BackgroundThe goal of this study was to characterize viral loads and factors affecting viral clearance in persons with severe influenza MethodsThis was a 1-year prospective, observational study ...involving consecutive adults hospitalized with influenza. Nasal and throat swabs were collected at presentation, then daily until 1 week after symptom onset. Real-time reverse-transcriptase polymerase chain reaction to determine viral RNA concentration and virus isolation were performed. Viral RNA concentration was analyzed using multiple linear or logistic regressions or mixed-effect models ResultsOne hundred forty-seven inpatients with influenza A (H3N2) infection were studied (mean age ± standard deviation, 72±16 years). Viral RNA concentration at presentation positively correlated with symptom scores and was significantly higher than that among time-matched outpatients (control subjects). Patients with major comorbidities had high viral RNA concentration even when presenting >2 days after symptom onset (mean ± standard deviation, 5.06±1.85 vs 3.62±2.13 log10 copies/mL; P=.005; β, +0.86 95% confidence interval, +0.03 to +1.68). Viral RNA concentration demonstrated a nonlinear decrease with time; 26% of oseltamivir-treated and 57% of untreated patients had RNA detected at 1 week after symptom onset. Oseltamivir started on or before symptom day 4 was independently associated with an accelerated decrease in viral RNA concentration (mean β standard error, −1.19 0.43 and −0.68 0.33 log10 copies/mL for patients treated on day 1 and days 2–3, respectively; P<.05) and viral RNA clearance at 1 week (odds ratio, 0.10 95% confidence interval, 0.03–0.35 and 0.30 0.10–0.90 for patients treated on day 1–2 and day 3–4, respectively). Conversely, major comorbidities and systemic corticosteroid use for asthma or chronic obstructive pulmonary disease exacerbations were associated with slower viral clearance. Viral RNA clearance was associated with a shorter hospital stay (7.0 vs 13.5 days; P=.001) ConclusionPatients hospitalized with severe influenza have more active and prolonged viral replication. Weakened host defenses slow viral clearance, whereas antivirals started within the first 4 days of illness enhance viral clearance
Upper gastrointestinal bleeding (UGIB), especially peptic ulcer bleeding, remains one of the most important cause of hospitalisation and mortality world wide. In Asia, with a high prevalence of ...Helicobacter pylori infection, a potential difference in drug metabolism, and a difference in clinical management of UGIB due to variable socioeconomic environments, it is considered necessary to re-examine the International Consensus of Non-variceal Upper Gastrointestinal Bleeding with emphasis on data generated from the region. The working group, which comprised experts from 12 countries from Asia, recommended the use of the Blatchford score for selection of patients who require endoscopic intervention and which would allow early discharge of patients at low risk. Patients' comorbid conditions should be included in risk assessment. A pre-endoscopy proton pump inhibitor (PPI) is recommended as a stop-gap treatment when endoscopy within 24 h is not available. An adherent clot on a peptic ulcer should be treated with endoscopy combined with a PPI if the clot cannot be removed. Routine repeated endoscopy is not recommended. High-dose intravenous and oral PPIs are recommended but low-dose intravenous PPIs should be avoided. COX-2 selective non-steroidal anti-inflammatory drugs combined with a PPI are recommended for patients with very high risk of UGIB. Aspirin should be resumed soon after stabilisation and clopidogrel alone is no safer than aspirin plus a PPI. When dual antiplatelet agents are used, prophylactic use of a PPI reduces the risk of adverse gastrointestinal events.
Background & Aims The epidemiology of Helicobacter pylori infection has changed with improvements in sanitation and methods of eradication. We performed a systematic review and meta-analysis to ...evaluate changes in the global prevalence of H pylori infection. Methods We performed a systematic search of the MEDLINE and EMBASE databases for studies of the prevalence of H pylori infection published from January 1, 1970 through January 1, 2016. We analyzed data based on United Nations geoscheme regions and individual countries. We used a random effects model to calculate pooled prevalence estimates with 95% confidence intervals (CIs), weighted by study size. We extrapolated 2015 prevalence estimates to obtain the estimated number of individuals with H pylori infection. Results Among 14,006 reports screened, we identified 263 full-text articles on the prevalence of H pylori infection; 184 were included in the final analysis, comprising data from 62 countries. Africa had the highest pooled prevalence of H pylori infection (70.1%; 95% CI, 62.6−77.7), whereas Oceania had the lowest prevalence (24.4%; 95% CI, 18.5−30.4). Among individual countries, the prevalence of H pylori infection varied from as low as 18.9% in Switzerland (95% CI, 13.1−24.7) to 87.7% in Nigeria (95% CI, 83.1−92.2). Based on regional prevalence estimates, there were approximately 4.4 billion individuals with H pylori infection worldwide in 2015. Conclusions In a systematic review and meta-analysis to assess the prevalence of H pylori infection worldwide, we observed large amounts of variation among regions—more than half the world’s population is infected. These data can be used in development of customized strategies for the global eradication.
Gene delivery systems are essentially necessary for the gene therapy of human genetic diseases. Gene therapy is the unique way that is able to use the adjustable gene to cure any disease. The gene ...therapy is one of promising therapies for a number of diseases such as inherited disorders, viral infection and cancers. The useful results of gene delivery systems depend open the adjustable targeting gene delivery systems. Some of successful gene delivery systems have recently reported for the practical application of gene therapy.
The recent developments of viral gene delivery systems and non-viral gene delivery systems for gene therapy have briefly reviewed. The viral gene delivery systems have discussed for the viral vectors based on DNA, RNA and oncolytic viral vectors. The non-viral gene delivery systems have also treated for the physicochemical approaches such as physical methods and chemical methods. Several kinds of successful gene delivery systems have briefly discussed on the bases of the gene delivery systems such as cationic polymers, poly(L-lysine), polysaccharides, and poly(ethylenimine)s.
The goal of the research for gene delivery system is to develop the clinically relevant vectors such as viral and non-viral vectors that use to combat elusive diseases such as AIDS, cancer, Alzheimer, etc. Next step research will focus on advancing DNA and RNA molecular technologies to become the standard treatment options in the clinical area of biomedical application.
Summary
This systematic review was performed to compare the diagnostic accuracy of vertebral fracture assessment (VFA) with that of spinal radiography for identification of vertebral fractures (VFs). ...VFA appeared to have moderate sensitivity and high specificity for detecting VFs when compared with spinal radiography.
Introduction
VFs are recognized as the hallmark of osteoporosis, and a previous VF increases the risk of a future fracture. Therefore, the timely detection of VFs is important for prevention of further fractures. This systematic review examined the diagnostic accuracy of VFA using dual X-ray absorptiometry (DXA) to identify VFs.
Methods
We searched for potentially relevant studies using electronic databases, including Ovid-Medline, Ovid-EMBASE, Cochrane library, and four Korean databases, from their inception to May 2013. We compared the diagnostic accuracy of VFA with that of spinal radiography for detection of VFs by analyzing the sensitivity and specificity using a 2 × 2 contingency table. Subgroup analyses were also performed on studies with a low risk of bias and applicability.
Results
Twelve studies were analyzed for the diagnostic accuracy of VFA. The sensitivity and specificity were 0.70–0.93 and 0.95–1.00, respectively, analyzed on a per-vertebra basis, and 0.65–1.00 and 0.74–1.00 on a per-patient basis. The sensitivity and specificity of five studies in subgroups with a low risk of bias in the intervention test were 0.70–0.84 and 0.96–0.99, respectively. In studies with a low risk of bias in the patient selection, those based on a per-vertebra basis in three studies were 0.70–0.93 and 0.96–1.00, respectively.
Conclusions
VFA had moderate sensitivity and high specificity for detecting VF when compared with spinal radiography. However, the present findings are insufficient to assess whether spinal radiography should be replaced by VFA.
A neutral gastric pH is critical for the stability of clots over bleeding arteries. We investigated the effect of preemptive infusion of omeprazole before endoscopy on the need for endoscopic ...therapy.
Consecutive patients admitted with upper gastrointestinal bleeding underwent stabilization and were then randomly assigned to receive either omeprazole or placebo (each as an 80-mg intravenous bolus followed by an 8-mg infusion per hour) before endoscopy the next morning.
Over a 17-month period, 638 patients were enrolled and randomly assigned to omeprazole or placebo (319 in each group). The need for endoscopic treatment was lower in the omeprazole group than in the placebo group (60 of the 314 patients included in the analysis 19.1% vs. 90 of 317 patients 28.4%, P=0.007). There were no significant differences between the omeprazole group and the placebo group in the mean amount of blood transfused (1.54 and 1.88 units, respectively; P=0.12) or the number of patients who had recurrent bleeding (11 and 8, P=0.49), who underwent emergency surgery (3 and 4, P=1.00), or who died within 30 days (8 and 7, P=0.78). The hospital stay was less than 3 days in 60.5% of patients in the omeprazole group, as compared with 49.2% in the placebo group (P=0.005). On endoscopy, fewer patients in the omeprazole group had actively bleeding ulcers (12 of 187, vs. 28 of 190 in the placebo group; P=0.01) and more omeprazole-treated patients had ulcers with clean bases (120 vs. 90, P=0.001).
Infusion of high-dose omeprazole before endoscopy accelerated the resolution of signs of bleeding in ulcers and reduced the need for endoscopic therapy. (ClinicalTrials.gov number, NCT00164866 ClinicalTrials.gov .).
MicroRNAs (miRNAs) have been shown to offer great potential in the diagnosis of cancer. We investigated whether plasma miRNAs could discriminate between patients with and without colorectal cancer ...(CRC).
This study was divided into three phases: (1) marker discovery using real-time PCR-based miRNA profiling on plasma, corresponding cancerous and adjacent non-cancerous colonic tissues of five patients with CRC, along with plasma from five healthy individuals as controls; (2) marker selection and validation by real-time quantitative RT-PCR on a small set of plasma; and (3) independent validation on a large set of plasma from 90 patients with CRC, 20 patients with gastric cancer, 20 patients with inflammatory bowel disease (IBD) and 50 healthy controls.
Of the panel of 95 miRNAs analysed, five were upregulated both in plasma and tissue samples. All the five miRNAs were validated on the plasma of 25 patients with CRC and 20 healthy controls. Both miR-17-3p and miR-92 were significantly elevated in the patients with CRC (p<0.0005). The plasma levels of these markers were significantly reduced after surgery in 10 patients with CRC (p<0.05). Further validation with an independent set of plasma samples (n = 180) indicated that miR-92 differentiates CRC from gastric cancer, IBD and normal subjects. This marker yielded a receiver operating characteristic curve area of 88.5%. At a cut-off of 240 (relative expression in comparison to RNU6B snRNA), the sensitivity was 89% and the specificity was 70% in discriminating CRC from control subjects.
MiR-92 is significantly elevated in plasma of patients with CRC and can be a potential non-invasive molecular marker for CRC screening.
High-temperature superconductivity in cuprates emerges out of a highly enigmatic 'pseudogap' metal phase. The mechanism of high-temperature superconductivity is probably encrypted in the elusive ...relationship between the two phases, which spectroscopically is manifested as Fermi arcs--disconnected segments of zero-energy states--collapsing into d-wave point nodes upon entering the superconducting phase. Here, we reproduce this distinct cuprate phenomenology in the 5d transition-metal oxide Sr2 IrO4 . Using angle-resolved photoemission, we show that the clean, low-temperature phase of 6-8% electron-doped Sr2 IrO4 has gapless excitations only at four isolated points in the Brillouin zone, with a predominant d-wave symmetry of the gap. Our work thus establishes a connection between the low-temperature d-wave instability and the previously reported high-temperature Fermi arcs in electron-doped Sr2 IrO4 (ref. ). Although the physical origin of the d-wave gap remains to be understood, Sr2 IrO4 is the first non-cuprate material to spectroscopically reproduce the complete phenomenology of the cuprates, thus offering a new material platform to investigate the relationship between the pseudogap and the d-wave gap.
The aim of this study was to investigate factors affecting clinical outcomes of adults hospitalised with severe seasonal influenza.
A prospective, observational cohort study was conducted over 24 ...months (2007-2008) in two acute, general hospitals. Consecutive, hospitalised adult patients were recruited and followed once their laboratory diagnosis of influenza A/B was established (based on viral antigen detection and virus isolation from nasopharyngeal aspirates collected per protocol). Outcomes studied included in-hospital death, length of stay and duration of oxygen therapy. Factors affecting outcomes were analysed using multivariate Cox proportional hazards models. Sequencing analysis on the neuraminidase gene was performed for available H1N1 isolates.
754 patients were studied (influenza A, n=539; >75% H3N2). Their mean age was 70+/-18 years; co-morbidities and serious complications were common (61-77%). Supplemental oxygen and ventilatory support was required in 401 (53.2%) and 41 (5.4%) patients, respectively. 39 (5.2%) patients died; pneumonia, respiratory failure and sepsis were the causes. 395 (52%) patients received antiviral (oseltamivir) treatment. Omission of antiviral treatment was associated with delayed presentation or negative antigen detection results. The mortality rate was 4.56 and 7.42 per 1000 patient-days in the treated and untreated patients, respectively; among those with co-morbidities, it was 5.62 and 11.64 per 1000 patient-days, respectively. In multivariate analysis, antiviral use was associated with reduced risk of death (adjusted HR (aHR) 0.27 (95% CI 0.13 to 0.55); p<0.001). Improved survival was observed with treatment started within 4 days from onset. Earlier hospital discharge (aHR 1.28 (95% CI 1.04 to 1.57); p=0.019) and faster discontinuation of oxygen therapy (aHR 1.30 (95% CI 1.01 to 1.69); p=0.043) was associated with early treatment within 2 days. Few (n=15) H1N1 isolates in this cohort had the H275Y mutation.
Antiviral treatment for severe influenza is associated with reduced mortality and improved clinical outcomes.
Solidarity means strength: In new silole luminogens, the solid aggregates are stronger emitters than isolated molecules. The solid‐state emission is tunable by varying molecular structures of the ...luminogens. Increasing bulkiness of the substituents weakens intermolecular interactions and restricts intramolecular rotations, leading to a blue shift in emission color and a great increase in emission efficiency (see examples in picture).
PDF
