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.

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.

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.

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.

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.

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.

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.

A Case Study of Infant Physiologic Response to Skin-to-Skin Contact After Surgery for Complex Congenital Heart Disease.

BACKGROUND: Infants with complex congenital heart disease requiring surgical intervention within the first days or weeks of life may be the most seriously ill infants needing intensive nursing and medical care. Skin-to-skin contact (SSC) is well accepted and practiced as a positive therapeutic intervention in premature infants but is not routinely offered to infants in cardiac intensive care units. The physiologic effects of SSC in the congenital heart disease population must be examined before recommending incorporation of SSC into standard care routines. OBJECTIVE: The purpose of this case study was to describe the physiologic response to a single session of SSC in an 18-day-old infant with hypoplastic left heart syndrome. METHODS: Repeated measures of heart rate, respiratory rate, oxygen saturation, blood pressure, and temperature were recorded 30 minutes before SSC, during SSC (including interruptions for bottle and breast feedings), and 10 minutes after SSC was completed. RESULTS: All physiologic parameters were clinically acceptable throughout the 135-minute observation. CONCLUSION: This case study provides beginning evidence that SSC is safe in full-term infants after surgery for complex congenital heart disease. Further research with a larger sample is needed to examine the effects of SSC on infant physiology before surgery and earlier in the postoperative time period as well as on additional outcomes such as length of stay, maternal-infant interaction, and neurodevelopment.

Evaluation of stem-like side population cells in a recurrent nasopharyngeal carcinoma cell line.

BACKGROUND: Side population (SP) assay identifies cells with dye/drug extrusion ability, a characteristic of stem cells. Here, we determined if SP cells exist in a verified cell line originating from recurrent nasopharyngeal carcinoma (NPC) and a xenograft established from recurrent metastatic NPC. These cells were evaluated for stem-like properties via functional assays as well as for tumourigenicity. METHODS: We used Hoechst 33342 to identify the SP from non-SP (NSP) cells in HK1 NPC cell line and xeno-284 NPC xenograft. The cells were assayed for in vitro characteristics of cancer stem cells (CSC), gene expression and tumourigenicity ability. Student's t test was used to test for significance. RESULTS: Five to ten percent and less than 0.5% of HK1 and xeno-284 NPC cells, respectively, were SP cells. Fumitremorgin C (FTC), as opposed to verapamil, was effective in causing the cells to retain Hoechst 33342 dye. HK1 SP cells formed more holoclones, had more aldehyde dehydrogenase (ALDH) activity, divided asymmetrically and contained slow-proliferating cells. ABCG2, SOX2, TERT, MYC, Hedgehog, Notch, TGFß and Wnt signalling pathway genes were significantly upregulated in the SP cells. However, despite these differences in vitro, both HK1 SP and NSP cells had an overall similar tumourigenic potential in vivo. CONCLUSIONS: HK1 SP cells were ABCG2-specific as confirmed by FTC inhibition and gene expression data. Despite data from in vitro and gene expression experiments suggesting stem-like features, there was no significant difference in tumourigenic potential between SP and NSP cells. We conclude that SP assay alone is not sufficient to identify CSCs in HK1 cells. Our work also suggests the presence of a stem-cell like population among NPC cells which do not display increased tumourigenicity.

Use of a fundamental approach to spray-drying formulation design to facilitate the development of multi-component dry powder aerosols for respiratory drug delivery.

PURPOSE: A fundamental approach incorporating current theoretical models into aerosol formulation design potentially reduces experimental work for complex formulations. A D-amino acid mixture containing D-Leucine (D-Leu), D-Methionine, D-Tryptophan, and D-Tyrosine was selected as a model formulation for this approach. METHODS: Formulation design targets were set, with the aim of producing a highly dispersible D-amino acid aerosol. Particle formation theory and a spray dryer process model were applied with boundary conditions to the design targets, resulting in a priori predictions of particle morphology and necessary spray dryer process parameters. Two formulations containing 60% w/w trehalose, 30% w/w D-Leu, and 10% w/w remaining D-amino acids were manufactured. RESULTS: The design targets were met. The formulations had rugose and hollow particles, caused by deformation of a crystalline D-Leu shell while trehalose remained amorphous, as predicted by particle formation theory. D-Leu acts as a dispersibility enhancer, ensuring that both formulations: 1) delivered over 40% of the loaded dose into the in vitro lung region, and 2) achieved desired values of lung airway surface liquid concentrations based on lung deposition simulations. CONCLUSIONS: Theoretical models were applied to successfully achieve complex formulations with design challenges a priori. No further iterations to the design process were required.

Infant obesity and severe obesity growth patterns in the first two years of life.

Distinguishing an obesity growth pattern that originates during infancy is clinically important. Infancy based obesity prevention interventions may be needed while precursors of later health are forming. Infant obesity and severe obesity growth patterns in the first 2-years are described and distinguished from a normal weight growth pattern. A retrospective chart review was conducted. Body mass index (BMI) growth patterns from birth to 2-years are described for children categorized at 5-years as normal weight (n = 61), overweight (n = 47), obese (n = 41) and severely obese (n = 72) cohorts using WHO reference standards. BMI values were calculated at birth, 1-week; 2-, 4-, 6-, 9-, 12-, 15-, 18-months; and 2- and 5-years. Graphs of the longitudinal Analysis of Variance of Means of BMI values identified the earliest significant divergence of a cohort's average BMI pattern from other cohorts' patterns. ANOVA and Pearson Product Moment correlations were also performed. Statistically significant differences in BMI values and differences in growth patterns between cohorts were evident as early as 2-6 months post-birth. Children who were obese or severely obese at 5-years demonstrated a BMI pattern that differed within the first 2-years of life from that of children who were normal weight at 5-years. The earliest significant correlation between early BMI values and 5-year BMI value was at 4-months post-birth. The study fills an important gap by demonstrating early onset of an infant obesity growth pattern in full-term children who were healthy throughout their first 5 years of life.

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.

Utilising infant growth to predict obesity status at 5 years.

AIM: This study determines if an early life growth pattern in healthy infants can predict obesity at age 5. METHODS: Randomly selected from all healthy children born from 1997 to 2001 in a Midwestern US Health Maintenance Organization; growth patterns from birth to 5 years were described for children who were categorised by obesity classification at 5 years into normal weight (n = 61), overweight (n = 47), obese (n = 41) and morbidly obese (n = 72) cohorts using World Health Organization body mass index (BMI) criteria. A retrospective longitudinal analysis based on weighted least squares was performed on BMI by age (1 week; 2, 4, 6, 9, 12, 15 and 18 months; and 2, 3, 4 and 5 years). Graphs of the longitudinal repeated measures analysis of variance of means allowed identification of the earliest significant divergence of a cohort's average BMI pattern from other cohorts' patterns. RESULTS: Distinctions in growth patterns and BMIs were evident before 1-year post-birth. Children who were obese or morbidly obese at 5 years demonstrated a BMI pattern that differed from children who were normal weight at 5 years. CONCLUSIONS: Identifying obesity development in early life may assist with prevention of later obesity. The results merit future study. An early life BMI growth pattern is clinically important because it permits discrimination of those who do and do not fit a normal weight pattern, guiding individualised interventions in the first year of life while precursors of later health are still forming.

Ergonomic procedure for heel sticks and shots in Kangaroo Care (skin-to-skin) position.

Kangaroo Care (KC) has been recommended as a pain-reducing strategy in neonates; however, KC has not been widely used to minimize procedural pain caused in part by nurses'/phlebotomists' discomfort when positioning themselves and the infant for blood drawing and injections. Therefore, an ergonomically designed setup incorporating the use of KC was introduced into clinical practice to facilitate blood draws and injections. The step-by-step procedure used for heel sticks and injections is presented in this manuscript. After implementing the ergonomic step-by-step protocol, complaints of discomfort by nurses and phlebotomists ceased, and an additional benefit was that infant pain responses were significantly reduced.

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.

Dynamic electrostatic charge of lactose-salbutamol sulphate powder blends dispersed from a Cyclohaler®.

CONTEXT: Electrostatic forces have been claimed to be a mechanism for aerosol deposition in the lungs. However, the extent of its influence on aerosol performance is not clear, particularly for carrier-drug formulations. OBJECTIVES: To prepare lactose-salbutamol powder blends, varying in blend ratio, and identify any relationships between salbutamol dose, electrostatic characteristics and in vitro aerosol performance. METHODS: Decanted lactose and micronized salbutamol sulfate was mixed to produce five blends (equivalent to 50, 100, 200, 300 and 400 µg salbutamol per 33 mg of powder). 33 ± 1 mg of a blend was loaded into a Cyclohaler™ and dispersed into the electrical Next Generation Impactor (eNGI) at an air flow rate of 60 L/min. This was conducted in triplicate for all five lactose-salbutamol blends. RESULTS: Fine particle fraction increased with salbutamol dose, from 5.89 ± 1.42 to 21.35 ± 2.91%. Specific charge (charge divided by mass) distributions for each blend were greatest in magnitude for the 50 µg blend and similar in magnitude between all other blends. However, in eNGI Stage 1 (>8.06 µm), specific charge decreased from 100 µg (-170.4 ± 45.8 pC/µg) to 400 µg (-10.0 ± 9.1 pC/µg). CONCLUSIONS: The improvement in fine particle fraction with increased salbutamol dose was indicative of fine drug binding to high and low energy sites on the lactose carrier surface. This finding was supported by electrostatic charge results, but the aerosol charge itself was not found to influence aerosol performance by electrostatic forces.

The contribution of different formulation components on the aerosol charge in carrier-based dry powder inhaler systems.

PURPOSE: To measure aerosol performance of a lactose carrier/salbutamol sulphate powder blend and identify contributions of non-formulation and formulation components on the resulting aerosol charge. METHODS: A 67.5:1 (%w/w) blend of 63-90 microm lactose with salbutamol sulphate, and lactose alone (with and without the blending process), was dispersed from a Cyclohaler into the electrical Next Generation Impactor at 30, 60 and 90 L/min. Mass and charge profiles were measured from each dispersion, as a function of impactor stage. The charge profile from an empty capsule in the Cyclohaler was also studied. RESULTS: Lactose deposition from the blend was significantly greater, and net charge/mass ratios were smaller, in the pre-separator compared to formulations without drug. Fine particle fraction of salbutamol sulphate increased with flow rate (9.2 +/- 2.5% to 14.7 +/- 2.7%), but there was no change in net charge/mass ratio. The empty capsule produced a cycle of alternating net positive and negative discharges ( approximately 200 pC to 4 nC). CONCLUSIONS: Capsule charge can ionize surrounding air and influence net charge measurements. Detachment of fine drug during aerosolisation may reduce net specific charge and lead to increased lactose deposition in the pre-separator. Increase in FPF may be due to increased force of detachment rather than electrostatic forces.

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.

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.