•Novel coronavirus (SARS-Coronavirus-2:SARS-CoV-2) which emerged in Wuhan, China, has spread to multiple countries rapidly.•This is the first case of meningitis associated with SARS-CoV-2 who was ...brought in by ambulance.•The specific SARS-CoV-2 RNA was not detected in the nasopharyngeal swab but was detected in a CSF.•This case warns the physicians of patients who have CNS symptoms.
Novel coronavirus (SARS-Coronavirus-2:SARS-CoV-2) which emerged in Wuhan, China, has spread to multiple countries rapidly. We report the first case of meningitis associated with SARS-CoV-2 who was brought in by ambulance due to a convulsion accompanied by unconsciousness. He had never been to any foreign countries. He felt generalized fatigue and fever (day 1). He saw doctors nearby twice (day 2 and 5) and was prescribed Laninamivir and antipyretic agents, His family visited his home and found that he was unconsciousness and lying on the floor in his vomit. He was immediately transported to this hospital by ambulance (day 9). Under emergency transport, he had transient generalized seizures that lasted about a minute. He had obvious neck stiffness. The specific SARS-CoV-2 RNA was not detected in the nasopharyngeal swab but was detected in a CSF. Anti- HSV 1 and varicella-zoster IgM antibodies were not detected in serum samples. A brain MRI showed hyperintensity along the wall of right lateral ventricle and hyperintense signal changes in the right mesial temporal lobe and hippocampus, suggesting the possibility of SARS-CoV-2 meningitis. This case warns the physicians of patients who have CNS symptoms.
•A concept of AnMBR-PN/A process was proposed for mainstream treatment.•In-situ FA/FNA exposure eliminated Nitrospira while retained Nitosonomas community.••DO limitation prevented switch of the NOB ...community in the mainstream conditions.•The effluent TN of the mainstream PN/A system was lower than 10 mg-N/L.•Enhanced hydrodynamic shear force resulted in sludge settleability deterioration.
In this pilot-scale study, an innovative mainstream treatment process that couples the anaerobic membrane reactor (AnMBR) with a one-stage PN/A system was proposed for advancing the concept of carbon neutrality in the municipal wastewater treatment plant. This work demonstrates the start-up procedure of a pilot-scale one-stage PN/A system for mainstream treatment. The 255-day start-up of the one-stage PN/A system involved the cultivation of ammonium-oxidizing bacteria (AOB) from the activated sludge, suppression of nitrite-oxidizing bacteria (NOB), investigation of in-situ growth kinetics of anammox bacteria (AnAOB), and the 50-day operation of the pilot-scale AnMBR-PN/A process for natural mainstream treatment. It is verified in the pilot-scale system for the first time that the in-situ free ammonia (FA) and free nitrous acid (FNA) exposure could effectively eliminate the Nitrospira (the NOB genus) while retaining the Nitosonomas (the AOB genus) community in the suspended sludge. NOB community rebounding was not detected even at the mainstream conditions with low nitrogen concentrations (Influent ammonium concentration=38±6 mg-NH4+-N/L) by intermittent aeration to control the system dissolved oxygen (DO) below 0.5 mg/L. The results of the mainstream treatment showed that the average effluent total nitrogen (TN) in the coupled process was generally lower than 10 mg-N/L, which meets the discharge limits of most prefectures in Japan. The investigated results of the in-situ anammox bacteria (AnAOB) growth kinetics suggested that the promoted start-up strategy of taking advantage of the warm months with higher mainstream temperature to achieve the rapid in-situ growth of the AnAOB is applicable in the investigated regions. From the perspective of the removal performance of the TN and organic substance, the AnMBR-PN/A process has great potential as the layouts of the carbon-neutral mainstream wastewater treatment plants.
Display omitted
•A 1670-L mainstream IFAS type PN/A at decreasing temperatures of 25, 20 and 15°C.•The NLR was 0.21–0.24 kg-N/m3/d and the NRE was 65.9–75.4%.•Insufficient treatment capacity of AOB results in ...reduction of nitrogen removal at 15°C.•Candidatus Brocadia and Candidatus Kuenenia were main AnAOB and almost enriched on carriers.•NOB was suppressed by the strategy of intermittent aeration and low DO.
Partial nitritation-anammox (PN/A) is a promising deammonification process to develop energy-neutral wastewater treatment plants. However, the mainstream application of PN/A still faces the challenges of low nitrogen concentration and low temperatures, and has not been studied under a realistic condition of large-scale reactor (kiloliter level), real municipal wastewater (MWW) and seasonal temperatures. In this research, a pilot-scale one-stage PN/A, with integrated fixed-film activated sludge (IFAS) configuration, was operated to treat the real MWW pretreated by anaerobic membrane bioreactor. The removal efficiency of total nitrogen (TN) was 79.4%, 75.7% and 65.9% at 25, 20 and 15°C, corresponding to the effluent TN of 7.3, 9.7 and 12.0 mg/L, respectively. The suppression of ammonium-oxidizing bacteria (AOB) and anammox bacteria (AnAOB) occurred at lower temperatures, and the significant decrease in AOB treatment capacity was the reason for the poorer nitrogen removal at 15°C. Biomass retention and microbial segregation were successfully achieved. Specifically, Candidatus_Brocadia and Candidatus_Kuenenia were main AnAOB genera and mainly enriched on carriers, Nitrosomonas and uncultured f_Chitinophagaceae were main AOB genera and mainly distributed in suspended sludge and retained by sedimentation tank. Moreover, nitrite-oxidizing bacteria (NOB) were sufficiently suppressed by intermittent aeration and low dissolved oxygen, the presence of heterotrophic bacteria upgraded the PN/A to a simultaneous partial nitritation, anammox, denitrification, and COD oxidation (SNADCO) system, which improved the overall removal of TN and COD. The results of this investigation clearly evidence the strong feasibility of PN/A as a mainstream nitrogen removal process in temperate climates.
Display omitted
Display omitted
•Mass flows of C and N were redesigned by AnMBR-PN/A.•Removal efficiencies of COD and TN were 90.3%-95.1% and 75.0%-81.7%, respectively.•48.4%-63.1% of C was captured as CH4 and ...26.7%-39.7% of C was captured as sludge.•8.5%-16.1% of N was entrapped by membrane and 45.3%-58.1% of N was removed by PN/A.•AnMBR and PN/A mutually complement each other ensured excellent system performance.
A pilot-scale anaerobic membrane bioreactor (AnMBR) integrated with a one-stage partial nitritation-anammox (PN/A) reactor was operated for the treatment of municipal wastewater (MWW) at seasonal temperatures of 15–25 °C. The removal efficiencies of COD and total nitrogen (TN) were always > 90% and > 75% respectively. The methanogenesis and PN/A were identified as the primary removal pathways of COD and TN, respectively, and were suppressed at low temperatures. With the temperature dropped from 25 °C to 20 °C to 15 °C, the methane-accounted COD decreased from 63.1% to 59.6% to 48.4%, and the PN/A-accounted TN decreased from 58.1% to 51.7% to 45.3%. The AnMBR and PN/A mutually complement each other in this combined process, as the AnMBR removed 8.5%-16.1% of TN by sludge entrainment and the PN/A reactor removed 2.6%-3.4% of COD by denitrification and aerobic oxidation. These results highlighted the strong feasibility of applying the AnMBR-PN/A process to the treatment of MWW in temperate climate.
Tumor metastasis is the most common cause of cancer death. Elucidation of the mechanism of tumor metastasis is therefore important in the development of novel, effective anti-cancer therapies to ...reduce cancer mortality. Interaction between cancer cells and surrounding stromal cells in the tumor microenvironment is a key factor in tumor metastasis. Using a co-culture assay system with human prostate cancer LNCaP cells and primary human prostate stromal cells, we identified epithelial membrane protein 1 (EMP1) as a gene with elevated expression in the cancer cells. The orthotopic injection of LNCaP cells overexpressing EMP1 (EMP1-LNCaP cells) into the prostate of nude mice induced lymph node and lung metastases, while that of control LNCaP cells did not. EMP1-LNCaP cells had higher cell motility and Rac1 activity than control LNCaP cells. These results were also observed in other lines of cancer cells. We newly identified copine-III as an intracellular binding partner of EMP1. Knockdown of copine-III attenuated the increased cell motility and Rac1 activity in EMP1-LNCaP cells. Reduced cell motility and Rac1 activity following knockdown of copine-III in EMP1-LNCaP cells were recovered by re-expression of wild-type copine-III, but not of a copine-III mutant incapable of interacting with EMP1, suggesting the importance of the EMP1-copine-III interaction. Phosphorylated and activated Src and a Rac guanine nucleotide exchange factor Vav2 were found to be involved in the EMP1-induced enhancement of cell motility and Rac1 activation. Moreover, EMP1 was highly expressed in prostate cancer samples obtained from patients with higher Gleason score. These results demonstrate that upregulation of EMP1 significantly increases cancer cell migration that leads to tumor metastasis, suggesting that EMP1 may play an essential role as a positive regulator of tumor metastasis.
Major depression is often a relapsing disorder. It is therefore important to start its treatment with therapies that maximize the chance of not only getting the patients well but also keeping them ...well. We examined the associations between initial treatments and sustained response by conducting a network meta‐analysis of randomized controlled trials (RCTs) in which adult patients with major depression were randomized to acute treatment with a psychotherapy (PSY), a protocolized antidepressant pharmacotherapy (PHA), their combination (COM), standard treatment in primary or secondary care (STD), or pill placebo, and were then followed up through a maintenance phase. By design, acute phase treatment could be continued into the maintenance phase, switched to another treatment or followed by discretionary treatment. We included 81 RCTs, with 13,722 participants. Sustained response was defined as responding to the acute treatment and subsequently having no depressive relapse through the maintenance phase (mean duration: 42.2±16.2 weeks, range 24‐104 weeks). We extracted the data reported at the time point closest to 12 months. COM resulted in more sustained response than PHA, both when these treatments were continued into the maintenance phase (OR=2.52, 95% CI: 1.66‐3.85) and when they were followed by discretionary treatment (OR=1.80, 95% CI: 1.21‐2.67). The same applied to COM in comparison with STD (OR=2.90, 95% CI: 1.68‐5.01 when COM was continued into the maintenance phase; OR=1.97, 95% CI: 1.51‐2.58 when COM was followed by discretionary treatment). PSY also kept the patients well more often than PHA, both when these treatments were continued into the maintenance phase (OR=1.53, 95% CI: 1.00‐2.35) and when they were followed by discretionary treatment (OR=1.66, 95% CI: 1.13‐2.44). The same applied to PSY compared with STD (OR=1.76, 95% CI: 0.97‐3.21 when PSY was continued into the maintenance phase; OR=1.83, 95% CI: 1.20‐2.78 when PSY was followed by discretionary treatment). Given the average sustained response rate of 29% on STD, the advantages of PSY or COM over PHA or STD translated into risk differences ranging from 12 to 16 percentage points. We conclude that PSY and COM have more enduring effects than PHA. Clinical guidelines on the initial treatment choice for depression may need to be updated accordingly.
Background The tumor microenvironment, of which cancer-associated fibroblasts (CAFs) and tumor-associated macrophages (TAMs) are the major cellular components, plays an important role in tumor ...progression. This study evaluated the significance of podoplanin-positive CAFs and CD204-positive TAMs, which may reflect tumor-promoting CAFs and TAMs, as risk factors for recurrence in patients with stage I lung adenocarcinoma. Methods The expression of podoplanin in CAFs and CD204 in TAMs was analyzed by immunohistochemistry in 304 patients with stage I lung adenocarcinoma who underwent surgical resection between September 1992 and July 2004. The recurrence-free proportion (RFP) was estimated using the Kaplan-Meier method. Results The presence of podoplanin-positive CAFs and the higher number of CD204-positive TAMs were associated with a lower 5-year RFP ( P < .001 and P = .001, respectively). Podoplanin-positive CAFs were an independently statistically significant risk factor for recurrence with the highest hazard ratio (3.474, P = .029, by multivariate Cox proportional hazards model). According to subgroup analyses combining podoplanin-positive CAFs and other independent risk factors (visceral pleural invasion and intratumoral vascular invasion), the 5-year RFPs were 95.6%, 92.3%, 80.5%, and 30.3% ( P = .294, P = .067, and P < .001) for patients with zero, one, two, or three risk factors, respectively. Conclusions Podoplanin-positive CAFs were the most powerful independent risk factor for recurrence in patients with stage I lung adenocarcinoma. Podoplanin-positive CAFs may be useful for identifying patients with a high risk of recurrence who might benefit from adjuvant chemotherapy.
Although the global market of Mobile Health Apps (mHealth apps) continues to grow dramatically, most mHealth apps still not only lack evidence base but have even not been evaluated for the basic ...usability or functionality. The User Version of the Mobile App Rating Scale (uMARS) was developed to allow end users to assess mHealth apps objectively and subjectively. However, there is no Japanese version of uMARS to date.
The purpose of this study is (1) to develop a validated Japanese version of uMARS and (2) to assess the translated version’s reliability and validity in evaluating mHealth apps.
The original uMARS was adapted for Japanese use by four specialists using universalist cross-cultural methods. Translation/back-translation was reviewed by the author of the original version of uMARS, and confirmed. Its reliability and validity were further evaluated as part of a prospective cohort study of postoperative patients using a new mHealth app.
Conceptual equivalence was analyzed and all items in all subcategories of the original uMARS were included in the Japanese version. Internal consistency was deemed acceptable for all subscales of objective and subjective quality with a Cronbach's alpha of 0.75–0.85. Test-retest reliability of all subscales was also acceptable with intraclass correlation coefficients (ICCs) of 0.57–0.88. Convergent/divergent validity and concurrent validity were also considered acceptable.
A Japanese version of uMARS was cross-culturally validated and found to be as reliable as the original uMARS. This Japanese version of uMARS is expected to become a standard tool in assessing the quality of mHealth apps in Japan.
In endometriosis, M2 macrophages (MΦ) are dominant and promote the development of endometriosis lesions. However, the factor(s) which induces M2 MΦ are unknown. In the present study, we focused on ...interleukin (IL)-33, known as an alarmin and investigated its expression and its role in endometriosis, especially from the point of the relevance with MΦ. The expression of IL-33 in endometriosis lesions was examined by immunohistochemistry. The cystic fluid of ovarian cysts/tumors was obtained and used to measure IL-33 concentration. Endometriotic stromal cells (ESC) and MΦ derived from patients were used for in vitro experiments. IL-33 was detected in the epithelium and stromal cells of endometriotic lesions. The mean IL-33 concentration in the cystic fluid of endometriomas was significantly higher than that in non-endometriomas (2.2 ng/ml vs. 0.02 ng/ml, P < 0.01). IL-1β induced IL-33 mRNA expression in ESC via p38 MAPK activation. With IL-33 stimulation, peritoneal MΦ polarized to M2 MΦ and produced IL-1β mRNA with a 2.2-fold increase, which was negated with soluble ST2, a decoy receptor of IL-33. IL-33, derived from endometriotic lesions, stimulated MΦ to produce IL-1β, which results in increasing IL-33 production in ESC. This cycle may continue to exacerbate the endometriotic lesions.
Problem
Pre‐ovulatory mature follicles are not readily induced from gonadotropin (Gn)‐independent early follicles in the poor ovarian response (POR) state, characterized by reduced number of ...retrieved oocytes. Bone morphogenetic protein (BMP), which is expressed in the ovary, contributes to early folliculogenesis, but its precise underlying mechanism remains unknown. The purpose of this study was to examine the effects of BMP‐2 on granulosa cells (GCs) of Gn‐independent early follicles.
Method of study
Sphingosine kinase 1 (SPHK1) localization, which produces sphingosine 1‐phosphate (S1P), was examined in human early follicles by immunohistochemistry. SPHK1 mRNA levels were examined in Gn‐independent bovine GCs (bGCs) and human nonluteinized granulosa cell line (HGrC1) cells. Phosphorylated Yes‐associated protein (YAP) expression was evaluated by Western blot, and its localization was evaluated immunocytochemically in bGCs. Verteporfin, a selective YAP inhibitor, was used to explore the influence of YAP on BMP‐2‐induced bGCs proliferation.
Results
The expression of SPHK1 was observed in human GCs of primary and secondary follicles. BMP‐2 significantly induced SPHK1 mRNA expression in bGCs and HGrC1 cells. Both BMP‐2 and S1P decreased phosphorylated YAP protein levels and induced the nuclear translocation of YAP significantly, thereby increasing the number of bGCs by suppressing the Hippo pathway. This BMP‐2‐induced cell proliferation was completely blocked by verteporfin.
Conclusion
This is a first report showing that BMP‐2 up‐regulated SPHK1 mRNA expression in GCs and promoted GCs proliferation through Hippo pathway suppression. Thus, BMP‐2 contributes to Gn‐independent folliculogenesis via SPHK1, suggesting a potential therapeutic strategy for the POR patients with follicular dysgenesis.
PDF
