The role of autotransplantation in end-stage hepatic alveolar echinococcosis (AE) is unclear. We aimed to present our 15-case experience and propose selection criteria for autotransplantation. All ...patients were considered to have unresectable hepatic AE by conventional resection due to critical invasion to retrohepatic vena cava, hepatocaval region along with three hepatic veins, and the tertiary portal and arterial branches. All patients successfully underwent ex vivo extended right hepatectomy and autotransplantation without intraoperative mortality. The median autograft weight was 706 g (380–1000 g); operative time was 15.5 hours (11.5–20.5 hours); and anhepatic time was 283.8 minutes (180–435 min). Postoperative hospital stay was 32.3 days (12–60 days). Postoperative complication Clavien–Dindo grade IIIa or higher occurred in three patients including one death that occurred 12 days after the surgery due to acute liver failure. One patient was lost to follow-up after the sixth month. Thirteen patients were followed for a median of 21.6 months with no relapse. This is the largest reported series of patients with end-stage hepatic AE treated with liver autotransplantation. The technique requires neither organ donor nor postoperative immunosuppressant. The early postoperative mortality was low with acceptable morbidity. Preoperative precise assessment and strict patient selection are of utmost importance.
Prohibitin (PHB) is indispensable for Ras-induced Raf-1 activation, cell migration and growth; however, the exact role of PHB in the molecular pathogenesis of cancer metastasis remains largely ...unexamined. Here, we found a positive correlation between plasma membrane-associated PHB and the clinical stages of cancer. The level of PHB phosphorylated at threonine 258 (T258) and tyrosine 259 (Y259) in human cancer-cell membranes correlated with the invasiveness of cancer cells. Overexpression of phosphorylated PHB (phospho-PHB) in the lipid-raft domain of the cell membrane enhanced cell migration/invasion through PI3K/Akt and Raf-1/ERK activation. It also enhanced epithelial-mesenchymal transition, matrix metalloproteinase-2 activity and invasiveness of cancer cells in vitro. Immunoprecipitation analysis demonstrated that phospho-PHB associated with Raf-1, Akt and Ras in the membrane and was essential for the activation of Raf-1 signaling by Ras. Mice implanted with cancer cells stably overexpressing PHB in the plasma membrane showed enlarged cervical tumors, enhanced metastasis and shorter survival time compared with mice implanted with cancer cells without PHB overexpression. Dephosphorylation of PHB at T258 by site-directed mutagenesis diminished the in vitro and in vivo effects of PHB. These results suggest that increase in phospho-PHB T258 in the raft domain of the plasma membrane has a role in the Ras-driven activation of PI3K/Akt and Raf-1/ERK-signaling cascades and results in the promotion of cancer metastasis.
Objectives
To evaluate the negative effect of physical restraint use on the hospital outcomes of older patients.
Design
A retrospective cohort study.
Setting
Internal medicine wards of a tertiary ...medical center in Taiwan.
Participants
Subjects aged 65 years and over who were admitted during April to Dec 2017 were recruited for study.
Measurements
Demographic data, geriatric assessments (polypharmacy, visual impairment, hearing impairment, activities of daily living before and after admission, risk of pressure sores, change in consciousness level, mood condition, history of falls in the previous year, risk of malnutrition and pain) and hospital conditions (admission route, department of admission, length of hospital stay and mortality) were collected for analysis.
Results
Overall, 4,352 participants (mean age 78.7±8.7 years, 60.2% = male) were enrolled and 8.3% had physical restraint. Results of multivariate logistic regression showed that subjects with physical restraints were at greater risk of functional decline (adjusted odds ratio 2.136, 95% confidence interval 1.322–3.451, p=0.002), longer hospital stays (adjusted odds ratio 5.360, 95% confidence interval 3.627–7.923, p<0.001) and mortality (adjusted odds ratio 4.472, 95% confidence interval 2.794–7.160, p<0.001) after adjustment for covariates.
Conclusion
The use of physical restraints during hospitalization increased the risk of adverse hospital outcomes, such as functional decline, longer length of hospital stay and mortality.
The measurement of the energy spectrum of cosmic ray helium nuclei from 70 GeV to 80 TeV using 4.5 years of data recorded by the Dark Matter Particle Explorer (DAMPE) is reported in this work. A ...hardening of the spectrum is observed at an energy of about 1.3 TeV, similar to previous observations. In addition, a spectral softening at about 34 TeV is revealed for the first time with large statistics and well controlled systematic uncertainties, with an overall significance of 4.3σ. The DAMPE spectral measurements of both cosmic protons and helium nuclei suggest a particle charge dependent softening energy, although with current uncertainties a dependence on the number of nucleons cannot be ruled out.
Objectives
To determine whether nutritional status can predict 3-year cognitive and functional decline, as well as 4-year all-cause mortality in older adults.
Design
Prospectively longitudinal cohort ...study.
Setting and participants
The study recruited 354 men aged 65 years and older in the veteran’s retirement community.
Measures
Baseline nutritional status was evaluated using the Mini-Nutritional Assessment-Short Form (MNA-SF). Cognitive function and Activities of Daily Living (ADL) function were determined by the Mini-Mental State Examination (MMSE) and the Barthel Index, respectively. Three-year cognitive and functional decline were respectively defined as a >3 point decrease in the MMSE scores and lower ADL scores than at baseline. Univariate and multivariable logistic regression analyses were conducted to identify nutritional status as a risk factor in poor outcome. The Kaplan-Meier method and Cox proportional regression models were used to estimate the effect of malnutrition risk on the mortality.
Results
According to MNS-SF, the prevalence of risk of malnutrition was 53.1% (188/354). Multivariate logistic regression found risk of malnutrition significantly associated with 3-year cognitive decline (Adjusted odds ratio OR 2.07, 95% Confidence Interval CI 1.05–4.08, P =0.036) and functional decline (Adjusted OR 1.83, 95% CI 1.01–3.34, P =0.047) compared with normal nutritional status. The hazard ratio (HR) for all-cause mortality was 1.8 times higher in residents at risk of malnutrition (Adjusted HR 1.82, 95% CI 1.19–2.79, P =0.006).
Conclusions
Our results provide strong evidence that risk of malnutrition can predict not only cognitive and functional decline but also risk of all-cause mortality in older men living in a veteran retirement’s community. Further longitudinal studies are needed to explore the causal relationship among nutrition, clinical outcomes, and the effect of an intervention for malnutrition.
Summary
Our network meta-analysis analyzed the effects of glucagon-like peptide-1 receptor agonists (GLP-1 RAs) on fracture risk. By combining data from randomized controlled trials, we found that ...GLP-1 RAs were associated with a decreased bone fracture risk, and exenatide is the best option agent with regard to the risk of fracture. This study is registered with PROSPERO (CRD42018094433).
Introduction
Data on the effects of GLP-1 RAs on fracture risk are conflicted. This study aimed to analyze the available evidence on the effects of GLP-1 RAs on fracture risk in type 2 diabetes mellitus patients.
Methods
Electronic databases were searched for relevant published articles, and unpublished studies presented at
ClinicalTrials.gov
were searched for relevant clinical data. All analyses were performed with STATA 12.0 and R software (Version 3.4.4). We estimated the risk ratio (RR) and 95% confidence interval (CI) by combining RRs for fracture effects of included trials.
Results
There were 54 eligible random control trials (RCTs) with 49,602 participants, including 28,353 patients treated with GLP-1 RAs. Relative to placebo, exenatide (RR, 0.17; 95% CI 0.03–0.67) was associated with lowest risk of fracture among other GLP-1 RAs. Exenatide had the highest probability to be the safest option with regard to the risk of fracture (0.07 ‰), followed by dulaglutide (1.04%), liraglutide (1.39%), albiglutide (5.61%), lixisenatide (8.07%), and semaglutide (18.72%). A statistically significant inconsistency was observed in some comparisons.
Conclusion
The Bayesian network meta-analysis suggests that GLP-1 RAs were associated with a decreased bone fracture risk compared to users of placebo or other anti-hyperglycemic drugs in type 2 diabetes mellitus patients, and exenatide is the best option agent with regard to the risk of fracture.
Fast radio bursts (FRBs) are millisecond-duration radio transients of unknown physical origin observed at extragalactic distances
. It has long been speculated that magnetars are the engine powering ...repeating bursts from FRB sources
, but no convincing evidence has been collected so far
. Recently, the Galactic magnetar SRG 1935+2154 entered an active phase by emitting intense soft γ-ray bursts
. One FRB-like event with two peaks (FRB 200428) and a luminosity slightly lower than the faintest extragalactic FRBs was detected from the source, in association with a soft γ-ray/hard-X-ray flare
. Here we report an eight-hour targeted radio observational campaign comprising four sessions and assisted by multi-wavelength (optical and hard-X-ray) data. During the third session, 29 soft-γ-ray repeater (SGR) bursts were detected in γ-ray energies. Throughout the observing period, we detected no single dispersed pulsed emission coincident with the arrivals of SGR bursts, but unfortunately we were not observing when the FRB was detected. The non-detection places a fluence upper limit that is eight orders of magnitude lower than the fluence of FRB 200428. Our results suggest that FRB-SGR burst associations are rare. FRBs may be highly relativistic and geometrically beamed, or FRB-like events associated with SGR bursts may have narrow spectra and characteristic frequencies outside the observed band. It is also possible that the physical conditions required to achieve coherent radiation in SGR bursts are difficult to satisfy, and that only under extreme conditions could an FRB be associated with an SGR burst.
The extension of the cosmic-ray spectrum beyond 1 petaelectronvolt (PeV; 10
electronvolts) indicates the existence of the so-called PeVatrons-cosmic-ray factories that accelerate particles to PeV ...energies. We need to locate and identify such objects to find the origin of Galactic cosmic rays
. The principal signature of both electron and proton PeVatrons is ultrahigh-energy (exceeding 100 TeV) γ radiation. Evidence of the presence of a proton PeVatron has been found in the Galactic Centre, according to the detection of a hard-spectrum radiation extending to 0.04 PeV (ref.
). Although γ-rays with energies slightly higher than 0.1 PeV have been reported from a few objects in the Galactic plane
, unbiased identification and in-depth exploration of PeVatrons requires detection of γ-rays with energies well above 0.1 PeV. Here we report the detection of more than 530 photons at energies above 100 teraelectronvolts and up to 1.4 PeV from 12 ultrahigh-energy γ-ray sources with a statistical significance greater than seven standard deviations. Despite having several potential counterparts in their proximity, including pulsar wind nebulae, supernova remnants and star-forming regions, the PeVatrons responsible for the ultrahigh-energy γ-rays have not yet been firmly localized and identified (except for the Crab Nebula), leaving open the origin of these extreme accelerators.
Six isonitrogenous (390 g kg⁻¹) and isoenergetic (16.2 kJ g⁻¹) diets with varying carbohydrate : lipid (CHO : L) ratios (202.5-1.74), were fed to triplicate groups of 25 fish in indoor recirculation ...system. Over 8-week-growth trial, best weight gain (WG), specific growth rate, feed conversion ratio, protein efficiency ratio and protein production value (P < 0.05) were observed in fish-fed diets with CHO : L ratio of 7.5. Fish fed either the lowest (1.7) or highest (202.5) CHO : L ratio tended to produce lower (P < 0.05) growth and feed conversion efficiencies. The values of viscerosomatic index, hepatosomatic index and intraperitoneal fat ratio increased as dietary CHO : L ratios decreased. There were no significant differences in whole body and liver crude protein among dietary treatments. Whole body and liver lipid increased as CHO : L ratios decreased. Plasma cholesterol and triacylglyceride levels increased linearly as dietary CHO : L ratios decreased. Activities of glucokinase and pyruvate kinase were stimulated by elevated levels of dietary carbohydrate; however, activities of lipase (LPS) and alkaline phosphatase were stimulated by elevated levels of dietary lipid. Based on a second-order polynomial regression analysis of WG against dietary carbohydrate and lipid levels, 275 g kg⁻¹ of carbohydrate and 59 g kg⁻¹ of lipid, corresponding to a CHO : L ratio of 4.7, in a diet holding 390 g kg⁻¹ of crude protein and 16.3 kJ g⁻¹ of gross energy, proved to be optimal for grass carp. These results indicated that utilization of dietary lipid and carbohydrate was moderate in grass carp, but the fish were a little more capable of utilizing lipid compared with carbohydrate.
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