Vaccine innovation model: A technology transfer perspective in pandemic contexts

This work identifies the innovations that made it possible for the Bio-Manguinhos/Fiocruz Immunobiological Technology Institute to engage in the entire production of the Oxford/AstraZeneca vaccine (ChAdOx1 nCov-19) in Brazil, just 1.8 years after the COVID-19 pandemic was declared. The results were summarized in a case-based innovation model composed of 11 workstreams, 32 stages, 22 gates, 11 innovations, and 38 events. In terms of research contributions, three were found: (i) the identification of firm and government-level innovations allowing the substantial reduction in the COVID-19 vaccine time-to-market in Brazil; (ii) the presentation of empirical evidence supporting the new Outbreak Paradigm for vaccine research, development, and production; and (iii) the proposition of a conceptual model for describing innovations through the vaccine value chain in pandemic contexts, particularly when technology transfer is involved.     

Preoperative comprehensive malignancy risk estimation for thyroid nodules: Development and verification of a network-based prediction model

BackgroundIn order to avoid excessive treatment of thyroid nodules in the clinic, it is necessary to find a simple and practical analysis method to comprehensively and accurately reflect benign or malignant thyroid nodules. This study aimed to construct and validate a comprehensive and reliable network-based predictive model using a variety of imaging and laboratory criteria for thyroid nodules to stratify the risk of malignancy prior to surgery.MethodsWe retrospectively analyzed data from patients who underwent surgical treatment for thyroid nodules at the Thyroid and Breast Diagnosis and Treatment Center of Weifang Hospital of Traditional Chinese Medicine between January 2018 and December 2020. Binary logical regression analysis was performed to predict whether nodules were malignant or benign. The developmental dataset included 457 patients (January 2018–December 2020). The validation set included separate data points (n = 225, January 2018–December 2020).ResultsIn this study, criteria that showed significant predictive value for malignant nodules included TI-RADS: 4b (p = 0.065); Bethesda IV, Bethesda V, Bethesda VI (P < 0.0001); BRAF^V600E mutation (P < 0.0001); Calcitonin>5 pg/ml (p = 0.0037); and FNA-Tg>30 ng/ml (p = 0.0003). A 10-grade risk scoring system was developed. The risk of malignancy risk ranged from 2.06% to 100% and was positively associated with increasing risk grade. The areas under the receiver-operating characteristic curve of the development and validation sets were 0.972 and 0.946, respectively.ConclusionA simple, comprehensive and reliable web-based predictive model was designed using a variety of imaging and laboratory criteria to stratify thyroid nodules by probability of malignancy.     

Cytokine and LL-37 gene expression levels in Bartonella spp. seropositive and seronegative patients of a rheumatology clinic

PurposeThe variation in the immune response to Bartonella spp. infection in humans remains unclear. The present study compares the expression of selected interleukins, cytokines and cathelicidin (LL-37) in rheumatology clinic patients suffering from musculoskeletal symptoms with healthy blood donors. The patients had previously been tested for the presence of Bartonella henselae antibodies.MethodsGene expression of LL-37, interleukin (IL)-2, IL-4, IL-6, IL-12, interferon-(IFN)-γ, and tumor necrosis factor (TNF-α)-α was determined in blood samples using quantitative Polymerase Chain Reaction (qPCR). Statistical analysis was prepared with STATISTICA.ResultsStatistically significant differences in the mRNA levels of the tested cytokines (IFN-γ, TNF-α, IL-2, IL-4, IL-6, IL-12; p<0.0001) were observed between the healthy controls and patients; however, no difference was observed for LL37 mRNA (p ?= ?0.1974). No significant differences in mRNA expression were observed between IgG in anti-Bartonella seropositive and seronegative individuals (p>0.05). The only significant differences between the Bartonella spp. DNA positive and negative patients, indicated by PCR, were observed for TNF-α and IL-12 mRNA (p ?= ?0.0045 and p ?= ?0.0255, respectively).ConclusionA broadly similar immune response to the tested cytokines was observed among the participants irrespective of anti-Bartonella spp. IgG seropositivity. However, the Bartonella DNA-positive participants demonstrated significantly lower expression of IL-12 and TNF-α mRNA; this may indicate that these bacteria have a suppressive influence on the immune system.     

Repurposing of parenterally administered active substances used to treat pain both systemically and locally

Pain is a constant in our lives. The efficacy of drug therapy administered by the parenteral route is often limited either by the physicochemical characteristics of the drug itself or its adsorption–distribution–metabolism–excretion (ADME) mechanisms. One promising alternative is the design of innovative drug delivery systems that can improve the pharmacokinetics |(PK) and/or reduce the toxicity of traditionally used drugs. In this review, we discuss several products that have been approved by the main regulatory agencies (i.e., nano- and microsystems, implants, and oil-based solutions), highlighting the newest technologies that govern both locally and systemically the delivery of drugs. Finally, we also discuss the risk assessment of the scale-up process required, given the impact that this approach could have on drug manufacturing.Teaser: The management of pain by way of the parenteral route can be improved using complex drug delivery systems (e.g., micro- and nanosystems) which require high-level assessment and shorten the regulatory pathway.     

Process evaluation of implementation strategies to reduce potentially inappropriate medication prescribing in older population: A scoping review

ObjectivesSeveral implementation strategies can reduce potentially inappropriate medication (PIM) prescribing. Although use of PIMs has declined in recent years, it remains prevalent. Various strategies exist to improve the appropriateness of medication use. However, little is known about the processes of these different implementation strategies. This scoping review aims to investigate how the process evaluation of implementation strategies for reducing PIM prescribing in the older population has been studied.MethodsWe searched for process evaluations of implementation strategies for reducing PIM prescribing in PUBMED, SCOPUS and Web of Science published between January 2000 and November 2019 in English. We applied the following inclusion criteria: patients aged ≥65 years, validated PIM criteria, and implementation process evaluated. The review focuses on decision support for health care professionals. We described the findings of the process evaluations, and compared the authors’ concepts of process evaluation of the included publications to those of Proctor et al.( 2010).ResultOf 9131 publications screened, 29 met our inclusion criteria. Different process evaluation conceptualizations were identified. Most process evaluations took place in the initial stages of the process (acceptability, adoption, appropriateness, and feasibility) and sustainability and implementation costs were seldom evaluated. None of the included publications evaluated fidelity.Multifaceted interventions were the most studied implementation strategies. Medication review was more common in acceptability evaluations, multidisciplinary interventions in adoption evaluations, and computerized systems and educational interventions in feasibility evaluations. Process evaluations were studied from the health care professionals’ viewpoint in most of the included publications, but the management viewpoint was missing.DiscussionThe conceptualization of process evaluation in the field of PIM prescribing is indeterminate. There is also a current gap in the knowledge of sustainability and implementation costs. Clarifying the conceptualization of implementation process evaluation is essential in order to effectively translate research knowledge into practice.     

林兰教授运用柴胡芍药枳实甘草汤临证探析

林兰教授对柴胡芍药枳实甘草汤有独特的理论见解。柴胡芍药枳实甘草汤证的病机，在经为邪郁少阳、气机壅滞，主气郁；在腑为经隧挛急、胆气不降。柴胡芍药枳实甘草汤和解少阳，理气开滞，舒挛止痛，为临床舒畅气血、治疗气郁之名方，临证可用于甲状腺疾病、肝胆疾病、乳腺疾病、妇科疾病及多种疑难杂症。     

Hepatitis B and circadian rhythm of the liver

The circadian rhythm in humans is determined by the central clock located in the hypothalamus’s suprachiasmatic nucleus, and it synchronizes the peripheral clocks in other tissues. Circadian clock genes and clock-controlled genes exist in almost all cell types. They have an essential role in many physiological processes, including lipid metabolism in the liver, regulation of the immune system, and the severity of infections. In addition, circadian rhythm genes can stimulate the immune response of host cells to virus infection. Hepatitis B virus (HBV) infection is the leading cause of liver disease and liver cancer globally. HBV infection depends on the host cell, and hepatocyte circadian rhythm genes are associated with HBV replication, survival, and spread. The core circadian rhythm proteins, REV-ERB and brain and muscle ARNTL-like protein 1, have a crucial role in HBV replication in hepatocytes. In addition to influencing the virus’s life cycle, the circadian rhythm also affects the pharmacokinetics and efficacy of antiviral vaccines. Therefore, it is vital to apply antiviral therapy at the appropriate time of day to reduce toxicity and improve the effectiveness of antiviral treatment. For these reasons, understanding the role of the circadian rhythm in the regulation of HBV infection and host responses to the virus provides us with a new perspective of the interplay of the circadian rhythm and anti-HBV therapy. Therefore, this review emphasizes the importance of the circadian rhythm in HBV infection and the optimization of antiviral treatment based on the circadian rhythm-dependent immune response.