Comprehensive Systems Approach Research Articles

Evaluation of the impact of a 20-week exercise referral scheme on Mauritian adults diagnosed with non-communicable diseases

AbstractThe escalating prevalence of non-communicable diseases (NCD) presents a concern in Mauritius. These diseases, caused by many factors, reflect the social, economic and environmental conditions within which people live and work. Type 2 diabetes mellitus, hypertension and obesity are the most prevalent among Mauritian adults. Within the framework of a comprehensive systems approach aiming at addressing the social determinants of health, there is a need for customised strategies for both management and prevention of non-communicable diseases. One such example is exercise referral. Exercise referral schemes (ERS) represent an emerging tool for helping people become more physically active and healthier. Evidence of their effectiveness is equivocal and lacks contextual insight into their value in a Mauritian context. Hence, this study serves to bridge this gap. We report the outcomes of a 20-week ERS. Two hundred sixty consenting adults recruited from Area Health Centres (AHC) and Mediclinic’s around Mauritius were assigned to one of two groups: intervention group (ERS + guidance and support by exercise referral consultant) or control group (exercise ‘advice’ from a general practitioner). Body mass index (BMI), grip strength, waist circumference, fasting blood sugar (FBS), HbA1c, lipid profile and blood pressure were measured at week 0, 10 and 20. This quasi-experimental longitudinal study successfully demonstrated improvements in parameters associated with risk factors for coronary heart disease, particularly among women in the intervention group. Significant reductions in weight, waist circumference, FBS and BMI at week 10 and 20 were noted. A less pronounced decline in parameters was observed in men, except for waist circumference, which reached near significance (p = 0.076). Using female participants as a primary focal point, this study supports the notion of exercise referral as part of a holistic treatment plan to control NCDs. We advocate future ERS initiatives prioritise a patient-centred comprehensive approach in design and implementation to ensure successful outcomes.

Implementasi Konsep Akuntansi Syariah Dalam Pembangunan Infrastruktur Pada Ekonomi Biru Di Indonesia

There are 514 urban areas in the archipelagic nation of Indonesia (Ministry of Home Affairs, 2016). There are many cities in Indonesia that are able to provide a sense of comfort and security for their residents, this of course has an impact on population growth. However, the amount of waste that can be generated and stored is limited by the carrying capacity of the urban environment. Using the idea of ​​a "green city" which consists of nine elements of road infrastructure, traffic, green open space, clean water, noise, energy, housing, clean air and buildings is one way to overcome the above problems. All these qualities need to be utilized immediately with a comprehensive systems approach and in accordance with economic, social and environmental principles in sustainable development. Blue economy approaches can be used to eliminate waste. The “blue economy” is a term that is becoming increasingly popular in today's seas and oceans. The aim of this concept is to combine sea base development opportunities with environmental management and protection. Four conceptual interpretations of the blue economy were determined through research into the dominant discourse in international economic policy documents. How the blue economy works is also examined through an “in practice” analysis of the blue economy and related actors. Next, the scope and focus of the blue economy is explored specifically on the maritime industry, which is included or excluded in various conceptualizations. This analysis reveals areas of agreement and conflict. The consensus range reflects the growing trend towards the commercialization and valuation of nature, delineating and defining maritime boundaries and enhancing the security of the world's oceans. There are several areas of conflict, particularly disputes over the legitimacy of individuals as part of the “blue economy”, highly carbon-intensive industries such as oil and gas and the growing deep sea mining industry. Oceans are becoming increasingly important in terms of potential international trade opportunities through intermediaries and buyers. the behavior of the model supporting such a relationship in the ocean is acceptable from a regular and economic point of view. The relationship between land and sea is increasing in the role and importance of the "blue economy" as the term emerges in the background. . A literature review was conducted to analyze the correct definition of the blue economy. This definition is analyzed based on the minimum requirements that are important for the blue economy. This article also tries to compile various types of activities related to marine services. This is done to determine what can be considered priority areas for blue economic growth. The blue economy concept is based on national economic development. This is comprehensively useful for achieving overall national development. Environmental accounting is stated as a process of reducing negative values ​​and creating positive values ​​in environmental accountability.

The Barriers to Universal Health Coverage in India and the Strategies to Address Them: A Key Informant Study.

India has adopted several policies toward improving access to healthcare and has been an enthusiastic signatory to several global health policies to achieve Universal Health Coverage (UHC). However, despite these policy commitments, there has been limited success in realizing these goals. The COVID-19 pandemic has highlighted the urgent need for health system re-design and amplified the calls for such reforms. We seek to understand the views of a diverse group of policy actors in India to address the following research questions: what are the (i) conceptualizations of UHC, (ii) main barriers to realizing UHC, and (iii) policy strategies to address these barriers. We collected data through in-depth interviews with 38 policy actors from diverse backgrounds and analyzed using the Framework Method to develop themes both inductively and deductively using the Control Knob Framework of health systems. There was congruence in the conceptualization of UHC by policy actors. Quality of care, equity, financial risk protection, and a comprehensive set of services were the most commonly cited features. The lack of a comprehensive systems approach to health policies, inadequate and inefficient health financing mechanisms, and fragmentation between public and private sectors were identified as the main barriers to UHC. Contrasting views about specific strategies, health financing, provider payments, organization of the delivery system, and regulation emerged as the key policy interventions to address these barriers. This is the first systematic examination of a diverse set of policy actors' problem analyses and suggestions to advance UHC goals in India. The study underscores the need to recognize the complex and interlinked nature of health system reforms and initiate a departure from path-dependent vertical interventions to bring about transformative change.

Comprehensive application of a systems approach to obesity prevention: a scoping review of empirical evidence.

A systems approach to obesity prevention is increasingly urged. However, confusion exists on what a systems approach entails in practice, and the empirical evidence on this new approach is unclear. This scoping review aimed to identify and synthesise studies/programmes that have comprehensively applied a systems approach to obesity prevention in intervention development, delivery/implementation, and evaluation. By searching international databases and grey literature, only three studies (10 publications) met inclusion criteria, which might be explained partially by suboptimal reporting. No conclusion on the effectiveness of this approach can be drawn yet due to the limited evidence base. We identified common features shared by the included studies, such as measuring ongoing changes, in addition to endpoint outcomes, and supporting capacity building. Some facilitators and barriers to applying a comprehensive systems approach in practice were identified. More well-designed and reported studies are needed, especially from low- and middle-income countries.

Risk Management Options to Reduce Human Salmonellosis Cases Due to Consumption of Raw Poultry

Salmonella cases due to cross-contamination by, or consumption of, raw poultry continue to be a major public health concern. Processors have yet to identify an effective “kill step” in raw poultry production, and food safety interventions may target many compartments of the supply chain, from breeder and grandparent flocks to consumer cooking practices, complicating the prioritization of specific areas to effectively manage risk. Moreover, raw poultry can be contaminated by diverse Salmonella serovars, ranging from multidrug resistant Salmonella Infantis to pansusceptible Salmonella Kentucky sequence type 152, which has substantially reduced likelihood of causing human disease. “Farm-to-table” risk models help assess the public health impact of different Salmonella risk management strategies and thereby inform policy priorities. This article provides an overview of risk management practices that should be considered and evaluated in Salmonella risk assessments, including risk management strategies focusing on (i) preharvest; (ii) slaughter and further processing; (iii) consumer product handling; and (iv) regulatory approaches. Data and model needs to allow assessment of these risk management strategies are also discussed. The information presented here represents a critical step in ensuring that future Salmonella risk assessment and risk management efforts represent a comprehensive systems approach and consider all potential options for Salmonella risk reduction.

Factors Associated With Police Bringing Children to a Psychiatric Emergency Room.

Sensational headlines describing police entanglements with young children have prompted questions about how often these incidents occur and why. The authors of this cross-sectional study examined the factors associated with police versus nonpolice arrivals to the psychiatric emergency room and those predicting subsequent police arrivals. Electronic medical records of children ages 5.0-12.9 years brought to a comprehensive psychiatric emergency program (CPEP) at a university hospital were reviewed to determine whether a child was brought by police ("police arrival") in response to a 911 call by school personnel, a mental health or other medical professional, or a caregiver. Extracted data included the child's age, sex, race-ethnicity, family makeup, insurance status, arrival status, referral source, diagnosis, disposition, treatment, number of CPEP and police encounters, and occurrences of aggression and suicidality. Multilevel and ordinary logistic regression models were used to identify factors associated with a first and subsequent police arrival. Of 339 children with CPEP encounters from September 2017 to April 2018, 103 (30%) had had at least one police arrival. Children brought by police were more likely than peers brought by caregivers to be Black or Latinx, have Medicaid, come from families without two parents, and have aggressive outbursts or suicidal behavior. Results from multilevel logistic regression indicated that aggressive outbursts and suicidality were most significantly and consistently associated with experiencing both a first and subsequent police arrival. Clinical and sociodemographic differences in police arrivals highlight the need for a comprehensive systems approach for children, especially marginalized youths, who need psychiatric emergency care.

Closing the loopholes in circular economy definitions and assessments using ontological criteria, with a demonstration for Australia

The burgeon concept of Circular Economy (CE) has fundamental issues hindering clarity and comprehensive assessments. This paper uses established ontological criteria to review and improve the CE definition and (assessment) frameworks. The review reveals that mainstream CE definitions and assessments are fuzzy, shift problems, oversimplified and not synchronized. This causes many loopholes that not lead towards sustainability. Therefore, an improved definition and framework is proposed, specifically for CE of XL to XS regions (scales from planetary to neighborhoods). A CE should strive towards self-sufficiency on each scale to avoid problems shifting to other regions or future society. The framework elaborates on a comprehensive systems-approach, which connects the triple bottom line across nine ecosystem processes, eight societal processes, and six economic production processes. The proposed definition and framework are demonstrated in an assessment of regional pressures and their impacts of Australia with 2020 data. The framework aims to better inform decision-makers on trade-offs between vital processes to minimize unintended problem shifting. The definition and framework have improved universal application for meaningful comparisons and optimization towards a sustainable CE in any region.

A Multi-Systems Approach to Human Movement after ACL Reconstruction: The Nervous System

Postoperative rehabilitation of anterior cruciate ligament (ACL) reconstruction mainly focuses on the restoration of strength and range of motion with a long-term goal to return athletes to their prior level of activity. Of those wanting to return to sport, many are either unable and/or experience protracted recovery despite extensive rehabilitation. To holistically care for patients recovering from ACL reconstructions, reframing rehabilitation to consider a comprehensive systems approach (including musculoskeletal, cardiovascular, endocrine, and neurologic systems) may help improve treatment outcomes. The American Physical Therapy Association has adopted a vision statement that embraces the concept of a ‘movement system,’ but validation of the movement system has been challenging. Application of a multi-physiologic systems approach may provide a unique perspective to better understand the nervous system and its interactions after ACL reconstruction. The purpose is to focus on the nervous system contributions to a multi-physiologic system approach to rehabilitation from ACL reconstruction. Level of Evidence 5

Access to Burn Care in Low- and Middle-Income Countries: An Assessment of Timeliness, Surgical Capacity, and Affordability in a Regional Referral Hospital in Tanzania.

This study investigates patients’ access to surgical care for burns in a low- and middle-income setting by studying timeliness, surgical capacity, and affordability. A survey was conducted in a regional referral hospital in Manyara, Tanzania. In total, 67 patients were included. To obtain information on burn victims in need of surgical care, irrespective of time lapsed from the burn injury, both patients with burn wounds and patients with contractures were included. Information provided by patients and/or caregivers was supplemented with data from patient files and interviews with hospital administration and physicians. In the burn wound group, 50% reached a facility within 24 hours after the injury. Referrals from other health facilities to the regional referral hospital were made within 3 weeks for 74% in this group. Of contracture patients, 74% had sought healthcare after the acute burn injury. Of the same group, only 4% had been treated with skin grafts beforehand, and 70% never received surgical care or a referral. Together, both groups indicated that lack of trust, surgical capacity, and referral timeliness were important factors negatively affecting patient access to surgical care. Accounting for hospital fees indicated patients routinely exceeded the catastrophic expenditure threshold. It was determined that healthcare for burn victims is without financial risk protection. We recommend strengthening burn care and reconstructive surgical programs in similar settings, using a more comprehensive health systems approach to identify and address both medical and socioeconomic factors that determine patient mortality and disability.

School-entry requirements for HPV vaccination: part of the patchwork for HPV-related cancer prevention

ABSTRACT Human papillomavirus (HPV) vaccination can prevent six types of HPV-related cancers, and approximately, 54.2% of adolescents are up-to-date with the HPV vaccine in the United States. While moderate success has been achieved with provider- and parent-focused interventions, HPV vaccination in the U.S. lags well behind desired goals. In order to maximize HPV vaccination and prevention of HPV-related cancers, it may be prudent to consider state policy approaches, such as school-entry requirements as part of the patchwork of provider, parent, and structural interventions. In this paper, we reviewed the history of efforts to implement school-entry requirements for HPV vaccine, the challenges and benefits associated with implementing these requirements, and the evidence for the effectiveness of school-entry requirements. In addition, we presented new data from Rhode Island’s Immunization Information System (IIS) showing how their school-entry requirement, implemented in 2015, has impacted HPV vaccination rates. These registry data indicate that HPV vaccination rates improved significantly after the 2014–2015 school year and policy implementation, and add to the ongoing evidence supporting the value of school-entry requirements for HPV vaccination. School-entry requirements should be considered alongside other initiatives and policies for promoting HPV vaccine uptake. Taking a comprehensive systems approach to HPV vaccination is needed.

A readiness framework to evaluate local economy for an entrepreneurial university

PurposeThe purpose of this paper is to propose a framework for the transformation from a second-generation university to an entrepreneurial university. The work is practical and innovative, which provides the foundation for further work in this field.Design/methodology/approachBased on a systematic review of relevant studies on entrepreneurial universities, this paper proposed an evaluation framework with clear logic and practicability. This paper also provided a basis for further research. The restrictions of each factor were defined by the readiness framework, and the consequences of entrepreneurial activities on local economic development were analyzed by using the proposed model. The proposed conceptual framework aided policymakers in completing a much-needed assessment of the impact of organizational policies, practices and structures on the entrepreneurial activities and transformation from second-generation universities to third-generation organizations.FindingsThe proposed readiness framework led to the development of organizational interventions that facilitated successful entrepreneurial activities. The quantitative indicators of different university types were demonstrated in this study. The quantitative validation of the integrated framework suggested that university heads and policymakers can encourage and develop academic entrepreneurship by using a comprehensive systems approach for the identification, protection and commercialization of university’s intellectual property.Originality/valueThis paper provides a framework for policymakers or decision makers to better understand whether a local university is ready for entrepreneurship. This framework also provides a direction for future quantitative research.

Evaluating health service coverage in Ghana’s Volta Region using a modified Tanahashi model

ABSTRACT Background: The United Nations 2030 Sustainable Development Goals have reaffirmed the international community’s commitment to maternal, newborn, and child health, with further investments in achieving quality essential service coverage and financial protection for all. Objective: Using a modified version of the 1978 Tanahashi model as an analytical framework for measuring and assessing health service coverage, this paper aims to examine the system of care at the community level in Ghana’s Volta Region to highlight the continued reforms needed to achieve Universal Health Coverage. Methods: The Tanahashi model evaluates health system coverage through five key measures that reflect different stages along the service provision continuum: availability of services; accessibility; initial contact with the health system; continued utilization; and quality coverage. Data from cross-sectional household and health facility surveys were used in this study. Immunization and antenatal care services were selected as tracer interventions to serve as proxies to assess systems bottlenecks. Results: Financial access and quality coverage were identified as the biggest bottlenecks for both tracer indicators. Financial accessibility, measured by enrollment in Ghana’s National Health Insurance Scheme was poor with 16.94% presenting valid membership cards. Childhood immunization was high but dropped modestly from 93.8% at initial contact to 76.7% quality coverage. For antenatal care, estimates ranged from 65.9% at initial visit to 25.1% quality coverage. Conclusion: Results highlight the difficulty in achieving high levels of quality service coverage and the large variations that exist within services provided at the primary care level. While vertical investments have been prioritized to benefit specific health services, a comprehensive systems approach to primary health care needs to be further strengthened to reach Ghana’s Universal Health Coverage objectives.

Global childhood cancer survival estimates and priority-setting: a simulation-based analysis.

Accurate childhood cancer survival estimates are crucial for policy makers and clinicians for priority-setting and planning decisions. However, observed survival estimates are lacking for many countries, and when available, wide variation in outcomes is reported. Understanding the barriers to optimising survival can help improve childhood cancer outcomes. We aimed to provide estimates of global childhood cancer survival, accounting for the impact of multiple factors that affect cancer outcomes in children. We developed a microsimulation model to simulate childhood cancer survival for 200 countries and territories worldwide, accounting for clinical and epidemiologic factors, including country-specific treatment variables, such as availability of chemotherapy, radiation, and surgery. To ensure model results were consistent with reported survival data, we calibrated the model to estimates from the CONCORD-2 and CONCORD-3 studies using an Approximate Bayesian Computation approach. We estimated 5-year net survival for diagnosed cases of childhood cancer in each country and territory and estimated potential survival gains of seven policy interventions focused on improving treatment availability and delivery (ie, increasing the availability of chemotherapy, radiation, general surgery, neurosurgery, or ophthalmic surgery, reducing treatment abandonment, and improving the quality of care to the mean of high-income countries) implemented in isolation or as packages. Our model estimated that, for diagnosed cases, global 5-year net childhood cancer survival is currently 37·4% (95% uncertainty interval 34·7-39·8), with large variation by region, ranging from 8·1% (4·4-13·7) in eastern Africa to 83·0% (81·6-84·4) in North America. Among the seven policy interventions modelled, each individually provided small gains, increasing global 5-year net survival to between 38·4% (35·8-40·9) and 44·6% (41·7-47·4). 5-year net survival increased more substantially when policy interventions were bundled into packages that improved service delivery (5-year net survival 50·2% [47·3-53·0]) or that expanded treatment access (54·1% [50·1-58·5]). A comprehensive systems approach consisting of all policy interventions yielded superadditive gains with a global 5-year net survival of 53·6% (51·5-55·6) at 50% scale-up and 80·8% (79·5-82·1) at full implementation. Childhood cancer survival varies widely by region, with especially poor survival in Africa. Although expanding access to treatment (chemotherapy, radiation, and surgery) and addressing financial toxicity are essential, investments that improve the quality of care, at both the health-system and facility level, are needed to improve childhood cancer outcomes globally. Boston Children's Hospital, Dana-Farber Cancer Institute, Harvard TH Chan School of Public Health, Harvard Medical School, National Cancer Institute, SickKids, St Jude Children's Research Hospital, Union for International Cancer Control, Children with Cancer UK Davidson and O'Gorman Fellowship.

Improving Working Conditions to Promote Worker Safety, Health, and Wellbeing for Low-Wage Workers: The Workplace Organizational Health Study.

This paper addresses a significant gap in the literature by describing a study that tests the feasibility and efficacy of an organizational intervention to improve working conditions, safety, and wellbeing for low-wage food service workers. The Workplace Organizational Health Study tests the hypothesis that an intervention targeting the work organization and environment will result in improvements in workers’ musculoskeletal disorders and wellbeing. This ongoing study is being conducted in collaboration with a large food service company. Formative evaluation was used to prioritize outcomes, assess working conditions, and define essential intervention elements. The theory-driven intervention is being evaluated in a proof-of-concept trial, conducted to demonstrate feasibility and potential efficacy using a cluster randomized design. Ten worksites were randomly assigned to intervention or control conditions. The 13-month intervention uses a comprehensive systems approach to improve workplace policies and practices. Using principles of participatory engagement, the intervention targets safety and ergonomics; work intensity; and job enrichment. The evaluation will provide a preliminary assessment of estimates of the intervention effect on targeted outcomes and inform understanding of the intervention implementation across worksites. This study is expected to provide insights on methods to improve working conditions in support of the safety and wellbeing of low-wage workers.

Systems pharmacology-based investigation of Sanwei Ganjiang Prescription: related mechanisms in liver injury

AbstractLiver injury remains a significant global health problem and has a variety of causes, including oxidative stress (OS), inflammation, and apoptosis of liver cells. There is currently no curative therapy for this disorder. Sanwei Ganjiang Prescription (SWGJP), derived from traditional Chinese medicine (TCM), has shown its effectiveness in long-term liver damage therapy, although the underlying molecular mechanisms are still not fully understood. To explore the underlining mechanisms of action for SWGJP in liver injury from a holistic view, in the present study, a systems pharmacology approach was developed, which involved drug target identification and multilevel data integration analysis. Using a comprehensive systems approach, we identified 43 candidate compounds in SWGJP and 408 corresponding potential targets. We further deciphered the mechanisms of SWGJP in treating liver injury, including compound-target network analysis, target-function network analysis, and integrated pathways analysis. We deduced that SWGJP may protect hepatocytes through several functional modules involved in liver injury integrated-pathway, such as Nrf2-dependent anti-oxidative stress module. Notably, systems pharmacology provides an alternative way to investigate the complex action mode of TCM.

A systems pharmacology-oriented discovery of a new therapeutic use of the TCM formula Liuweiwuling for liver failure

Multiple components of traditional Chinese medicine (TCM) formulae determine their treatment targets for multiple diseases as opposed to a particular disease. However, discovering the unexplored therapeutic potential of a TCM formula remains challenging and costly. Inspired by the drug repositioning methodology, we propose an integrated strategy to feasibly identify new therapeutic uses for a formula composed of six herbs, Liuweiwuling. First, we developed a comprehensive systems approach to enrich drug compound-liver disease networks to analyse the major predicted diseases of Liuweiwuling and discover its potential effect on liver failure. The underlying mechanisms were subsequently predicted to mainly attribute to a blockade of hepatocyte apoptosis via a synergistic combination of multiple effects. Next, a classical pharmacology experiment was designed to validate the effects of Liuweiwuling on different models of fulminant liver failure induced by D-galactosamine/lipopolysaccharide (GalN/LPS) or thioacetamide (TAA). The results indicated that pretreatment with Liuweiwuling restored liver function and reduced lethality induced by GalN/LPS or TAA in a dose-dependent manner, which was partially attributable to the abrogation of hepatocyte apoptosis by multiple synergistic effects. In summary, the integrated strategy discussed in this paper may provide a new approach for the more efficient discovery of new therapeutic uses for TCM formulae.

Strategies to Reduce Greenhouse Gas Emissions from Laparoscopic Surgery.

To determine the carbon footprint of various sustainability interventions used for laparoscopic hysterectomy. We designed interventions for laparoscopic hysterectomy from approaches that sustainable health care organizations advocate. We used a hybrid environmental life cycle assessment framework to estimate greenhouse gas emissions from the proposed interventions. We conducted the study from September 2015 to December 2016 at the University of Pittsburgh (Pittsburgh, Pennsylvania). The largest carbon footprint savings came from selecting specific anesthetic gases and minimizing the materials used in surgery. Energy-related interventions resulted in a 10% reduction in carbon footprint per case but would result in larger savings for the whole facility. Commonly implemented approaches, such as recycling surgical waste, resulted in less than a 5% reduction in greenhouse gases. To reduce the environmental emissions of surgeries, health care providers need to implement a combination of approaches, including minimizing materials, moving away from certain heat-trapping anesthetic gases, maximizing instrument reuse or single-use device reprocessing, and reducing off-hour energy use in the operating room. These strategies can reduce the carbon footprint of an average laparoscopic hysterectomy by up to 80%. Recycling alone does very little to reduce environmental footprint. Public Health Implications. Health care services are a major source of environmental emissions and reducing their carbon footprint would improve environmental and human health. Facilities seeking to reduce environmental footprint should take a comprehensive systems approach to find safe and effective interventions and should identify and address policy barriers to implementing more sustainable practices.

Integrated Systems Approach Reveals Sphingolipid Metabolism Pathway Dysregulation in Association with Late-Onset Alzheimer's Disease.

Late-onset Alzheimer’s disease (LOAD) and age are significantly correlated such that one-third of Americans beyond 85 years of age are afflicted. We have designed and implemented a pilot study that combines systems biology approaches with traditional next-generation sequencing (NGS) analysis techniques to identify relevant regulatory pathways, infer functional relationships and confirm the dysregulation of these biological pathways in LOAD. Our study design is a most comprehensive systems approach combining co-expression network modeling derived from RNA-seq data, rigorous quality control (QC) standards, functional ontology, and expression quantitative trait loci (eQTL) derived from whole exome (WES) single nucleotide variant (SNV) genotype data. Our initial results reveal several statistically significant, biologically relevant genes involved in sphingolipid metabolism. To validate these findings, we performed a gene set enrichment analysis (GSEA). The GSEA revealed the sphingolipid metabolism pathway and regulation of autophagy in association with LOAD cases. In the execution of this study, we have successfully tested an integrative approach to identify both novel and known LOAD drivers in order to develop a broader and more detailed picture of the highly complex transcriptional and regulatory landscape of age-related dementia.

In Memoriam: Stephen Malkin

In Memoriam: Stephen Malkin

Molecular and cellular signatures underlying superior immunity against Bordetella pertussis upon pulmonary vaccination

Mucosal immunity is often required for protection against respiratory pathogens but the underlying cellular and molecular mechanisms of induction remain poorly understood. Here, systems vaccinology was used to identify immune signatures after pulmonary or subcutaneous immunization of mice with pertussis outer membrane vesicles. Pulmonary immunization led to improved protection, exclusively induced mucosal immunoglobulin A (IgA) and T helper type 17 (Th17) responses, and in addition evoked elevated systemic immunoglobulin G (IgG) antibody levels, IgG-producing plasma cells, memory B cells, and Th17 cells. These adaptive responses were preceded by unique local expression of genes of the innate immune response related to Th17 (e.g., Rorc) and IgA responses (e.g., Pigr) in addition to local and systemic secretion of Th1/Th17-promoting cytokines. This comprehensive systems approach identifies the effect of the administration route on the development of mucosal immunity, its importance in protection against Bordetella pertussis, and reveals potential molecular correlates of vaccine immunity to this reemerging pathogen.