A race to net zero-early lessons from healthcare's decarbonization marathon.

Climate change poses a threat to healthcare systems; at the same time, healthcare systems contribute to a worsening climate. Climate-induced disasters are predicted to increase both the demand for healthcare services while also posing a threat to the integrity of healthcare systems' infrastructures and supply chains. Many healthcare organizations have taken initiatives to prepare for such disasters through implementing carbon emission-reduction practices and infrastructure reinforcement, through globally recognized frameworks and strategies known as Scopes 1, 2, and 3, and decarbonization. We explored the efforts of these early adopters to understand how they are thinking about and addressing climate change's impacts on healthcare. Through a process of reviewing the peer-reviewed literature, publicly available published documents, annual sustainability reports, conference presentations, and participation in a national decarbonization collaborative, we (1) provide a diverse set of examples showcasing the variety of ways healthcare systems are responding; (2) identify a set of emergent key themes to implementing decarbonization practices, such as the role of an organizational culture of iterative improvement and building systems of cross-organizational collaboration; and (3) synthesize the identifiable set of driving factors for long-term sustainability of these decarbonization efforts.

Climate change poses a threat to healthcare systems, while, at the same time, healthcare systems contribute to climate change. Disasters caused by climate change are expected to increase demand for healthcare services and affect healthcare infrastructure and supply chains. Some healthcare organizations have taken steps to prepare for these challenges by implementing carbon-reduction practices and infrastructure reinforcement. To do this, they are using globally recognized frameworks for reducing carbon emissions. Researchers studied these early adopters and their efforts to address climate change in healthcare. They reviewed a variety of published documents, annual sustainability reports, and conference presentations and identified key themes for implementing these carbon-reduction practices. They also identified driving factors for the long-term sustainability of these efforts. This research can help healthcare organizations better prepare for and address the challenges posed by climate change.

Quantification of trivalent non-replicating rotavirus vaccine antigens in the presence of aluminum adjuvant.

Parenterally administered rotavirus vaccines may overcome the low efficacy observed in resource-poor regions that use live oral formulations. We have reported work on a trivalent nonreplicating rotavirus vaccine (NRRV) for parenteral administration consisting of the recombinant tetanus toxoid P2 CD4 epitope fused to a truncated VP8* fragment (P2-VP8*) for the P[4], P[6], and P[8] serotypes of rotavirus adjuvanted with aluminum. An essential part of developing this vaccine candidate was devising quantification methods for each antigen in the trivalent NRRV in the presence of aluminum adjuvant. This report describes the development of quantitative inhibition enzyme-linked immunosorbent assays (ELISAs) for in vitro antigenicity determination of the adjuvanted trivalent NRRV using serotype-specific monoclonal antibodies (mAbs) against each of the P2-VP8* antigens. Adjuvanted trivalent vaccine samples are titrated and incubated with a constant concentration of specific mAbs against each NRRV P2-VP8* antigen variant. Unbound mAbs are measured by ELISA to indirectly quantify the amount of each antigen present in the trivalent vaccine. Sensitive, specific, and reproducible inhibition ELISAs were developed and qualified for each antigen and used for final product quantification and release testing without desorption of the vaccine antigen.

Landscape analysis for a community-designed intervention to enhance early childhood development in San Francisco.

To determine the appropriate components for a community-based intervention for early childhood development, a broad series of stakeholder interviews was completed in a three-month period (January-March 2019) and a systematic review of their responses was performed. Additionally, 11 citywide assessment reports for child equity were reviewed and added to the information matrix. We performed this population-based assessment in San Francisco, a dense urban environment with roughly 43,000 children under the age of 5. The city has high rates of income inequity, with roughly half of the children considered to be living in low-income or poverty conditions. Interviews were conducted with 34 stakeholders representing various sectors, including community organizations, government, healthcare, and academia. Nine main concerns surrounding low-income families and children (LIFC) living in San Francisco were extracted from stakeholder interviews. The concerns were divided into subcategories based on a socioecological health model. City-funded, community-based, family resource centers were an identified space for performing an early childhood health intervention supporting LIFC. Furthermore, any proposed intervention to support LIFC must be implemented with a culturally tailored focus, as a one-size-fits-all, clinic-based model is not desired. Community-engaged and culturally specific activities are requested and required for effectively promoting early childhood development in an urban environment. In this article we propose that additional work towards implementing community-based interventions with support from the clinic are needed.

Formulation and preclinical studies with a trivalent rotavirus P2-VP8 subunit vaccine.

More effective rotavirus vaccines are essential for preventing extensive diarrheal morbidity and mortality in children under five years of age in low-resource regions. Nonreplicating rotavirus vaccines (NRRV) administered parenterally provide an alternate vaccination method to the current licensed oral vaccine. Live attenuated vaccines and may generate increased efficacy in low-resource settings because the parenteral administration route bypasses some of the challenges associated with oral administration, including differences in intestinal environments. Work described here supports development of a trivalent NRRV vaccine for parenteral administration to avoid complications of the gastrointestinal route. Recombinant VP8* subunit proteins representing some of the most prevalent strains of rotavirus infecting humans - DS-1 (P[4]), 1076 (P[6]), and Wa (P[8]) - were combined with an aluminum adjuvant and the P2 epitope of tetanus toxoid to enhance the immune response to this NRRV antigen. Vaccine formulation development included selection of aluminum hydroxide (Alhydrogel®) as an appropriate adjuvant as well as an optimal buffer to maintain antigen stability and optimize antigen binding to the adjuvant. Characterization assays were used to select the lead vaccine formulation and monitor formulation stability. The NRRV liquid formulation was stable for one year at 2°C to 8°C and four weeks at 37°C. Immunogenicity of the NRRV formulation was evaluated using a guinea pig model, where we demonstrated that the adjuvant provided a 20-fold increase in neutralization titer against a homologous antigen and that the P2-fusion also enhanced the serum neutralizing antibody responses. This vaccine candidate is currently being evaluated in human clinical trials.

Cytochrome P450BM-3 reduces aldehydes to alcohols through a direct hydride transfer.

Cytochrome P450BM-3 catalyzed the reduction of lipophilic aldehydes to alcohols efficiently. A k(cat) of ∼25 min(-1) was obtained for the reduction of methoxy benzaldehyde with wild type P450BM-3 protein which was higher than in the isolated reductase domain (BMR) alone and increased in specific P450-domain variants. The reduction was caused by a direct hydride transfer from preferentially R-NADP(2)H to the carbonyl moiety of the substrate. Weak substrate-P450-binding of the aldehyde, turnover with the reductase domain alone, a deuterium incorporation in the product from NADP(2)H but not D(2)O, and no inhibition by imidazole suggests the reductase domain of P450BM-3 as the potential catalytic site. However, increased aldehyde reduction by P450 domain variants (P450BM-3 F87A T268A) may involve allosteric or redox mechanistic interactions between heme and reductase domains. This is a novel reduction of aldehydes by P450BM-3 involving a direct hydride transfer and could have implications for the metabolism of endogenous substrates or xenobiotics.