Toward the boosted loading of cisplatin drug into liposome nanocarriers.

Current challenges in oncology are largely associated with the need to improve the effectiveness of cancer treatment and to reduce drug's side effects. An effective strategy to cope with these challenges is behind designing and developing drug delivery systems based on smart nanomaterials and approved anticancer drugs. The present study offers a novel and straightforward approach to efficiently load the cisplatin drug into the newly constructed liposome-based nanosystems as well a reliable technique for monitoring this process based on capillary electrophoresis hyphenated with inductively coupled plasma tandem mass spectrometry. The proposed drug-loading methodology comprises liposome formation via a simple ethanol-injection method and propels increased drug encapsulation using tailor-made freeze-thawing or lyophilization-hydration procedures. To optimize liposome generation and drug encapsulation, the effects of dilution medium and liposome composition (types of phospholipids and their percentage ratio) have been investigated in detail. It was shown that modest alterations of the composition of three-component phospholipid liposomes and parameters of the freeze-thawing procedure have a strong impact on the formation of cisplatin-liposome systems. The obtained cisplatin-liposome formulation features a remarkable degree of drug encapsulation, over 100 mg L-1, and holds promise for further preclinical development as a potent drug-delivery platform.

Characterization and mapping of the neutron fields around Bruce Power's 177Lu isotope production system.

Bruce Power operates a first-of-its-kind isotope production system (IPS) that enables continuous production of 177Lu within Canada Deuterium Uranium (CANDU) commercial power reactors. Located on the reactivity mechanisms deck of Unit 7, just outside of reactor containment but in close proximity to the primary heat transport (PHT) pumps, this facility offers unique advantages for 177Lu production. However, employees working in this area encounter a radiation hazard which consists primarily of photoneutrons. These originate from the base of the PHT pumps and are only present when the reactor is operating. This study evaluates neutron exposure at Bruce Power's IPS by using a nested neutron spectrometer (NNS) to determine the neutron energy spectra and absolute dosimetric quantities such as the ambient dose equivalent, H*(10). The results from the NNS are then compared to surveys performed by a portable neutron rem meter (Model NP-2 by Nuclear Research Corporation), routinely used by Bruce Power staff for workplace monitoring. While the Model NP-2 generally showed consistent results across locations, a 50% dose correction factor was identified when operators were harvesting 177Lu from the IPS. This finding highlights an opportunity to reduce the neutron dose that is assigned to operators when producing 177Lu.

Transmission potential of mpox in mainland China, June-July 2023: estimating reproduction number during the initial phase of the epidemic.

Despite reporting very few mpox cases in early 2023, mainland China observed a surge of over 500 cases during the summer. Amid ambiguous prevention strategies and stigma surrounding mpox transmission, the epidemic silently escalated. This study aims to quantify the scale of the mpox epidemic and assess the transmission dynamics of the virus by estimating the effective reproduction number (Re) during its early phase. Publicly available data were aggregated to obtain daily mpox case counts in mainland China, and the Re value was estimated using an exponential growth model. The mean Re value was found to be 1.57 (95% credible interval [1.38-1.78]), suggesting a case doubling time of approximately 2 weeks. This estimate was compared with Re values from 16 other countries' national outbreaks in 2022 that had cumulative case count exceeding 700 symptomatic cases by the end of that year. The Re estimates for these outbreaks ranged from 1.13 for Portugal to 2.31 for Colombia. The pooled mean Re was 1.49 (95% credible interval [1.32-1.67]), which aligns closely with the Re for mainland China. These findings underscore the need for immediate and effective control measures including targeted vaccination campaigns to mitigate the further spread and impact of the epidemic.

Reconstruction and analysis of the transmission network of African swine fever in People's Republic of China, August 2018-September 2019.

Introduction of African swine fever (ASF) to China in mid-2018 and the subsequent transboundary spread across Asia devastated regional swine production, affecting live pig and pork product-related markets worldwide. To explore the spatiotemporal spread of ASF in China, we reconstructed possible ASF transmission networks using nearest neighbour, exponential function, equal probability, and spatiotemporal case-distribution algorithms. From these networks, we estimated the reproduction numbers, serial intervals, and transmission distances of the outbreak. The mean serial interval between paired units was around 29 days for all algorithms, while the mean transmission distance ranged 332 -456 km. The reproduction numbers for each algorithm peaked during the first two weeks and steadily declined through the end of 2018 before hovering around the epidemic threshold value of 1 with sporadic increases during 2019. These results suggest that 1) swine husbandry practices and production systems that lend themselves to long-range transmission drove ASF spread; 2) outbreaks went undetected by the surveillance system. Efforts by China and other affected countries to control ASF within their jurisdictions may be aided by the reconstructed spatiotemporal model. Continued support for strict implementation of biosecurity standards and improvements to ASF surveillance is essential for halting transmission in China and spread across Asia.

Optimization and characterization of a coincidence beta-ray spectrometer.

Aimed at beta spectrometry and dosimetry for mixed beta-gamma fields, a Si-plastic scintillator coincidence beta-ray spectrometer has been developed. The spectrometer collects pure beta-ray spectra by rejecting the gamma-ray detection events through coincidence. Both pulse height and arrival time of each detection event were recorded in list mode by a compact digital processing system. Spectral measurements were carried out using mixed beta-gamma fields from 90Sr/90Y and 137Cs sources for various beta and gamma count rates to evaluate the system performance. Coincidence beta spectra were collected for four fixed beta count rates (7.3-241 cps) from 90Sr/90Y while the gamma count rate from 137Cs was varied from 500 to 8000 cps. The coincidence beta spectrum was stable and unperturbed by the gamma detection events for most measurements while notable perturbation was observed in the low energy region when the beta to gamma count ratio is very low.

Effect of Health Insurance Status and Visitation Restrictions on Virtual Visitation Technology in the Neonatal Intensive Care Unit.

OBJECTIVE: This study aimed to examine the relationship between virtual technology system utilization and insurance status or type of visitation restrictions in a single-center neonatal intensive care unit. STUDY DESIGN: Prospective cohort study with separate analyses performed based on insurance status (public vs. nonpublic) and "in effect" unit visitation restrictions. The three study epochs based on patient visitation restrictions were Epoch 1 (July to October 2019) with standard visitation restrictions, Epoch 2 (November 2019 to February 2020) with respiratory syncytial virus/influenza visitation restrictions, and Epoch 3 (March to June 2020) with coronavirus disease 2019 (COVID-19) visitation restrictions, respectively. RESULTS: Families of 357 infants used web-based cameras through most of the infant's hospitalization (median: 86.05%, Q3: 97.9%) with 165,795 total camera logins, indicating consistent utilization. There was a trend for fewer logins per infant and significantly longer time to consent (p = 0.03) in the Public Insurance group. Unit visitation restrictions impacted the time to consent, the shortest being in Epoch 3 during the COVID-19 pandemic (p = 0.03). CONCLUSION: Virtual visitation technology is well embraced by neonatal instensive care unit families; however, gaps in access and use among subgroups signals a form of social inequality that needs to be explored further. KEY POINTS: · Virtual visitation technology can bridge the distance gap for families of hospitalized infants.. · Utilization of virtual technology is affected by socioeconomic factors and seasonal unit visitation restrictions.. · Factors influencing disparities in access and utilization of virtual technology need to be investigated further..

Nanoscale Ion-Exchange Materials: From Analytical Chemistry to Industrial and Biomedical Applications.

Nano-sized ion exchangers (NIEs) combine the properties of common bulk ion-exchange polymers with the unique advantages of downsizing into nanoparticulate matter. In particular, being by nature milti-charged ions exchangers, NIEs possess high reactivity and stability in suspensions. This brief review provides an introduction to the emerging landscape of various NIE materials and summarizes their actual and potential applications. Special attention is paid to the different methods of NIE fabrication and studying their ion-exchange behavior. Critically discussed are different examples of using NIEs in chemical analysis, e.g., as solid-phase extraction materials, ion chromatography separating phases, modifiers for capillary electrophoresis, etc., and in industry (fuel cells, catalysis, water softening). Also brought into focus is the potential of NIEs for controlled drug and contrast agent delivery.

A National Case-Crossover Study on the Risk of Kidney Injury Requiring Dialysis after Sepsis.

BACKGROUND: Patients with sepsis-associated acute kidney injury (AKI) are at risk of kidney damage, potentially necessitating acute temporary or chronic dialysis. Our study aims to estimate the odds ratio (OR) of preceding sepsis among patients requiring their first dialysis. METHODS: A nationwide population-based case-only study was conducted using claims records from the National Health insurance database of Taiwan. All patients over 20 years of age who underwent their first dialysis between 2004 and 2016 were included in the study. The six months prior to their first dialysis served as a self-control period. RESULTS: The study included 147,201 patients who required acute temporary and 75,031 patients who required chronic dialysis. The odds ratios for patients needing acute temporary dialysis after 1, 2, 3, and 4 weeks of exposure periods were 15.8, 10.7, 9.2, and 8.4, respectively. The ORs for patients requiring chronic dialysis were 7.0, 4.1, 4.2, and 3.7, respectively. CONCLUSIONS: Our findings indicate that sepsis was substantially associated with an increased risk of renal failure. The risk was highest during the first week following sepsis for both acute temporary and chronic dialysis cases.

Enhanced edible plant production using nano-manganese and nano-iron fertilizers: Current status, detection methods and risk assessment.

BACKGROUND: Nanotechnology offers many benefits in the globally important field of food production and human nutrition, particularly by implementing agricultural nanoproducts. Of these, edible plant fertilizers enriched with nanosized forms of essential metals, Mn and Fe, are growing in importance with the advantages of enhanced action on plant roots. SCOPE AND APPROACH: This review focuses on the importance of tracking the bioaccumulation and biodistribution of these pertinent nanofertilizers. An emphasis is given to the critical analysis of the state-of-the-art analytical strategies to examine the Mn and Fe nanoparticles in edible plant systems as well as to shedding light on the vast gap in the methodologies dedicated to the speciation, in vitro simulation, and safety testing of these promising nanomaterials. Also provided are guidances for the food chemists and technologists on the lights and shadows of particular analytical approaches as a matter of authors' expertise as analytical chemists. KEY FINDINGS AND CONCLUSIONS: While the use of nanotechnology in agriculture seems to be growing increasingly, there is still a lack of analytical methodologies capable of investigating novel Mn- and Fe-based nanomaterials as potential fertilizers. Only the advent of reliable analytical tools in the field could bridge the gaps in our knowledge about processes in which those materials participate in the plant systems and their effects on crop production and quality of the produced food.

A Standardized, 3-Tiered, Seizure Burden-Based Protocol for the Treatment of Neonatal Seizures.

OBJECTIVE: To evaluate use of a standardized, 3-tiered, seizure burden-based protocol for treatment of all electroencephalography (EEG)-confirmed seizures in a level IV neonatal intensive care unit (NICU). STUDY DESIGN: All infants admitted to the NICU with EEG-confirmed seizures over a 25-month period were enrolled in the study. We compared short-term outcomes before and after implementation of a standardized, 3-tiered protocol. RESULTS: A total of 107 infants were enrolled in the study. Use of midazolam infusions was reduced by 53.7% (p = 0.02). Midazolam infusion duration increased from 4 to 7.5 days (p = 0.003); however, when excluding 3 outliers, there was no significant difference between groups (-p = 0.67). Duration of EEG monitoring decreased from 5 to 3 days (p = 0.005). Hospital length of stay was unchanged. CONCLUSION: Implementation of a standardized, 3-tiered protocol for treatment of neonatal seizures improved short-term outcomes. Although not measured directly, reductions in EEG duration and midazolam use are promising indicators of overall seizure burden. More research is needed to evaluate impact on long-term neurodevelopmental outcomes.

Phase II study of dose-adjusted EPOCH as initial therapy for adults with high-risk acute lymphoblastic leukemia.

Treatments for adults with newly-diagnosed acute lymphoblastic leukemia (ALL) may be prohibitively toxic and/or resource-intense. To address this, we performed a phase II study of dose-adjusted etoposide, prednisone, vincristine, cyclophosphamide, and doxorubicin (DA-EPOCH). Imatinib or dasatinib was added for Ph + disease; rituximab was added when CD20+. Fifty-three patients were evaluable: 28 with Ph + disease, and 25 with Ph-. All patients had ≥1 high-risk clinical feature. Measurable residual disease-negativity by multiparameter flow cytometry within 4 cycles was achieved in 71% in patients with Ph + ALL and 64% in Ph - ALL. Median overall survival (OS) was 49 months, with a 2-year OS of 71%. Median relapse-free survival (RFS) in the 47 patients that attained morphologic remission was 24 months, with a 2-year RFS of 57%. Early mortality was 2%. In summary, DA-EPOCH yields deep and durable remissions in adults with ALL comparable to some resource-intense strategies but with a low rate of treatment-related death.

Mass Spectrometry Insight for Assessing the Destiny of Plastics in Seawater.

Plastic pollution has become an increasingly serious environmental issue that requires using reliable analytical tools to unravel the transformations of primary plastics exposed to the marine environment. Here, we evaluated the performance of the isotope ratio mass spectrometry (IRMS) technique for identifying the origin of polymer material contaminating seawater and monitoring the compositional alterations due to its chemical degradation. Of twenty-six plastic specimens available as consumer products or collected from the Mediterranean Sea, five plastics were shown to originate from biobased polymeric materials. Natural abundance carbon and hydrogen isotope measurements revealed that biopolymers incline to substantial chemical transformation upon a prolonged exposure to seawater and sunlight irradiation. To assess the seawater-mediated aging that leads to the release of micro/nano fragments from plastic products, we propose to use microfiltration. Using this non-destructive separation technique as a front end to IRMS, the fragmentation of plastics (at the level of up to 0.5% of the total mass for plant-derived polymers) was recorded after a 3-month exposure and the rate and extent of disintegration were found to be substantially different for the different classes of polymers. Another potential impact of plastics on the environment is that toxic metals are adsorbed on their surface from the seashore water. We addressed this issue by using inductively coupled mass spectrometry after nitric acid leaching and found that several metals occur in the range of 0.1-90 µg per g on naturally aged plastics and accumulate at even higher levels (up to 10 mg g-1) on pristine plastics laboratory-aged in contaminated seawater. This study measured the degradation degree of different polymer types in seawater, filling in the gaps in our knowledge about plastic pollution and providing a useful methodology and important reference data for future research.

Analysis of Engineered Nanoparticles in Seawater Using ICP-MS-Based Technology: From Negative to Positive Samples.

A growing global emission of engineered nanoparticles (ENPs) into the aquatic environment has become an emerging safety concern that requires methods capable of identifying the occurrence and possibly determining the amounts of ENPs. In this study, we employed sector-field inductively coupled mass spectrometry to assess the presence of ENPs in coastal seawater samples collected from the Black Sea in regions suffering different anthropogenic impacts. Ultrafiltration through commercial 3 kDa membrane filters was shown to be feasible to separate the ENPs from the bulk seawater, and the subsequent ultrasound-mediated acidic dissolution makes the metals constituting the ENPs amenable to analysis. This procedure allowed the ENPs bearing Cu, Zn, V, Mo, and Sn to be for the first time quantitated in seashore surface water, their concentration ranging from 0.1 to 1.0 µg L-1 (as metal) and related to the presence of industry and/or urban stress. While these levels are decreased by natural dilution and possible sedimentation, the monitored ENPs remain measurable at a distance of 2 km from the coast. This can be attributed not only to local emission sources but also to some natural backgrounds.

Seawater analysis of engineered nanoparticles using ICP-MS-based technology: Addressing challenges with the development of reliable monitoring strategy.

With an increasing production and use of engineered nanoparticles (ENPs), inevitably grows their release into the environment. This makes it important to determine in what quantitates they occur in aquatic systems like seawater. However, even when using the most sensitive ICP-MS technique, quantification of very low seawater concentrations of ENPs is still concept rather than the fact. To approach this goal, a unified protocol for the preparation of seawater samples for ICP-MS analysis has been developed in this study using a selection of silver, titanium dioxide and zinc oxide nanoparticles. In order to minimize the risk of particle loss, the effect of sample pH was examined and it was found out that a moderate in-field acidification (to pH 7.5) ensures particle stability prior to analysis. Ultrafiltration through commercial 3 kDa membrane filters was shown feasible to separate the ENPs from the bulk seawater sample provided that the filter unit is pre-conditioned with 0.1 M copper nitrate to avoid ionic metal adsorption. The following ultrasound-mediated dissolution in 30% HNO3 directly in the filer unit and ultrafiltration makes the metals constituting the ENPs amenable to analysis. The latter was for the first time performed using high-resolution ICP-MS method validated according to the common EU standards. The limits of detection attained here were as low as 0.06, 0.09, and 17.5 µg L-1 for Ag, TiO2, and ZnO nanoparticles, respectively. Accuracy of the method was tested with uncontaminated open-sea water spiked with ENPs and recoveries were acceptable ranging from 85 to 110%.

Implicit and explicit learning of socio-emotional information in a dynamic interaction with a virtual avatar.

Implicit learning (IL) deals with the non-conscious acquisition of structural regularities from the environment. IL is often deemed essential for acquiring regularities followed by social stimuli (e.g., other persons' behavior), hence is hypothesized to play a role in typical social functioning. However, our understanding of how this process might operate in social contexts is limited for two main reasons. First, while IL is highly sensitive to the characteristics of the surface stimuli upon which it operates, most IL studies have used surface stimuli with limited social validity (e.g., letters, symbols, etc.). Second, while the social environment is dynamic (i.e., our behaviors and reactions influence those of our social partners and vice-versa), the bulk of IL research employed noninteractive paradigms. Using a novel task, we examine whether IL is involved in the acquisition of regularities from a dynamic interaction with a realistic real-life-like agent. Participants (N = 115) interacted with a cinematic avatar that displayed different facial expressions. Their task was to regulate the avatar's expression to a specified level. Unbeknownst to them, an equation mediated the relationship between their responses and the avatar's expressions. Learning occurred in the task, as participants gradually increased their ability to bring the avatar in the target state. Subjective measures of awareness revealed that participants acquired both implicit and explicit knowledge from the task. This is the first study to show that IL operates in interactive situations upon socially relevant surface stimuli, facilitating future investigations of the role that IL plays in (a)typical social functioning.

Corrigendum: Absolute winding number differentiates mouse spatial navigation strategies with genetic risk for Alzheimer's disease.

[This corrects the article DOI: 10.3389/fnins.2022.848654.].

Impact of a Standardized Nutrition Bundle Including Donor Human Milk on Hospital Outcomes in Very Low Birth-Weight (VLBW) Infants in a Safety-Net Hospital.

BACKGROUND: Standardized protocols have been shown to reduce clinical practice variation and improve patient outcomes. PURPOSE: To measure the impact of a standardized nutrition bundle inclusive of donor human milk (DHM) on hospital outcomes of very low birth-weight (VLBW) infants in a safety-net hospital. METHODS: The study used the Model for Improvement methodology to drive improvement in practice. Outcome measures consisted of necrotizing enterocolitis (NEC), mortality, growth at 36 weeks' postmenstrual age and discharge, as well as volume and type of milk consumption during hospitalization. FINDINGS: NEC rate decreased from 16.67% in the control group to 6.78% in the standardized nutrition bundle group (P = .07). Similarly, there was significant reduction in mortality with the bundled intervention (15.6% in the control group vs 1.6% in the nutrition bundle group; P = .006). Time to first (15 vs 27.5 hours of life; P < .001) and full-volume enteral feeding (8.5 vs 10 days; P = .086) were reduced in the standardized nutrition bundle group compared with the control group. The human milk volume almost doubled with the intervention. IMPLICATIONS FOR PRACTICE: Our standardized nutrition bundle protocol inclusive of DHM resulted in lower NEC rates and reduced mortality. The implementation of the DHM program proved to be cost-effective and saved lives. Our findings may help guide development of a structured approach to nutrition protocols inclusive of DHM that can be adapted by other units located in safety-net hospitals. IMPLICATIONS FOR RESEARCH: Future research on ethnic and racial barriers to access and affordability of DHM is warranted and much needed.

Correlation between times to SARS-CoV-2 symptom onset and secondary transmission undermines epidemic control efforts.

Severe acute respiratory coronavirus 2 (SARS-CoV-2) infections have been associated with substantial presymptomatic transmission, which occurs when the generation interval-the time between infection of an individual with a pathogen and transmission of the pathogen to another individual-is shorter than the incubation period-the time between infection and symptom onset. We collected a dataset of 257 SARS-CoV-2 transmission pairs in Japan during 2020 and jointly estimated the mean incubation period of infectors (4.8 days, 95 % CrI: 4.4-5.1 days), mean generation interval to when they infect others (4.3 days, 95 % credible interval [CrI]: 4.0-4.7 days), and the correlation (Kendall's tau: 0.5, 95 % CrI: 0.4-0.6) between these two epidemiological parameters. Our finding of a positive correlation and mean generation interval shorter than the mean infector incubation period indicates ample infectiousness before symptom onset and suggests that reliance on isolation of symptomatic COVID-19 cases as a focal point of control efforts is insufficient to address the challenges posed by SARS-CoV-2 transmission dynamics.

Transmission Dynamics and Effectiveness of Control Measures during COVID-19 Surge, Taiwan, April-August 2021.

An unprecedented surge of COVID-19 cases in Taiwan in May 2021 led the government to implement strict nationwide control measures beginning May 15. During the surge, the government was able to bring the epidemic under control without a complete lockdown despite the cumulative case count reaching >14,400 and >780 deaths. We investigated the effectiveness of the public health and social measures instituted by the Taiwan government by quantifying the change in the effective reproduction number, which is a summary measure of the ability of the pathogen to spread through the population. The control measures that were instituted reduced the effective reproduction number from 2.0-3.3 to 0.6-0.7. This decrease was correlated with changes in mobility patterns in Taiwan, demonstrating that public compliance, active case finding, and contact tracing were effective measures in preventing further spread of the disease.