Many persistent transmitted plant viruses, including rice stripe virus (RSV), cause serious damage to crop production worldwide. Although many reports have indicated that a successful insect-mediated ...virus transmission depends on a proper interaction between the virus and its insect vector, the mechanism(s) controlling this interaction remained poorly understood. In this study, we used RSV and its small brown planthopper (SBPH) vector as a working model to elucidate the molecular mechanisms underlying the entrance of RSV virions into SBPH midgut cells for virus circulative and propagative transmission. We have determined that this non-enveloped tenuivirus uses its non-structural glycoprotein NSvc2 as a helper component to overcome the midgut barrier(s) for RSV replication and transmission. In the absence of this glycoprotein, purified RSV virions were unable to enter SBPH midgut cells. In the RSV-infected cells, this glycoprotein was processed into two mature proteins: an amino-terminal protein (NSvc2-N) and a carboxyl-terminal protein (NSvc2-C). Both NSvc2-N and NSvc2-C interact with RSV virions. Our results showed that the NSvc2-N could bind directly to the surface of midgut lumen via its N-glycosylation sites. Upon recognition, the midgut cells underwent endocytosis followed by compartmentalization of RSV virions and NSvc2 into early and then late endosomes. The NSvc2-C triggered cell membrane fusion via its highly conserved fusion loop motifs under the acidic condition inside the late endosomes, leading to the release of RSV virions from endosomes into cytosol. In summary, our results showed for the first time that a rice tenuivirus utilized its glycoprotein NSvc2 as a helper component to ensure a proper interaction between its virions and SBPH midgut cells for its circulative and propagative transmission.
A progressive damage model is proposed herein to predict the response and failure of fiber reinforced plastic laminates subjected to impact loadings. The present model is mainly composed of three ...parts: First, quadratic stress based failure criteria are presented to predict the onset of various damage modes. Second, the post-damage softening response is controlled by a linear form damage evolution law combined with the fracture energy approach. Stiffness progressive reduction is characterized by a variable determined by equivalent displacement for each failure mode and in doing so the mesh dependency can be reduced appreciably. Third, strain rate dependency of the strength and the modulus of FRP laminated materials are also considered. Comparisons are made between the present numerical results and some available test data. It transpires that the present model predictions are in good agreement with the experimental observations in terms of force-displacement curve, deformation profile, ballistic limit and residual velocity.
•A three-dimensional progressive damage model for FRP laminates is developed.•Various failure modes such as fiber breakage, matrix cracking, in-plane shear failure and delemination are considered.•Fracture energy approach is incorporated into the model to reduce mesh dependency.•The present model predictions are in good agreement with available experimental observations.
The red stars indicate chiral centres. https://doi.org/10.1371/journal.pmed.1003252.g001 Today, although Plasmodium falciparum is resistant to chloroquine everywhere except in Haiti and Central ...America north of the Panama Canal, chloroquine remains a first-line treatment option for non-falciparum malaria 5. The quoted average values for terminal phase elimination half-lives for chloroquine (approximately 38 days) and hydroxychloroquine (approximately 54 days) may not represent significant differences 13, 14, 41. ...the initial plasma or whole-blood concentration profile in the treatment of acute illness is determined mainly by distribution processes and not by drug elimination 13, 16, 18, 20. ...plasma levels (with adequate centrifugation of blood samples at 2,000g for >10 minutes) are half those in serum. The exact mechanism of antiviral action is unclear, as these drugs may interfere with nearly every step of cellular infection and replication—i.e., viral fusion, viral penetration, nucleic acid replication, viral protein glycosylation, virus assembly, new virus particle transport, and virus release 29, 50, 51.
This study aimed to evaluate cone-beam computed tomography setup errors during cervical cancer treatment and the effects of these errors on acute radiation toxicity and treatment efficacy. A total of ...170 cervical cancer patients were randomly divided into image-guided radiation therapy (IGRT; 86 patients) and intensity-modulated radiation therapy (IMRT; 84 patients) groups to receive IGRT and IMRT, respectively. After correcting setup errors for the 86 patients in the IGRT group, the X-, Y- and Z-axis errors were smaller than the corresponding errors before correction (P < 0.01, P < 0.05, and P < 0.05, respectively). The setup errors unevenly influenced the affected organs and dosage distributions in the targeted regions. The frequencies of patients with grade 0 or I urinary toxicity were 86.0% (74/86) and 44.0% (37/84) in the IGRT and IMRT groups, respectively (P < 0.01), whereas the frequencies of patients with grade 0 or I gastrointestinal toxicity were 83.7% (72/86) and 53.6% (45/84) in the IGRT and IMRT groups, respectively (P < 0.01). The two groups had similar response rates (P > 0.05). IGRT significantly corrected and reduced setup errors during cervical cancer treatment and enhanced the dosage distribution accuracy within the affected organs and targeted regions. IGRT can reduce the adverse effect of radiotherapy, thereby achieving improved efficacy during cervical cancer treatment.
Shortages of personal protective equipment during the coronavirus disease 2019 (COVID-19) pandemic have led to the extended use or reuse of single-use respirators and surgical masks by frontline ...healthcare workers. The evidence base underpinning such practices warrants examination.
To synthesize current guidance and systematic review evidence on extended use, reuse, or reprocessing of single-use surgical masks or filtering face-piece respirators.
We used the World Health Organization, the European Centre for Disease Prevention and Control, the US Centers for Disease Control and Prevention, and Public Health England websites to identify guidance. We used Medline, PubMed, Epistemonikos, Cochrane Database, and preprint servers for systematic reviews.
Two reviewers conducted screening and data extraction. The quality of included systematic reviews was appraised using AMSTAR-2. Findings were narratively synthesized.
In total, 6 guidance documents were identified. Levels of detail and consistency across documents varied. They included 4 high-quality systematic reviews: 3 focused on reprocessing (decontamination) of N95 respirators and 1 focused on reprocessing of surgical masks. Vaporized hydrogen peroxide and ultraviolet germicidal irradiation were highlighted as the most promising reprocessing methods, but evidence on the relative efficacy and safety of different methods was limited. We found no well-established methods for reprocessing respirators at scale.
Evidence on the impact of extended use and reuse of surgical masks and respirators is limited, and gaps and inconsistencies exist in current guidance. Where extended use or reuse is being practiced, healthcare organizations should ensure that policies and systems are in place to ensure these practices are carried out safely and in line with available guidance.
Several quinoline and structurally related antimalarial drugs are associated with cardiovascular side effects, particularly hypotension and electrocardiographic QT interval prolongation. A prolonged ...QT interval is a sensitive but not specific risk marker for the development of Torsade de Pointes-a potentially lethal polymorphic ventricular tachyarrhythmia. The increasing use of quinoline and structurally related antimalarials in mass treatments to eliminate malaria rapidly highlights the need to review their cardiovascular safety profiles.
The primary objective of this systematic review was to describe the documented clinical and electrocardiographic cardiovascular side effects of quinine, mefloquine, lumefantrine, piperaquine, halofantrine, chloroquine, sulfadoxine-pyrimethamine, amodiaquine, and primaquine. Trials in healthy subjects or patients with Plasmodium falciparum or P. vivax infection were included if at least two ECGs were conducted during the trial. All trial designs were included except case reports and pooled analyses. Secondary outcomes were the methods adopted by trials for measuring and reporting the QT interval.
Data from trials published between 1982 and July 2016 were included. A total of 177 trials met the inclusion criteria. 35,448 participants received quinoline antimalarials in these trials, of which 18,436 participants underwent ECG evaluation. Subjects with co-medication use or comorbidities including cardiovascular disease were excluded from the majority of trials. Dihydroartemisinin-piperaquine was the drug most studied (5083 participants). Despite enormous use over the past 60 years, only 1076, 452, and 150 patients had ECG recordings reported in studies of chloroquine, amodiaquine, and primaquine respectively. Transiently high concentrations of quinine, quinidine, and chloroquine following parenteral administration have all been associated with hypotension, but there were no documented reports of death or syncope attributable to a cardiovascular cause, nor of electrocardiographic recordings of ventricular arrhythmia in these trials. The large volume of missing outcome information and the heterogeneity of ECG interval reporting and measurement methodology did not allow pooled quantitative analysis of QT interval changes.
No serious cardiac adverse effects were recorded in malaria clinical trials of 35,548 participants who received quinoline and structurally related antimalarials with close follow-up including 18,436 individuals who underwent ECG evaluation. While these findings provide further evidence of the rarity of serious cardiovascular events after treatment with these drugs, they also underscore the need for continued strengthening of pharmacovigilance systems for robust detection of rare drug adverse events in real-world populations. A standardised approach to measurement and reporting of ECG data in malaria trials is also needed.
PROSPERO CRD42016036678.
Outcomes of surgical treated patients with giant retrocerebellar arachnoid cysts with the available typically preferred techniques frequently are unsatisfactory.
We hypothesized that a pressure ...gradient may exist between the cyst and the ventricular system that may be responsible for the posterior fossa–related symptoms and headaches, and, if so, that connecting both cavities by means of a shunt catheter (i.e., cystoventricular stent), the pressure differences would equilibrate and the symptoms resolve. To prove our hypothesis, we decided to simultaneously monitor the intracyst pressure and the intraventricular pressure.
This was a retrospective chart review analysis of 5 consecutive patients with giant retrocerebellar arachnoid cysts treated between 2014 and 2016.
Four patients underwent 3 days of continuous intracranial pressure monitoring, and 1 patient was monitored in the surgical suit. Cyst and ventricular pressures tended to be within normal accepted values in all patients, and a pressure gradient was noticed only in the 2 patients with previous cyst surgeries. All patients were treated with a cystoventricular stent, and overall, had long-term sustained good outcomes, with resolution of symptoms in 3 and significant improvement in 2.
Patients with symptomatic large retrocerebellar arachnoid cysts do not seem to have increased intracranial pressure, and regardless of the presence or absence of a pressure gradient between the cyst and the ventricles, a cystoventricular stent seems to be effective and the best first surgical option to offer.
•Retrocerebellar arachnoid cysts do not seem to cause increased intracranial pressure.•A cystoventricular stent is an effective and best first surgical option for giant retrocerebellar arachnoid cysts.•There seems to exist no pressure gradient between retrocerebellar arachnoid cysts and the ventricular system.
Background Enhanced recovery (ER) pathways have become increasingly integrated into surgical practice. Studies that compare ER and traditional pathways often focus on outcomes confined to inpatient ...hospitalization and rarely assess a patient's functional recovery. The aim of this study was to compare functional outcomes for patients treated on an Enhanced Recovery in Liver Surgery (ERLS) pathway vs a traditional pathway. Study Design One hundred and eighteen hepatectomy patients rated symptom severity and life interference using the validated MD Anderson Symptom Inventory preoperatively and postoperatively at every outpatient visit until 31 days after surgery. The ERLS protocol included patient education, narcotic-sparing anesthesia and analgesia, diet advancement, restrictive fluid administration, early ambulation, and avoidance of drains and tubes. Results Seventy-five ERLS pathway patients were clinically comparable with 43 patients simultaneously treated on a traditional pathway. The ERLS patients reported lower immediate postoperative pain scores and experienced fewer complications and decreased length of stay. As measured by symptom burden on life interference, ERLS patients were more likely to return to baseline functional status in a shorter time interval. The only independent predictor of faster return to baseline interference levels was treatment on an ERLS pathway (p = 0.021; odds ratio = 2.62). In addition, ERLS pathway patients were more likely to return to intended oncologic therapy (95% vs 87%) at a shorter time interval compared to patients on the traditional pathway (44.7 vs 60.2 days). Conclusions In oncologic liver surgery, enhanced recovery's primary mechanism of action is reduction in life interference by postoperative surgical symptoms, allowing patients to return sooner to normal function and adjuvant cancer therapies.
•Impedance features for 316L stainless steel in hot concentrated seawater.•Pitting is under mixed control of charge transfer and diffusion processes.•Thin salt layer forms on the electrode surface ...and retards the oxygen diffusion.•Pits propagate slowly in the simulated distillation environments.
The corrosion behaviour of 316L stainless steel was studied in the concentrated artificial seawater at 72°C, i.e., the simulated low temperature-multi effect distillation environments, by using electrochemical measurement techniques. The corrosion state changes from spontaneous passivation to pitting after about 1150h of immersion. Pitting corrosion is under mixed control of charge transfer and diffusion processes in the long-term immersion. The salt deposits retard the diffusion of oxygen to the metal surface. The pit depth only reaches about 38μm after one year of immersion due to the alloying effect of Mo, low dissolved oxygen levels and weak occlusion states.
Deep learning-based approaches have been paramount in recent years, mainly due to their outstanding results in several application domains, ranging from face and object recognition to handwritten ...digit identification. Convolutional neural networks (CNNs) have attracted a considerable attention since they model the intrinsic and complex brain working mechanisms. However, one main shortcoming of such models concerns their overfitting problem, which prevents the network from predicting unseen data effectively. In this paper, we address this problem by means of properly selecting a regularization parameter known as dropout in the context of CNNs using meta-heuristic-driven techniques. As far as we know, this is the first attempt to tackle this issue using this methodology. Additionally, we also take into account a default dropout parameter and a dropout-less CNN for comparison purposes. The results revealed that optimizing dropout-based CNNs is worthwhile, mainly due to the easiness in finding suitable dropout probability values, without needing to set new parameters empirically.
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