Two-year audit of compliance in the preparation and administration of medications by nursing staff in a mother-and-child university hospital center.

OBJECTIVE: Audits are essential for reviewing and improving the medication-use process. Identifying areas for improvement can limit the risk of errors when preparing and administering drugs. Pediatric centers face specific challenges in ensuring the safety of the medication-use process. The objective of this study was to observe and compare compliance with criteria for the preparation and administration of medications by nurses in a mother-and-child university hospital center over two consecutive years. METHODS: This observational cross-sectional study was conducted in a Canadian mother-and-child university hospital center. Audits were conducted over a 1-month period in 16 and 18 nursing care sectors in 2021 and 2022, respectively. The standardized audit evaluated compliance with prespecified criteria related to the preparation and administration of medication by nursing staff (77 criteria for 2021 and 82 criteria for 2022). The auditors comprised nurses and a pharmacist trained by the research team. Compliance was compared between years and assessed through a chi-square test. RESULTS: The audit consisted of 522 observations in 2021 and 448 observations in 2022. Overall compliance was 76% in 2021 and 66% in 2022. The compliance rate by criterion ranged from 16% to 100%. In 2021 and 2022, 51 (84%) and 52 (87%) of the criteria, respectively, had compliance rates of more than 75%, and 12 (20%) and eight (13%), respectively, had 100% compliance. There were statistically significant decreases in compliance for nine of the 39 criteria for preparation of medications, notably prior hand hygiene (91%% vs. 84%, p = 0.002), and for six of the 17 criteria for administration of medications, including mentioning possible adverse effects to the patient (41% vs- 30%, p = 0.008). CONCLUSION: In this study, compliance was over 75% for most of the criteria. However, for a few criteria, we observed a decrease in compliance from 2021 to 2022. Various hypotheses are proposed to explain these decreases, such as the COVID-19 pandemic.

PCSK7: A novel regulator of apolipoprotein B and a potential target against non-alcoholic fatty liver disease.

BACKGROUND: Epidemiological evidence links the proprotein convertase subtilisin/kexin 7 (PCSK7) to triglyceride (TG) metabolism. We associated the known PCSK7 gain-of-function non-coding SNP rs236918 with higher levels of plasma apolipoprotein B (apoB) and the loss-of-function coding variant p.Pro777Leu (SNP rs201598301) with lower apoB and TG. Herein, we aimed to unravel the in vivo role of liver PCSK7. METHODS: We biochemically defined the functional role of PCSK7 in lipid metabolism using hepatic cell lines and Pcsk7-/- mice. Our findings were validated following subcutaneous administration of hepatocyte-targeted N-acetylgalactosamine (GalNAc)-antisense oligonucleotides (ASOs) against Pcsk7. RESULTS: Independent of its proteolytic activity, membrane-bound PCSK7 binds apoB100 in the endoplasmic reticulum and enhances its secretion. Mechanistically, the loss of PCSK7/Pcsk7 leads to apoB100 degradation, triggering an unfolded protein response, autophagy, and ß-oxidation, eventually reducing lipid accumulation in hepatocytes. Non-alcoholic fatty liver disease (NAFLD) was induced by a 12-week high fat/fructose/cholesterol diet in wild type (WT) and Pcsk7-/- mice that were then allowed to recover on a 4-week control diet. Pcsk7-/- mice recovered more effectively than WT mice from all NAFLD-related liver phenotypes. Finally, subcutaneous administration of GalNAc-ASOs targeting hepatic Pcsk7 to WT mice validated the above results. CONCLUSIONS: Our data reveal hepatic PCSK7 as one of the major regulators of apoB, and its absence reduces apoB secretion from hepatocytes favoring its ubiquitination and degradation by the proteasome. This results in a cascade of events, eventually reducing hepatic lipid accumulation, thus supporting the notion of silencing PCSK7 mRNA in hepatocytes for targeting NAFLD.

Early Childhood Educators' Perceptions of Their Emotional State, Relationships with Parents, Challenges, and Opportunities During the Early Stage of the Pandemic.

This article presents a study about the impact of COVID-19 on childcare center educators in Quebec (Canada). Regulated childcare services were closed due to the pandemic between March 16 and May 31, 2020, in areas considered "hot" (highly affected by the pandemic). During this time, some centers were transformed into "emergency childcare services" available to parents considered to be essential workers. Therefore, few children attended, and most educators worked remotely. In May 2020, 372 educators completed an online questionnaire regarding their emotional state, challenges, and learning opportunities. Results indicate that half of the respondents reported a decrease in their level of well-being at work and an increase in their stress level. Educators working remotely were more likely to report a lower level of stress than when working with children at daycare (36.1% vs 19.7%). Despite these findings, educators estimated that the parents who used their emergency childcare service presented either high (37.7%) or average (32.2%) levels of wellbeing. The factors that educators identified as facilitating their interactions with families included parental recognition of their work (11.68%) and direct contact with them (12.62%). While many tasks accomplished at home were done for the first time during this period (i.e., creating video capsules for children and parents, virtual meetings with children and colleagues), a large majority of respondents reported that these tasks made them feel useful. Working at their own pace (34.7%) was seen as the principal advantage of remote working. Finally, 28.84% mentioned that the reduced ratio (1:2 or 1:3) was a facilitating factor that they would like to maintain during the upcoming reopening phase. The discussion uses the Job Demands and Resources theoretical framework (Bakker and Demerouti in Wellbeing 3(2):1-28, 2014; Dicke et al. in J Occupat Health Psychol 23(2): 262-277, 2017) to explain the educators' work-related demands and emotional state in both remote and CPE working pandemic contexts. In conclusion, we argued that this pandemic reveals the complexity, but also the essential nature of the work of early childhood educators, in particular by identifying their needs for support and recognition essential to their professional commitment.

Shedding of cancer susceptibility candidate 4 by the convertases PC7/furin unravels a novel secretory protein implicated in cancer progression.

The proprotein convertases (PCs) are responsible for the maturation of precursor proteins, and are involved in multiple and critical biological processes. Over the past 30 years, the PCs have had great translational applications, but the physiological roles of PC7, the seventh member of the family, are still obscure. Searching for new substrates of PC7, a quantitative proteomics screen for selective enrichment of N-glycosylated polypeptides secreted from hepatic HuH7 cells identified two human type-II transmembrane proteins of unknown function(s): Cancer Susceptibility Candidate 4 (CASC4) and Golgi Phosphoprotein of 130 kDa (GPP130/GOLIM4). Concentrating on CASC4, its mutagenesis characterized the PC7/Furin-shedding site to occur at KR66↓NS, in HEK293 cells. We defined PC7 and Furin trafficking and activity, and demonstrated that CASC4 shedding occurs in acidic endosomes and/or in the trans-Golgi Network. Our data unraveled a cancer-protective role for CASC4, because siRNA silencing of endogenous CASC4 expression in the invasive triple-negative breast cancer human cell line MDA-MB-231 resulted in a significantly increased cellular migration and invasion. Conversely, MDA-MB-231 cells stably expressing CASC4 exhibited reduced migration and invasion, which can be explained by an increased number of paxillin-positive focal adhesions. This phenotypic cancer-protective role of CASC4 is reversed in cells overexpressing an optimally PC7/Furin-cleaved CASC4 mutant, or upon overexpression of the N-terminally convertase-generated membrane-bound segment. This phenotype was associated with increased formation of podosome-like structures, especially evident in cells overexpressing the N-terminal fragment. In accord, breast cancer patients' data sets show that high CASC4 and PCSK7 expression levels predict a significantly worse prognosis compared to high CASC4 but low PCSK7 levels. In conclusion, CASC4 shedding not only disrupts its anti-migratory/invasive role, but also generates a membrane-bound fragment that drastically modifies the actin cytoskeleton, resulting in an enhanced cellular migration and invasion. This phenotype might be clinically relevant in the prognosis of breast cancer patients.

The motif EXEXXXL in the cytosolic tail of the secretory human proprotein convertase PC7 regulates its trafficking and cleavage activity.

Many secretory proteins are activated by cleavage at specific sites. The proprotein convertases (PCs) form a family of nine secretory subtilisin-like serine proteases, seven of which cleave at specific basic residues within the trans-Golgi network, granules, or at the cell surface/endosomes. The seventh member, PC7, is a type-I transmembrane (TM) protein with a 97-residue-long cytosolic tail (CT). PC7 sheds human transferrin receptor 1 (hTfR1) into soluble shTfR1 in endosomes. To better understand the physiological roles of PC7, here we focused on the relationship between the CT-regulated trafficking of PC7 and its ability to shed hTfR1. Deletion of the TMCT resulted in soluble PC7 and loss of its hTfR1 shedding activity. Extensive CT deletions and mutagenesis analyses helped us zoom in on three residues in the CT, namely Glu-719, Glu-721, and Leu-725, that are part of a novel motif, EXEXXXL725, critical for PC7 activity on hTfR1. NMR studies of two 14-mer peptides mimicking this region of the CT and its Ala variants revealed that the three exposed residues are on the same side of the molecule. This led to the identification of adaptor protein 2 (AP-2) as a protein that recognizes the EXEXXXL725 motif, thus representing a potentially new regulator of PC7 trafficking and cleavage activity. Immunocytochemistry of the subcellular localization of PC7 and its Ala variants of Leu-725 and Glu-719 and Glu-721 revealed that Leu-725 enhances PC7 localization to early endosomes and that, together with Glu-719 and Glu-721, it increases the endosomal activity of PC7 on hTfR1.

Proprotein convertase 7 (PCSK7) reduces apoA-V levels.

The locus of the human proprotein convertase subtilisin-kexin type-7 (PC7) gene (PCSK7) is on chromosome 11q23.3 close to the gene cluster APOA5/APOA4/APOC3/APOA1, a region implicated in the regulation of lipoprotein metabolism. A GWAS reported the association of PCSK7 SNPs with plasma triglyceride (TG), and exome sequencing of African Americans revealed the association of a low-frequency coding variant of PC7 (R504H; SNP rs142953140) with a ~ 30% TG reduction. Another PCSK7 SNP rs508487 is in linkage disequilibrium with a promoter variant of the liver-derived apolipoprotein A-V (apoA-V), an indirect activator of the lipoprotein lipase (LpL), and is associated with elevated TG levels. We thus hypothesized that PC7 regulates the levels/activity of apoA-V. Studies in the human hepatic cell line HuH7 revealed that wild-type (WT) PC7 and its endoplasmic reticulum (ER)-retained forms bind to and enhance the degradation of human apoA-V in acidic lysosomes in a nonenzymatic fashion. PC7-induced degradation of apoA-V is inhibited by bafilomycin A1 and the alkalinizing agents: chloroquine and NH4 Cl. Thus, the PC7-induced apoA-V degradation implicates an ER-lysosomal communication inhibited by bafilomycin A1. In vitro, the natural R504H mutant enhances PC7 Ser505 phosphorylation at the structurally exposed Ser-X-Glu507 motif recognized by the secretory kinase Fam20C. Co-expression of the phosphomimetic PC7-S505E with apoA-V resulted in lower degradation compared to WT, suggesting that Ser505 phosphorylation of PC7 lowers TG levels via reduced apoA-V degradation. In agreement, in Pcsk7-/- mice fed high-fat diet, plasma apoA-V levels and adipocyte LpL activity are increased, providing an in vivo mechanistic link for a role of liver PC7 in enhanced TG storage in adipocytes.

The mediating role of cognitive ability on the relationship between motor proficiency and early academic achievement in children.

The aim of this study was to examine the relationship between motor proficiency and academic achievement in 7 years-old children. A mediating model in which the relation between motor proficiency and academic achievement is mediated by cognitive ability was tested. Participants included 152 children from the longitudinal study Jeunes enfants et leurs milieux de vie (Young Children and their Environments). Motor proficiency was evaluated with the Bruininks-Oseretsky Test of Motor Proficiency (BOT2), cognitive ability with the Wechsler Intelligence Scale for Children-Fourth Edition (WISC-IV) and academic achievement with the Wechsler Individual Achievement Test II (WIAT II). Results showed that motor proficiency, cognitive ability and academic achievement were positively correlated with each other. A structural equation modeling analysis revealed that motor proficiency had a positive effect on academic achievement through an indirect path via cognitive ability. These results highlight the fundamental importance of motor skills in children's academic achievement in early school years.

A Reproducible and Individualized Method to Predict Osmolality of Compounded Pediatric Parenteral Nutrition Solutions.

BACKGROUND: Osmolality is a well-known factor in complications associated with parenteral nutrition (PN). The osmolality of compounded pediatric PN solutions is often inappropriately approximated by theoretical osmolarity, which carries a major risk of underestimation, especially in highly concentrated solutions. Only a few studies have proposed equations to overcome this problem, and to date their accuracy in settings other than those of their development has not been assessed. We propose a reproducible method to develop a predictive model of osmolality adapted to local practice, and we compare its predictive performance to osmolarity calculation and other equations. METHODS: From measures performed on dilutions of basic components of PN solutions, a predictive model establishing the relationship between the quantitative and qualitative composition of a PN solution and its osmolality was developed. This model was validated in routine practice on daily compounded pediatric PN solutions, and its predictive performance was compared with osmolarity calculation, 2 previously published predictive equations, and multilinear regression. RESULTS: We measured the osmolality of 321 routinely produced PN solutions. The model predicted osmolality with a mean relative error of -0.28% (±2.75%). All the other ways to approximate osmolality were less precise and sometimes provided critically underestimated values (from -16.67% to -33.24%). CONCLUSIONS: Our model predicted osmolality accurately and may be used in routine practice in any setting once adapted to the local production practice. Approximations by osmolarity severely underestimate actual osmolality. Keeping osmolarity <800 mOsm/L seems sufficient to ensure that actual osmolality does not exceed 1000 mOsm/kg.

Accidents and Incidents Related to Intravenous Drug Administration: A Pre-Post Study Following Implementation of Smart Pumps in a Teaching Hospital.

INTRODUCTION: Smart pumps are expected to prevent and reduce medication errors. The implementation of smart pumps requires a significant effort and collaboration of physicians, nurses, pharmacists, and other stakeholders. OBJECTIVES: The main objective of this study was to evaluate the impact of new smart pumps on reported drug-related accidents and incidents (AIs). METHOD: This is a descriptive retrospective pre-post study conducted at a women's and pediatric hospital with 500 beds. A strong multidisciplinary team (nurse, pharmacist, pharmacy resident, physician, biomedical technician, information technology technician, patient safety officer, manager) was involved in the planning, implementation, and monitoring technology implementation. A total of 1045 smart pumps were implemented in 2011 in our hospital. The reported number of AIs related to intravenous drug administration (AIIV) before and after the implementation of 1045 smart pumps were collected. RESULTS: A total of 2911 AI events related to medications, devices, and equipment were self-reported by clinical staff in the pre-phase (Y0), 3523 in the post-phase (Y1), and 2788 in the post-phase (Y2). The total AIIV increased from 1432 in Y0 to 1834 in Y1 and decreased to 1389 in Y2. CONCLUSIONS: We observed no risk reduction associated with the implementation of smart pumps in a 500 bed mother-child hospital. Further studies are required to explore the details of the potential risk reduction associated with the use of smart pumps.

Evaluation of CLINDE as potent translocator protein (18 kDa) SPECT radiotracer reflecting the degree of neuroinflammation in a rat model of microglial activation.

BACKGROUND: The translocator protein (TSPO; 18 kDa), the new name of the peripheral-type benzodiazepine receptor, is localised in mitochondria of glial cells and expressed in very low concentrations in normal brain. Their expression rises after microglial activation following brain injury. Accordingly, TSPO are potential targets to evaluate neuroinflammatory changes in a variety of CNS disorders. PURPOSE: To date, only a few effective tools are available to explore TSPO by SPECT. We characterised here 6-chloro-2-(4'iodophenyl)-3-(N,N-diethyl)-imidazo[1,2-a]pyridine-3-acetamide or CLINDE in a rat model with different stages of excitotoxic lesion. METHODS: Excitotoxicity was induced in male Wistar rats by unilateral intrastriatal injection of different amounts of quinolinic acid (75, 150 or 300 nmol). Six days later, two groups of rats (n = 5-6/group) were i.v. injected with [(125)I]-CLINDE (0.4 MBq); one group being pre-injected with PK11195 (5 mg/kg). Brains were removed 30 min after tracer injection and the radioactivity of cerebral areas measured. Complementary ex vivo autoradiography, in vitro autoradiography ([(3)H]-PK11195) and immunohistochemical studies (OX-42) were performed on brain sections. RESULTS: In the control group, [(125)I]-CLINDE binding was significantly higher (p < 0.001) in lesioned than that in intact side. This binding disappeared in rats pre-treated with PK11195 (p < 0.001), showing specific binding of CLINDE to TSPO. Ex vivo and in vitro autoradiographic studies and immunohistochemistry were consistent with this, revealing a spatial correspondence between radioactivity signal and activated microglia. Regression analysis yielded a positive relation between the ligand binding and the degree of neuroinflammation. CONCLUSION: These results demonstrate that CLINDE is suitable for TSPO in vivo SPECT imaging to explore their involvement in neurodegenerative disorders associated with microglial activation.