Changes in the Proteome of the Circle of Willis during Aging Reveal Signatures of Vascular Disease.

Approximately 70% of all strokes occur in patients over 65 years old, and stroke increases the risk of developing dementia. The circle of Willis (CoW), the ring of arteries at the base of the brain, links the intracerebral arteries to one another to maintain adequate cerebral perfusion. The CoW proteome is affected in cerebrovascular and neurodegenerative diseases, but changes related to aging have not been described. Here, we report on a quantitative proteomics analysis comparing the CoW from five young (2-3-month-old) and five aged male (18-20-month-old) mice using gene ontology (GO) enrichment, ingenuity pathway analysis (IPA), and iPathwayGuide tools. This revealed 242 proteins that were significantly dysregulated with aging, among which 189 were upregulated and 53 downregulated. GO enrichment-based analysis identified blood coagulation as the top biological function that changed with age and integrin binding and extracellular matrix constituents as the top molecular functions. Consistent with these findings, iPathwayGuide-based impact analysis revealed associations between aging and the complement and coagulation, platelet activation, ECM-receptor interaction, and metabolic process pathways. Furthermore, IPA analysis revealed the enrichment of 97 canonical pathways that contribute to inflammatory responses, as well as 59 inflammation-associated upstream regulators including 39 transcription factors and 20 cytokines. Thus, aging-associated changes in the CoW proteome in male mice demonstrate increases in metabolic, thrombotic, and inflammatory processes.

Proteomics-Based Serum Alterations of the Human Protein Expression after Out-of-Hospital Cardiac Arrest: Pilot Study for Prognostication of Survivors vs. Non-Survivors at Day 1 after Return of Spontaneous Circulation (ROSC).

BACKGROUND: Targeted temperature management (TTM) is considered standard therapy for patients after out-of-hospital cardiac arrest (OHCA), cardiopulmonary resuscitation (CPR), and return of spontaneous circulation (ROSC). To date, valid protein markers do not exist to prognosticate survivors and non-survivors before the end of TTM. The aim of this study is to identify specific protein patterns/arrays, which are useful for prediction in the very early phase after ROSC. MATERIAL AND METHODS: A total of 20 adult patients with ROSC (19 male, 1 female; 69.9 ± 9.5 years) were included and dichotomized in two groups (survivors and non-survivors at day 30). Serum samples were drawn at day 1 after ROSC (during TTM). Three panels (organ failure, metabolic, neurology, inflammation; OLINK, Uppsala, Sweden) were utilised. A total of four proteins were found to be differentially regulated (>2- or <-0.5-fold decrease; t-test). Bioinformatic platforms were utilised to analyse pathways and identify signalling cascades and to screen for potential biomarkers. RESULTS: A total of 276 proteins were analysed and revealed only 11 statistically significant protein alterations (Siglec-9, LAYN, SKR3, JAM-B, N2DL-2, TNF-B, BAMBI, NUCB2, STX8, PTK7, and PVLAB). Following the Bonferroni correction, no proteins were found to be regulated as statistically significant. Concerning the protein fold change for clinical significance, four proteins (IL-1 alpha, N-CDase, IL5, CRH) were found to be regulated in a clinically relevant context. CONCLUSIONS: Early analysis at 1 day after ROSC was not sufficiently possible during TTM to prognosticate survival or non-survival after OHCA. Future studies should evaluate protein expression later in the course after ROSC to identify promising protein candidates.

Strategies for Success: Simple Education Interventions to Equip Nursing Students in Rural Liberia.

Severe shortages of skilled health workforce remain a major barrier to universal health coverage in low income countries including Liberia where nurses and midwives form more than 50% of the health workforce. According to the 2018 Service Availability and Readiness Assessment (SARA) report, Liberia has 10.7 core healthcare workers per 10,000 people, far below the WHO benchmark of 23/10,000 people. High quality training for nurses and midwives is one of the most important strategies to addressing these health workforce shortages. Since 2015, William V.S Tubman University (TU) faculty and Partners in Health (PIH) have partnered in nursing and midwifery education to address nursing and midwifery workforce shortages in Southeast Liberia. In our collaboration we have sought to not only increase the quantity of graduate nurses and midwives but also improve the quality of the training to ensure they are equipped to serve the population. TU strives to produce highly competent generic nurses who will excel in their clinical practice and future specialized training. By applying the theory of deliberate practice, learners are allowed to practice and self-evaluate repeatedly until they attain proficiency. Simulation training was adopted early in the training of nurses and midwives at TU to ensure students are well-prepared for real-life patient care. TU also established a preceptorship program to ensure that students receive skilled mentorship during clinical rotations. Internship for graduating senior Nursing/Midwifery students, where they focus on enhancing psychomotor and assessment skills, professional communication, safety and organization, medication administration and documentation, ensures successful integration into clinical practice after graduation. This progression of the student nurse or midwife from the exposure in the skills lab during pre-clinical modules, to individual preceptorship during clinical rotations to a structured internship experience with an intensive pre-internship "boot camp" have been the major innovations that have helped our partnership flourish. The foundation of these interventions is strong and sustained investment in nursing and midwifery faculty both at the university and the health facilities.

COVID-19-related knowledge, attitudes and practices: a mixed-mode cross-sectional survey in Liberia.

OBJECTIVES: To examine the knowledge, attitudes and practices (KAP) of COVID-19 of rural and urban residents in Liberia to inform the development of local social and behaviour change communication strategies. DESIGN: Cross-sectional, mixed-mode (online and telephone) survey using non-probability sampling. SETTING: All 15 counties in Liberia with a focus on Maryland County. PARTICIPANTS: From 28 May to 28 June 2020, data were collected from a total of 431 adults aged 18 years and older (telephone 288 (66.8%); online 143 (33.2%)) out of a total of 741 contacts. MAIN OUTCOME MEASURES: KAP scores. Frequencies and proportions were calculated, followed by univariate and multivariable analyses to examine the association between KAP scores and the sociodemographic variables. RESULTS: Around 69% of the online survey respondents were younger than 35 years of age, compared with 56% in the telephone interviews. The majority (87%) of online respondents had completed tertiary education, compared with 77% of the telephone respondents. Male participants, on average, achieved higher knowledge (52%) and attitude scores (72%), in contrast to females (49% and 67%, respectively). Radio (71%) was the most cited source for COVID-19 information, followed by social media (63%). After controlling for sociodemographic variables, adaptive regression modelling revealed that survey mode achieved 100% importance for predicting knowledge and practice levels with regard to COVID-19. CONCLUSIONS: The survey population demonstrated moderate COVID-19 knowledge, with significant differences between survey mode and educational level. Correct knowledge of COVID-19 was associated with appropriate practices in Maryland County. Generalisation of survey findings must be drawn carefully owing to the limitations of the sampling methods. Yet, given the differences in knowledge gaps between survey modes, sex, education, occupation and place of residence, it is recommended that information is tailored to different audiences.

Coming to grips with life upside down: how myosin fiber type and metabolic properties of sloth hindlimb muscles contribute to suspensory function.

Sloths exhibit almost obligatory suspensory locomotion and posture. These behaviors require both strength and fatigue resistance, although we previously found muscle fiber type characteristics in the forelimbs of sloths that belied these initial expectations. Based on locomotor roles of the forelimbs versus hindlimbs in propulsion and braking, respectively, sloth hindlimb musculature should be adapted for force production and energy savings by a near homogeneous expression of slow myosin heavy chain (MHC) fibers. This hypothesis was tested by determining MHC fiber type (%) distribution and energy metabolism in the hindlimbs of three-toed (B. variegatus, N = 5) and two-toed (C. hoffmanni, N = 3) sloths. A primary expression of the slow MHC-1 isoform was found in the hindlimbs of both species. Slow MHC fiber type (%) was significantly greater in the flexors of B. variegatus, whereas expression of fast MHC-2A fibers was significantly greater in the extensors of C. hoffmannni. MHC-1 fibers were largest in cross-sectional area (CSA) and comprised the greatest %CSA in each muscle sampled from both species. Enzyme assays showed elevated activity for anaerobic enzymes (CK and LDH) compared with low-to-moderate activity for aerobic enzymes (3-HAD and CS), and only CK activity was related to body size. These findings emphasize a joint stabilization role by the hindlimbs during suspension, especially in smaller three-toed sloths, and suggest that larger two-toed sloths could have muscles further modified for greater power output and/or prolonged arboreal maneuvering. Moreover, modifications to muscle metabolism rather than MHC expression may be more reflective of functional adaptation in sloth limbs.

Short communication: Multistate outbreak of Listeria monocytogenes infections retrospectively linked to unpasteurized milk using whole-genome sequencing.

Unpasteurized milk can contain harmful bacteria such as Listeria monocytogenes. In 2016, the US Food and Drug Administration notified the Centers for Disease Control and Prevention (Atlanta, GA) that L. monocytogenes isolated from unpasteurized chocolate milk from a Pennsylvania dairy was closely related, by whole-genome sequencing, to L. monocytogenes isolates collected from blood specimens of 2 patients (in California and Florida) in 2014. The California and Florida patients consumed unpasteurized milk from the Pennsylvania dairy. Both were >65 yr old and were hospitalized in 2014; the Florida patient died. Isolates from the 2 patients had indistinguishable pulsed-field gel electrophoresis patterns and were closely related by whole-genome multilocus sequence typing analysis (by 2 alleles) to the isolate from unpasteurized chocolate milk produced by the Pennsylvania dairy in 2015. Together, epidemiologic and laboratory information indicated a common origin. This is the first multistate listeriosis outbreak linked to unpasteurized milk in the United States detected using whole-genome multilocus sequence analysis.

An Integrative Literature Review of Patient Turnover in Inpatient Hospital Settings.

High patient turnover can result in fragmentation of nursing care. It can also increase nursing workload and thus impede the ability of nurses to provide safe and high-quality care. We reviewed 20 studies that examined patient turnover in relation to nursing workload, staffing, and patient outcomes as well as interventions in inpatient hospital settings. The studies consistently addressed the importance of accounting for patient turnover when estimating nurse staffing needs. They also showed that patient turnover varied by time, day, and unit type. Researchers found that higher patient turnover was associated with adverse events; however, further research on this topic is needed because evidence on the effect of patient turnover on patient outcomes is not yet strong and conclusive. We suggest that researchers and administrators need to pay more attention to patterns and levels of patient turnover and implement managerial strategies to reduce nursing workload and improve patient outcomes.

Improving the selective cancer killing ability of ZnO nanoparticles using Fe doping.

This work reports a new method to improve our recent demonstration of zinc oxide (ZnO) nanoparticles (NPs) selectively killing certain human cancer cells, achieved by incorporating Fe ions into the NPs. Thoroughly characterized cationic ZnO NPs (∼6 nm) doped with Fe ions (Zn(1-x )Fe (x) O, x = 0-0.15) were used in this work, applied at a concentration of 24 µg/ml. Cytotoxicity studies using flow cytometry on Jurkat leukemic cancer cells show cell viability drops from about 43% for undoped ZnO NPs to 15% for ZnO NPs doped with 7.5% Fe. However, the trend reverses and cell viability increases with higher Fe concentrations. The non-immortalized human T cells are markedly more resistant to Fe-doped ZnO NPs than cancerous T cells, confirming that Fe-doped samples still maintain selective toxicity to cancer cells. Pure iron oxide samples displayed no appreciable toxicity. Reactive oxygen species generated with NP introduction to cells increased with increasing Fe up to 7.5% and decreased for >7.5% doping.

Effect of educational preparation on the accuracy of linear growth measurement in pediatric primary care practices: results of a multicenter nursing study.

Consistently monitoring a child's linear growth is one of the least invasive, most sensitive tools to identify normal physiologic functioning and a healthy lifestyle. However, studies, mostly from the United Kingdom, indicate that children are frequently measured incorrectly. Inaccurate linear measurements may result in some children having undetected growth disorders whereas others with normal growth being referred for costly, unwarranted specialty evaluations. This study presents the secondary analysis of a primary study that used a randomized control study design to demonstrate that a didactic educational intervention resulted in significantly more children being measured accurately within eight pediatric practices. The secondary analysis explored the influence of the measurer's educational level on the outcome of accurate linear measurement. Results indicated that RNs were twice as likely as non-RNs to measure children accurately.