DNA density is a better indicator of a nuclear bleb than lamin B loss.

Nuclear blebs are herniations of the nucleus that occur in diseased nuclei that cause nuclear rupture leading to cellular dysfunction. Chromatin and lamins are two of the major structural components of the nucleus that maintain its shape and function, but their relative roles in nuclear blebbing remain elusive. Lamin B is reported to be lost in blebs by qualitative data while quantitative studies reveal a spectrum of lamin B levels in nuclear blebs dependent on perturbation and cell type. Chromatin has been reported to be decreased or de-compacted in nuclear blebs, but again the data are not conclusive. To determine the composition of nuclear blebs, we compared the immunofluorescence intensity of lamin B and DNA in the main nucleus body and nuclear bleb across cell types and perturbations. Lamin B nuclear bleb levels varied drastically across MEF wild type and chromatin or lamins perturbations, HCT116 lamin B1-GFP imaging, and human disease model cells of progeria and prostate cancer. However, DNA concentration was consistently decreased to about half that of the main nucleus body across all measured conditions. Using Partial Wave Spectroscopic (PWS) microscopy to measure chromatin density in the nuclear bleb vs body we find similar results that DNA is consistently less dense in nuclear blebs. Thus, our data spanning many different cell types and perturbations supports that decreased DNA is a better marker of a nuclear bleb than lamin B levels that vary widely.

The experience and role of mentorship for paediatric occupational therapists.

INTRODUCTION: Within Australia, the introduction of the National Disability Insurance Scheme has led to a growth in paediatric occupational therapists working in community settings. This growth has increased the demand for support from more senior paediatric occupational therapists to novice clinicians. Mentoring has long been valued by occupational therapists as a means to provide this support. Despite its apparent benefit, there is limited research on the contribution of mentoring as distinct from supervision, and its impact on mentees' skills and confidence in providing care. This study examined the contribution of mentorship to the development of professional capability in paediatric occupational therapy practice from the perspective of mentors and mentees. METHODS: Interpretive description methodology was used. In-depth interviews were conducted with nine mentors and eight mentees from three Australian states. Data were analysed inductively and thematically. FINDINGS: All participants reflected on the challenges presented by the complexity of practice, requiring a knowledge base that mentees perceived they did not possess. The essential nature of non-judgemental, emotional support allowed mentees to feel safe to discuss their concerns when they were often overwhelmed by practice. Mentorship was viewed as capacity building, building competence by scaffolding clinical reasoning and supporting theory to practice translation while developing resilience to cope with complexity. CONCLUSION: Study participants reported that successful mentorship assisted novice practitioners to integrate knowledge and skills required for complex clinical and professional reasoning. The emotional support provided through the relationship supported novice therapists to build their confidence and resilience while promoting professional identity and socialisation into the profession. The study raised questions related to how the profession best supports novice paediatric therapists in the current employment contexts, and the need to review how bodies of knowledge relevant to paediatrics are brought together to be used by both novice clinicians and senior therapists, who support them, for translation to effective practice.

Comparison of Newer Hand-Held Ultrasound Devices for Post-Dive Venous gas Emboli Quantification to Standard Echocardiography.

Decompression sickness (DCS) can result from the growth of bubbles in tissues and blood during or after a reduction in ambient pressure, for example in scuba divers, compressed air workers or astronauts. In scuba diving research, post-dive bubbles are detectable in the venous circulation using ultrasound. These venous gas emboli (VGE) are a marker of decompression stress, and larger amounts of VGE are associated with an increased probability of DCS. VGE are often observed for hours post-dive and differences in their evolution over time have been reported between individuals, but also for the same individual, undergoing a same controlled exposure. Thus, there is a need for small, portable devices with long battery lives to obtain more ultrasonic data in the field to better assess this inter- and intra-subject variability. We compared two new handheld ultrasound devices against a standard device that is currently used to monitor post-dive VGE in the field. We conclude that neither device is currently an adequate replacement for research studies where precise VGE grading is necessary.

Clinical evaluation of the BioFire Global Fever Panel for the identification of malaria, leptospirosis, chikungunya, and dengue from whole blood: a prospective, multicentre, cross-sectional diagnostic accuracy study.

BACKGROUND: Acute febrile illness is a common presentation for patients at hospitals globally. Assays that can diagnose a variety of common pathogens in blood could help to establish a diagnosis for targeted disease management. We aimed to evaluate the performance of the BioFire Global Fever Panel (GF Panel), a multiplex nucleic acid amplification test performed on whole blood specimens run on the BioFire FilmArray System, in the diagnosis of several pathogens that cause acute febrile illness. METHODS: We did a prospective, multicentre, cross-sectional diagnostic accuracy study to evaluate the GF Panel. Consenting adults and children older than 6 months presenting with fever in the previous 2 days were enrolled consecutively in sub-Saharan Africa (Ghana, Kenya, Tanzania, Uganda), southeast Asia (Cambodia, Thailand), central and South America (Honduras, Peru), and the USA (Washington, DC; St Louis, MO). We assessed the performance of six analytes (chikungunya virus, dengue virus [serotypes 1-4], Leptospira spp, Plasmodium spp, Plasmodium falciparum, and Plasmodium vivax or Plasmodium ovale) on the GF Panel. The performance of the GF Panel was assessed using comparator PCR assays with different primers followed by bidirectional sequencing on nucleic acid extracts from the same specimen. We calculated the positive percent agreement and negative percent agreement of the GF Panel with respect to the comparator assays. This study is registered with ClinicalTrials.gov, NCT02968355. FINDINGS: From March 26, 2018, to Sept 30, 2019, 1965 participants were enrolled at ten sites worldwide. Of the 1875 participants with analysable results, 980 (52·3%) were female and the median age was 22 years (range 0-100). At least one analyte was detected in 657 (35·0%) of 1875 specimens. The GF Panel had a positive percent agreement for the six analytes evaluated as follows: chikungunya virus 100% (95% CI 86·3-100), dengue virus 94·0% (90·6-96·5), Leptospira spp 93·8% (69·8-99·8), Plasmodium spp 98·3% (96·3-99·4), P falciparum 92·7% (88·8-95·6), and P vivax or P ovale 92·7% (86·7-96·6). The GF Panel had a negative percent agreement equal to or greater than 99·2% (98·6-99·6) for all analytes. INTERPRETATION: This 1 h sample-to-answer, molecular device can detect common causative agents of acute febrile illness with excellent positive percent agreement and negative percent agreement directly in whole blood. The targets of the assay are prevalent in tropical and subtropical regions globally, and the assay could help to provide both public health surveillance and individual diagnoses. FUNDING: BioFire Defense, Joint Project Manager for Medical Countermeasure Systems and US Army Medical Materiel Development Activity, and National Institute of Allergy and Infectious Diseases.

A Metabolic Intervention for Improving Human Cognitive Performance During Hypoxia.

BACKGROUND: During hypoxia an operators cognitive performance may decline. This decline is linked to altered brain metabolism, resulting in decreased adenosine triphosphate (ATP) production. Ketone bodies are an alternative substrate to glucose for brain metabolic requirements; previous studies have shown that the presence of elevated ketone bodies in the blood maintains brain ATP levels and reduces cerebral glycolysis during hypoxia. Thus, ketones may be a strategy to mitigate cognitive decline in hypoxia. Ketone ester (KE) consumption allows rapid elevation of blood ketone levels; therefore, we investigated the effects of consuming a KE drink on cognitive performance during hypoxia. Here, we report results of a pilot study.METHODS: There were 11 subjects who completed a cognitive performance test battery under conditions of normoxia and hypoxia following consumption of a KE drink and a placebo control drink.RESULTS: Significant hypoxia effects (O2 saturation minimum was found to range between 63 and 88 in subjects) were found for blink duration (Ph2 0.665) and blink rate (Ph2 0.626), indicating that the hypoxia condition was associated with longer blink durations and lower blink rates. Significant hypoxia effects were likewise observed for a code substitution task (Ph2 0.487), indicating that performance on the task was significantly disrupted by the hypoxia stressor. KE consumption had a significant effect on blink duration (Ph2 0.270) and the code substitution task (Ph2 0.309).DISCUSSION: These finding suggest that some effects of acute hypoxia can be mitigated by nutritional ketosis.Coleman K, Phillips J, Sciarini M, Stubbs B, Jackson O, Kernagis D. A metabolic intervention for improving human cognitive performance during hypoxia. Aerosp Med Hum Perform. 2021; 92(7):556562.

Comparison of capillary and venous blood for malaria detection using two PCR-based assays in febrile patients in Sierra Leone.

BACKGROUND: Rapid and sensitive diagnostics are critical tools for clinical case management and public health control efforts. Both capillary and venous blood are currently used for malaria detection and while diagnostic technologies may not be equally sensitive with both materials, the published data on this subject are scarce and not conclusive. METHODS: Paired clinical samples of venous and capillary blood from 141 febrile individuals in Bo, Sierra Leone, were obtained between January and May 2019 and tested for the presence of Plasmodium parasites using two multiplexed PCR assays: the FilmArray-based Global Fever Panel (GFP) and the TaqMan-based Malaria Multiplex Sample Ready (MMSR) assay. RESULTS: No significant differences in Plasmodium parasite detection between capillary and venous blood for both assays were observed. The GFP assay was more sensitive than MMSR for all markers that could be compared (Plasmodium spp. and Plasmodium falciparum) in both venous and capillary blood. CONCLUSIONS: No difference was found in malaria detection between venous and capillary blood using two different PCR-based detection assays. This data gives support for use of capillary blood, a material which can be obtained easier by less invasive methods, for PCR-based malaria diagnostics, independent of the platform.

Repurposing of Tranilast for Potential Neuropathic Pain Treatment by Inhibition of Sepiapterin Reductase in the BH4 Pathway.

Tetrahydrobiopterin (BH4) is a cofactor in the production of various signaling molecules including nitric oxide, dopamine, adrenaline, and noradrenaline. BH4 levels are critical for processes associated with cardiovascular function, inflammation, mood, pain, and neurotransmission. Increasing pieces of evidence suggest that BH4 is upregulated in chronic pain. Sepiapterin reductase (SPR) catalyzes both the reversible reduction of sepiapterin to dihydrobiopterin (BH2) and 6-pyruvoyl-tetrahydrobiopterin to BH4 within the BH4 pathway. Therefore, inhibition of SPR by small molecules can be used to control BH4 production and ultimately alleviate chronic pain. Here, we have used various in silico and in vitro experiments to show that tranilast, licensed for use in bronchial asthma, can inhibit sepiapterin reduction by SPR. Docking and molecular dynamics simulations suggest that tranilast can bind to human SPR (hSPR) at the same site as sepiapterin including S157, one of the catalytic triad residues of hSPR. Colorimetric assays revealed that tranilast was nearly twice as potent as the known hSPR inhibitor, N-acetyl serotonin. Tranilast was able to inhibit hSPR activity both intracellularly and extracellularly in live cells. Triple quad mass spectrophotometry of cell lysates showed a proportional decrease of BH4 in cells treated with tranilast. Our results suggest that tranilast can act as a potent hSPR inhibitor and therefore is a valid candidate for drug repurposing in the treatment of chronic pain.

The Mediterranean Diet in the Stroke Belt: A Cross-Sectional Study on Adherence and Perceived Knowledge, Barriers, and Benefits.

The Mediterranean diet (MedDiet) is recommended by the current Dietary Guidelines for Americans, yet little is known about the perceived barriers and benefits to the diet in the U.S., particularly in the Stroke Belt (SB). Thus, the purpose of this study was to examine MedDiet adherence and perceived knowledge, benefits, and barriers to the MedDiet in the U.S. A cross-sectional study was conducted on 1447 participants in the U.S., and responses were sorted into geographic groups: the SB, California (CA), and all other US states (OtherUS). Linear models and multivariable linear regression analysis was used for data analysis. Convenience, sensory factors, and health were greater barriers to the MedDiet in the SB group, but not the OtherUS group (p < 0.05). Weight loss was considered a benefit of the MedDiet in the SB (p < 0.05), while price and familiarity were found to be less of a benefit (p < 0.05). Respondents with a bachelor's degree or greater education had greater total MEDAS scores (p < 0.05) and obese participants had a lower MedDiet adherence score (p < 0.05). Our results identify key barriers and benefits of the MedDiet in the SB which can inform targeted MedDiet intervention studies.

Behavioral Interventions to Reduce Infections in Pediatric Long-term Care Facilities: The Keep It Clean for Kids Trial.

Children in pediatric long-term care facilities (pLTCF) represent a highly vulnerable population and infectious outbreaks occur frequently, resulting in significant morbidity, mortality, and resource use. The purpose of this quasi-experimental trial using time series analysis was to assess the impact of a 4-year theoretically based behavioral intervention on infection prevention practices and clinical outcomes in three pLTCF (288 beds) in New York metropolitan area including 720 residents, ages 1 day to 26 years with mean lengths of stay: 7.9-33.6 months. The 5-pronged behavioral intervention included explicit leadership commitment, active staff participation, work flow assessments, training staff in the World Health Organization "'five moments of hand hygiene (HH)," and electronic monitoring and feedback of HH frequency. Major outcomes were HH frequency, rates of infections, number of hospitalizations associated with infections, and outbreaks. Mean infection rates/1000 patient days ranged from 4.1-10.4 pre-intervention and 2.9-10.0 post-intervention. Mean hospitalizations/1000 patient days ranged from 2.3-9.7 before and 6.4-9.8 after intervention. Number of outbreaks/1000 patient days per study site ranged from 9-24 pre- and 9-18 post-intervention (total = 95); number of cases/outbreak ranged from 97-324 (total cases pre-intervention = 591 and post-intervention = 401). Post-intervention, statistically significant increases in HH trends occurred in one of three sites, reductions in infections in two sites, fewer hospitalizations in all sites, and significant but varied changes in the numbers of outbreaks and cases/outbreak. Modest but inconsistent improvements occurred in clinically relevant outcomes. Sustainable improvements in infection prevention in pLTCF will require culture change; increased staff involvement; explicit administrative support; and meaningful, timely behavioral feedback.

Anticorrosive Self-Assembled Hybrid Alkylsilane Coatings for Resorbable Magnesium Metal Devices.

Magnesium (Mg) and its alloys are promising candidates for use as resorbable materials for biomedical devices that can degrade in situ following healing of the defect, eliminating the need for a second surgery to remove the device. Hydrogen gas is the main product of magnesium corrosion, and one of the limitations for use of Mg devices in clinic is the formation of gas pockets around them. One potential solution to this problem is reducing the rate of corrosion to the levels at which H2 can diffuse through the body fluids. The study's aim was to evaluate the potential of hybrid alkylsilane self-assembled multilayer coatings to reduce Mg corrosion and to modify physicochemical properties of the coatings using surface functionalization. The coating was made by copolymerization of n-Decyltriethoxysilane and Tetramethoxysilane followed by dip coating of metal discs. This resulted in a formation of homogeneous, micron thick, and defect free coating. The coated surface was more hydrophobic than bare Mg, however functionalization of the coating with 3-aminopropyltriethoxysilane reduced the hydrophobicity of the coating. The coatings reduced several fold the rate of Mg corrosion based on the H2 evolution and other assessment methods, and effectively prevented the initial corrosion burst over the first 24 h. In vitro tissue culture studies demonstrated cytocompatibility of the coatings. These results reveal excellent anticorrosive properties and good cytocompatibility of the hybrid alkylsilane coatings and suggest great potential for use of these coatings on resorbable Mg devices.

Is hand hygiene frequency associated with the onset of outbreaks in pediatric long-term care?

BACKGROUND: Studies in adult long-term care facilities (LTCFs) have shown a correlation between hand hygiene (HH) and viral outbreak reduction, but no such studies have been conducted in pediatric LTCFs where the epidemiology of viral pathogens is different. METHODS: We compared electronically monitored facility-wide HH frequency in the weeks immediately prior to outbreaks of acute respiratory or gastrointestinal infections versus control weeks in a 137-bed pediatric LTCF from October 2012-August 2015. Control weeks were the 8-14 day (control 1) and 15-21 day (control 2) periods prior to the onset of each outbreak. RESULTS: There was no difference in HH frequency in the weeks leading up to the outbreaks versus control weeks (odds ratio [OR], 1.0; 95% confidence interval CI, 1.00-1.001 using control 1 and OR, 1.0; 95% CI, 1.00-1.001 using control 2). CONCLUSIONS: Our findings differed from those in adult LTFCs, possibly because of the greater contact between residents and staff in the pediatric setting, increased susceptibility to viral pathogens because of immunologic immaturity, or differences in the types of pathogens prevalent in each setting. Although HH may be important for limiting the number of residents infected during outbreaks, we found no association between HH frequency and subsequent outbreak onset.

Impact of Infection Prevention and Control Initiatives on Acute Respiratory Infections in a Pediatric Long-Term Care Facility.

We evaluated the collective impact of several infection prevention and control initiatives aimed at reducing acute respiratory infections (ARIs) in a pediatric long-term care facility. ARIs did not decrease overall, though the proportion of infections associated with outbreaks and average number of cases per outbreak decreased. Influenza rates decreased significantly. Infect Control Hosp Epidemiol 2016;37:859-862.

Assessing Nursing Care Needs of Children With Complex Medical Conditions: The Nursing-Kids Intensity of Care Survey (N-KICS).

UNLABELLED: Recent medical advances have resulted in increased survival of children with complex medical conditions (CMC), but there are no validated methods to measure their care needs. OBJECTIVES/METHODS: To design and test the Nursing-Kids Intensity of Care Survey (N-KICS) tool and describe intensity of nursing care for children with CMC. RESULTS: The psychometric evaluation confirmed an acceptable standard for reliability and validity and feasibility. Intensity scores were highest for nursing care related to infection control, medication administration, nutrition, diaper changes, hygiene, neurological and respiratory support, and standing program. CONCLUSIONS: Development of a psychometrically sound measure of nursing intensity will help evaluate and plan nursing care for children with CMC.

Direct costs of acute respiratory infections in a pediatric long-term care facility.

Acute respiratory tract infections (ARI) are a major burden in pediatric long-term care. We analyzed the financial impact of ARI in 2012-2013. Costs associated with ARI during the respiratory viral season were ten times greater than during the non-respiratory viral season, $31 224 and $3242 per 1000 patient-days, respectively (P < 0·001). ARI are burdensome for pediatric long-term care facilities not only because of the associated morbidity and mortality, but also due to the great financial costs of prevention.

Health care-associated infection outbreaks in pediatric long-term care facilities.

Children in pediatric long-term care facilities (pLTCFs) have complex medical conditions and increased risk for health care-associated infections (HAIs). We performed a retrospective study from January 2010-December 2013 at 3 pLTCFs to describe HAI outbreaks and associated infection control interventions. There were 62 outbreaks involving 700 cases in residents and 250 cases in staff. The most common interventions were isolation precautions and education and in-services. Further research should examine interventions to limit transmission of infections in pLTCFs.