Early Bird Gets the Flu: What Should Be Done About Waning Intraseasonal Immunity Against Seasonal Influenza?

Recently published studies highlight the growing evidence for waning immunity within a single influenza season among vaccinated individuals. However, the public health efforts to increase vaccination coverage has resulted in earlier administration of vaccines. We find this approach to be suboptimal, as the benefits of early vaccination could be lost during peak months of influenza activity. Immunity generated by influenza vaccines is a complex scientific issue with many contributing factors. We advocate for a nuanced approach to the seasonal vaccine program- one that considers duration of immunity as much as it considers coverage. As we strive for higher rates of vaccination, we must also improve the efficacy of the vaccine and the public health programs that are responsible for distributing and administering the vaccine.

Wastewater surveillance for SARS-CoV-2 to support return to campus: Methodological considerations and data interpretation.

The COVID-19 pandemic has been challenging for various institutions such as school systems due to widespread closures. As schools re-open their campuses to in-person education, there is a need for frequent screening and monitoring of the virus to ensure the safety of students and staff and to limit risk to the surrounding community. Wastewater surveillance (WWS) of SARS-CoV-2 is a rapid and economical approach to determine the extent of COVID-19 in the community. The focus of this review is on the emergence of WWS as a tool for safe return to school campuses, taking into account methodological considerations such as site selection, sample collection and processing, SARS-CoV-2 quantification, and data interpretation. Recently published studies on the implementation of COVID-19 WWS on school and college campuses were reviewed. While there are several logistical and technical challenges, WWS can be used to inform decision-making at the school campus and/or building level.

Nanofibrous spongy microspheres to deliver rabbit mesenchymal stem cells and anti-miR-199a to regenerate nucleus pulposus and prevent calcification.

Lower back pain is mainly caused by intervertebral disc degeneration, in which calcification is frequently involved. Here novel nanofibrous spongy microspheres (NF-SMS) are used to carry rabbit bone marrow mesenchymal stromal cells (MSCs) to regenerate nucleus pulposus tissues. NF-SMS are shown to significantly enhance the MSC seeding, proliferation and differentiation over control microcarriers. Furthermore, a hyperbranched polymer (HP) with negligible cytotoxicity and high microRNA (miRNAs) binding affinity is synthesized. The HP can complex with anti-miR-199a and self-assemble into "double shell" polyplexes which are able to achieve high transfection efficiency into MSCs. A double-emulsion technique is used to encapsulate these polyplexes in biodegradable nanospheres (NS) to enable sustained anti-miR-199 delivery. Our results demonstrate that MSC/HP-anti-miR-199a/NS/NF-SMS constructs can promote the nucleus pulposus (NP) phenotype and resist calcification in vitro and in a subcutaneous environment. Furthermore, injection of MSC/HP-anti-miR-199a/NS/NF-SMS can stay in place, produce functional extracellular matrix, maintain disc height and prevent intervertebral disc (IVD) calcification in a rabbit lumbar degeneration model.

Controlled release of odontogenic exosomes from a biodegradable vehicle mediates dentinogenesis as a novel biomimetic pulp capping therapy.

Mineralized enamel and dentin provide protection to the dental pulp, which is vital tissue rich with cells, vasculature, and nerves in the inner tooth. Dental caries left untreated threaten exposure of the dental pulp, providing facile access for bacteria to cause severe infection both in the pulp and systemically. Dental materials which stimulate the formation of a protective dentin bridge after insult are necessary to seal the pulp chamber in an effort to maintain natural dentition and prevent pulpal infection. Dental materials to date including calcium hydroxide paste, mineral trioxide aggregate, and glass ionomer resin, are used with mixed results. Herein we exploited the cell-cell communicative properties of exosomes, extracellular vesicles derived from both mineralizing primary human dental pulp stem cells (hDPSCs) and an immortalized murine odontoblast cell line (MDPC-23), to catalyze the formation of a reactionary dentin bridge by recruiting endogenous stem cells of the dental pulp, through an easy-to-handle delivery vehicle which allows for their therapeutic controlled delivery at the pulp interface. Exosomes derived from both hDPSCs and MDPCs upregulated odontogenic gene expression and increased mineralization in vitro. We designed an amphiphilic synthetic polymeric vehicle from a triblock copolymer which encapsulates exosomes by polymeric self-assembly and maintains their biologic integrity throughout release up to 8-12 weeks. The controlled release of odontogenic exosomes resulted in a reparative dentin bridge formation, superior to glass-ionomer cement alone in vivo, in a rat molar pulpotomy model after six weeks. We have developed a platform for the encapsulation and controlled, tunable release of cell-derived exosomes, which maintains their advantageous physiologic properties reflective of the donor cells. This platform is used to modulate downstream recipient cells towards a designed dentinogenic trajectory in vitro and in vivo. Additionally, we have demonstrated the utility of an immortalized cell line to produce a high yield of exosomes with cross-species efficacy.

Hybrid polymer biomaterials for bone tissue regeneration.

Native tissues possess unparalleled physiochemical and biological functions, which can be attributed to their hybrid polymer composition and intrinsic bioactivity. However, there are also various concerns or limitations over the use of natural materials derived from animals or cadavers, including the potential immunogenicity, pathogen transmission, batch to batch consistence and mismatch in properties for various applications. Therefore, there is an increasing interest in developing degradable hybrid polymer biomaterials with controlled properties for highly efficient biomedical applications. There have been efforts to mimic the extracellular protein structure such as nanofibrous and composite scaffolds, to functionalize scaffold surface for improved cellular interaction, to incorporate controlled biomolecule release capacity to impart biological signaling, and to vary physical properties of scaffolds to regulate cellular behavior. In this review, we highlight the design and synthesis of degradable hybrid polymer biomaterials and focus on recent developments in osteoconductive, elastomeric, photoluminescent and electroactive hybrid polymers. The review further exemplifies their applications for bone tissue regeneration.

Microspheres Assembled from Chitosan-Graft-Poly(lactic acid) Micelle-Like Core-Shell Nanospheres for Distinctly Controlled Release of Hydrophobic and Hydrophilic Biomolecules.

To simultaneously control inflammation and facilitate dentin regeneration, a copolymeric micelle-in-microsphere platform is developed in this study, aiming to simultaneously release a hydrophobic drug to suppress inflammation and a hydrophilic biomolecule to enhance odontogenic differentiation of dental pulp stem cells in a distinctly controlled fashion. A series of chitosan-graft-poly(lactic acid) copolymers is synthesized with varying lactic acid and chitosan weight ratios, self-assembled into nanoscale micelle-like core-shell structures in an aqueous system, and subsequently crosslinked into microspheres through electrostatic interaction with sodium tripolyphosphate. A hydrophobic biomolecule either coumarin-6 or fluocinolone acetonide (FA) is encapsulated into the hydrophobic cores of the micelles, while a hydrophilic biomolecule either bovine serum albumin or bone morphogenetic protein 2 (BMP-2) is entrapped in the hydrophilic shells and the interspaces among the micelles. Both hydrophobic and hydrophilic biomolecules are delivered with distinct and tunable release patterns. Delivery of FA and BMP-2 simultaneously suppresses inflammation and enhances odontogenesis, resulting in significantly enhanced mineralized tissue regeneration. This result also demonstrates the potential for this novel delivery system to deliver multiple therapeutics and to achieve synergistic effects.

Controlled drug release for tissue engineering.

Tissue engineering is often referred to as a three-pronged discipline, with each prong corresponding to 1) a 3D material matrix (scaffold), 2) drugs that act on molecular signaling, and 3) regenerative living cells. Herein we focus on reviewing advances in controlled release of drugs from tissue engineering platforms. This review addresses advances in hydrogels and porous scaffolds that are synthesized from natural materials and synthetic polymers for the purposes of controlled release in tissue engineering. We pay special attention to efforts to reduce the burst release effect and to provide sustained and long-term release. Finally, novel approaches to controlled release are described, including devices that allow for pulsatile and sequential delivery. In addition to recent advances, limitations of current approaches and areas of further research are discussed.

A survey of hospitals to determine the prevalence and characteristics of healthcare coalitions for emergency preparedness and response.

Previous reports have identified the development of healthcare coalitions as the foundation for disaster response across the United States. This survey of acute care hospitals characterizes the current status of participation by US hospitals in healthcare coalitions for emergency preparedness planning and response. The survey results show the nearly universal nature of a coalition approach to disaster response. The results suggest a need for wide stakeholder involvement but also for flexibility in structure and organization. Based on the survey results, the authors make recommendations to guide the further development of healthcare coalitions and to improve local and national response to disasters.

Response to the sudden closure of St. Vincent's Hospital: learning from a real, no-notice, prolonged surge event.

We qualitatively examined the impact of the permanent closure of St. Vincent's Hospital in New York City on the remaining hospitals in the area and analyzed how these hospitals responded to this event. We conducted a descriptive survey consisting of interviews with clinical (n = 24) and administrative (n = 11) staff from 4 hospitals in lower Manhattan after the sudden closure of St. Vincent's Hospital. These hospitals experienced a sudden and sustained increase in patient volume. Each was faced with specific constraints (eg, finances, physical plant, bureaucracy), but they developed similar strategic responses. Generally applicable principles included: soliciting innovative ideas from clinical staff, reexamining previous proposals to improve efficiency, fast-tracking stalled capacity-building projects, and focusing on improving patient care and flow. Three broad tactical themes were apparent: increases in staff and staff hours, use of alternative sites of care, and implementing novel ways of operating. The impact on hospital operations resulting from the closure of St. Vincent's Hospital is a surrogate medical surge event and met thresholds for activating emergency operations plans. Novel operating methods used in response to this surge event offer practical and broadly applicable principles that might improve medical surge management in other hospitals.

Mass vaccination for the 2009 H1N1 pandemic: approaches, challenges, and recommendations.

The 2009 H1N1 pandemic stimulated a nationwide response that included a mass vaccination effort coordinated at the federal, state, and local levels. This article examines a sampling of state and local efforts during the pandemic in order to better prepare for future public health emergencies involving mass distribution, dispensing, and administration of medical countermeasures. In this analysis, the authors interviewed national, state, and local leaders to gain a better understanding of the accomplishments and challenges of H1N1 vaccination programs during the 2009-10 influenza season. State and local health departments distributed and administered H1N1 vaccine using a combination of public and private efforts. Challenges encountered during the vaccination campaign included the supply of and demand for vaccine, prioritization strategies, and local logistics. To improve the response capabilities to deal with infectious disease emergencies, the authors recommend investing in technologies that will assure a more timely availability of the needed quantities of vaccine, developing local public health capacity and relationships with healthcare providers, and enhancing federal support of state and local activities. The authors support in principle the CDC recommendation to vaccinate annually all Americans over 6 months of age against seasonal influenza to establish a standard of practice on which to expand the ability to vaccinate during a pandemic. However, expanding seasonal influenza vaccination efforts will be an expensive and long-term investment that will need to be weighed against anticipated benefits and other public health needs. Such investments in public health infrastructure could be important for building capacity and practice for distributing, dispensing, and administering countermeasures in response to a future pandemic or biological weapons attack.

Stigma, health disparities, and the 2009 H1N1 influenza pandemic: how to protect Latino farmworkers in future health emergencies.

At the outset of the 2009 H1N1 influenza ("swine flu") pandemic, Mexican nationals and Mexican commodities were shunned globally, and, in the United States, some media personalities characterized Mexican immigrants as disease vectors who were a danger to the country. We investigated instances in the U.S. of stigmatization of Latino migrant and seasonal farmworkers (MSFWs) and developed guidance for officials in curtailing its effects. At the same time, we explored social factors that make farmworkers more vulnerable to influenza infection and its complications, including high rates of underlying medical conditions, limited access to health care, and certain circumstances that interfere with the ability to implement community mitigation measures. This article reviews study findings and concludes with advice to policymakers and practitioners on the need to mitigate stigmatization in future outbreaks, to create public health preparedness systems that better protect migrant and seasonal farmworkers, and to undertake larger reforms to reduce institutional conditions that render farmworkers at greater risk for morbidity and mortality during health emergencies.

Antibiotic resistance.

Antibiotic resistance poses serious challenges to health and national security, and policy changes will be required to mitigate the consequences of antibiotic resistance. Resistance can arise in disease-causing bacteria naturally, or it can be deliberately introduced to a biological weapon. In either case, life-saving drugs are rendered ineffective. Resistant bacterial infections are difficult to treat, and there are few new antibiotics in the drug development pipeline. This article describes how antibiotic resistance affects health and national security, how bacteria become antibiotic resistant, and what should be done now so antibiotics will be available to save lives in the future.