Gold nanoparticle biodistribution in pregnant mice following intravenous administration varies with gestational age.

The use of nanoparticles (NPs) to deliver therapeutics to reproductive organs is an emerging approach to safely and effectively treat mothers and babies facing pregnancy complications. This study investigates the biodistribution of two different sized gold-based NPs in pregnant mice following systemic delivery as a function of gestational age. Poly(ethylene glycol)-coated 15 nm gold nanoparticles or 150 nm diameter silica core/gold nanoshells were intravenously administered to pregnant mice at gestational days (E)9.5 or 14.5. NP distribution was analyzed twenty-four hours later by inductively coupled plasma-mass spectrometry and silver staining of histological specimens. More NPs accumulated in placentas than embryos and delivery to these tissues was greater at E9.5 than E14.5. Neither NP type affected fetal weight or placental weight, indicating minimal short-term toxicity in early to mid-stage pregnancy. These findings warrant continued development of NPs as tools to deliver therapeutics to reproductive tissues safely.

Nudging tourists to donate for conservation: Experimental evidence on soliciting voluntary contributions for coastal management.

This research examines the donation behavior of tourists who are asked to donate to coastal conservation aimed at addressing a bundled mix of land and sea issues. Historically, the governance and financing of land and sea conservation have been separated; yet coastal tourism directly involves a mix of activities and development challenges which link land and sea together on the coast. Marine parks, and numerous studies examining their funding schemes, have typically focused on mandatory user fees targeting specific types of activities. For example, many studies focus only on scuba divers' willingness to pay (WTP) for marine conservation. Alternative funding mechanisms, such as voluntary contributions, may be preferred, or even necessary, to traditional government imposed fees, but much less is known about effective implementation. Relatively few studies focus on bundled cross-boundary conservation activities (i.e., land and sea conservation) from all visitors of a marine park (i.e., beachgoers, surfers, boaters, snorkelers) and its encompassing coastal area. In this study we target tourists visiting a popular island and employ field experimental methods to explore the optimal donation request mechanism and pricing levels that influence real voluntary payments for conservation. The field experiment examines voluntary payments under the treatment conditions: open-ended, a set of several suggested donation amounts, and default opt-in and opt-out at two price levels. The field experiment was conducted with tourists on the island of Gili Trawangan, Indonesia. Results reveal that tourists are willing to donate to bundled land-sea conservation issues and that there is a significantly higher propensity to donate in all treatment conditions compared to the open-ended condition. The default opt-out conditions garnered the highest rate of donations at 75% and 62% respectively for the lower and higher set amounts. The mean donation amount was largest in the higher default opt-out condition. Our results suggest that the optimal method of requesting voluntary donations is a set default amount requiring users to opt-out if they do not wish to donate. Implementing a default opt-out eco-donation targeting all types of visitors represents a significant source of funding and illustrates the potential for donations to finance land and sea conservation efforts, an important avenue for future investigation in many interconnected systems that have been historically governed and financed separately.

A straightforward cell culture insert model to incorporate biochemical and biophysical stromal properties into transplacental transport studies.

Introduction: The placental extracellular matrix (ECM) dynamically remodels over pregnancy and in disease. How these changes impact placental barrier function is poorly understood as there are limited in vitro models of the placenta with a modifiable stromal compartment to mechanistically investigate these extracellular factors. We developed a straightforward method to incorporate uniform hydrogels into standard cell culture inserts for transplacental transport studies. Methods: Uniform polyacrylamide (PAA) gels were polymerized within cell culture inserts by (re)using the insert packaging to create a closed, controllable environmental chamber. PAA pre-polymer solution was added dropwise via a syringe to the cell culture insert and the atmosphere was purged with an inert gas. Transport and cell culture studies were conducted to validate the model. Results: We successfully incorporated and ECM functionalized uniform PAA gels to cell culture inserts enable cell adhesion and monolayer formation. Imaging and analyte transport studies validated gel formation and expected mass transport results and successful cell studies confirmed cell viability, monolayer formation, and that the model could be used transplacental transport studies. Detailed methods and validation protocols are included. Discussion: It is well appreciated that ECM biophysical and biochemical properties impact cell phenotype and cell signaling in many tissues including the placenta. The incorporation of a PAA gel within a cell culture insert enables independent study of placental ECM biophysical and biochemical properties in the context of transplacental transport. These straightforward and low-cost methods to build three dimensional cellular models are readily adoptable by the wider scientific community.

Systematic development of ionizable lipid nanoparticles for placental mRNA delivery using a design of experiments approach.

Ionizable lipid nanoparticles (LNPs) have gained attention as mRNA delivery platforms for vaccination against COVID-19 and for protein replacement therapies. LNPs enhance mRNA stability, circulation time, cellular uptake, and preferential delivery to specific tissues compared to mRNA with no carrier platform. However, LNPs are only in the beginning stages of development for safe and effective mRNA delivery to the placenta to treat placental dysfunction. Here, we develop LNPs that enable high levels of mRNA delivery to trophoblasts in vitro and to the placenta in vivo with no toxicity. We conducted a Design of Experiments to explore how LNP composition, including the type and molar ratio of each lipid component, drives trophoblast and placental delivery. Our data revealed that utilizing C12-200 as the ionizable lipid and 1,2-dioleoyl-sn-glycero-3-phosphoethanolamine (DOPE) as the phospholipid in the LNP design yields high transfection efficiency in vitro. Analysis of lipid molar composition as a design parameter in LNPs displayed a strong correlation between apparent pKa and poly (ethylene) glycol (PEG) content, as a reduction in PEG molar amount increases apparent pKa. Further, we present one LNP platform that exhibits the highest delivery of placental growth factor mRNA to the placenta in pregnant mice, resulting in synthesis and secretion of a potentially therapeutic protein. Lastly, our high-performing LNPs have no toxicity to both the pregnant mice and fetuses. Our results demonstrate the feasibility of LNPs as a platform for mRNA delivery to the placenta, and our top LNP formulations may provide a therapeutic platform to treat diseases that originate from placental dysfunction during pregnancy.

Delivery and short-term maternal and fetal safety of vaginally administered PEG-PLGA nanoparticles.

At the onset of pregnancy, people with preexisting conditions face additional challenges in carrying their pregnancy to term, as the safety of the developing fetus and pregnant person is a significant factor of concern. Nanoparticle (NP)-based therapies have displayed success against various conditions and diseases in non-pregnant patients, but the use of NPs in maternal-fetal health applications needs to be better established. Local vaginal delivery of NPs is a promising administration route with the potential to yield high cargo retention in the vagina and improved therapeutic efficacy compared to systemic administration that results in rapid NP clearance by the hepatic first-pass effect. In this study, we investigated the biodistribution and short-term toxicity of poly(ethylene glycol)-poly(lactic-co-glycolic acid) (PEG-PLGA) NPs in pregnant mice following vaginal delivery. The NPs were either loaded with DiD fluorophores for tracking cargo distribution (termed DiD-PEG-PLGA NPs) or included Cy5-tagged PLGA in the formulation for tracking polymer distribution (termed Cy5-PEG-PLGA NPs). DiD-PEG-PLGA NPs were administered at gestational day (E)14.5 or 17.5, and cargo biodistribution was analyzed 24 h later by fluorescence imaging of whole excised tissues and histological sections. No gestational differences in DiD distribution were observed, so Cy5-PEG-PLGA NPs were administered at only E17.5 to evaluate polymer distribution in the reproductive organs of pregnant mice. Cy5-PEG-PLGA NPs distributed to the vagina, placentas, and embryos, whereas DiD cargo was only observed in the vagina. NPs did not impact maternal, fetal, or placental weight, suggesting they display no short-term effects on maternal or fetal growth. The results from this study encourage future investigation into the use of vaginally delivered NP therapies for conditions affecting the vagina during pregnancy.

Lipid Nanoparticle Composition Drives mRNA Delivery to the Placenta.

Ionizable lipid nanoparticles (LNPs) have gained attention as mRNA delivery platforms for vaccination against COVID-19 and for protein replacement therapies. LNPs enhance mRNA stability, circulation time, cellular uptake, and preferential delivery to specific tissues compared to mRNA with no carrier platform. However, LNPs have yet to be developed for safe and effective mRNA delivery to the placenta as a method to treat placental dysfunction. Here, we develop LNPs that enable high levels of mRNA delivery to trophoblasts in vitro and to the placenta in vivo with no toxicity. We conducted a Design of Experiments to explore how LNP composition, including the type and molar ratio of each lipid component, drives trophoblast and placental delivery. Our data revealed that a specific combination of ionizable lipid and phospholipid in the LNP design yields high transfection efficiency in vitro . Further, we present one LNP platform that exhibits highest delivery of placental growth factor mRNA to the placenta in pregnant mice, which demonstrates induced protein synthesis and secretion of a therapeutic protein. Lastly, our high-performing LNPs have no toxicity to both the pregnant mice and fetuses. Our results demonstrate the feasibility of LNPs as a platform for mRNA delivery to the placenta. Our top LNPs may provide a therapeutic platform to treat diseases that originate from placental dysfunction during pregnancy.

Adding value to stretched communities through nursing actions: the Wellington South Nursing Initiative.

Nurses provide health services to many groups with unmet health needs. Communities with consistently unmet needs are generally 'stretched' as they are under pressure. For children and families this pressure impacts their ability to live healthy lifestyles. The Wellington South Nursing Initiative involves two nurses providing an innovative population-based nursing service to stretched urban communities, particularly children and families, predominantly through networking and project work. Projects are specifically focused activities developed and implemented to address areas of health need. The projects cluster around five overarching areas: enhancing individual and community potential, growing safer families and communities, minimising negative harmful or risky behaviour, maximising general health and wellbeing and addressing specific health needs. Critical elements of the nurses' practice are the use of public health principles combined with a community development approach, relational practice and working for sustainability. The initiative provides important insights into how nurses can enter and work with communities and enhance the potential of children, families and the wider community.

Tourist willingness to pay for local green hotel certification.

This study aims to understand tourists' willingness to pay a price premium for a local green hotel certification, and is one of only a few in the literature for small-island tourism destinations in emerging economies with their unique and pressing sustainability challenges. In a survey of 535 tourists visiting Gili Trawangan, Indonesia, facing numerous waste management and coral reef conservation issues, the willingness to pay extra for sustainable hotel services was elicited. There were five discrete pricing levels across the surveys that ranged from $0.75 USD to $7.50 USD extra per night. We examined the relationship of the respondents' payment choice to their socio-demographic attributes and attitudes regarding environmental issues such as climate change. The main findings and practical implications of the study are: (1) to demonstrate the broad willingness to pay for sustainable hotel services. Findings indicate at all price levels (between $0.75 USD and $7.50 USD), more than 50% of tourists are willing to pay. (2) To estimate a lower bound mean willingness to pay per night for a local green hotel certificate of $1.55USD and 1.34€ EUR, and (3) To identify individual attributes that influence willingness to pay. Findings indicate environmental knowledge and preferences play a role. These results can be used generally to incorporate evidence-based practices into the development of a green hotel marketing strategy, and to help define the target market for small-scale green hotel certification. Additionally, we propose a finance strategy for funding local and sustainable initiatives that support the hotel industry and the island's infrastructure through the premiums collected from the 'Gili Green Award' certificate.

Diseases and conditions that impact maternal and fetal health and the potential for nanomedicine therapies.

Maternal mortality rates in the United States have steadily increased since 1987 to the current rate of over 16 deaths per 100,000 live births. Whereas most of these deaths are related to an underlying condition, such as cardiovascular disease, many pregnant women die from diseases that emerge as a consequence of pregnancy. Both pre-existing and emergent diseases and conditions are difficult to treat in pregnant women because of the potential harmful effects of the treatment on the developing fetus. Often the health of the woman and the health of the baby are at odds and must be weighed against each other when medical treatment is needed, frequently leading to iatrogenic preterm birth. However, the use of engineered nanomedicines has the potential to fill the treatment gap for pregnant women. This review describes several conditions that may afflict pregnant women and fetuses and introduces how engineered nanomedicines may be used to treat these illnesses. Although the field of maternal-fetal nanomedicine is in its infancy, with additional research and development, engineered nanotherapeutics may greatly improve outcomes for pregnant women and their offspring in the future.

Virtual reality as a tool for environmental conservation and fundraising.

Anecdotal evidence from philanthropic fundraisers shows that virtual reality (VR) technology increases empathy and can influence people toward pro-environmental behavior. Non-profit organizations are increasingly marketing their causes using virtual reality and they report increased donations when VR technology is employed. In VR, users are immersed in situations intended to feel more like the real world through technology, such as 360° video viewed through 3D headsets that block out visual and auditory distractions. The framing of the message as either positive or negative has long shown to have an effect on behavior, although consensus on the impact of framing has not been reached in relation to encouraging contributions to public goods. This paper focuses on field experiments used to investigate the effects of varying degrees of visual immersion and positive versus negative message framing on respondents' contributions to a conservation charity. Participants were exposed to a five-minute underwater film about coral reefs and the importance of protecting them. We employed a 2x2 experimental design using 3D head-mounted displays comparing 360° film footage vs. unidirectional film and a positive message vs. a negative message. After watching the film, each participant completed a short questionnaire and had the opportunity to donate to a marine conservation charity. In addition, we tested a control treatment where no video was observed. The video was filmed in Indonesia which is host to some of the world's most biodiverse reefs that are under great threat from human activity. We also conducted the study in Indonesia, sampling a total of 1006 participants from the Bogor city area and tourists on the island of Gili Trawangan-which is popular for scuba diving and snorkeling. We find significant differences in observed behavior and reported emotions between all treatments compared to the control condition. Among the tourist sample, we find significant differences between the 360° film with a negative message which garnered significantly larger average donation amounts compared to the unidirectional film with both positive and negative framing. Overall, we can infer from these studies that virtual reality is an effective way to raise awareness of environmental threats and encourage behavioral action, especially when tailored to target groups. New technology, such as the VR head-mounted display, is highly effective at attracting interest which is an important point to encourage organizations to invest in new technologies.

Design of nanomaterials for applications in maternal/fetal medicine.

Pregnancy complications are commonplace and the challenges of treatment during pregnancy with few options available pose a risk to the health of both the mother and baby. Patients suffering from conditions such as preeclampsia, placenta accreta, and intrauterine growth restriction have few treatment options apart from emergency caesarean section. Fortunately, researchers are beginning to develop nanomedicine-based therapies that could be utilized to treat conditions affecting the mother, placenta, or fetus to improve the prognosis for mothers and their unborn children. This review summarizes the field's current understanding of nanoparticle biodistribution and therapeutic effect following systemic or vaginal administration and overviews the design parameters researchers should consider when developing nanomedicines for maternal/fetal health. It also describes safety considerations for nanomedicines to limit undesirable maternal or fetal side effects and discusses future work that should be performed to advance nanomedicine for maternal/fetal health. With additional development and implementation, the application of nanomedicine to treat pregnancy complications may mitigate the need for emergency caesarean sections and allow pregnancies to extend to term.

The Perinuclear ER Scales Nuclear Size Independently of Cell Size in Early Embryos.

Nuclear size plays pivotal roles in gene expression, embryo development, and disease. A central hypothesis in organisms ranging from yeast to vertebrates is that nuclear size scales to cell size. This implies that nuclei may reach steady-state sizes set by limiting cytoplasmic pools of size-regulating components. By monitoring nuclear dynamics in early sea urchin embryos, we found that nuclei undergo substantial growth in each interphase, reaching a maximal size prior to mitosis that declined steadily over the course of development. Manipulations of cytoplasmic volume through multiple chemical and physical means ruled out cell size as a major determinant of nuclear size and growth. Rather, our data suggest that the perinuclear endoplasmic reticulum, accumulated through dynein activity, serves as a limiting membrane pool that sets nuclear surface growth rate. Partitioning of this local pool at each cell division modulates nuclear growth kinetics and dictates size scaling throughout early development.

Significant Unresolved Questions and Opportunities for Bioengineering in Understanding and Treating COVID-19 Disease Progression.

COVID-19 is a disease that manifests itself in a multitude of ways across a wide range of tissues. Many factors are involved, and though impressive strides have been made in studying this novel disease in a very short time, there is still a great deal that is unknown about how the virus functions. Clinical data has been crucial for providing information on COVID-19 progression and determining risk factors. However, the mechanisms leading to the multi-tissue pathology are yet to be fully established. Although insights from SARS-CoV-1 and MERS-CoV have been valuable, it is clear that SARS-CoV-2 is different and merits its own extensive studies. In this review, we highlight unresolved questions surrounding this virus including the temporal immune dynamics, infection of non-pulmonary tissue, early life exposure, and the role of circadian rhythms. Risk factors such as sex and exposure to pollutants are also explored followed by a discussion of ways in which bioengineering approaches can be employed to help understand COVID-19. The use of sophisticated in vitro models can be employed to interrogate intercellular interactions and also to tease apart effects of the virus itself from the resulting immune response. Additionally, spatiotemporal information can be gleaned from these models to learn more about the dynamics of the virus and COVID-19 progression. Application of advanced tissue and organ system models into COVID-19 research can result in more nuanced insight into the mechanisms underlying this condition and elucidate strategies to combat its effects.

Mask Reuse in the COVID-19 Pandemic: Creating an Inexpensive and Scalable Ultraviolet System for Filtering Facepiece Respirator Decontamination.

As the current COVID-19 pandemic illustrates, not all hospitals and other patient care facilities are equipped with enough personal protective equipment to meet the demand in a crisis. Health care workers around the world use filtering facepiece respirators to protect themselves and their patients, yet during this global pandemic they are forced to reuse what are intended to be single-use masks. This poses a significant risk to these health care workers along with the people they are trying to protect. Ultraviolet germicidal irradiation (UVGI) has been validated previously as a method to effectively decontaminate these masks between use. However, not all facilities have access to the expensive commercial ultraviolet type C (UV-C) lamp decontamination equipment required for UVGI. UV-C bulbs are sitting idle in biosafety cabinets at universities and research facilities around the world that have been shuttered to slow the spread of COVID-19. These bulbs may also be available in existing medical centers where infectious diseases are commonly treated. We developed a method to modify existing light fixtures or create custom light fixtures that are compatible with new or existing UV-C bulbs. This system is scalable; can be created for less than US$50, on site and at the point of need; and leverages resources that are currently untapped and sitting unused in public and private research facilities during the pandemic. The freely accessible design can be easily modified for use around the world. Health care facilities can obtain this potentially lifesaving UVGI resource with minimal funds by collaborating with research facilities to obtain the UV-C meters and UV-C bulbs if they are unavailable from other sources. Although mask reuse is not ideal, we must do what we can in emergency situations to protect our health care workers responding to the pandemic and the communities they serve.

Innovative nursing leadership in youth health.

Along with introducing the New Zealand Primary Health Care Strategy the Ministry of Health funded 11 primary health care nursing innovation projects for three years. One of these was sited in the Hutt Valley District Health Board region at what was originally known as the Hutt Valley Youth Service and later named the Vibe service. The funding supported employment of a clinical nurse leader who later, during the course of the project, qualified as a Nurse Practitioner (NP). The dynamic leadership provided by the nurse extended beyond service boundaries benefiting policy decision making throughout the District Health Board region and contributing to youth health and service development nationally. In return for fostering such leadership Vibe gained access to new dimensions of youth health care. It became apparent that high calibre clinical leadership, a major component of the NP scope of practice in primary health care, improves outcomes for the clientele, increases satisfaction for the team members and provides a model for potential NPs wherever they are situated.

Nucleoplasmin is a limiting component in the scaling of nuclear size with cytoplasmic volume.

How nuclear size is regulated relative to cell size is a fundamental cell biological question. Reductions in both cell and nuclear sizes during Xenopus laevis embryogenesis provide a robust scaling system to study mechanisms of nuclear size regulation. To test if the volume of embryonic cytoplasm is limiting for nuclear growth, we encapsulated gastrula-stage embryonic cytoplasm and nuclei in droplets of defined volume using microfluidics. Nuclei grew and reached new steady-state sizes as a function of cytoplasmic volume, supporting a limiting component mechanism of nuclear size control. Through biochemical fractionation, we identified the histone chaperone nucleoplasmin (Npm2) as a putative nuclear size effector. Cellular amounts of Npm2 decrease over development, and nuclear size was sensitive to Npm2 levels both in vitro and in vivo, affecting nuclear histone levels and chromatin organization. We propose that reductions in cell volume and the amounts of limiting components, such as Npm2, contribute to developmental nuclear size scaling.

Reliability of the Sedation-Agitation Scale between nurses and doctors.

This study determined the inter-rater reliability of the Sedation-Agitation Scale (SAS) when used by staff in a tertiary level general intensive care unit (ICU). The study was designed to answer the question in the 'real world', with minimum patient exclusion criteria, do nurses and doctors rate ICU patient's sedation levels using the SAS similarly? A convenient sample of 35 nursing and seven medical staff and a randomly selected sample of 69 patients were used. A nurse and a doctor rated each patient simultaneously using the SAS, with a systematic five-stage arousal process. The results showed that there was exact agreement between the nurses' and doctors' scores in 74% of assessments. The weighted kappa finding of 0.82 indicates very good agreement (reliability). The mean SAS scores recorded for nurses (2.33+/-1.21) and doctors (2.36+/-1.35) were similar. Intraclass correlations for single measures (r=.921, p<.001) and average measures (r=.959, p<.001) indicated individuals who completed multiple ratings did not introduce bias. Where there was a difference between the paired ratings, these were only one level of the SAS away from each other. This research indicates nurses and doctors rate patients' levels of sedation similarly using the SAS. It also provides support for the use of the instrument in general ICUs outside the USA. Research is now needed to determine the value of the SAS in guiding clinical decision-making related to sedation management.

The experience of the nurse at triage influences the timing of CPAP intervention.

Increasing attention in the last decade has shown that intervention of continuous positive airway pressure therapy (CPAP) in cardiogenic pulmonary oedema (CPO) markedly improves the outcome of patients presenting with acute respiratory failure. This study used a non-experimental correlational design to research the relationship between the experience of the nurse, with the application of CPAP to patients presenting to a metropolitan emergency department with CPO and to establish what difference, if any, CPAP made to outcomes. A retrospective audit of records was used to extract data on all 54 patients that received CPAP over a 12-month period. The primary outcome measures were off CPAP within 2 h, transfer to intensive care unit (ICU) or cardiac care unit (CCU) and secondary outcome measures were length of hospital stay and death. There was a trend towards more experienced nurses attending patients who required immediate treatment or treatment within 10 min. These patients were more likely to be recognised at triage as requiring CPAP therapy. The early application of CPAP reduced hospital mortality, length of stay, and the need for intubation and ventilation. Attention needs to be given on how best to educate nurses so that more patients presenting with acute respiratory failure can benefit from nurses' decision-making regarding the commencement of CPAP.