Pathogens are often not identified in severe community-acquired pneumonia (CAP), and the few studies using polymerase chain reaction (PCR) techniques for virus detection are from temperate countries.
...This study assesses if PCR amplification improves virus and bacteria detection, and if viral infection contributes to mortality in severe CAP in a tropical setting, where respiratory pathogens have less well-defined seasonality.
In this cohort study of patients with severe CAP in an intensive care unit, endotracheal aspirates for intubated patients and nasopharyngeal swabs for non-intubated patients were sent for PCR amplification for respiratory viruses. Blood, endotracheal aspirates for intubated patients, and sputum for non-intubated patients were analysed using a multiplex PCR system for bacteria.
Out of 100 patients, using predominantly cultures, bacteria were identified in 42 patients; PCR amplification increased this number to 55 patients. PCR amplification identified viruses in 32 patients. In total, only bacteria, only viruses, and both bacteria and viruses were found in 37, 14, and 18 patients, respectively. The commonest viruses were influenza A H1N1/2009 and rhinovirus; the commonest bacterium was Streptococcus pneumoniae. Hospital mortality rates for patients with no pathogens, bacterial infection, viral infection, and bacterial-viral co-infection were 16.1, 24.3, 0, and 5.6%, respectively (p = 0.10). On multivariable analysis, virus detection was associated with lower mortality (adjusted odds ratio 0.12, 95% confidence interval 0.2-0.99; p = 0.049).
Viruses and bacteria were detected in 7 of 10 patients with severe CAP with the aid of PCR amplification. Viral infection appears to be independently associated with lower mortality.
In this paper, we present the design, fabrication and preliminary evaluation of a soft robotic glove which can be used with functional Magnetic Resonance imaging (fMRI) during the hand continuous ...passive motion (CPM) in rehabilitation. The device comprises of two major components: a) soft pneumatic actuators and b) a glove. The soft pneumatic actuators, which are made of silicon elastomers, generate a bending motion and actuate the finger joints upon pressurization. As the device contains no ferromagnetic materials and operates pneumatically, we hypothesize that the device is MR-compatible. Our results show that the device did not cause artifacts to the fMRI images during CPM. This study demonstrated the possibility of using fMRI and MR-compatible soft robotic glove (MRC-Glove) to study motor performances of the brain during CPM rehabilitation and unravel the effects of rehabilitation robotics on brain stimulation.
In this paper, we present the design of a soft wearable exoskeleton that comprises of a glove embedded with pneumatic actuators of variable stiffness for hand assistive and rehabilitation ...application. The device is lightweight and easily wearable due to the usage of soft pneumatic actuators. A key feature of the device is the variable stiffness of the actuators at different localities that not only conform to the finger profile during actuation, but also provides customizability for different hand dimensions. The actuators can achieve different bending profiles with variable stiffness implemented at different localities. Therefore, the device is able to perform different hand therapy exercises such as full fist, straight fist, hook fist and table top. The device was characterized in terms of its range of motion and maximum force output. Experiments were conducted to examine the differences between active and passive actuation. The results showed that the device could achieve hand grasping and pinching with acceptable range of motion and force.
Surface modification and wetting state transformation of ZnO based nanomaterials have been extensively investigated due to their substantial roles in current industrial applications. In this work, we ...demonstrated the formation of highly crystalline and ordered Bi/ZnO nanorods arrays (Bi/ZNRs) grown on FTO substrate via a feasible hydrothermal method, as a function of reaction time (t). The lateral diameter of the nanostructures were found increased from 23 nm to 43 nm when the reaction time increased from 30 min to 90 min. An in-depth analysis and incisive mechanism of crystal growth under the function of reaction time were proposed. The crystal defect which originated from different Bi incorporation pathways has been declared as the main factor altering the optical energy, electrical properties and band structure of Bi/ZNRs. The Bi/ZNRs showed a higher localize current of 14.5 pA as compared to pristine ZNRs under an 6V applied bias condition, revealing the nature of Bi as a pentavalent dopant that contributed to a density of free electron. Additionally, the Bi/ZNRs also revealed a red shifted in optical energy band gap and exhibit a wetting transition from hydrophobic to hydrophilic textured surface. The novel nanostructures reported herein exhibit interesting physical and optical properties for the fabrication of high performance optoelectronic devices.
Charge transport dynamics in ZnO based inverted organic solar cell (IOSC) has been characterized with transient photocurrent spectroscopy and localised photocurrent mapping-atomic force microscopy. ...The value of maximum exciton generation rate was found to vary from 2.6 × 1027 m−3s−1 (Jsat = 79.7 A m−2) to 2.9 × 1027 m−3s−1 (Jsat = 90.8 A m−2) for devices with power conversion efficiency ranging from 2.03 to 2.51%. These results suggest that nanorods served as an excellent electron transporting layer that provides efficient charge transport and enhances IOSC device performance. The photovoltaic performance of OSCs with various growth times of ZnO nanorods have been analysed for a comparison between AM1.5G spectrum and local solar spectrum. The simulated PCE of all devices operating under local spectrum exhibited extensive improvement with the gain of 13.3–13.7% in which the ZnO nanorods grown at 15 min possess the highest PCE under local solar with the value of 2.82%.
Display omitted
•Surface modification of ZnO nanoparticle to nanorod via low temperature approach.•ZnO nanorod shows a high localised current in CF-AFM analysis.•Mechanistic study on the exciton generation and dissociation process in the interface.•A novel numerical method to predict the outdoor performance of solar devices.
While immune checkpoint blockade (ICB) has shown promise in patients with hepatocellular carcinoma (HCC), it is associated with modest response rates and immune-related adverse events (irAEs) are ...common. In this study, we aimed to decipher immune trajectories and mechanisms of response and/or irAEs in patients with HCC receiving anti-programmed cell death 1 (anti-PD-1) therapy.
Pre- and on-treatment peripheral blood samples (n = 60) obtained from 32 patients with HCC (Singapore cohort) were analysed by cytometry by time-of-flight and single-cell RNA sequencing, with flow cytometric validation in an independent Korean cohort (n = 29). Mechanistic validation was conducted by bulk RNA sequencing of 20 pre- and on-treatment tumour biopsies and using a murine HCC model treated with different immunotherapeutic combinations.
Single-cell analyses identified CXCR3+CD8+ effector memory T (TEM) cells and CD11c+ antigen-presenting cells (APC) as associated with response (p = 0.0004 and 0.0255, respectively), progression-free survival (p = 0.00079 and 0.0015, respectively), and irAEs (p = 0.0034 and 0.0125, respectively) in anti-PD-1-treated patients with HCC. Type-1 conventional dendritic cells were identified as the specific APC associated with response, while 2 immunosuppressive CD14+ myeloid clusters were linked to reduced irAEs. Further analyses of CXCR3+CD8+ TEM cells showed cell-cell interactions specific to response vs. irAEs, from which the anti-PD-1 and anti-TNFR2 combination was harnessed to uncouple these effects, resulting in enhanced response without increased irAEs in a murine HCC model.
This study identifies early predictors of clinical response to anti-PD-1 ICB in patients with HCC and offers mechanistic insights into the immune trajectories of these immune subsets at the interface between response and toxicity. We also propose a new combination immunotherapy for HCC to enhance response without exacerbating irAEs.
NCT03695952.
Response rates to immune checkpoint blockade (ICB) treatment in hepatocellular carcinoma (HCC) remain modest and adverse events are common. Herein, we identified early predictors of response and gained an in-depth understanding of the immunological mechanisms behind response and adverse events in patients with HCC treated with ICB. We also proposed a new combination immunotherapy for HCC that enhances response without exacerbating adverse events.
Display omitted
•Distinct immune subsets are linked to response and toxicity in immunotherapy.•Antigen-presenting cells and CD8 TEM cell function act as an interface between response and toxicity.•Diverging immune trajectories of immune subsets contribute to either response or toxicity.•TNFR2 inhibition uncouples response and toxicity in anti-PD-1 immunotherapy.
Hepatocellular carcinoma (HCC) often develops following chronic hepatitis B virus (HBV) infection and responds poorly to immune checkpoint blockade. Here, we examined the antigen specificities of ...HCC-infiltrating T cells and their relevance to tumor control. Using highly multiplexed peptide-MHC tetramer staining of unexpanded cells from blood, liver, and tumor tissues from 46 HCC patients, we detected 91 different antigen-specific CD8+ T cell populations targeting HBV, neoantigen, tumor-associated, and disease-unrelated antigens. Parallel high-dimensional analysis delineated five distinct antigen-specific tissue-resident memory T (Trm) cell populations. Intratumoral and intrahepatic HBV-specific T cells were enriched for two Trm cell subsets that were PD-1loTOXlo, despite being clonally expanded. High frequencies of intratumoral terminally exhausted T cells were uncommon. Patients with tumor-infiltrating HBV-specific CD8+ Trm cells exhibited longer-term relapse-free survival. Thus, non-terminally exhausted HBV-specific CD8+ Trm cells show hallmarks of active involvement and effective antitumor response, implying that these cells could be harnessed for therapeutic purposes.
Display omitted
•Broad analysis of CD8+ T cell antigen specificity in HBV-HCC patient blood, liver, tumor•Tumor-infiltrating HBV-specific T cells correlate with superior relapse-free survival•Five Trm subsets are enriched in liver- and tumor-infiltrating HBV-specific T cells•HBV-specific Trm cells have expanded TCR clones and lack hallmarks of terminal exhaustion
Hepatocellular carcinoma (HCC) often develops following chronic hepatitis B virus (HBV) infection and responds poorly to immune checkpoint blockade. Cheng et al. examine the antigen specificities of HCC-infiltrating T cells and reveal that HBV-specific Trm cells are phenotypically distinct, clonally expanded, and are not terminally exhausted, suggesting that these cells may be harnessed for therapeutic purposes.
IntroductionDietary niacin may prevent gallstones, a major cause of acute pancreatitis (AP), by increasing plasma high density lipoprotein and lowering triglycerides, both associated with reduced ...rates of gallstones. Niacin may interact with other sex-specific risk factors affecting lipids namely hormone replacement therapy (HRT) and parity. This epidemiological study investigated whether dietary niacin reduces the risk of developing symptomatic gallstones (SGs), for the first time using 7-day food diaries (7-DFDs), the most accurate dietary assessment method in large prospective studies.Methods25,639 participants (54.7% women), aged 40–74 years, enrolled in the European Prospective Investigation into Cancer-Norfolk (EPIC-Norfolk). At recruitment, participants completed 7-DFDs which recorded 1 week’s diet including information on recipes, brands, and portion sizes. Nutrient intakes were calculated using a computer program containing nutrient information on 11,000 foods. The cohort was monitored for 14 years to identify participants developing SGs. Cox proportional hazards regression models estimated the sex-specific hazard ratios (HRs), for SGs for quartiles of niacin intake, adjusted for covariates. Binary analyses were performed using the UK reference nutrient intake (RNI) for niacin, and in sensitivity analyses according to HRT use and parity.ResultsSGs developed in 200 women (mean time to diagnosis=6.0 years SD=2.9 years) and 95 men (mean time to diagnosis=5.9 years SD=3.0 years), and 10.3% of diagnoses were AP. In women, total dietary niacin was associated with a reduced risk of SGs (highest vs lowest quartile HR=0.59 95% CI=0.39–0.91; HR trend=0.85 95% CI=0.74–0.98 p=0.022). The population attributable fraction for niacin intake was 16.3%. Eating the UK RNI for niacin was inversely associated with the risk of SGs in parous women (HR=0.63 95% CI=0.45–0.89 p=0.009), but not in nulliparous women (HR=1.65 95% CI=0.45–6.00 p=0.447). Meeting the UK RNI for niacin was inversely associated with the risk of SGs in women who had never used HRT (HR=0.53 95% CI=0.35–0.81 p=0.003), but not in previous or current users. In men, there were no significant associations for niacin (HR trend=0.92 95% CI=0.75–1.13 p=0.430).ConclusionsThis data supports a role for dietary deficiencies of niacin in the development of SGs in women, but not men, with effect modification according to HRT use and parity. If further epidemiological studies confirm our findings, then dietary recommendations to increase niacin intake may help prevent the complications of gallstones, including AP.
PDF
