Characteristics of immunisation support programmes in Canada: a scoping review and environmental scan.

OBJECTIVE: To identify, characterise and map the existing knowledge about programmes that provide immunisation support to Canadians and barriers and facilitators to their delivery. DESIGN: Scoping review and environmental scan. INTRODUCTION: Vaccine hesitancy may be associated with unmet support needs of individuals. Immunisation support programmes that provide multicomponent approaches can improve vaccine confidence and equitable access. INCLUSION CRITERIA: Canadian programmes that focus on providing information about immunisation for the general public, but excluding articles targeting health professionals. The primary concept involves mapping the characteristics of programmes and our secondary concept examines barriers and facilitators to programme delivery. METHODS: The Joanna Briggs Institute (JBI) methodology guided this review, reported using the Preferred Reporting Items for Systematic Reviews and Meta-Analyses extension for Scoping Reviews. A search strategy was developed and translated for six databases in November 2021 (updated October 2022). Unpublished literature was identified through the Canadian Agency for Drugs and Technologies in Health Grey Matters checklist and other relevant sources. Stakeholders (n=124) from Canadian regional health authorities were also contacted by email for publicly accessible information. Two independent raters screened and extracted data from identified material. Results are presented in tabular form. RESULTS: The search strategy and environmental scan resulted in 15 287 sources. A total of 161 full-text sources were reviewed after applying eligibility criteria, resulting in 50 articles. Programmes were delivered in multiple Canadian provinces, focusing on various vaccine types. All programmes aimed to increase vaccine uptake and were mostly provided in person. Multidisciplinary delivery teams based on collaborations among multiple entities were credited as a facilitator to programme delivery across settings. Limitations on programme resources, attitudes of programme staff and participants, and systems organisation were identified as barriers to delivery. CONCLUSIONS: This review highlighted characteristics of immunisation support programmes across various settings and described multiple facilitators and barriers. These findings can inform future interventions that aim to support Canadians in making decisions about immunisation.

Interaction between Chinese medicine and digoxin: Clinical and research update.

Background: Digoxin is one of the most widely and commonly used cardiac drug, which plays an irreplaceable role in treating heart failure and arrhythmia. The 2010 Edition of Pharmacopoeia of the People's Republic of China stipulates that the effective range of digoxin plasma concentration is 0.5-2.0 ng/mL and it is toxic at plasma concentration >2 ng/mL. Its effective plasma drug concentration is close to the toxic concentration, and large individual differences in the effects of the drug have been observed. It is often used in combination with other drugs, but drug interactions have a great impact on the plasma concentration of digoxin and lead to adverse reactions (ADRs), such as poisoning. Most of the reported drug interactions are with Western drugs. However, there are many combinations of traditional Chinese medicine (TCM) and Western drugs, TCM interacting with digoxin comprises monomer components, single medicines, and Chinese patent medicines. Aim of the study: We aimed i) to provide an overview of the TCM formulations affecting the pharmacology of digoxin and their mechanisms of action and ii) to provide a theoretical reference for the safe and rational use of digoxin in combination with TCM in clinical practice and to avoid ADRs. Methods: A literature search of electronic databases, including PubMed, MEDLINE, Cochrane Library, Web of Science, China National Knowledge Infrastructure, and WANFANG Data, was performed to search for articles published between 1 January 1960, and 1 August 2022. Search terms used included "digoxin," "traditional Chinese medicine," "Chinese patent medicine," and "adverse reactions" and their combinations. Results: A total of 49 articles were obtained, including clinical reports, pharmacological experiments and in vitro experiments. The mechanisms of action affecting the pharmacology of digoxin are complex. TCM formulations may affect the pharmacology of digoxin in vivo by influencing gastrointestinal motility or gastric juice pH, regulating P-glycoprotein levels, exerting cumulative pharmacological effects, and enhancing the sensitivity of the heart to digoxin. Although studies have shown that some TCM formulations interact with digoxin, they may be influenced by the complexity of the composition and the pharmacological effects of the TCM, the sensitivity of digoxin concentration determination methods, etc. The results of existing studies are controversial and further in-depth studies are required. Conclusion: Combinations of digoxin and TCM formulations are commonly used. This article serves as a reference to understand the interactions between TCM formulations and digoxin to avoid the occurrence of ADRs and improve the efficacy and safety of digoxin.

Complement C3 and Activated Fragment C3a Are Involved in Complement Activation and Anti-Bacterial Immunity.

In the complement system, C3 is a central component in complement activation, immune defense and immune regulation. In all pathways of complement activation, the pivotal step is conversion of the component C3 to C3b and C3a, which is responsible to eliminate the pathogen and opsonization. In this study, we examined the immunological properties of C3 and its activated fragment C3a from Japanese flounder (Paralichthys olivaceus) (PoC3 and PoC3a), a teleost species with important economic value. PoC3 is composed of 1655 amino acid residues, contains the six domains and highly conserved GCGEQ sequence of the C3 family. We found that PoC3 expression occurred in nine different tissues and was upregulated by bacterial challenge. In serum, PoC3 was able to bind to a broad-spectrum of bacteria, and purified native PoC3 could directly kill specific pathogen. When PoC3 expression in Japanese flounder was knocked down by siRNA, serum complement activity was significantly decreased, and bacterial replication in fish tissues was significantly increased. Recombinant PoC3a (rPoC3a) exhibited apparent binding capacities to bacteria and Japanese flounder peripheral blood leukocytes (PBL) and induce chemotaxis of PBL. Japanese flounder administered rPoC3a exhibited enhanced resistance against bacterial infection. Taken together, these results indicate that PoC3 is likely a key factor of complement activation, and PoC3 and PoC3a are required for optimal defense against bacterial infection in teleost.

miR-296-5p Inhibits the Secretion of Pulmonary Surfactants in Pulmonary Epithelial Cells via the Downregulation of Wnt7b/ß-Catenin Signaling.

Neonatal respiratory distress syndrome (NRDS) is a common disease that occurs in premature infants. However, the mechanisms underlying the disease remain unclear. microRNAs (miRNAs) have been indicated to play a crucial role in the development of NRDS. In this study, we aimed to explore the regulatory mechanisms of miR-296-5p in NRDS. The expression levels of miR-296-5p in preterm infants with NRDS were determined using quantitative reverse-transcription polymerase chain reaction (RT-qPCR). A549 cells were transfected with lentiviral vectors encoding miR-296-5p, and the transfection efficiency was determined using RT-qPCR. Flow cytometry and CCK8 assay were performed to measure apoptosis and proliferation of A549 cells, respectively. The protein levels of pulmonary surfactant SP-A (SFTPA1), SP-B, Wnt7b, and ß-catenin were measured using western blotting. We demonstrated an upregulation of miR-296-5p in NRDS. The miR-296-5p was successfully overexpressed in A549 cells via lentivirus transfection, and the upregulation of miR-296-5p inhibited cell proliferation and secretion of SP-A and SP-B and also induced downregulation of the Wnt7b/ß-catenin in vitro. Therefore, miR-296-5p inhibits cell proliferation and secretion of pulmonary surfactants in A549 cells via downregulation of Wnt7b/ß-catenin signaling.

The Translocation and Assembly Module (TAM) of Edwardsiella tarda Is Essential for Stress Resistance and Host Infection.

Translocation and assembly module (TAM) is a protein channel known to mediate the secretion of virulence factors during pathogen infection. Edwardsiella tarda is a Gram-negative bacterium that is pathogenic to a wide range of farmed fish and other hosts including humans. In this study, we examined the function of the two components of the TAM, TamA and TamB, of E. tarda (named tamA Et and tamB Et, respectively). TamAEt was found to localize on the surface of E. tarda and be recognizable by TamAEt antibody. Compared to the wild type, the tamA and tamB knockouts, TX01ΔtamA and TX01ΔtamB, respectively, were significantly reduced in motility, flagella formation, invasion into host cells, intracellular replication, dissemination in host tissues, and inducing host mortality. The lost virulence capacities of TX01ΔtamA and TX01ΔtamB were restored by complementation with the tamA Et and tamB Et genes, respectively. Furthermore, TX01ΔtamA and TX01ΔtamB were significantly impaired in the ability to survive under low pH and oxidizing conditions, and were unable to maintain their internal pH balance and cellular structures in acidic environments, which led to increased susceptibility to lysozyme destruction. Taken together, these results indicate that TamAEt and TamBEt are essential for the virulence of E. tarda and required for E. tarda to survive under stress conditions.

Prevention of systemic inflammation and neuroprotective effects of Qingda granules against angiotensin II-mediated hypertension.

Qingxuan Jiangya Decoction (QXJYD), prescribed by academician Ke-ji Chen, has long been used as a Traditional Chinese Medicine formula in blood pressure control and has achieved good clinical outcomes in hypertensive patients. Qingda granules (QDGs), which is a formula simplified from QXJYD, might serve as a novel anti-hypertensive pharmaceutical. However, the functional mechanism of QDGs remains unclear. This study aimed to evaluate the effect of QDGs against the elevation of blood pressure, systemic inflammation and brain injury in Ang II-mediated hypertensive mice. Ang II-mediated hypertensive mice were treated with 28.63mg QDG of per mouse every day. The blood pressure of all mice was measured on days 0, 1, 3, 5, 7, 14 and 28 by using the tail-cuff plethysmograph method. Following 28 days of treatment, the mice were sacrificed and their whole blood and brain tissues were used for analysis. The results showed that QDGs significantly decreased elevated systolic and diastolic blood pressure in Ang II-mediated hypertensive mice while body weight did not change, which demonstrated anti-hypertensive activities of QDGs without obvious toxicity. QDGs significantly attenuated the level of serum cytokines (IL-6, TNF-a) and chemokines (MCP-1, MIP-1a, RANTES) in the Ang II-mediated hypertensive mice. Moreover, pathological staining showed that QDGs significantly ameliorated cerebral histopathology changes, reduced the loss of neurons and activations of astrocytes. Additionally, QDGs inhibited neuronal apoptosis by down-regulation of Bax expression and up-regulation of Bcl-2 expression. These results suggested that QDGs exhibited excellent anti-hypertensive properties by preventing systemic inflammation and providing neuroprotective effects against Ang II-mediated hypertension.

The trypsin-like serine protease domain of Paralichthys olivaceus complement factor I regulates complement activation and inhibits bacterial growth.

In mammals, complement factor I (CFI) is a serine protease in serum and plays a pivotal role in the regulation of complement activation. In the presence of cofactor, CFI cleaves C3b to iC3b, and further degrades iC3b to C3c and C3d. In teleost, the function of CFI is poorly understood. In this study, we examined the immunological property of CFI from Japanese flounder (Paralichthys olivaceus) (PoCFI), a teleost species with important economic value. PoCFI is composed of 597 amino acid residues and possesses a trypsin-like serine protease (Tryp) domain. We found that PoCFI expressions occurred in nine different tissues and were upregulated by bacterial challenge. Recombinant PoCFI-Tryp (rPoCFI-Tryp) inhibited complement activation and degraded C3b in serum. rPoCFI-Tryp exhibited apparent binding capacities to a board-spectrum of bacteria and inhibited bacterial growth. These results provide the first evidence to indicate that CFI in teleost negatively regulates complement activation via degradation C3b, and probably plays a role in host immune defense against bacterial infection.

Bis(nitrato-κO)(3-oxapentane-1,5-diamine-κN,O,N')zinc(II).

In the title compound, [Zn(NO(3))(2)(C(4)H(12)N(2)O)], the Zn(II) atom is N,O,N'-chelated by a 3-oxapentane-1,5-diamine ligand and is further coordinated by two nitrate anions in a distorted trigonal-bipyramidal geometry. Inter-molecular N-H⋯O hydrogen bonding is present in the crystal structure. A short O⋯O contact of 2.816 (8) Šis observed between the nitrate anions of adjacent mol-ecules.