as an example. GSE15197 (mRNA) and GSE56914 (miRNA) from the Gene Expression Omnibus (GEO) were selected to explore key genes and novel ceRNA networks in PAH by a series of integrated bioinformatic analysis. To be more scientific, a part of pairs in identified ceRNA network were detected in hypoxia-induced HPASMCs. And the dual-luciferase assay was performed to certify the relationship between miRNAs and mRNAs. KEY FINDINGS: Totally, 311 differentially expressed genes (DEGs) were identified and functional enrichment analysis illuminated that the majority of DEGs were enriched in proliferation, anti-apoptosis, inflammation and cancer-related pathways. And 10 hub genes were determined via Cytohubba after PPI network construction. Sequentially, with stepwise reverse prediction and pan-cancer co-expression analysis from mRNA to LncRNA in TargetScan, miRNet, ENCORI (Starbase V3.0) databases, a crucially ceRNA network was identified including 14 LncRNAs, 2 miRNAs, and 3 mRNAs. Further, in hypoxia-induced HPASMCs, the alterations of mRNAs, miRNAs and LncRNAs and their relationship were in accordance with the results we identified. SIGNIFICANCE: Consequently, the unique hub genes and ceRNA network we proposed may advance our understanding of the molecular mechanisms in PAH.

Cocrystals to tune oily vitamin E into crystal vitamin E.

d-α-tocopherol (d-αToc), the most biologically active form of natural Vitamin E, is oily in appearance and unstable to oxygen. Esterification and encapsulation are generally needed to stabilize and solidify d-αToc for the purpose of its expanding applications. In this study, we propose a more effective way to stabilize and solidify d-αToc oil in one step. By cocrystallization, the melting point of d-αToc is significantly increased, such that the oily d-αToc is successfully transformed into solid form at room temperature. The single crystal structure of d-αToc was firstly uncovered and the molecular interaction in cocrystals was revealed. Crystalline Vitamin E shows high stability to light and temperature. Its spherical crystallization affords good powder flowability, which is extremely important as food or feed additives. Moreover, cocrystal Vitamin E remains the original form of tocopherol without esterification and thus has a great advantage on higher bioavailability. Cocrystallization of oily d-αToc spares the use of acetic ester and a mass of excipients, which is of great environmental importance and greatly reduces the production cost.

Genomic analysis of the meningococcal ST-4821 complex-Western clade, potential sexual transmission and predicted antibiotic susceptibility and vaccine coverage.

INTRODUCTION: The ST-4821 complex (cc4821) is a leading cause of serogroup C and serogroup B invasive meningococcal disease in China where diverse strains in two phylogenetic groups (groups 1 and 2) have acquired fluoroquinolone resistance. cc4821 was recently prevalent among carriage isolates in men who have sex with men in New York City (USA). Genome-level population studies have thus far been limited to Chinese isolates. The aim of the present study was to build upon these with an extended panel of international cc4821 isolates. METHODS: Genomes of isolates from Asia (1972 to 2017), Europe (2011 to 2018), North America (2007), and South America (2014) were sequenced or obtained from the PubMLST Neisseria database. Core genome comparisons were performed in PubMLST. RESULTS: Four lineages were identified. Western isolates formed a distinct, mainly serogroup B sublineage with alleles associated with fluoroquinolone susceptibility (MIC <0.03 mg/L) and reduced penicillin susceptibility (MIC 0.094 to 1 mg/L). A third of these were from anogenital sites in men who have sex with men and had unique denitrification gene alleles. Generally 4CMenB vaccine strain coverage was reliant on strain-specific NHBA peptides. DISCUSSION: The previously identified cc4821 group 2 was resolved into three separate lineages. Clustering of western isolates was surprising given the overall diversity of cc4821. Possible association of this cluster with the anogenital niche is worthy of monitoring given concerns surrounding antibiotic resistance and potential subcapsular vaccine escape.

Clinical observation of the combined use of propofol and etomidate in painless gastroscopy.

OBJECTIVE: This study is aims to compare the anesthetic safety of propofol combined with etomidate for painless gastroscopy. METHODS: Three hundred patients undergoing painless gastroscopy were randomly assigned to P, PE1, and PE2 groups. Patients were anesthetized with propofol (P group) or propofol combined with etomidate (volume ratio 1: 1, PE1 group; volume ratio 2: 1, PE2 group). The hemodynamics and adverse reactions were observed. The sleep quality satisfaction and nature of dreams were recorded. RESULTS: Compared with pre-anesthesia, the mean arterial pressure and heart rate of the 3 groups were significantly slower during the examination and at the end of the examination. PE1 group had a higher incidence of muscle spasm, body moving, choking, and deglutition. The incidence of hypoxemia and injection pain was higher in P group. P and PE2 group had higher sleep quality satisfaction and dream incidence after awaking. However, there was no difference in the nature of dreams among 3 groups. CONCLUSION: Our data indicate that the combination of 10 ml 1.0% propofol and 5 ml 0.2% etomidate for painless gastroscopy reduces adverse reactions while not affecting the patients respiratory function. Moreover, it is safe and effective, which is worthy of clinical application and promotion.

Meningococcal disease surveillance in the Asia-Pacific region (2020): The global meningococcal initiative.

The degree of surveillance data and control strategies for invasive meningococcal disease (IMD) varies across the Asia-Pacific region. IMD cases are often reported throughout the region, but the disease is not notifiable in some countries, including Myanmar, Bangladesh and Malaysia. Although there remains a paucity of data from many countries, specific nations have introduced additional surveillance measures. The incidence of IMD is low and similar across the represented countries (<0.2 cases per 100,000 persons per year), with the predominant serogroups of Neisseria meningitidis being B, W and Y, although serogroups A and X are present in some areas. Resistance to ciprofloxacin is also of concern, with the close monitoring of antibiotic-resistant clonal complexes (e.g., cc4821) being a priority. Meningococcal vaccination is only included in a few National Immunization Programs, but is recommended for high-risk groups, including travellers (such as pilgrims) and people with complement deficiencies or human immunodeficiency virus (HIV). Both polysaccharide and conjugate vaccines form part of recommendations. However, cost and misconceptions remain limiting factors in vaccine uptake, despite conjugate vaccines preventing the acquisition of carriage.

The everchanging epidemiology of meningococcal disease worldwide and the potential for prevention through vaccination.

Neisseria meningitidis is a major cause of bacterial meningitis and septicaemia worldwide and is associated with high case fatality rates and serious life-long complications among survivors. Twelve serogroups are recognised, of which six (A, B, C, W, X and Y) are responsible for nearly all cases of invasive meningococcal disease (IMD). The incidence of IMD and responsible serogroups vary widely both geographically and over time. For the first time, effective vaccines against all these serogroups are available or nearing licensure. Over the past two decades, IMD incidence has been declining across most parts of the world through a combination of successful meningococcal immunisation programmes and secular trends. The introduction of meningococcal C conjugate vaccines in the early 2000s was associated with rapid declines in meningococcal C disease, whilst implementation of a meningococcal A conjugate vaccine across the African meningitis belt led to near-elimination of meningococcal A disease. Consequently, other serogroups have become more important causes of IMD. In particular, the emergence of a hypervirulent meningococcal group W clone has led many countries to shift from monovalent meningococcal C to quadrivalent ACWY conjugate vaccines in their national immunisation programmes. Additionally, the recent licensure of two protein-based, broad-spectrum meningococcal B vaccines finally provides protection against the most common group responsible for childhood IMD across Europe and Australia. This review describes global IMD epidemiology across each continent and trends over time, the serogroups responsible for IMD, the impact of meningococcal immunisation programmes and future needs to eliminate this devastating disease.

Evolutionary analysis of gyrA gene from Neisseria meningitidis bacterial strains of clonal complex 4821 collected in China between 1978 and 2016.

BACKGROUND: Neisseria meningitidis (N.meningitidis) bacteria belonging to clonal complex 4821 (CC4821) have been mainly reported in China and have been characterized by a high resistance rate to ciprofloxacin (CIP). The aim of this study was to assess the evolution of the DNA gyrase A (gyrA) gene from N.meningitidis CC4821 strains collected in China between 1978 and 2016. The complete sequence of gyrA gene from 77 strains are reported in this study and analyzed in the context of publicly available sequences from N. meningitidis of other CCs as well as other Neisseria species. RESULTS: The phylogenetic analysis of CC4821 gyrA gene reveals at least 5 distinct genetic clusters. These clusters are not CC4821-specific showing that gyrA evolution is independent of CC4821 evolution. Some clusters contain sequences from other Neisseria species. Recombination within N.meningitidis strains and between Neisseria species was identified in SimPlot analysis. Finally, amino acid substitutions within GyrA protein were analyzed. Only one position, 91 (83 in E.coli gyrA gene), was linked to CIP resistance. Thirty-one additional putative resistance markers were identified, as amino acid substitutions were only found in resistant strains. CONCLUSIONS: The evolution of gyrA gene of CC4821 N.meningitidis strains is not dependent on CC4821 evolution or on CIP resistance phenotype. Only amino acid 91 is linked to CIP resistance phenotype. Finally, recombination inter- and intra-species is likely to result in the acquisition of various resistance markers, 31 of them being putatively mapped in the present study. Analyzing the evolution of gyrA gene within CC4821 strains is critical to monitor the CIP resistance phenotype and the acquisition of new resistance markers. Such studies are necessary for the control of the meningococcal disease and the development of new drugs targeting DNA gyrase.