Regulation of type 2 inflammation by type I interferons

Rhinovirus-induced asthma exacerbations are a major cause of morbidity and mortality in patients. Experimental clinical infection studies indicate rhinovirus augments type 2 inflammation in asthma. Additionally, asthmatic lung cells have impaired type I interferon production in response to rhinovirus stimulation. Evidence suggests co-regulation of type I interferon signalling and type 2 immunity exists; therefore, we hypothesised that type I interferon deficiency in asthma leads to the reduced regulation of type 2 immunity, resulting in exacerbation of allergen-induced type 2 inflammation during rhinovirus infection. To investigate the role of type I interferon signalling, type I interferon receptor (IFNAR1) knockout mice, an anti-IFNAR1 blocking antibody and recombinant interferon-β therapy were used in mouse models of rhinovirus-induced airways disease. Impaired IFNAR1 signalling resulted in enhanced eosinophilic inflammation in response to allergen challenge and rhinovirus infection, which was associated with increased CCL24 and Th2 chemokines CCL17 and CCL22. Recombinant interferon-β treatment had limited effects on responses to the combination of allergen and rhinovirus, but suppressed allergen-induced CCL17. In THP1-derived macrophages, interferon-β co-treatment and pre-treatment suppressed IL-4 and TNFα-induced Th2 chemokine production. Microarray analysis was performed on these cells to help identify the regulatory mechanism of type I interferon on Th2 chemokine expression. Interferon-β pre-treatment significantly upregulated PTPN6 (encoding SHP1, a phosphatase that regulates STAT6 activity) expression compared with IL-4 and TNFα-stimulated cells. Western blot analysis did not identify differences in STAT6 phosphorylation following interferon-β treatment, or differences in SHP1 protein levels. These findings support a role for type I interferon in the negative regulation of type 2 inflammation in both the presence and absence of rhinovirus; however, this mechanism has yet to be identified. Impaired interferon responses in asthma may contribute to enhanced type 2 immunity that is considered pathological in allergic airways inflammation and virus-induced asthma exacerbations.Open Acces

COVID-19 and cognitive performance: a Mendelian randomization study

BackgroundA substantial proportion of individuals with COVID-19 experienced cognitive impairment after resolution of SARS-CoV-2 infection. We aimed to evaluate whether genetic liability to SARS-CoV-2 infection per se, or more severe COVID-19, is causally linked to cognitive deficit.MethodsWe firstly performed univariable Mendelian randomization (MR) analysis to examine whether genetic liability to SARS-CoV-2 infection, hospitalized and severe COVID-19 is causally associated with cognitive performance. To dissect the causal pathway, multivariable MR (MVMR) analysis was conducted by adjusting for five inflammatory markers [C-reactive protein, interleukin (IL)-1β, IL-6, IL-8, and tumour necrosis factor α, as proxies of systemic inflammation].ResultsIn univariable MR analysis, host genetic liability to SARS-CoV-2 infection was associated with lower cognitive performance [inverse variance weighted (IVW) analysis, estimate: −0.023; 95% Confidence Interval (CI): −0.038 to −0.009]. Such causal association was attenuated in MVMR analysis when we adjusted for the five correlated inflammatory markers in one analysis (IVW analysis, estimate: −0.022; 95% CI: −0.049 to 0.004). There was insufficient evidence of association for genetic liability to hospitalized and severe COVID-19 with cognitive performance.ConclusionThe causal effect of host genetic liability to SARS-CoV-2 infection on reduced cognitive performance may be mediated by systemic inflammation. Future studies examining whether anti-inflammatory agents could alleviate cognitive impairment in SARS-CoV-2-infected individuals are warranted

Effect of synthesis methods on properties of copper oxide doped titanium dioxide photocatalyst in dye photodegradation of rhodamine B

Copper oxide modified titanium dioxide photocatalysts have been widely reported for their excellent performance in the wastewater treatment. However, there is lack of information on the effect of different synthesis methods towards the properties and catalytic activity of the photocatalyst. In this research, a series of copper oxide doped titanium dioxide (Cu TiO2) photocatalysts were synthesized via three different methods of sonochemical, impregnation and physical mixing. Cu TiO2 of varied molar ratios of Cu dopant to TiO2 TR595 (1:99, 2:98, 3:97 and 4:96) were prepared. Comparison of physical-chemical properties and photocatalytic activity among the synthesized samples and unmodified TiO2 TR595 were made. X-ray diffraction analysis depicted the formation of TiO2 rutile phase in all samples. Besides, diffuse reflectance UV-visible analysis proved that the synthesized samples were active under visible light region. According to the Tauc plot and photoluminescence spectra, the band gap energies and recombination rate of electron-hole pairs of Cu TiO2 samples decreased upon loading of Cu. Moreover, EDX analysis confirmed the existence of Ti and Cu in all the samples. The photocatalytic efficiencies of the synthesized samples were discovered through photodegradation of Rhodamine B organic dye under 6 hours of visible light irradiation. Amongst, Cu TiO2 photocatalysts synthesized via sonochemical method with molar ratio of 2:98 produced the highest photocatalytic activity of 65% which attributed to the lowest recombination rate of photogenerated charge carriers and availability of large number of reactive oxidative species

Perceived Cultural Importance and Actual Self-Importance of Values in Cultural Identification

Cross-cultural psychologists assume that core cultural values define to a large extent what a culture is. Typically, core values are identified through an actual self-importance approach, in which core values are those that members of the culture as a group strongly endorse. In this article, the authors propose a perceived cultural importance approach to identifying core values, in which core values are values that members of the culture as a group generally believe to be important in the culture. In 5 studies, the authors examine the utility of the perceived cultural importance approach. Results consistently showed that, compared with values of high actual self-importance, values of high perceived Cultural importance play a more important role in cultural identification. These findings have important implications for conceptualizing and measuring cultures.Psychology, SocialSSCI53ARTICLE2337-3549

Transient receptor potential cation channel, subfamily V, member 4 and airway sensory afferent activation: Role of adenosine triphosphate

BackgroundSensory nerves innervating the airways play an important role in regulating various cardiopulmonary functions, maintaining homeostasis under healthy conditions and contributing to pathophysiology in disease states. Hypo-osmotic solutions elicit sensory reflexes, including cough, and are a potent stimulus for airway narrowing in asthmatic patients, but the mechanisms involved are not known. Transient receptor potential cation channel, subfamily V, member 4 (TRPV4) is widely expressed in the respiratory tract, but its role as a peripheral nociceptor has not been explored.ObjectiveWe hypothesized that TRPV4 is expressed on airway afferents and is a key osmosensor initiating reflex events in the lung.MethodsWe used guinea pig primary cells, tissue bioassay, in vivo electrophysiology, and a guinea pig conscious cough model to investigate a role for TRPV4 in mediating sensory nerve activation in vagal afferents and the possible downstream signaling mechanisms. Human vagus nerve was used to confirm key observations in animal tissues.ResultsHere we show TRPV4-induced activation of guinea pig airway–specific primary nodose ganglion cells. TRPV4 ligands and hypo-osmotic solutions caused depolarization of murine, guinea pig, and human vagus and firing of Aδ-fibers (not C-fibers), which was inhibited by TRPV4 and P2X3 receptor antagonists. Both antagonists blocked TRPV4-induced cough.ConclusionThis study identifies the TRPV4-ATP-P2X3 interaction as a key osmosensing pathway involved in airway sensory nerve reflexes. The absence of TRPV4-ATP–mediated effects on C-fibers indicates a distinct neurobiology for this ion channel and implicates TRPV4 as a novel therapeutic target for neuronal hyperresponsiveness in the airways and symptoms, such as cough

A handbook for using elder academy as a platform of other learning experiences

This handbook will discuss how school syllabus, Other Learning Experiences (OLE) and Elder Academy (EA) can be integrated. It will provide some structures for schools as a reference and help develop a comprehensive learning plan. Besides, the handbook will mention different roles and responsibilities of stakeholders, as well as the suggestions and guidelines for assessment. The programs and activities in the “Elder Academy at Lingnan” will be taken as examples to demonstrate the guidelines. This can provide a better understanding of the operation mode of the integration between school curricula, OLE and EA. Hence, interested stakeholders can perform their own plans more systematically and effectively.https://commons.ln.edu.hk/osl_book/1000/thumbnail.jp

Maximizing the potential of aggressive mouse tumor models in preclinical drug testing.

Atypical teratoid rhabdoid tumor (ATRT) is an aggressive embryonal brain tumor among infants and young children. Two challenges exist for preclinical testing in ATRT. First, genetically quiet, ATRT is a difficult tumor to target molecularly. Tumor cells need to divide to propagate tumor growth-intercepting the common crossroads in cell cycle progression is a feasible strategy. KIF11 is needed for bipolar spindle formation in metaphase. We identified KIF11 as a universal target of all ATRT-molecular-subtypes. Ispinesib, a KIF11-inhibitor, effectively inhibited tumor proliferation in all seven cell lines. A second challenge-a major challenge in preclinical drug testing in-vivo among aggressive tumor models, is the narrow therapeutic window to administer drugs within the limited murine lifespan. Our most aggressive ATRT tumor model was lethal in all mice within ~ 1 month of tumor implantation. Such short-surviving mouse models are difficult to employ for preclinical drug testing due to the narrow time window to administer drugs. To overcome this time restriction, we developed a clinical staging system which allowed physically-fit mice to continue treatment, in contrast to the conventional method of fixed drug-dose-duration regimen in preclinical testing which will not be feasible in such short-surviving mouse models. We validated this approach in a second embryonal brain tumor, medulloblastoma. This is a clinically relevant, cost-efficient approach in preclinical testing for cancer and non-cancer disease phenotypes. Widely used preclinical mouse models are not the most accurate and lack the aggressive tumor spectrum found within a single tumor type. Mice bearing the most aggressive tumor spectrum progress rapidly in the limited murine life-span, resulting in a narrow therapeutic window to administer drugs, and are thus difficult to employ in preclinical testing. Our approach overcomes this challenge. We discovered ispinesib is efficacious against two embryonal brain tumor types

Prevalence, awareness and control of hypertension in Malaysia from 1980-2018: a systematic review and meta-analysis

Background: Hypertension is a common public health problem worldwide and is a well-known risk factor for increased risk of cardiovascular diseases, contributing to high morbidity and mortality. However, there has been no systematic review and meta-analysis of a multiethnic population such as that of Malaysia. Aim: To determine the trend in prevalence, awareness and control rate of hypertension in Malaysia. Methods: Systematic searches were conducted in six databases (PubMed, Scopus, Ovid, CINAHL, Malaysian Medical Repository and Malaysia Citation Index) for articles published between 1980 and 2018. Two authors reviewed the studies and performed quality assessment and data extraction independently. Pooled estimates of hypertension prevalence, awareness and control rate were calculated using the DerSimonian-Laird random-effects model. Subgroup and sensitivity analyses were performed. Results: We included 56 studies involving a total of 241796 participants. The overall pooled prevalence of hypertension aged ≥ 18 years was 29.7%. The prevalence of hypertension was the lowest in the 1980s (16.2%, 95% confidence interval (CI): 13.4, 19.0), increasing up to 36.8% (95%CI: 6.1, 67.5) in the 1990s, then decreasing to 28.7% (95%CI: 21.7, 35.8) in the 2000s and 26.8% (95%CI: 21.3, 32.3) in the 2010s. The prevalence of awareness was 51.4% (95%CI: 46.6, 56.3), while 33.3% (95%CI: 28.4, 38.2) of those on treatment had achieved control of their blood pressure. Conclusion: In Malaysia, three in ten adults aged ≥ 18 years have hypertension, while four in ten adults aged ≥ 30 years have hypertension. Five out of ten people are aware of their hypertension status and only one-third of those under treatment achieved control of their hypertension. Concerted efforts by policymakers and healthcare professionals to improve awareness and control of hypertension should be of high priority