Rapid and sensitive determination of residual prion infectivity from prion-decontaminated surfaces.

Prion diseases are untreatable fatal transmissible neurodegenerative diseases that affect a wide range of mammals, including humans, and are caused by PrPSc, the infectious self-templating conformation of the host-encoded protein, PrPC. Prion diseases can be transmitted via surfaces (e.g., forceps, EEG electrodes) in laboratory and clinical settings. Here, we use a combination of surface swabbing and real-time quaking-induced conversion (RT-QuIC) to test for residual surface-associated prions following prion disinfection. We found that treatment of several prion-contaminated laboratory and clinically relevant surfaces with either water or 70% EtOH resulted in robust detection of surface-associated prions. In contrast, treatment of surfaces with sodium hypochlorite resulted in a failure to detect surface-associated prions. RT-QuIC analysis of prion-contaminated stainless steel wires paralleled the findings of the surface swab studies. Importantly, animal bioassay and RT-QuIC analysis of the same swab extracts are in agreement. We report on conditions that may interfere with the assay that need to be taken into consideration before using this technique. Overall, this method can be used to survey laboratory and clinical surfaces for prion infectivity following prion decontamination protocols.IMPORTANCEPrion diseases can be accidentally transmitted in clinical and occupational settings. While effective means of prion decontamination exist, methods for determining the effectiveness are only beginning to be described. Here, we analyze surface swab extracts using real-time quaking-induced conversion (RT-QuIC) to test for residual prions following prion disinfection of relevant clinical and laboratory surfaces. We found that this method can rapidly determine the efficacy of surface prion decontamination. Importantly, examination of surface extracts with RT-QuIC and animal bioassay produced similar findings, suggesting that this method can accurately assess the reduction in prion titer. We identified surface contaminants that interfere with the assay, which may be found in clinical and laboratory settings. Overall, this method can enhance clinical and laboratory prion safety measures.

Hospitalization Patterns for Rural-Residing Children from 2002 to 2017.

OBJECTIVE: The closure of inpatient pediatric units within general hospitals has contributed to the regionalization of pediatric care. For children in rural areas, the distance traveled for hospitalization impacts the quality of care for children, the impact upon families, and the preparedness for disaster planning within rural communities. We assessed trends in location of hospitalization over time for rural-residing children. METHODS: Using the Healthcare Cost and Utilization Project's State Inpatient Databases, we studied 256,947 hospitalizations for rural-residing children 0-17 years of age within eight states (CO, FL, KY, NC, NJ, NY, OR, WA) from 2002-2017. Level of rurality was defined by Rural-Urban Commuting Area Codes: micropolitan, small rural, and isolated rural. Birth, psychiatric, and surgical hospitalizations were excluded. Trends in number of hospitalizations by hospital location, interfacility transfer (IFT), and whether the hospital location was the same level of rurality as the patient's home residence were assessed with the Cochran-Armitage trend test. RESULTS: From 2002 to 2017, hospitalizations for rural-residing children decreased by 52.7% (56,168 to 26,548) and IFTs increased from 6.7% to 26.5% (p<.001). The proportion of total hospitalizations within metropolitan areas for rural-residing children increased from 32.2% to 72.8% (p<.001). Local-area agreement between the patient's residence and hospital utilized decreased from 53.6% to 21.5% (p<.001). CONCLUSIONS: Although overall hospitalizations for rural-residing children decreased, IFTs increased, and the proportion hospitalized in metropolitan areas increased. The impact of this shift in inpatient health services on efficiency and quality of care for rural-residing children needs further exploration.

Effectiveness of the Addressing Reproductive Coercion in Health Settings (ARCHES) intervention among abortion clients in Bangladesh: a cluster-randomized controlled trial.

Background: The Addressing Reproductive Coercion in Health Settings (ARCHES) intervention trains existing providers to address reproductive coercion (RC) and intimate partner violence (IPV) within routine family planning counseling. This study evaluated the effectiveness of a single ARCHES counseling session as adapted for use with abortion clients in Bangladesh. Methods: In this cluster-randomized controlled trial conducted between January 2019 and January 2021, health facilities with an abortion clinic with infrastructure for private counseling and onsite violence support services were eligible. Six facilities in Bangladesh met inclusion criteria, and matched pairs randomization with parallel assignment and a 1:1 allocation ratio was used to randomize three facilities to ARCHES and three facilities to control, which implemented standard counseling. Blinding was not possible as providers in intervention facilities participated in a three-day ARCHES training. Participants were abortion clients aged 18-49 years who could provide safe recontact information and be interviewed privately. The primary outcome was past three-month modern contraceptive use without interruption or interference. The trial was registered on clinicaltrials.gov (NCT03539315) on 29 May 2018. Findings: A total of 1492 intervention participants and 1237 control participants were enrolled. Available data were analyzed at each follow-up period: 1331 intervention and 1069 control participants at the three-month follow-up, and 1269 intervention and 1050 control participants at the twelve-month follow-up. ARCHES was associated with higher likelihood of modern contraceptive use at the three-month follow-up (adjusted RR = 1.08, 95% CI: 1.06-1.10) and the twelve-month follow-up (adjusted RR = 1.06, 95% CI: 1.02-1.10). ARCHES was also associated with decreased incident pregnancy, decreased IPV, and increased knowledge of IPV support services. Interpretation: The ARCHES intervention is effective in increasing post-abortion modern contraceptive use and decreasing incident pregnancy and IPV among abortion clients in Bangladesh. Implementation of ARCHES should be considered in facilities with sufficient privacy for counseling. Funding: Society of Family Planning (#SFPRF11-07) and Ipas.

Pediatric cancers and family financial toxicity in the Philippines: insights for Southeast Asia and similarly resourced settings.

Cancer is a leading cause of death among children in the Philippines, a low-middle-income country of over 110 million people. In this Comment, we describe how financial toxicity affects families of pediatric patients with cancer in the Philippines. We explore direct costs of care, indirect costs such as transportation and lodging, and psychosocial sequelae, in the Filipino medical system and sociocultural contexts. We present examples of successful interventions in the Philippines and in similarly resourced settings, with the goal of galvanizing further research, clinical interventions, and policy-level changes, aimed at mitigating family financial toxicity for pediatric patients with cancer in the Philippines and globally.

The Science, Engineering, and Validation of Marine Carbon Dioxide Removal and Storage.

Scenarios to stabilize global climate and meet international climate agreements require rapid reductions in human carbon dioxide (CO2) emissions, often augmented by substantial carbon dioxide removal (CDR) from the atmosphere. While some ocean-based removal techniques show potential promise as part of a broader CDR and decarbonization portfolio, no marine approach is ready yet for deployment at scale because of gaps in both scientific and engineering knowledge. Marine CDR spans a wide range of biotic and abiotic methods, with both common and technique-specific limitations. Further targeted research is needed on CDR efficacy, permanence, and additionality as well as on robust validation methods-measurement, monitoring, reporting, and verification-that are essential to demonstrate the safe removal and long-term storage of CO2. Engineering studies are needed on constraints including scalability, costs, resource inputs, energy demands, and technical readiness. Research on possible co-benefits, ocean acidification effects, environmental and social impacts, and governance is also required.

Large contribution of in-cloud production of secondary organic aerosol from biomass burning emissions.

Organic compounds released from wildfires and residential biomass burning play a crucial role in shaping the composition of the atmosphere. The solubility and subsequent reactions of these compounds in the aqueous phase of clouds and fog remain poorly understood. Nevertheless, these compounds have the potential to become an important source of secondary organic aerosol (SOA). In this study, we simulated the aqueous SOA (aqSOA) from residential wood burning emissions under atmospherically relevant conditions of gas-liquid phase partitioning, using a wetted-wall flow reactor (WFR). We analyzed and quantified the specific compounds present in these emissions at a molecular level and determined their solubility in clouds. Our findings reveal that while 1% of organic compounds are fully water-soluble, 19% exhibit moderate solubility and can partition into the aqueous phase in a thick cloud. Furthermore, it is found that the aqSOA generated in our laboratory experiments has a substantial fraction being attributed to the formation of oligomers in the aqueous phase. We also determined an aqSOA yield of 20% from residential wood combustion, which surpasses current estimates based on gas-phase oxidation. These results indicate that in-cloud chemistry of organic gases emitted from wood burning can serve as an efficient pathway to produce organic aerosols, thus potentially influencing climate and air quality.

The EMERGE framework to measure empowerment for health and development.

RATIONALE: Women's empowerment is a UN Sustainable Development Goal and a focus of global health and development but survey measures and data on gender empowerment remain weak. Existing indicators are often disconnected from theory; stronger operationalization is needed. OBJECTIVE: We present the EMERGE Framework to Measure Empowerment, a framework to strengthen empowerment measures for global health and development. METHOD: We initiated development of this framework in 2016 as part of EMERGE - an initiative designed to build the science of survey research and availability of high-quality survey measures and data on gender empowerment. The framework is guided by existing theories of empowerment, evidence, and expert input. We apply this framework to understand women's empowerment in family planning (FP) via review of state of the field measures. RESULTS: Our framework offers concrete measurable constructs to assess critical consciousness and choice, agency and backlash, and goal achievement as the empowerment process, recognizing its operation at multiple levels-from the individual to the collective. Internal attributes, social norms, and external contexts and resources create facilitators or barriers to the empowerment process. Review of best evidence FP measures assessing empowerment constructs, social norms, and key influencers (e.g., partners and providers) show a strong landscape of measures, including those with women, partners, and providers, but they are limited in assessing translation of choice to agency to achievement of women's self-determined fertility or contraceptive goals, instead relying on assumption of contraceptive use as the goal. We see no measures on collective empowerment toward women's reproductive choice and rights. CONCLUSION: The EMERGE Framework can guide development and analysis of survey measures on empowerment and is needed as the current state of the field shows limited coverage of empowerment constructs even in areas which have received more study, such as family planning.

Simulation Training for Emergency Sternotomy in the Cardiovascular Intensive Care Unit.

BACKGROUND: Emergency resternotomy in the intensive care unit for a patient who has undergone cardiac surgery can be daunting for surgeons and critical care staff. Clinicians involved are often unfamiliar with the surgical instruments and techniques needed. LOCAL PROBLEM: After an emergency intensive care unit resternotomy resulted in suboptimal performance and outcome, protocols for emergency resternotomy were established and improved. METHODS: Education and simulation training were used to improve staff comfort and familiarity with the needed techniques and supplies. The training intervention included simulations to provide hands-on experience, improve staff familiarity with resternotomy trays, and streamline emergency sternotomy protocols. Preintervention and postintervention surveys were used to assess participants' familiarity with the implemented plans and algorithms. RESULTS: All 44 participants (100%) completed the preintervention survey, and 41 of 44 participants (93%) returned the postintervention survey. After the intervention, 95% of respondents agreed that they were prepared to be members of the team for an emergency intensive care unit sternotomy, compared with 52% of respondents before the intervention. After the intervention, 95% of respondents strongly agreed or agreed that they could identify patients who might need emergency sternotomy, compared with 50% before the intervention. The results also showed improvement in staff members' understanding of team roles, activation and use of the emergency sternotomy protocol, and differences between guidelines for resuscitating patients who experience cardiac arrest after cardiac surgery and the post-cardiac arrest Advanced Cardiovascular Life Support protocol. CONCLUSION: Results of this quality improvement project suggest that simulation training improves staff comfort with and understanding of emergency resternotomy.

Perioperative Health Interventions in Children With Chronic Neuromuscular Conditions Undergoing Major Musculoskeletal Surgery: A Scoping Review.

BACKGROUND AND OBJECTIVES: Children with chronic neuromuscular conditions (CCNMC) have many coexisting conditions and often require musculoskeletal surgery for progressive neuromuscular scoliosis or hip dysplasia. Adequate perioperative optimization may decrease adverse perioperative outcomes. The purpose of this scoping review was to allow us to assess associations of perioperative health interventions (POHI) with perioperative outcomes in CCNMC. METHODS: Eligible articles included those published from January 1, 2000 through March 1, 2022 in which the authors evaluated the impact of POHI on perioperative outcomes in CCNMC undergoing major musculoskeletal surgery. Multiple databases, including PubMed, Embase, Cumulative Index of Nursing and Allied Health Literature, Web of Science, the Cochrane Library, Google Scholar, and ClinicalTrials.gov, were searched by using controlled vocabulary terms and relevant natural language keywords. Preferred Reporting Items for Systematic Reviews and Meta-Analyses Extension for Scoping Reviews guidelines were used to perform the review. A risk of bias assessment for included studies was performed by using the Risk of Bias in Non-randomized Studies of Interventions tool. RESULTS: A total of 7013 unique articles were initially identified, of which 6286 (89.6%) were excluded after abstract review. The remaining 727 articles' full texts were then reviewed for eligibility, resulting in the exclusion of 709 (97.5%) articles. Ultimately, 18 articles were retained for final analysis. The authors of these studies reported various impacts of POHI on perioperative outcomes, including postoperative complications, hospital length of stay, and hospitalization costs. Because of the heterogeneity of interventions and outcome measures, meta-analyses with pooled data were not feasible. CONCLUSIONS: The findings reveal various impacts of POHI in CCNMC undergoing major musculoskeletal surgery. Multicenter prospective studies are needed to better address the overall impact of specific interventions on perioperative outcomes in CCNMC.

Surgical Technique And Clinical Implications Of Transcatheter Aortic Valve Bioprosthesis Explantation.

There has been a worldwide rapid adoption of transcatheter aortic valve replacement (TAVR) as an alternative to surgical aortic valve replacement (SAVR) for patients with severe aortic stenosis. Currently, more TAVR explants with SAVRs are performed than TAVR-in TAV. TAVR explantation is a technically hazardous procedure mainly due to significant aortic neo-endothelialization which incorporates the TAVR valve. Surgical techniques for TAVR explantation are not well established and surgeon experience at present is limited. In this manuscript, we describe our technique for surgical explantation of transcatheter aortic bioprosthesis. Familiarity with the procedure and its clinical implications is essential for all cardiac surgeons.

Qualitative Monitoring of Proto-Peptide Condensation by Differential FTIR Spectroscopy.

Condensation processes such as wet-dry cycling are thought to have played significant roles in the emergence of proto-peptides. Here, we describe a simple and low-cost method, differential Fourier transform infrared (FTIR) spectroscopy, for qualitative analysis of peptide condensation products in model primordial reactions. We optimize differential FTIR for depsipeptides and apply this method to investigate their polymerization in the presence of extraterrestrial dust simulants.

Real-Time Identification of Aerosol-Phase Carboxylic Acid Production Using Extractive Electrospray Ionization Mass Spectrometry.

Comprehensive identification of aerosol sources and their constituent organic compounds requires aerosol-phase molecular-level characterization with a high time resolution. While real-time chemical characterization of aerosols is becoming increasingly common, information about functionalization and structure is typically obtained from offline methods. This study presents a method for determining the presence of carboxylic acid functional groups in real time using extractive electrospray ionization mass spectrometry based on measurements of [M - H + 2Na]+ adducts. The method is validated and characterized using standard compounds. A proof-of-concept application to α-pinene secondary organic aerosol (SOA) shows the ability to identify carboxylic acids even in complex mixtures. The real-time capability of the method allows for the observation of the production of carboxylic acids, likely formed in the particle phase on short time scales (<120 min). Our research explains previous findings of carboxylic acids being a significant component of SOA and a quick decrease in peroxide functionalization following SOA formation. We show that the formation of these acids is commensurate with the increase of dimers in the particle phase. Our results imply that SOA is in constant evolution through condensed-phase processes, which lower the volatility of the aerosol components and increase the available condensed mass for SOA growth and, therefore, aerosol mass loading in the atmosphere. Further work could aim to quantify the effect of particle-phase acid formation on the aerosol volatility distributions.

Growing the global cancer care system: success stories from around the world and lessons for the future.

Despite major biomedical advancements in various realms of oncology, the benefits of these developments are not equitably distributed, particularly in underresourced settings. Although much work has described the challenges and systemic barriers in global cancer control, in this article we focus on success stories. This article describes clinical care delivered at Rwanda's Butaro Cancer Center of Excellence, the cancer research collaborations under India's National Cancer Grid, and the efforts of Latin America's Institute of Cancer of São Paulo in advancing cancer care and training. These examples highlight the potential of strategic collaborations and resource allocation strategies in improving cancer care globally. We emphasize the critical role of partnerships between physicians and allied health professionals, funders, and policy makers in enhancing access to treatment and infrastructure, advancing contextualized research and national guidelines, and establishing regional and global collaborations. We also draw attention to challenges faced in diverse global settings and outline benchmarks to measure success in the fight against cancer.

Local incomplete combustion emissions define the PM2.5 oxidative potential in Northern India.

The oxidative potential (OP) of particulate matter (PM) is a major driver of PM-associated health effects. In India, the emission sources defining PM-OP, and their local/regional nature, are yet to be established. Here, to address this gap we determine the geographical origin, sources of PM, and its OP at five Indo-Gangetic Plain sites inside and outside Delhi. Our findings reveal that although uniformly high PM concentrations are recorded across the entire region, local emission sources and formation processes dominate PM pollution. Specifically, ammonium chloride, and organic aerosols (OA) from traffic exhaust, residential heating, and oxidation of unsaturated vapors from fossil fuels are the dominant PM sources inside Delhi. Ammonium sulfate and nitrate, and secondary OA from biomass burning vapors, are produced outside Delhi. Nevertheless, PM-OP is overwhelmingly driven by OA from incomplete combustion of biomass and fossil fuels, including traffic. These findings suggest that addressing local inefficient combustion processes can effectively mitigate PM health exposure in northern India.

Tools used to measure the impact of comorbidities on surgical outcomes in children with complex chronic conditions: A scoping review.

AIM: To identify and describe assessment tools used to measure the impact of comorbidities on postoperative outcomes in children with complex chronic conditions (CCC). METHOD: This was a scoping review using five electronic databases. The search was conducted in March 2022 by a medical librarian. There were no date or language restrictions. Included studies were full-text articles published in peer-reviewed journals that described a tool used to measure the impact of comorbidities in children with CCC to assess postoperative outcomes. A standardized data charting tool was used. RESULTS: A total of 2157 articles were retrieved. Five studies reporting on six comorbidity measures met inclusion criteria. All were cohort studies and were secondary analyses of data from an administrative database (n = 4) or a patient registry (n = 1). Sample sizes ranged from 645 to 25 747 participants. One paper described the assessment of reliability. Only one form of validity - predictive validity - was assessed in three papers for five measures. INTERPRETATION: Findings from this scoping review revealed a paucity of comorbidity assessment tools validated for use with children with CCC; significant conceptual and measurement challenges exist in the current scientific literature.

Major source categories of PM2.5 oxidative potential in wintertime Beijing and surroundings based on online dithiothreitol-based field measurements.

Fine particulate matter (PM2.5) causes millions of premature deaths each year worldwide. Oxidative potential (OP) has been proposed as a better metric for aerosol health effects than PM2.5 mass concentration alone. In this study, we report for the first time online measurements of PM2.5 OP in wintertime Beijing and surroundings based on a dithiothreitol (DTT) assay. These measurements were combined with co-located PM chemical composition measurements to identify the main source categories of aerosol OP. In addition, we highlight the influence of two distinct pollution events on aerosol OP (spring festival celebrations including fireworks and a severe regional dust storm). Source apportionment coupled with multilinear regression revealed that primary PM and oxygenated organic aerosol (OOA) were both important sources of OP, accounting for 41 ± 12 % and 39 ± 10 % of the OPvDTT (OP normalized by the sampled air volume), respectively. The small remainder was attributed to fireworks and dust, mainly resulting from the two distinct pollution events. During the 3.5-day spring festival period, OPvDTT spiked to 4.9 nmol min-1 m-3 with slightly more contribution from OOA (42 ± 11 %) and less from primary PM (31 ± 15 %). During the dust storm, hourly-averaged PM2.5 peaked at a very high value of 548 µg m-3 due to the dominant presence of dust-laden particles (88 % of total PM2.5). In contrast, only mildly elevated OPvDTT values (up to 1.5 nmol min-1 m-3) were observed during this dust event. This observation indicates that variations in OPvDTT cannot be fully explained using PM2.5 alone; one must also consider the chemical composition of PM2.5 when studying aerosol health effects. Our study highlights the need for continued pollution control strategies to reduce primary PM emissions, and more in-depth investigations into the source origins of OOA, to minimize the health risks associated with PM exposure in Beijing.

Effects of Sociodemographic and Child Opportunity Index on Pediatric Plastic and Oral and Maxillofacial Surgical Volume Trends in the COVID-19 Pandemic.

Background: The coronavirus disease 2019 (COVID-19) pandemic caused disruptions to pediatric surgical care. Although surgical capacity has returned to the prepandemic state, barriers to surgical access may still exist for children who are medically underserved. We assessed pediatric plastic and oral and maxillofacial surgical volumes by sociodemographic characteristics before and during the COVID-19 pandemic. Methods: A 72-month retrospective cohort analysis of 10,681 pediatric plastic and oral and maxillofacial procedures between 2016 and 2021 was conducted. Multivariable logistic regression and interrupted time series analyses were used to analyze surgical volume trends by sociodemographic groups and Child Opportunity Index (COI). Results: Compared with prepandemic, patients undergoing procedures were more likely to be older than 18 years (P < 0.001) and Hispanic/Latino (adjusted odds ratio 1.38; 95% confidence interval, 1.14-1.68; P < 0.01). Surgical volume trends among patients from the lowest COI levels were lower than where they were estimated to have been if the pandemic did not occur (P = 0.040). Patients who spoke a primary language other than English or Spanish (P = 0.02) and patients with the lowest COI levels (P = 0.04) continued to have unrecovered surgical volumes. Conclusions: There were differences in the sociodemographic case-mix of patients undergoing plastic and oral and maxillofacial surgical procedures before and during the pandemic, and surgical volumes did not recover at the same rate for all patients. Further research can determine why certain sociodemographic groups and patients with low COI levels had decreased surgical access compared with prepandemic trends, and develop interventions focused on equitable pediatric surgical access.

Machine Learning Analysis Using RNA Sequencing to Distinguish Neuromyelitis Optica from Multiple Sclerosis and Identify Therapeutic Candidates.

This study aims to identify RNA biomarkers distinguishing neuromyelitis optica (NMO) from relapsing-remitting multiple sclerosis (RRMS) and explore potential therapeutic applications leveraging machine learning (ML). An ensemble approach was developed using differential gene expression analysis and competitive ML methods, interrogating total RNA-sequencing data sets from peripheral whole blood of treatment-naïve patients with RRMS and NMO and healthy individuals. Pathway analysis of candidate biomarkers informed the biological context of disease, transcription factor activity, and small-molecule therapeutic potential. ML models differentiated between patients with NMO and RRMS, with the performance of certain models exceeding 90% accuracy. RNA biomarkers driving model performance were associated with ribosomal dysfunction and viral infection. Regulatory networks of kinases and transcription factors identified biological associations and identified potential therapeutic targets. Small-molecule candidates capable of reversing perturbed gene expression were uncovered. Mitoxantrone and vorinostat-two identified small molecules with previously reported use in patients with NMO and experimental autoimmune encephalomyelitis-reinforced discovered expression signatures and highlighted the potential to identify new therapeutic candidates. Putative RNA biomarkers were identified that accurately distinguish NMO from RRMS and healthy individuals. The application of multivariate approaches in analysis of RNA-sequencing data further enhances the discovery of unique RNA biomarkers, accelerating the development of new methods for disease detection, monitoring, and therapeutics. Integrating biological understanding further enhances detection of disease-specific signatures and possible therapeutic targets.