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Wastewater reclamation and reuse have the potential to supplement water supplies, offering resiliency in times of drought and helping meet increased water demands associated with population growth. Non-potable water reuse represents the largest potential reuse market. Yet economic constraints for new water reuse infrastructure and safety concerns due to microbial water quality, and especially viral pathogen exposure, limit widespread implementation of water reuse. Cost-effective, real-time methods to measure or indicate viral quality of recycled water would do much to instill greater confidence in the practice. This manuscript discusses advancements in monitoring and modeling of viral health risks in the context of water reuse. First, we describe the current wastewater reclamation processes and treatment technologies with an emphasis on virus removal. Second, we review technologies for the measurement of viruses, both culture- and molecular-based, along with their advantages and disadvantages. We introduce promising viral surrogates and specific pathogenic viruses that can serve as indicators of viral risk for water reuse. We suggest metagenomic analyses for viral screening and flow cytometry for quantification of virus-like particles as new approaches to complement more traditional methods. Third, we describe modeling to assess health risks through quantitative microbial risk assessments (QMRAs), the most common strategy to couple data on virus concentrations with human exposure scenarios. We then explore the potential of artificial neural networks (ANNs) to incorporate suites of data from wastewater treatment processes, water quality parameters, and viral surrogates. We recommend ANNs as a means to utilize existing water quality data, alongside new complementary measures of viral quality, to achieve cost-effective strategies to assess risks associated with infectious human viruses in recycled water. Given the review, we conclude that technologies are ready for identifying and implementing viral surrogates for health risk reduction in the next decade. Incorporating modeling with monitoring data would likely result in more robust assessment of water reuse risk.

Wastewater surveillance for the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is an emerging approach to help identify the risk of a coronavirus disease (COVID-19) outbreak. This tool can contribute to public health surveillance at both community (wastewater treatment system) and institutional (e.g., colleges, prisons, and nursing homes) scales. This paper explores the successes, challenges, and lessons learned from initial wastewater surveillance efforts at colleges and university systems to inform future research, development and implementation. We present the experiences of 25 college and university systems in the United States that monitored campus wastewater for SARS-CoV-2 during the fall 2020 academic period. We describe the broad range of approaches, findings, resources, and impacts from these initial efforts. These institutions range in size, social and political geographies, and include both public and private institutions. Our analysis suggests that wastewater monitoring at colleges requires consideration of local information needs, sewage infrastructure, resources for sampling and analysis, college and community dynamics, approaches to interpretation and communication of results, and follow-up actions. Most colleges reported that a learning process of experimentation, evaluation, and adaptation was key to progress. This process requires ongoing collaboration among diverse stakeholders including decision-makers, researchers, faculty, facilities staff, students, and community members.

Perioperative bleeding is a potentially devastating complication in neurosurgical patients, and plasma fibrinogen concentration has been identified as a potential modifiable risk factor for perioperative bleeding. The aim of this study was to evaluate preconditioning with Crotalus atrox venom (Cv-PC) as potential preventive therapy for reducing perioperative hemorrhage in the rodent model of surgical brain injury (SBI). C. atrox venom contains snake venom metalloproteinases that cleave fibrinogen into fibrin split products without inducing clotting. Separately, fibrinogen split products induce fibrinogen production, thereby elevating plasma fibrinogen levels. Thus, the hypothesis was that preconditioning with C. atrox venom will produce fibrinogen spilt products, thereby upregulating fibrinogen levels, ultimately improving perioperative hemostasis during SBI. We observed that Cv-PC SBI animals had significantly reduced intraoperative hemorrhage and postoperative hematoma volumes compared to those of vehicle preconditioned SBI animals. Cv-PC animals were also found to have higher levels of plasma fibrinogen at the time of surgery, with unchanged prothrombin time. Cv-PC studies with fractions of C. atrox venom suggest that snake venom metalloproteinases are largely responsible for the improved hemostasis by Cv-PC. Our findings indicate that Cv-PC increases plasma fibrinogen levels and may provide a promising therapy for reducing perioperative hemorrhage in elective surgeries.

BackgroundGlobal health academic partnerships are centered around a core tension: they often mirror or reproduce the very cross-national inequities they seek to alleviate. On the one hand, they risk worsening power dynamics that perpetuate health disparities; on the other, they form an essential response to the need for healthcare resources to reach marginalized populations across the globe.ObjectivesThis study characterizes the broader landscape of global health academic partnerships, including challenges to developing ethical, equitable, and sustainable models. It then lays out guiding principles of the specific partnership approach, and considers how lessons learned might be applied in other resource-limited settings.MethodsThe experience of a partnership between the Ministry of Health in Nepal, the non-profit healthcare provider Possible, and the Health Equity Action and Leadership Initiative at the University of California, San Francisco School of Medicine was reviewed. The quality and effectiveness of the partnership was assessed using the Tropical Health and Education Trust Principles of Partnership framework.ResultsVarious strategies can be taken by partnerships to better align the perspectives of patients and public sector providers with those of expatriate physicians. Actions can also be taken to bring greater equity to the wealth and power gaps inherent within global health academic partnerships.ConclusionsThis study provides recommendations gleaned from the analysis, with an aim towards both future refinement of the partnership and broader applications of its lessons and principles. It specifically highlights the importance of targeted engagements with academic medical centers and the need for efficient organizational work-flow practices. It considers how to both prioritize national and host institution goals, and meet the career development needs of global health clinicians.

Perioperative bleeding is a potentially devastating complication in neurosurgical patients, and plasma fibrinogen concentration has been identified as a potential modifiable risk factor for perioperative bleeding. The aim of this study was to evaluate preconditioning with Crotalus atrox venom (Cv-PC) as potential preventive therapy for reducing perioperative hemorrhage in the rodent model of surgical brain injury (SBI). C. atrox venom contains snake venom metalloproteinases that cleave fibrinogen into fibrin split products without inducing clotting. Separately, fibrinogen split products induce fibrinogen production, thereby elevating plasma fibrinogen levels. Thus, the hypothesis was that preconditioning with C. atrox venom will produce fibrinogen spilt products, thereby upregulating fibrinogen levels, ultimately improving perioperative hemostasis during SBI. We observed that Cv-PC SBI animals had significantly reduced intraoperative hemorrhage and postoperative hematoma volumes compared to those of vehicle preconditioned SBI animals. Cv-PC animals were also found to have higher levels of plasma fibrinogen at the time of surgery, with unchanged prothrombin time. Cv-PC studies with fractions of C. atrox venom suggest that snake venom metalloproteinases are largely responsible for the improved hemostasis by Cv-PC. Our findings indicate that Cv-PC increases plasma fibrinogen levels and may provide a promising therapy for reducing perioperative hemorrhage in elective surgeries.

BackgroundGlobal health academic partnerships are centered around a core tension: they often mirror or reproduce the very cross-national inequities they seek to alleviate. On the one hand, they risk worsening power dynamics that perpetuate health disparities; on the other, they form an essential response to the need for healthcare resources to reach marginalized populations across the globe.ObjectivesThis study characterizes the broader landscape of global health academic partnerships, including challenges to developing ethical, equitable, and sustainable models. It then lays out guiding principles of the specific partnership approach, and considers how lessons learned might be applied in other resource-limited settings.MethodsThe experience of a partnership between the Ministry of Health in Nepal, the non-profit healthcare provider Possible, and the Health Equity Action and Leadership Initiative at the University of California, San Francisco School of Medicine was reviewed. The quality and effectiveness of the partnership was assessed using the Tropical Health and Education Trust Principles of Partnership framework.ResultsVarious strategies can be taken by partnerships to better align the perspectives of patients and public sector providers with those of expatriate physicians. Actions can also be taken to bring greater equity to the wealth and power gaps inherent within global health academic partnerships.ConclusionsThis study provides recommendations gleaned from the analysis, with an aim towards both future refinement of the partnership and broader applications of its lessons and principles. It specifically highlights the importance of targeted engagements with academic medical centers and the need for efficient organizational work-flow practices. It considers how to both prioritize national and host institution goals, and meet the career development needs of global health clinicians.

Neuroinflammation plays an important role in the pathophysiology of surgical brain injury (SBI). Phosphoinositide 3-kinase gamma (PI3Kγ), predominately expressed in immune and endothelial cells, activates multiple inflammatory responses. In the present study, we investigated the role of PI3Kγ and PI3Kγ-activated phosphodiesterase 3B (PDE3B) in neuroinflammation in a rat model of SBI. One hundred and fifty-two male Sprague Dawley rats (weight 280-350 g) were subjected to a partial right frontal lobe corticotomy model of SBI. A PI3Kγ pharmacological inhibitor (AS252424 or AS605240) was administered intraperitoneally. PI3Kγ siRNA, human recombinant active-PI3Kγ protein, or human recombinant active-PDE3B protein were administered intracerebroventricularly. Post-SBI assessments included neurobehavioral tests, brain water content, Western blot, and immunohistochemistry. Endogenous PI3Kγ levels were increased within peri-resection brain tissues after SBI, accompanied by increased brain water content and neurological functional deficits. There was a trend toward increased endogenous PDE3B phosphorylation after SBI. The selective PI3Kγ inhibitors AS252424 and AS605240 reduced brain water content surrounding corticotomy and improved neurological function after SBI. SBI increased and PI3Kγ inhibitor decreased levels of myeloperoxidase, cluster of differentiation 3, mast cell degranulation, E-selectin, and IL-1 in peri-resection brain tissues. Direct administration of human recombinant active-PI3Kγ protein and active-PDE3B protein countered the protective effect of AS252424. PI3Kγ siRNA reduced PI3Kγ levels, decreased brain water content within peri-resection brain tissues, and improved neurological function after SBI. Collectively, our findings suggest that PI3Kγ contributed to neuroinflammation after SBI. The use of selective PI3Kγ inhibitors may be a novel approach to ameliorating SBI via their anti-inflammation effects. Significance statement: Life-saving or elective neurosurgeries often involve unavoidable damages to neighboring, nondiseased brain tissues. Such surgical brain injury (SBI) is attributable exclusively to the neurosurgical procedure itself and may cause postoperative complications that exacerbate neurological function. Although the importance of this medical problem is fully acknowledged, intraoperative administration of adjunctive treatment such as steroids and mannitol to patients undergoing neurosurgery appear not to be efficient remedies for SBI. To date, the issue of perioperative neuroprotection specifically against SBI has not been well studied. Using a clinically relevant rat model of SBI, we are exploring a new neuroprotective strategy targeting phosphoinositide 3-kinase gamma (PI3Kγ). PI3Kγ activates multiple inflammatory responses. By attenuating neuroinflammation, selective PI3Kγ inhibition would limit postoperative complications and benefit neurological outcomes.