Summary
Background
Hepatitis C virus (HCV) infection has been linked to an increased risk of insulin resistance and carotid atherosclerosis.
Aim
To investigate the association between HCV infection ...and stroke, and the effect of interferon‐based therapy (IBT) on stroke risk in chronic hepatitis C (CHC) patients.
Methods
We conducted a retrospective cohort study that followed up 3113 subjects with a newly detected HCV infection and 12 452 age‐ and gender‐matched subjects without HCV infection selected from a random sample of 106 beneficiaries from the Taiwan National Health Insurance Program up to 5 years. Use of IBT was defined as treatment with interferon alpha, pegylated interferon alpha‐2a or pegylated interferon alpha‐2b for at least 3 months. The hazard ratio (HR) for newly detected stroke was calculated for subjects with HCV compared to those without HCV, and for IBT‐treated HCV patients compared to non‐IBT‐treated HCV patients while adjusting for possible confounding factors.
Results
The overall person‐years of follow‐up were 8624.11 in patients with HCV, 54 533.69 in patients without HCV, 666.65 in IBT‐treated patients, and 7886.49 in nontreated patients. The multivariable‐adjusted hazard ratio (HR) for newly detected stroke was 1.23 for subjects with HCV compared to the age‐ and sex‐matched subjects without HCV (adjusted HR = 1.23, 95% CI = 1.06–1.42, P = 0.008). Moreover, use of IBT significantly reduced the risk of stroke in HCV patients (adjusted HR = 0.39, 95% CI = 0.16–0.95, P = 0.039) after adjusting for known prognostic factors.
Conclusions
Interferon‐based therapy may reduce the long‐term risk of stroke in patients with chronic HCV infection.
White matter fiber tractography relies on fiber bundle orientation estimates from diffusion MR imaging. However, clinically feasible techniques such as DTI and diffusional kurtosis imaging use ...assumptions, which may introduce error into in vivo orientation estimates. In this study, fiber bundle orientations from DTI and diffusional kurtosis imaging are compared with diffusion spectrum imaging as a criterion standard to assess the performance of each technique.
For each subject, full DTI, diffusional kurtosis imaging, and diffusion spectrum imaging datasets were acquired during 2 independent sessions, and fiber bundle orientations were estimated by using the specific theoretic assumptions of each technique. Angular variability and angular error measures were assessed by comparing the orientation estimates. Tractography generated with each of the 3 reconstructions was also examined and contrasted.
Orientation estimates from all 3 techniques had comparable angular reproducibility, but diffusional kurtosis imaging decreased angular error throughout the white matter compared with DTI. Diffusion spectrum imaging and diffusional kurtosis imaging enabled the detection of crossing-fiber bundles, which had pronounced effects on tractography relative to DTI. Diffusion spectrum imaging had the highest sensitivity for detecting crossing fibers; however, the diffusion spectrum imaging and diffusional kurtosis imaging tracts were qualitatively similar.
Fiber bundle orientation estimates from diffusional kurtosis imaging have less systematic error than those from DTI, which can noticeably affect tractography. Moreover, tractography obtained with diffusional kurtosis imaging is qualitatively comparable with that of diffusion spectrum imaging. Because diffusional kurtosis imaging has a shorter typical scan time than diffusion spectrum imaging, diffusional kurtosis imaging is potentially more suitable for a variety of clinical and research applications.
A general therapeutic strategy to treat breast cancer is attractive as different subtypes of breast cancers often exhibit distinct response to existing cancer therapeutics. To this end, we prepare a ...catalyst couple of glucose oxidase (GOx) and gallic acid-ferrous (GA-Fe) nanocomplexes, a type of near-infrared (NIR) absorbing Fenton catalyst, to enable NIR-trigger in-situ gelation and enhanced chemodynamic/starvation therapy that appears to be effective for different types of breast cancer cells. In this system, GOx is mixed with GA-Fe in a solution of N,N-dimethylacrylamide (DMAA) and poly (ethylene glycol) double acrylate (PEGDA). Upon intratumoral injection and NIR laser exposure, such GA-Fe show rapid temperature increase, which would simultaneously increase the catalytic efficiencies of GA-Fe and GOx. The cascade production of hydroxyl radicals (•OH) from glucose is then initiated to enable polymerization of DMAA and PEGDA to form a hydrogel at the injection site within the tumor. The continuous production of cytotoxic •OH together with glucose depletion by the intratumorally fixed catalyst couple would further confer effective destruction of breast cancer tumors by such chemodynamic/starvation therapy. Our work presents a hydrogel-based therapeutic strategy for local treatment of solid tumors with high tumor destruction efficacy and low systemic toxicity.
Rats and mice are used for studying neuronal circuits underlying recognition memory due to their ability to spontaneously remember the occurrence of an object, its place and an association of the ...object and place in a particular environment. A joint employment of lesions, pharmacological interventions, optogenetics and chemogenetics is constantly expanding our knowledge of the neural basis for recognition memory of object, place, and their association. In this review, we summarize current studies on recognition memory in rodents with a focus on the novel object preference, novel location preference and object-in-place paradigms. The evidence suggests that the medial prefrontal cortex- and hippocampus-connected circuits contribute to recognition memory for object and place. Under certain conditions, the striatum, medial septum, amygdala, locus coeruleus and cerebellum are also involved. We propose that the neuronal circuitry for recognition memory of object and place is hierarchically connected and constructed by different cortical (perirhinal, entorhinal and retrosplenial cortices), thalamic (nucleus reuniens, mediodorsal and anterior thalamic nuclei) and primeval (hypothalamus and interpeduncular nucleus) modules interacting with the medial prefrontal cortex and hippocampus.
•An overview of neuroanatomy of recognition memory for object and place is introduced.•Strategies of optogenetics and chemogenetics are discussed in recognition memory.•Cell type- and pathway-specific mediations of the hippocampus modulate recognition memory.•Multiple cortical, thalamic and hypothalamic regions are involved in recognition memory.•A hierarchical interconnected model of recognition memory is proposed.
Abstract
Vanadium dioxide (VO
2
) is a promising material for thermochromic glazing. However, VO
2
thermochromic smart windows suffer from several problems that prevent commercialization: low ...luminous transmittance (
T
lum
) and low solar modulation ability (
ΔT
sol
). The solution to these problems can be sought from nature where the evolution of various species has enabled them to survive. Investigations into the morphology of moths eyes has shown that their unique nanostructures provide an excellent antireflection optical layer that helps moths sharply capture the light in each wavelength from a wide angle. Inspired by this mechanism, a VO
2
thermochromic smart window coated with a TiO
2
antireflection layer with a novel nano-cone structure, is presented in this study to achieve high
T
lum
and
ΔT
sol
. Optimization for the key structure parameters is summarized based on the FDTD numerical simulations. The optimized structure exhibits a
T
lum
of 55.4% with
ΔT
sol
of 11.3%, an improvement of about 39% and 72% respectively compared to the VO
2
window without an antireflection layer. Furthermore, wide-angle antireflection and polarization independence are also demonstrated by this nano-cone coating. This work provides an alternative method to enhance the optical performance of VO
2
smart windows.
Aim
To investigate the in vivo metabolic effects of treatment with BPR0912, a novel and potent peripheral cannabinoid receptor 1 (CB1R) antagonist, on both normal mice and diet‐induced obese (DIO) ...mice.
Methods
The acute peripheral effects of BPR0912 administration on gastrointestinal transit and energy metabolism in normal mice were investigated. The effects of chronic BPR0912 treatment were compared with those of rimonabant using DIO mice. Alterations to body weight and biochemical and metabolic variables were determined.
Results
Acute treatment with BPR0912 did not alter food intake or energy metabolism, but efficiently reversed CB1R‐mediated gastrointestinal delay. Chronic treatment of DIO mice with BPR0912 showed that BPR0912 exerts a food intake‐independent mechanism, which contributes to weight loss. Genes involved in β‐oxidation and thermogenesis were upregulated in white adipose tissue (WAT) in addition to increased lipolytic activity, whereas Ucp1 expression was induced in brown adipose tissue (BAT) and body temperature was elevated. Expression of the β2‐adrenoceptor was specifically elevated in both WAT and BAT in a manner dependent on the BPR0912 dose. Lastly, chronic BPR0912 treatment was more efficacious than rimonabant in reducing hepatic triglycerides in DIO mice.
Conclusion
BPR0912 exhibits significant in vivo efficacy in inducing food intake‐independent weight loss in DIO mice, while tending to reduce their hepatic steatosis. The thermogenic effects of BPR0912, as well as its modulation of protein and gene expression patterns in WAT and BAT, may enhance its efficacy as an anti‐obesity agent. The results of the present study support the benefits of the use of peripheral CB1R antagonists to combat metabolic disorders.
Dual blockade of PD-L1 and VEGF has enhanced anticancer immunity through multiple mechanisms and augmented antitumour activity in multiple malignancies. We aimed to assess the efficacy and safety of ...atezolizumab (anti-PD-L1) alone and combined with bevacizumab (anti-VEGF) in patients with unresectable hepatocellular carcinoma.
GO30140 is an open-label, multicentre, multiarm, phase 1b study that enrolled patients at 26 academic centres and community oncology practices in seven countries worldwide. The study included five cohorts, and the two hepatocellular carcinoma cohorts, groups A and F, are described here. Inclusion criteria for these two groups included age 18 years and older; histologically, cytologically, or clinically (per American Association for the Study of Liver Diseases criteria) confirmed unresectable hepatocellular carcinoma that was not amenable to curative treatment; no previous systemic treatment; and Eastern Cooperative Oncology Group performance status of 0 or 1. In group A, all patients received atezolizumab (1200 mg) and bevacizumab (15 mg/kg) intravenously every 3 weeks. In group F, patients were randomly assigned (1:1) to receive intravenous atezolizumab (1200 mg) plus intravenous bevacizumab (15 mg/kg) every 3 weeks or atezolizumab alone by interactive voice-web response system using permuted block randomisation (block size of two) and stratification factors of geographical region; macrovascular invasion, extrahepatic spread, or both; and baseline α-fetoprotein concentration. Primary endpoints were confirmed objective response rate in all patients who received the combination treatment for group A and progression-free survival in the intention-to-treat population in group F, both assessed by an independent review facility according to Response Evaluation Criteria in Solid Tumors version 1.1. In both groups, safety was assessed in all patients who received at least one dose of any study treatment. This study is registered with ClinicalTrials.gov, NCT02715531, and is closed to enrolment.
In group A, 104 patients were enrolled between July 20, 2016, and July 31, 2018, and received atezolizumab plus bevacizumab. With a median follow-up of 12·4 months (IQR 8·0–16·2), 37 (36%; 95% CI 26–46) of 104 patients had a confirmed objective response. The most common grade 3–4 treatment-related adverse events were hypertension (13 13%) and proteinuria (seven 7%). Treatment-related serious adverse events occurred in 25 (24%) patients and treatment-related deaths in three (3%) patients (abnormal hepatic function, hepatic cirrhosis, and pneumonitis). In group F, 119 patients were enrolled and randomly assigned (60 to atezolizumab plus bevacizumab; 59 to atezolizumab monotherapy) between May 18, 2018, and March 7, 2019. With a median follow-up of 6·6 months (IQR 5·5–8·5) for the atezolizumab plus bevacizumab group and 6·7 months (4·2–8·2) for the atezolizumab monotherapy group, median progression-free survival was 5·6 months (95% CI 3·6–7·4) versus 3·4 months (1·9–5·2; hazard ratio 0·55; 80% CI 0·40–0·74; p=0·011). The most common grade 3–4 treatment-related adverse events in group F were hypertension (in three 5% patients in the atezolizumab plus bevacizumab group; none in the atezolizumab monotherapy group) and proteinuria (in two 3% patients in the atezolizumab plus bevacizumab group; none in the atezolizumab monotherapy group). Treatment-related serious adverse events occurred in seven (12%) patients in the atezolizumab plus bevacizumab group and two (3%) patients in the atezolizumab monotherapy group. There were no treatment-related deaths.
Our study shows longer progression-free survival with a combination of atezolizumab plus bevacizumab than with atezolizumab alone in patients with unresectable hepatocellular carcinoma not previously treated with systemic therapy. Therefore, atezolizumab plus bevacizumab might become a promising treatment option for these patients. This combination is being compared with standard-of-care sorafenib in a phase 3 trial.
F Hoffmann-La Roche/Genentech.
Although SARS-CoV-2 infects the upper respiratory tract, we know little about the amount, type, and kinetics of antibodies (Ab) generated in the oral cavity in response to COVID-19 vaccination. We ...collected serum and saliva samples from participants receiving two doses of mRNA COVID-19 vaccines and measured the level of anti-SARS-CoV-2 Ab. We detected anti-Spike and anti-Receptor Binding Domain (RBD) IgG and IgA, as well as anti-Spike/RBD associated secretory component in the saliva of most participants after dose 1. Administration of a second dose of mRNA boosted the IgG but not the IgA response, with only 30% of participants remaining positive for IgA at this timepoint. At 6 months post-dose 2, these participants exhibited diminished anti-Spike/RBD IgG levels, although secretory component-associated anti-Spike Ab were more stable. Examining two prospective cohorts we found that participants who experienced breakthrough infections with SARS-CoV-2 variants had lower levels of vaccine-induced serum anti-Spike/RBD IgA at 2–4 weeks post-dose 2 compared to participants who did not experience an infection, whereas IgG levels were comparable between groups. These data suggest that COVID-19 vaccines that elicit a durable IgA response may have utility in preventing infection.
Our study finds that a local secretory component-associated IgA response is induced by COVID-19 mRNA vaccination that persists in some, but not all participants. The serum and saliva IgA response modestly correlate at 2–4 weeks post-dose 2. Of note, levels of anti-Spike serum IgA (but not IgG) at this timepoint are lower in participants who subsequently become infected with SARS-CoV-2. As new surges of SARS-CoV-2 variants arise, developing COVID-19 booster shots that provoke high levels of IgA has the potential to reduce person-to-person transmission. Display omitted
Adaptive control of solar and thermal radiation through windows is of pivotal importance for building energy saving. However, such synchronous passive regulations are challenging to be integrated ...into one thermochromic window. Here, we develop a solar and thermal regulatory (STR) window by integrating poly(
-isopropylacrylamide) (pNIPAm) and silver nanowires (AgNWs) into pNIPAm/AgNW composites. A hitherto unexplored mechanism, originating from the temperature-triggered water capture and release due to pNIPAm phase transition, is exploited to achieve simultaneous regulations of solar transmission and thermal emission. The STR window shows excellent solar modulation (58.4%) and thermal modulation (57.1%) and demonstrates effective regulation of indoor temperatures during both daytime and nighttime. Compared to other thermochromic technologies, the STR window reduces heat loss in cold environment while promotes heat dissipation in hot conditions, achieving efficient energy saving in all weathers. This dual solar and thermal regulation mechanism may provide unidentified insights into the advancement of smart window technology.
ABSTRACT
The aim of this study was to determine the impact of probiotic feeding and chronic heat stress on meat quality, total lipid and phospholipid contents, lipid oxidation, antioxidant capacity, ...and heat shock protein abundance of broiler breast muscle. A total of 240 male broilers (5 birds per pen) were subjected to 4 treatments consisting of a 2 × 2 factorial design. Broilers were kept at 21-32-21°C for 10 h daily (heat stress, HS) or 21°C (thermoneutral condition) and fed a regular diet or the diet mixed with probiotic (250 ppm of Sporulin containing 3 strains of Bacillus subtilis). A total of 48 broilers (12 birds/treatment) were harvested at 46 d. Neither HS nor probiotic had substantial impacts on water-holding capacity, shear force, and color characteristics. HS induced lipid oxidation as increased 2-thiobarbituric acid reactive substances (TBARS), in which probiotic feeding decreased TBARS value (P = 0.002) and phospholipid contents (P = 0.0033) in breast muscle of HS broilers. 2,2-Diphenyl-1-picrylhydrazyl (DPPH) radical scavenging activity was increased with HS (P < 0.0001), but no significant impact of probiotic supplementation was found. Neither probiotic nor HS affected catalase activity, but superoxide dismutase and glutathione peroxidase activities were lower in HS broilers compared to thermoneutral controls (P < 0.0001) and in probiotics-fed broilers (P < 0.0001) compared to their counterparts. In addition, a significant interaction between probiotic and HS was found at glutathione peroxidase activities, in which breast muscle of broilers fed probiotic at thermoneutral condition showed the highest activity (P < 0.05). Regarding heat shock protein (HSP) determination, HS slightly increased the levels of both HSP70 (P = 0.08) and HSP27 (P = 0.05), but no significant impacts of probiotic supplementation were found. Our results indicate that probiotic feeding could improve breast muscle weight without adverse impacts on meat quality attributes, as well as alleviate oxidative deterioration of breast muscle of broilers undergoing heat stress.
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