The SARS-CoV-2 Omicron variant has demonstrated enhanced transmissibility and escape of vaccine-derived immunity. Although first-generation vaccines remain effective against severe disease and death, ...robust evidence on vaccine effectiveness (VE) against all Omicron infections, irrespective of symptoms, remains sparse. We used a community-wide serosurvey with 5,310 subjects to estimate how vaccination histories modulated risk of infection in infection-naive Hong Kong during a large wave of Omicron BA.2 epidemic in January-July 2022. We estimated that Omicron infected 45% (41-48%) of the local population. Three and four doses of BNT162b2 or CoronaVac were effective against Omicron infection 7 days after vaccination (VE of 48% (95% credible interval 34-64%) and 69% (46-98%) for three and four doses of BNT162b2, respectively; VE of 30% (1-66%) and 56% (6-97%) for three and four doses of CoronaVac, respectively). At 100 days after immunization, VE waned to 26% (7-41%) and 35% (10-71%) for three and four doses of BNT162b2, and to 6% (0-29%) and 11% (0-54%) for three and four doses of CoronaVac. The rapid waning of VE against infection conferred by first-generation vaccines and an increasingly complex viral evolutionary landscape highlight the necessity for rapidly deploying updated vaccines followed by vigilant monitoring of VE.
Freshwater availability is changing worldwide. Here we quantify 34 trends in terrestrial water storage (TWS) observed by the Gravity Recovery and Climate Experiment (GRACE) satellites during ...2002-2016 and categorize their drivers as natural interannual variability, unsustainable groundwater consumption, or climate change. Several of these trends had been lacking thorough investigation and attribution, including massive changes in northwestern China and the Okavango delta. Others are consistent with climate model predictions. This observation-based assessment of how the world's water landscape is responding to human impacts and climate variations provides a blueprint for evaluating and predicting emerging threats to water and food security.
Both endoscopic obturation and transjugular intrahepatic portosystemic shunts (TIPSs) have proven to be effective in preventing rebleeding from gastric varices. This study compared the efficacy and ...complications of these modalities.
Cirrhotic patients with acute bleeding from gastric varices were considered for inclusion. After initial control, eligible patients were randomly allocated to two groups: TIPS (n = 35) and obturation using cyanoacrylate (n = 37). In the cyanoacrylate group, treatment was repeated regularly until gastric varices were obliterated. Patients of both groups received regular follow-up. The end points were gastric variceal rebleeding or death.
Stent shunt insertion was successful in all TIPS patients, and mean portal pressure gradient decreased from 21.4 +/- 7.5 mm Hg to 7.5 +/- 3.5 mm Hg ( P < 0.001). Variceal obliteration was achieved in 19 patients in the cyanoacrylate group (51 %) compared with seven TIPS patients (20 %) ( P < 0.02). After a median follow up of 33 months, upper gastrointestinal bleeding occurred in 15 TIPS patients (43 %) and 22 cyanoacrylate patients (59 %) ( P = 0.12). Rebleeding from gastric varices was encountered in four TIPS patients (11 %) and 14 cyanoacrylate patients (38 %) ( P = 0.014; odds ratio 3.6, 95 %CI 1.2 - 11.1). Blood transfusion requirements were lower in the TIPS group than in the cyanoacrylate group ( P < 0.01). Survival and frequency of complications were similar in both groups.
TIPS proved more effective than glue injection in preventing rebleeding from gastric varices, with similar survival and frequency of complications.
This article presents an overview of the developments in stainless steels made since the 1990s. Some of the new applications that involve the use of stainless steel are also introduced.
A brief ...introduction to the various classes of stainless steels, their precipitate phases and the status quo of their production around the globe is given first. The advances in a variety of subject areas that have been made recently will then be presented. These recent advances include (1) new findings on the various precipitate phases (the new J phase, new orientation relationships, new phase diagram for the Fe–Cr system, etc.); (2) new suggestions for the prevention/mitigation of the different problems and new methods for their detection/measurement and (3) new techniques for surface/bulk property enhancement (such as laser shot peening, grain boundary engineering and grain refinement). Recent developments in topics like phase prediction, stacking fault energy, superplasticity, metadynamic recrystallisation and the calculation of mechanical properties are introduced, too. In the end of this article, several new applications that involve the use of stainless steels are presented. Some of these are the use of austenitic stainless steels for signature authentication (magnetic recording), the utilisation of the cryogenic magnetic transition of the sigma phase for hot spot detection (the Sigmaplugs), the new Pt-enhanced radiopaque stainless steel (PERSS) coronary stents and stainless steel stents that may be used for magnetic drug targeting.
Besides recent developments in conventional stainless steels, those in the high-nitrogen, low-Ni (or Ni-free) varieties are also introduced. These recent developments include new methods for attaining very high nitrogen contents, new guidelines for alloy design, the merits/demerits associated with high nitrogen contents, etc.
While a number of human coronaviruses are believed to be originated from ancestral viruses in bats, it remains unclear if bat coronaviruses are ready to cause direct bat-to-human transmission. Here, ...we report the isolation of a MERS-related coronavirus, Tylonycteris-bat-CoV-HKU4, from lesser bamboo bats. Tylonycteris-bat-CoV-HKU4 replicates efficiently in human colorectal adenocarcinoma and hepatocarcinoma cells with cytopathic effects, and can utilize human-dipeptidyl-peptidase-4 and dromedary camel-dipeptidyl-peptidase-4 as the receptors for cell entry. Flow cytometry, co-immunoprecipitation and surface plasmon resonance assays show that Tylonycteris-bat-CoV-HKU4-receptor-binding-domain can bind human-dipeptidyl-peptidase-4, dromedary camel-dipeptidyl-peptidase-4, and Tylonycteris pachypus-dipeptidyl-peptidase-4. Tylonycteris-bat-CoV-HKU4 can infect human-dipeptidyl-peptidase-4-transgenic mice by intranasal inoculation with self-limiting disease. Positive virus and inflammatory changes were detected in lungs and brains of infected mice, associated with suppression of antiviral cytokines and activation of proinflammatory cytokines and chemokines. The results suggest that MERS-related bat coronaviruses may overcome species barrier by utilizing dipeptidyl-peptidase-4 and potentially emerge in humans by direct bat-to-human transmission.
Healthcare workers (HCWs) use personal protective equipment (PPE) in Ebola virus disease (EVD) situations. However, preventing the contamination of HCWs and the environment during PPE removal ...crucially requires improved strategies. This study aimed to compare the efficacy of three PPE ensembles, namely, Hospital Authority (HA) Standard Ebola PPE set (PPE1), Dupont Tyvek Model, style 1422A (PPE2), and HA isolation gown for routine patient care and performing aerosol-generating procedures (PPE3) to prevent EVD transmission by measuring the degree of contamination of HCWs and the environment.
A total of 59 participants randomly performed PPE donning and doffing. The trial consisted of PPE donning, applying fluorescent solution on the PPE surface, PPE doffing of participants, and estimation of the degree of contamination as indicated by the number of fluorescent stains on the working clothes and environment. Protocol deviations during PPE donning and doffing were monitored.
PPE2 and PPE3 presented higher contamination risks than PPE1. Environmental contaminations such as those originating from rubbish bin covers, chairs, faucets, and sinks were detected. Procedure deviations were observed during PPE donning and doffing, with PPE1 presenting the lowest overall deviation rate (%) among the three PPE ensembles (
0.05).
Contamination of the subjects' working clothes and surrounding environment occurred frequently during PPE doffing. Procedure deviations were observed during PPE donning and doffing. Although PPE1 presented a lower contamination risk than PPE2 and PPE3 during doffing and protocol deviations, the design of PPE1 can still be further improved. Future directions should focus on designing a high-coverage-area PPE with simple ergonomic features and on evaluating the doffing procedure to minimise the risk of recontamination. Regular training for users should be emphasised to minimise protocol deviations, and in turn, guarantee the best protection to HCWs.
Otomycosis is a superficial infection of the ear caused by fungi. The disease may occur in the pinna, external auditory canal and tympanic membrane of humans and animals.
Aspergillus niger
and
...Candida albicans
are the most prevalent fungal species responsible for otomycosis. In our study, the potential antifungal properties of a series of Schiff bases was examined. The synthesized compounds (
1-14
) were investigated for their minimum inhibitory concentration, minimum fungicidal concentration and zone of clearance against
Aspergillus niger
and
Candida albicans
. Compounds
5
and
6
with alkyl chain containing 6 or 7 carbon atoms exhibited an obvious fungicidal activity with the MIC/MFC ratio of 2. Zone of clearance study also demonstrated that both compounds
5
and
6
produced noticeable clear zones against the tested fungi as compared to fluconazole. The time-kill kinetic study showed that
Candida albicans
colonies were reduced by more than 3 logs after 24 h exposure to compound
5
at 4 and 8 × MIC levels. Both compounds
5
and
6
at a concentration of 50 μg mL
−1
exhibited satisfactory cell viability towards human skin keratinocytes. Our results suggest that these compounds may be considered as potential drug candidates for the treatment of
Aspergillus niger
and
Candida albicans
ear infections.
Two substituted 4-pyridylmethylene-4′-aniline Schiff bases showed antifungal activity against.
Aspergillus niger
and
Candida albicans
. They may be useful for the development of safe drug candidates for
A. niger
and
C. albicans
cases of otomycosis.
MicroRNAs (miRNAs) regulate mRNA stability and protein expression, and certain miRNAs have been demonstrated to act either as oncogenes or tumor suppressors. Differential miRNA expression signatures ...have been documented in many human cancers but the role of miRNAs in endometrioid endometrial cancer (EEC) remains poorly understood. This study identifies significantly dysregulated miRNAs of EEC cells, and characterizes their impact on the malignant phenotype. We studied the expression of 365 human miRNAs using Taqman low density arrays in EECs and normal endometriums. Candidate differentially expressed miRNAs were validated by quantitative real‐time PCR. Expression of highly dysregulated miRNAs was examined in vitro through the effect of anti‐/pre‐miRNA transfection on the malignant phenotype. We identified 16 significantly dysregulated miRNAs in EEC and 7 of these are novel findings with respect to EEC. Antagonizing the function of miR‐7, miR‐194 and miR‐449b, or overexpressing miR‐204, repressed migration, invasion and extracellular matrix‐adhesion in HEC1A endometrial cancer cells. FOXC1 was determined as a target gene of miR‐204, and two binding sites in the 3′‐untranslated region were validated by dual luciferase reporter assay. FOXC1 expression was inversely related to miR‐204 expression in EEC. Functional analysis revealed the involvement of FOXC1 in migration and invasion of HEC1A cells. Our results present dysfunctional miRNAs in endometrial cancer and identify a crucial role for miR‐204‐FOXC1 interaction in endometrial cancer progression. This miRNA signature offers a potential biomarker for predicting EEC outcomes, and targeting of these cancer progression‐ and metastasis‐related miRNAs offers a novel potential therapeutic strategy for the disease.
Fibroblast growth factors (FGFs) and their receptors are significant components during fundamental cellular processes. FGF18 plays a distinctive role in modulating the activity of both tumor cells ...and tumor microenvironment. This study aims to comprehensively investigate the expression and functional role of FGF18 in gastric cancer (GC) and elucidate its regulatory mechanisms. The upregulation of FGF18 was detected in seven out of eleven (63.6%) GC cell lines. In primary GC samples, FGF18 was overexpressed in genomically stable and chromosomal instability subtypes of GC and its overexpression was associated with poor survival. Knocking down FGF18 inhibited tumor formation abilities, induced G1 phase cell cycle arrest and enhanced anti-cancer drug sensitivity. Expression microarray profiling revealed that silencing of FGF18 activated ATM pathway but quenched TGF-β pathway. The key factors that altered in the related signaling were validated by western blot and immunofluorescence. Meanwhile, treating GC cells with human recombinant FGF18 or FGF18-conditioned medium accelerated tumor growth through activation of ERK-MAPK signaling. FGF18 was further confirmed to be a direct target of tumor suppressor, miR-590-5p. Their expressions showed a negative correlation in primary GC samples and more importantly, re-overexpression of FGF18 partly abolished the tumor-suppressive effect of miR-590-5p. Our study not only identified that FGF18 serves as a novel prognostic marker and a therapeutic target in GC but also enriched the knowledge of FGF-FGFR signaling during gastric tumorigenesis.
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