Accelerated and Biopredictive In Vitro Release Testing Strategy for Single Agent and Combination Long-Acting Injectables.

The purpose of this study was to develop an in vitro release testing (IVRT) strategy to predict the pre-clinical performance of single agent and combination long acting injectable (LAI) suspension products. Two accelerated IVRT methods were developed using USP apparatus 2 to characterize initial, intermediate, and terminal phases of drug release. Initial and intermediate phases were captured using a suspension cup with moderate agitation to ensure a constant, low surface area exposure of the LAI suspension to the release media. The terminal phase was obtained by exposing the LAI suspension to a high initial paddle speed. This resulted in smaller suspension particulates with high cumulative surface area that were dispersed throughout the release media, enabling rapid drug release. The in vitro release profiles obtained with these two methods in 48 h or less were independently time scaled to reflect the in vivo time scale of approximately 1800 h. Level-A in vitro in vivo correlations (IVIVCs) were separately developed for each method and active pharmaceutical ingredient (API) using in vivo absorption profiles obtained by deconvolution of rat plasma concentration-time profiles. The IVIVCs were successfully validated for each API. This work provides a framework for evaluating individual phases of drug release of complex LAIs to ultimately predict their in vivo performance.

Dynamic tracking of human umbilical cord mesenchymal stem cells (hUC-MSCs) following intravenous administration in mice model.

Introduction: In the past decades, human umbilical cord-derived mesenchymal stem cells (hUC-MSCs) have sparked interest in cellular therapy due to their immunomodulatory properties. Nevertheless, the fate of hUC-MSCs in the body remains poorly understood. This study aimed to investigate the biodistribution, homing and clearance of systemically administered hUC-MSCs in healthy BALB/c mice model. Methods: hUC-MSCs were labelled with GFP-Luc2 protein, followed by characterisation with flow cytometry. Upon intravenous infusion of transduced hUC-MSCs into the healthy BALB/c mice, the cells were dynamically monitored through the bioluminescent imaging (BLI) approach. Results: Transduction of hUC-MSCs with GFP-Luc2 not only preserved the characteristics of MSCs, but also allowed live monitoring of transduced cells in the mice model. Upon systemic administration, BLI showed that transduced hUC-MSCs first localised predominantly in the lungs of healthy BALB/c mice and mainly remained in the lungs for up to 3 days before eventually cleared from the body. At terminal sacrifice, plasma chemistry biomarkers remained unchanged except for C-peptide levels, which were significantly reduced in the hUC-MSCs group. Histopathological findings further revealed that hUC-MSCs infusion did not cause any adverse effects and toxicity to lung, liver and heart tissues. Conclusions: Collectively, systemically administrated hUC-MSCs was safe and demonstrated dynamic homing capacity before eventually disappearing from the body.

Analysis of NK-92 cytotoxicity in nasopharyngeal carcinoma cell lines and patient-derived xenografts using impedance-based growth method.

Natural killer (NK) cells are innate immune cells that can remove viral-infected tumour cells without antigen priming. This characteristic offers NK cells an edge over other immune cells as a potential therapy for nasopharyngeal carcinoma (NPC). In this study, we report how cytotoxicity was evaluated in target NPC cell lines and patient-derived xenograft (PDX) cells with effector NK-92, a commercially available NK cell line, by using xCELLigence RTCA system (a real-time, label-free impedance-based monitoring platform). Cell viability, proliferation and cytotoxicity were examined by RTCA. Cell morphology, growth and cytotoxicity were also monitored by microscopy. RTCA and microscopy showed that both target and effector cells were able to proliferate normally and to maintain original morphology in co-culture medium as they were in their own respective culture medium. As target and effector (T:E) cell ratios increased, cell viability as measured by arbitrary cell index (CI) values in RTCA decreased in all cell lines and PDX cells. NPC PDX cells were more sensitive to the cytotoxicity effect of NK-92 cells, than the NPC cell lines. These data were substantiated by GFP-based microscopy. We have shown how the RTCA system can be used for a high throughput screening of the effects of NK cells in cancer studies to obtain data such as cell viability, proliferation and cytotoxicity.

Skin-to-Skin Contact (Kangaroo Care) During the COVID-19 Pandemic.

Early recommendations to separate mothers from their newborns during the coronavirus disease 2019 (COVID-19) pandemic have created a detrimental separation practice. This article presents a review of the latest information regarding the (1) 3 modes of transmission of the virus to the neonate; (2) incidence, clinical signs, and severity of COVID-19 in the neonate; (3) factors to be considered to balance risk and benefits of separation and skin-to-skin contact (SSC) when conducting shared decision making; and (4) compendium of published SSC guidelines; and concludes with recommendations for safe practice of SSC to prevent and/or restrict COVID-19 infection in neonates.

Theory of heat stress management: Development and application in the operating room.

AIM: The Theory of Heat Stress Management addresses the phenomenon of occupational heat stress and applies the theory to surgical staff wearing personal protective equipment while performing surgery. This discussion paper relates development of the prescriptive middle range theory of heat stress management to inform and advance research and provide evidence to support new standards of care in clinical nursing practice. DESIGN: The prescriptive middle range theory was developed by summarizing essential elements of the theory, describing the linkages among the dimensions of the theory, enumerating nursing interventions and physiological, psychological and cognitive outcomes, stating relevant assumptions, defining and identifying relationships between the concepts of heat stress management in observable and measurable terms. DATA SOURCES: This discussion paper is based on the first author's experiences with occupational heat stress, observed improvements in surgical personnel's thermal comfort by using a cooling intervention and knowledge gained from an extensive integrated literature review and ongoing clinical research. IMPLICATIONS FOR NURSING: The middle range theory was developed to create awareness of the impact heat stress has on the health and well-being of all healthcare personnel at risk for heat stress due to wearing personal protective equipment. Nurses need to recognize individuals in thermally stressful environments, evaluate and monitor individuals' physiological and psychological responses and promote comfort by providing interventions to alleviate occupational heat stress. CONCLUSION: The Theory of Heat Stress Management combines dimensions specific to heat stress affecting surgical staff and provides a perspective that facilitates knowledge development, can enhance nursing practice and support exploration of the linkages and prescriptions of the theory through research. IMPACT: The predictive middle-range Theory of Heat Stress Management will guide nurses to promote the health and well-being of healthcare workers and influence and improve clinical nursing practice, education, and research related to heat stress management.

Occupational Heat Stress, Thermal Comfort, and Cognitive Performance in the OR: An Integrative Review.

Heat may cause a stress response in perioperative personnel who wear impervious protective surgical gowns that can trap body heat. Responses to heat may include changes in cognitive function, which may affect performance during operative and other invasive procedures. This integrative literature review sought to identify research articles investigating associations among occupational heat stress, thermal comfort, and cognitive performance. The review found that there is a paucity of research on this topic; however, articles that assessed cognitive performance under heat stress for foundry workers (n = 70), cyclists (n = 10), and untrained participants in simulated settings (n = 32) showed that heat may have negative effects on cognition by affecting memory, reaction time, and complex motor skills. Whether heat affects the cognitive performance of perioperative personnel is an important topic for future research.

Strategies discussed at the XIIth international conference on Kangaroo mother care for implementation on a countrywide scale.

AIM: Building strategies for the country-level dissemination of Kangaroo mother care (KMC) to reduce the mortality rate in preterm and low birth weight babies and improve quality of life. KMC is an evidence-based healthcare method for these infants. However, KMC implementation at the global level remains low. METHODS: The international network in Kangaroo mother brought 172 KMC professionals from 33 countries together for a 2-day workshop held in conjunction with the XIIth International KMC Conference in Bogota, Colombia, in November 2018. Participants worked in clusters to formulate strategies for country-level dissemination and scale-up according to seven pre-established objectives. RESULTS: The minimum set of indicators for KMC scale-up proposed by the internationally diverse groups is presented. The strategies for KMC integration and implementation at the country level, as well as the approaches for convincing healthcare providers of the safety of KMC transportation, are also described. Finally, the main aspects concerning KMC follow-up and KMC for term infants are presented. CONCLUSION: In this collaborative meeting, participants from low-, middle- and high-income countries combined their knowledge and experience to identify the best strategies to implement KMC at a countrywide scale.

Maternity Nurses' Knowledge about Sudden Unexpected Postnatal Collapse and Safe Newborn Positioning.

PURPOSE: Sudden unexpected postnatal collapse (SUPC) of healthy newborns in the first 2 days of life is increasing. These types of adverse events are known to be associated with unsafe positioning during skin-to-skin contact and breastfeeding. The purpose of the study was to determine maternity nurses' knowledge about SUPC and safe newborn positioning. DESIGN: Nurses who participate in a hosted listserv were solicited to complete a questionnaire. METHODS: An email with an embedded link to a 20-item questionnaire, the SUPC and Safe Positioning Knowledge Assessment Tool, and 16 demographic questions was sent to 605 maternity nurses in the United States who are part of a Perinatal Listserv for members of the Association of Women's Health, Obstetric and Neonatal Nurses. Scores were analyzed by mean, standard deviation, and percent correct answers. RESULTS: Fifty questionnaires were initiated (response rate of 8.2%), and 36 completed questionnaires (response rate of 5.9%) were analyzed. Maternity nurses' knowledge of SUPC was less than their knowledge of safe newborn positioning (61% correct vs. 72% correct; p < 0.001). CLINICAL IMPLICATIONS: Maternity nurses need more information about SUPC and safe newborn positioning, including risk factors, and effective strategies to reduce risk of preventable newborn harm.

The evolution of the science of kangaroo (mother) care (skin-to-skin contact).

In the early 1970s, researchers in Ohio, USA, investigated the effects of "Extra Contact" between mothers and their infants early after birth. The "Extra Contact" consisted of the skin-to-skin holding of the newborn infant on the mother's bare chest as soon as possible after birth. In the mid 1970s, Rey and Martinez in Bogota Colombia started investigating the same care method and they called it "Kangaroo Care" (KC). Infants are held upright, skin-to-skin on the mother's bare chest. KC, also referred to as Kangaroo Mother Care or Skin-to-Skin Contact, has been and continue to be investigated for its effects on a plethora of infant, maternal and family outcomes. Evolution of our understanding of the advantages of KC has dramatically changed the care of infants including at risk infants. This article provides a look at the past and present. It also provides insight on how we can shape the future to provide the optimal care for infants, mothers, and the whole family.

Dielectrophoretic deformation of breast cancer cells for lab on a chip applications.

This paper presents the development and experimental analysis of a curved microelectrode platform for the DEP deformation of breast cancer cells (MDA-MB-231). The platform is composed of arrays of curved DEP microelectrodes which are patterned onto a glass slide and samples containing MDA-MB-231 cells are pipetted onto the platform's surface. Finite element method is utilised to characterise the electric field gradient and DEP field. The performance of the system is assessed with MDA-MB-231 cells in a low conductivity 1% DMEM suspending medium. We applied sinusoidal wave AC potential at peak to peak voltages of 2, 5, and 10 Vpp at both 10 kHz and 50 MHz. We observed cell blebbing and cell shrinkage and analyzed the percentage of shrinkage of the cells. The experiments demonstrated higher percentage of cell shrinkage when cells are exposed to higher frequency and peak to peak voltage electric field.

Paid Family Leave to Enhance the Health Outcomes of Preterm Infants.

Prematurity is the largest contributor to perinatal morbidity and mortality. Preterm infants and their families are a significant vulnerable population burdened with limited resources, numerous health risks, and poor health outcomes. The social determinants of health greatly shape the economic and psychosocial resources that families possess to promote optimal outcomes for their preterm infants. The purposes of this article are to analyze the resource availability, relative risks, and health outcomes of preterm infants and their families and to discuss why universal paid family leave could be one potential public policy that would promote optimal outcomes for this infant population. First, we discuss the history of family leave in the United States and draw comparisons with other countries around the world. We use the vulnerable populations conceptual model as a framework to discuss why universal paid family leave is needed and to review how disparities in resource availability are driving the health status of preterm infants. We conclude with implications for research, nursing practice, and public policy. Although health care providers, policy makers, and other key stakeholders have paid considerable attention to and allocated resources for preventing and treating prematurity, this attention is geared toward individual-based health strategies for promoting preconception health, preventing a preterm birth, and improving individual infant outcomes. Our view is that public policies addressing the social determinants of health (e.g., universal paid family leave) would have a much greater impact on the health outcomes of preterm infants and their families than current strategies.

Characterization of the suspension stability of pharmaceuticals using a shadowgraphic imaging method.

A new shadowgraphic imaging method and an associated instrument for analyzing the physical stability of pharmaceutical suspensions are introduced in this paper. The new suspension tester consists mainly of a high-resolution camera that takes sequential shadowgraphic images of emulsions or suspensions and a 2D collimated LED for simultaneous whole-sample illumination in bright field. A built-in ultrasonic bath provides controlled initial agitation to the samples of interest. Sequential images acquired by the experimental setup were used to derive normalized transmission profiles from which an instability index was developed for quantitative stability comparison between samples. Instrument performance was verified by measuring the stability of a series of oil-in-water emulsions prepared with surfactant mixtures of different ratios. The new instrument correctly determined the required hydrophilic-lipophilic balance for sunflower oil to be 7.0. The stability of a pressurized suspension of spray dried lipid (DSPC) particles was monitored for 5 days after propellant filling. Although stable for the first 24 h, the lipid suspension was found to decrease in stability from day 1 to day 4. Morphological and spectroscopic analysis revealed that the suspended DSPC particles had reformed into large thin sheets of lipid, thereby causing the gradual stability decrease during the aging study. The effects of initial agitation on the stability of suspensions were demonstrated by agitating a suspension of micronized fluticasone propionate in propellant using a wrist action shaker and an ultrasonic bath respectively. A significant improvement of suspension stability was achieved by replacing the wrist action shaker method with ultrasonic agitation. Simultaneous illumination of the complete suspension, a high image acquisition rate, and controlled initial agitation are features that make this new suspension tester a suitable and more reliable instrument for investigating the stability of pressurized pharmaceutical suspensions.

Promoting Newborn Safety Using the RAPPT Assessment and Considering Apgar Criteria: A Quality Improvement Project.

PURPOSE: The aim of this project was to evaluate the implementation of the Respiratory, Activity, Perfusion, Position, and Tone (RAPPT) instrument in assessing the infant's transition to extrauterine life while in skin-to-skin contact (SSC). Sample/Design: Nurses (n = 17) completed a pretest and posttest of RAPPT and Apgar scoring knowledge, attended an in-service about accurate scoring, and were observed during 17 deliveries when newborns were in SSC. OUTCOME VARIABLES: Primary variables were knowledge scores, use of RAPPT, and accurate RAPPT scoring. Apgar scoring was also measured. RESULTS: Knowledge scores increased significantly after education, RAPPT scores were correctly assessed, and 1 of 17 newborns had a sudden unexpected postnatal collapse. Apgar scoring accuracy did not change and nurses reported that their Apgar scores were based on their overall impressions of the infant instead of Apgar criteria.

Dielectrophoresis-based microfluidic platforms for cancer diagnostics.

The recent advancement of dielectrophoresis (DEP)-enabled microfluidic platforms is opening new opportunities for potential use in cancer disease diagnostics. DEP is advantageous because of its specificity, low cost, small sample volume requirement, and tuneable property for microfluidic platforms. These intrinsic advantages have made it especially suitable for developing microfluidic cancer diagnostic platforms. This review focuses on a comprehensive analysis of the recent developments of DEP enabled microfluidic platforms sorted according to the target cancer cell. Each study is critically analyzed, and the features of each platform, the performance, added functionality for clinical use, and the types of samples, used are discussed. We address the novelty of the techniques, strategies, and design configuration used in improving on existing technologies or previous studies. A summary of comparing the developmental extent of each study is made, and we conclude with a treatment of future trends and a brief summary.

CD24, CD44 and EpCAM enrich for tumour-initiating cells in a newly established patient-derived xenograft of nasopharyngeal carcinoma.

Subpopulations of nasopharyngeal carcinoma (NPC) contain cells with differential tumourigenic properties. Our study evaluates the tumourigenic potential of CD24, CD44, EpCAM and combination of EpCAM/CD44 cells in NPC. CD44br and EpCAMbr cells enriched for higher S-phase cell content, faster-growing tumourigenic cells leading to tumours with larger volume and higher mitotic figures. Although CD44br and EpCAMbr cells significantly enriched for tumour-initiating cells (TICs), all cells could retain self-renewal property for at least four generations. Compared to CD44 marker alone, EpCAM/CD44dbr marker did not enhance for cells with faster-growing ability or higher TIC frequency. Cells expressing high CD44 or EpCAM had lower KLF4 and p21 in NPC subpopulations. KLF4-overexpressed EpCAMbr cells had slower growth while Kenpaullone inhibition of KLF4 transcription increased in vitro cell proliferation. Compared to non-NPC, NPC specimens had increased expression of EPCAM, of which tumours from advanced stage of NPC had higher expression. Together, our study provides evidence that EpCAM is a potentially important marker in NPC.

Modeling nasopharyngeal carcinoma in three dimensions.

Nasopharyngeal carcinoma (NPC) is a type of cancer endemic in Asia, including Malaysia, Southern China, Hong Kong and Taiwan. Treatment resistance, particularly in recurring cases, remains a challenge. Thus, studies to develop novel therapeutic agents are important. Potential therapeutic compounds may be effectively examined using two-dimensional (2D) cell culture models, three-dimensional (3D) spheroid models or in vivo animal models. The majority of drug assessments for cancers, including for NPC, are currently performed with 2D cell culture models. This model offers economical and high-throughput screening advantages. However, 2D cell culture models cannot recapitulate the architecture and the microenvironment of a tumor. In vivo models may recapitulate certain architectural and microenvironmental conditions of a tumor, however, these are not feasible for the screening of large numbers of compounds. By contrast, 3D spheroid models may be able to recapitulate a physiological microenvironment not observed in 2D cell culture models, in addition to avoiding the impediments of in vivo animal models. Thus, the 3D spheroid model offers a more representative model for the study of NPC growth, invasion and drug response, which may be cost-effective without forgoing quality.

Macro-Raman spectroscopy for bulk composition and homogeneity analysis of multi-component pharmaceutical powders.

A new macro-Raman system equipped with a motorized translational sample stage and low-frequency shift capabilities was developed for bulk composition and homogeneity analysis of multi-component pharmaceutical powders. Different sampling methods including single spot and scanning measurement were compared. It was found that increasing sample volumes significantly improved the precision of quantitative composition analysis, especially for poorly mixed powders. The multi-pass cavity of the macro-Raman system increased effective sample volumes by 20 times from the sample volume defined by the collection optics, i.e., from 0.02µL to about 0.4µL. A stochastic model simulating the random sampling process of polydisperse microparticles was used to predict the sampling errors for a specific sample volume. Comparison of fluticasone propionate mass fractions of the commercial products Flixotide® 250 and Seretide® 500 simulated for different sampling volumes with experimentally measured compositions verified that the effective sample volume of a single point macro-Raman measurement in the multi-pass cavity of this instrument was between 0.3µL and 0.5µL. The macro-Raman system was also successfully used for blend uniformity analysis. It was concluded that demixing occurred in the binary mixture of l-leucine and d-mannitol from the observation that the sampling errors indicated by the standard deviations of measured leucine mass fractions increased during mixing, and the standard deviation values were all larger than the theoretical lower limit determined by the simulation. Since sample volume was shown to have a significant impact on measured homogeneity characteristics, it was concluded that powder homogeneity analysis results, i.e., the mean of individual test results and absolute and relative standard deviations, must be presented together with the effective sample volumes of the applied testing techniques for any measurement of powder homogeneity to be fully meaningful.

Role of Baby-Friendly Hospital Care in Maternal Role Competence.

The objective of this pilot study was to determine women's perceptions of their levels of maternal role competence at discharge from a Baby-Friendly hospital. A convenience sample of 30 women completed two self-report questionnaires: a demographic questionnaire and the Perceived Maternal Parenting Self-Efficacy scale. Women report that they perceived high levels of maternal role competence with a mean total score of 69.80 (standard deviation = 6.86) out of 80. As women experience breastfeeding in Baby-Friendly hospitals, maternal role competence may develop with appropriate support.

A survey of skin-to-skin contact with perinatal nurses.

OBJECTIVE: This study explored perinatal nurses' knowledge, attitudes and practices of SSC, to identify knowledge-practice gaps. STUDY DESIGN: A descriptive cross-sectional survey design was completed by 101 perinatal nurses. Descriptive statistics and ordered logistical regression were used to describe and compare nurses' responses. RESULTS: The participants strongly agreed that it is nurses' responsibility to advocate for SSC. Significant differences (p<0.01) were reported in provision of SSC with eligible infants between nurses within and between practice settings, education levels, year experience and age differences. Education levels significantly influenced attitudes and implementation of SSC. Perinatal nurses' responses about how difficult it is to initiate SSC changes were affected by years of nursing practice (p<0.04). CONCLUSIONS: Perinatal nurses strongly believe in SSC practices, yet additional training regarding SSC implementation is needed. Education levels, primary practice settings and years of practice appear to influence nurses' implementation of SSC.