Barriers and facilitators to implementing pressure injury prevention and management guidelines in acute care: A mixed-methods systematic review.

BACKGROUND: Evidence-based pressure injury prevention and management is a global health service priority. Low uptake of pressure injury guidelines leads to compromised patient outcomes. Understanding clinicians' and patients' views on the barriers and facilitators to implementing guidelines and mapping the identified barriers and facilitators to the Theoretical Domains Framework and behaviour change techniques will inform an end-user and theoretically informed intervention to improve guideline uptake in the acute care setting. OBJECTIVES: To synthesise quantitative and qualitative evidence on i) hospital clinicians' and inpatients' perceptions and experiences of evidence-based pressure injury practices and ii) barriers and facilitators to implementing guidelines. DESIGN: A convergent integrated mixed-methods systematic review was conducted using the JBI approach. DATA SOURCE: English language peer-reviewed studies published from 2009 to August 2022 were identified from MEDLINE, EMBASE, CINAHL, PsycINFO and Cochrane Central Library. REVIEW METHODS: Included studies reported: i) acute care hospital clinicians' and patients' perceptions and experiences of evidence-based pressure injury practices and ii) barriers and facilitators to implementing guidelines. The Mixed Methods Appraisal Tool was used for critical appraisal. Quantitative data was transformed into qualitised data, then thematically synthesised with qualitative data, comparing clinicians' and patients' views. Barriers and facilitators associated with each main theme were mapped to the Theoretical Domains Framework and allocated to relevant behaviour change techniques. RESULTS: Fifty-five out of 14,488 studies of variable quality (29 quantitative, 22 qualitative, 4 mixed-methods) met the inclusion criteria. Four main themes represent factors thought to influence the implementation of evidence-based guidelines: 1) nurse-led multidisciplinary care, 2) patient participation in care, 3) practicability of implementation and 4) attitudes towards pressure injury prevention and management. Most barriers identified by clinicians were related to the third theme, whilst for patients, there were multiple barriers under theme 2. Barriers were mainly mapped to the Knowledge domain and Environmental Context and Resources domain and were matched to the behaviour change techniques of "instruction on how to perform a behaviour" and "restructuring the physical environment". Most facilitators mentioned by clinicians and patients were related to themes 1 and 2, respectively, and mapped to the Environmental Context and Resources domain. All patient-related attitudes in theme 4 were facilitators. CONCLUSIONS: These review findings highlight the most influential factors related to implementing evidence-based pressure injury care from clinicians' and patients' views and mapping these factors to the Theoretical Domains Framework and behaviour change techniques has contributed to developing a stakeholder-tailored implementation intervention in acute care settings. PROSPERO REGISTRATION: CRD42021250885.

The experience of being a spouse of a person with dementia in respect to their marital relationship in Japan.

BACKGROUND AND PURPOSE: While the marital relationship with partners with dementia has an impact on spousal carers' well-being, the spousal understandings or expectations of their marital relationship have not been fully identified. As the marital relationship is formed by individual backgrounds including society, culture and psychological status, the aim of this study was to identify the experience of being the spouse of a person with dementia in the context of their marital relationship. The study was conducted in Japan. RESEARCH DESIGN: To identify spousal experience of being, Heideggerian perspectives of interpretive phenomenology were applied. STUDY SAMPLE: Seven couples aged over 65 years, each comprising one partner with dementia who received home nursing, and their spouse participated in this study. DATA COLLECTION: The couples were observed, and semi-structured interviews were conducted. DATA ANALYSIS: Interpretive data analysis based on the Hermeneutic circle of Heideggerian perspectives was applied. RESULTS: In the findings, the experience of being a spouse, contextualised by spousal understandings of marital relationship, was formed through seven themes. The main context for spousal understanding of their marital relationship was helping each other as husband and wife, and this relationship was seen as natural and unchanging. It reflected on spousal potentiality of being, that is, living together indefinitely as before. Spouses tried to provide suitable care for their partners using memories while preserving a sense of identity, maintaining external relationships and accepting unanticipated internal responsibility. CONCLUSIONS: In conclusion, fulfilling unmet needs could help spouses to ease intense care load, which re-acknowledges their own and their partner's identity, and their relationship by reminiscing their past.

Characterizing the genomic variation and population dynamics of Plasmodium falciparum malaria parasites in and around Lake Victoria, Kenya.

Characterising the genomic variation and population dynamics of Plasmodium falciparum parasites in high transmission regions of Sub-Saharan Africa is crucial to the long-term efficacy of regional malaria elimination campaigns and eradication. Whole-genome sequencing (WGS) technologies can contribute towards understanding the epidemiology and structural variation landscape of P. falciparum populations, including those within the Lake Victoria basin, a region of intense transmission. Here we provide a baseline assessment of the genomic diversity of P. falciparum isolates in the Lake region of Kenya, which has sparse genetic data. Lake region isolates are placed within the context of African-wide populations using Illumina WGS data and population genomic analyses. Our analysis revealed that P. falciparum isolates from Lake Victoria form a cluster within the East African parasite population. These isolates also appear to have distinct ancestral origins, containing genome-wide signatures from both Central and East African lineages. Known drug resistance biomarkers were observed at similar frequencies to those of East African parasite populations, including the S160N/T mutation in the pfap2mu gene, which has been associated with delayed clearance by artemisinin-based combination therapy. Overall, our work provides a first assessment of P. falciparum genetic diversity within the Lake Victoria basin, a region targeting malaria elimination.

Pyrocatechol, a component of coffee, suppresses LPS-induced inflammatory responses by inhibiting NF-κB and activating Nrf2.

Coffee is a complex mixture of many bioactive compounds possessing anti-inflammatory properties. However, the mechanisms by which coffee exerts anti-inflammatory effects remains unclear and the active ingredients have not yet been identified. In this study, we found that coffee extract at more than 2.5%(v/v) significantly inhibited LPS-induced inflammatory responses in RAW264.7 cells and that anti-inflammatory activity of coffee required the roasting process. Interestingly, we identified pyrocatechol, a degradation product derived from chlorogenic acid during roasting, as the active ingredient exhibiting anti-inflammatory activity in coffee. HPLC analysis showed that 124 µM pyrocatechol was included in 100% (v/v) roasted coffee. A treatment with 5%(v/v) coffee extract and more than 2.5 µM pyrocatechol inhibited the LPS-induced activation of NF-κB and also significantly activated Nrf2, which acts as a negative regulator in LPS-induced inflammation. Furthermore, intake of 60% (v/v) coffee extract and 74.4 µM pyrocatechol, which is the concentration equal to contained in 60% (v/v) coffee, markedly inhibited the LPS-induced inflammatory responses in mice. Collectively, these results demonstrated that pyrocatechol, which was formed by the roasting of coffee green beans, is one of the ingredients contributing to the anti-inflammatory activity of coffee.

Epidemiology, risk factors, and co-infection of vector-borne pathogens in goats from Sistan and Baluchestan province, Iran.

Several vector-borne pathogens restrict livestock farming and have significant economic impact worldwide. In endemic areas livestock are exposed to different tick species carrying various pathogens which could result in co-infection with several tick-borne pathogens in a single host. Although the co-infection of and the interaction among pathogens are critical factors to determine the disease outcome, pathogen interactions in the vector and the host are poorly understood. In this study, we surveyed the presence of Babesia ovis, Theileria ovis, Theileria lestoquardi, Anaplasma ovis, Anaplasma phagocytophilum, and Anaplasma marginale in 200 goats from 3 different districts in Sistan and Baluchestan province, Iran. Species-specific diagnostic PCRs and sequence analysis revealed that 1.5%, 12.5%, and 80% of samples were positive for T. lestoquardi, T. ovis, and A. ovis, respectively. Co-infections of goats with up to 3 pathogens were seen in 22% of the samples. We detected a significant association between T. ovis infection and age, T. ovis infection and location (Zabol), and A. ovis infection and location (Sarbaz) by multivariate logistic regression analysis. In addition, by analyzing the data with respect to Plasmodium caprae infection in these goats, a negative correlation was found between P. caprae and A. ovis infection. This study contributes to understanding the epidemiology of vector-borne pathogens and their interplay in goats.

Author Correction: Genetic homogeneity of goat malaria parasites in Asia and Africa suggests their expansion with domestic goat host.

A correction to this article has been published and is linked from the HTML and PDF versions of this paper. The error has been fixed in the paper.

Close relationship of Plasmodium sequences detected from South American pampas deer (Ozotoceros bezoarticus) to Plasmodium spp. in North American white-tailed deer.

We report, for the first time, the presence of ungulate malaria parasites in South America. We conducted PCR-based surveys of blood samples of multiple deer species and water buffalo from Brazil and detected Plasmodium sequences from pampas deer (Ozotoceros bezoarticus) samples. Phylogenic analysis revealed that the obtained sequences are closely related to the Plasmodium odocoilei clade 2 sequence from North American white-tailed deer (Odocoileus virginianus). Nucleotide differences suggest that malaria parasites in South American pampas deer and North American P. odocoilei clade 2 branched more recently than the Great American Interchange.

Genetic homogeneity of goat malaria parasites in Asia and Africa suggests their expansion with domestic goat host.

Plasmodium was first identified in a goat in Angola in 1923, and only recently characterized by DNA isolation from a goat blood sample in Zambia. Goats were first domesticated in the Fertile Crescent approximately 10,000 years ago, and are now globally distributed. It is not known if the Plasmodium identified in African goats originated from parasites circulating in the local ungulates, or if it co-evolved in the goat before its domestication. To address this question, we performed PCR-based surveillance using a total of 1,299 goat blood samples collected from Sudan and Kenya in Africa, Iran in west Asia, and Myanmar and Thailand in southeast Asia. Plasmodium DNA was detected from all locations, suggesting that the parasite is not limited to Africa, but widely distributed. Whole mitochondrial DNA sequences revealed that there was only one nucleotide substitution between Zambian/Kenyan samples and others, supporting the existence of a goat-specific Plasmodium species, presumably Plasmodium caprae, rather than infection of goats by local ungulate malaria parasites. We also present the first photographic images of P. caprae, from one Kenyan goat sample.

Selections, frameshift mutations, and copy number variation detected on the surf 4.1 gene in the western Kenyan Plasmodium falciparum population.

BACKGROUND: Plasmodium falciparum SURFIN4.1 is a putative ligand expressed on the merozoite and likely on the infected red blood cell, whose gene was suggested to be under directional selection in the eastern Kenyan population, but under balancing selection in the Thai population. To understand this difference, surf 4.1 sequences of western Kenyan P. falciparum isolates were analysed. Frameshift mutations and copy number variation (CNV) were also examined for the parasites from western Kenya and Thailand. RESULTS: Positively significant departures from neutral expectations were detected on the surf 4.1 region encoding C-terminus of the variable region 2 (Var2) by 3 population-based tests in the western Kenyan population as similar in the Thai population, which was not covered by the previous analysis for eastern Kenyan population. Significant excess of non-synonymous substitutions per nonsynonymous site over synonymous substitutions per synonymous site was also detected in the Var2 region. Negatively significant departures from neutral expectations was detected on the region encoding Var1 C-terminus consistent to the previous observation in the eastern Kenyan population. Parasites possessing a frameshift mutation resulting a product without intracellular Trp-rich (WR) domains were 22/23 in western Kenya and 22/36 in Thailand. More than one copy of surf 4.1 gene was detected in western Kenya (4/24), but no CNV was found in Thailand (0/36). CONCLUSIONS: The authors infer that the high polymorphism of SURFIN4.1 Var2 C-terminus in both Kenyan and Thai populations were shaped-up by diversifying selection and maintained by balancing selection. These phenomena were most likely driven by immunological pressure. Whereas the SURFIN4.1 Var1 C-terminus is suggested to be under directional selection consistent to the previous report for the eastern Kenyan population. Most western Kenyan isolates possess a frameshift mutation that would limit the expression of SURFIN4.1 on the merozoite, but only 60% of Thai isolates possess this frameshift, which would affect the level and type of the selection pressure against this protein as seen in the two extremities of Tajima's D values for Var1 C-terminus between Kenyan and Thai populations. CNV observed in Kenyan isolates may be a consequence of this frameshift mutation to increase benefits on the merozoite surface.

Ungulate malaria parasites.

Haemosporida parasites of even-toed ungulates are diverse and globally distributed, but since their discovery in 1913 their characterization has relied exclusively on microscopy-based descriptions. In order to bring molecular approaches to bear on the identity and evolutionary relationships of ungulate malaria parasites, we conducted Plasmodium cytb-specific nested PCR surveys using blood from water buffalo in Vietnam and Thailand, and goats in Zambia. We found that Plasmodium is readily detectable from water buffalo in these countries, indicating that buffalo Plasmodium is distributed in a wider region than India, which is the only area in which buffalo Plasmodium has been reported. Two types (I and II) of Plasmodium sequences were identified from water buffalo and a third type (III) was isolated from goat. Morphology of the parasite was confirmed in Giemsa-reagent stained blood smears for the Type I sample. Complete mitochondrial DNA sequences were isolated and used to infer a phylogeny in which ungulate malaria parasites form a monophyletic clade within the Haemosporida, and branch prior to the clade containing bird, lizard and other mammalian Plasmodium. Thus it is likely that host switching of Plasmodium from birds to mammals occurred multiple times, with a switch to ungulates independently from other mammalian Plasmodium.

Evaluation of trabecular bone formation in a canine model surrounding a dental implant fixture immobilized with an antimicrobial peptide derived from histatin.

JH8194 induces osteoblast differentiation, although it was originally designed to improve antifungal activity. This suggests that JH8194 is useful for implant treatment. Therefore, the aim of this study was to evaluate the osseointegration capacity of JH8194-modified titanium dental implant fixtures (JH8194-Fi). The implants were randomly implanted into the edentulous ridge of dog mandibles. Healing abutments were inserted immediately after implant placement. Three weeks later, peri-implant bone levels, the first bone-to-implant contact points, and trabecular bone formation surrounding the implants were assessed by histological and digital image analyses based on microcomputed tomography (microCT). The histological analysis revealed an enhancement of mature trabecular bone around the JH8194-Fi compared with untreated fixtures (control-Fi). Similarly, microCT combined with analysis by Zed View™ also showed increased trabecular bone formation surrounding the JH8194-Fi compared with the control-Fi (Student's t-test, P < 0.05). JH8194 may offer an alternative biological modification of titanium surfaces to enhance trabecular bone formation around dental implants, which may contribute to the transient acquirement of osseointegration and the long-term success of implant therapy.

Molecular dynamics calculations of wild type vs. mutant protein C: relationship between binding affinity to endothelial cell protein C receptor and hereditary disease.

Molecular dynamics simulations of the protein C gamma-carboxyglutamic acid (Gla) domain and endothelial cell protein C receptor (EPCR) complex were performed to determine the effect of a hereditary disease, which results in a mutation (Gla 25 --> Lys) in the protein C Gla domain. Our results suggest that the Gla 25 --> Lys mutation causes a significant reduction in the binding force between protein C Gla domain and EPCR due to destabilization of the helix structure of EPCR and displacement of a Ca2+ ion.

One novel and one recurrent mutation in the PROS1 gene cause type I protein S deficiency in patients with pulmonary embolism associated with deep vein thrombosis.

We investigated the molecular basis of type I protein S (PS) deficiency in two unrelated Japanese families, in which both probands developed pulmonary embolism associated with deep vein thrombosis. Nucleotide sequencing of amplified DNA revealed distinct point mutations in the PROS1 gene of the probands, which were designated protein S Sapporo 1 and protein S Sapporo 2. Additional mutations in the PROS1 gene were excluded by DNA sequencing of all exons and intron/exon boundaries. In the 25-year-old Japanese male patient who carried protein S Sapporo 1, we identified a heterozygous A-to-T change in the invariant ag dinucleotide of the acceptor splice site of intron f of the PROS1 gene. This mutation is a novel splice site mutation that impairs normal mRNA splicing, leading to exon 7 skipping, which was confirmed by platelet mRNA analysis. Translation of this mutant transcript would result in a truncated protein that lacks the entire epidermal growth factor-like domain 3 of the PS molecule. In a 31-year-old Japanese male and his younger brother who each carried protein S Sapporo 2, we detected a previously described heterozygous T-to-C transition at nucleotide position 1147 in exon 10 of the PROS1 gene, which predicts an amino acid substitution of tryptophan by arginine at residue 342 in the laminin G1 domain of the PS molecule. Both mutations would cause misfolding of the PS protein, resulting in the impairment of secretion, which is consistent with the type I PS deficiency phenotype.

Protein C Sapporo (protein C Glu 25 --> Lys): a heterozygous missense mutation in the Gla domain provides new insight into the interaction between protein C and endothelial protein C receptor.

Interaction of the gamma-carboxyglutamic acid (Gla) domain of protein C with endothelial protein C receptor (EPCR) is a critical step for efficient activation of protein C, though interactions by mutants in the Gla domain of protein C with EPCR have been rarely evaluated. We identified a 44-year-old Japanese woman with a history of recurrent thromboembolism as an inherited missense mutation, the first such case reported in Japan, which involved a protein C Gla 25 mutation. Total protein C antigen and Gla protein C antigen levels in the proband were normal. Protein C activity measured with an anticoagulant assay was reduced, whereas that measured with an amidolytic assay was normal. She was therefore phenotypically diagnosed as type IIb protein C deficiency. Direct sequencing of the PCR fragments revealed a heterozygous G to A transition at nucleotide position 1462 in exon 3, which predicted an amino acid substitution of Glu 25 by Lys. Her mother and one son were also heterozygous for this mutation. A molecular dynamics simulation of Gla 25-->Lys/EPCR complex in water suggested that the affinity between the molecules was decreased compared to the wild type Gla domain/EPCR complex. Since Gla 25 has been shown to play an important role in protein C function, not only in membrane phospholipid binding but also in binding to EPCR, our findings provide new insight into the mechanism by which the Glu 25-->Lys mutation induces type IIb protein C deficiency in individuals.

A unique role of an amino terminal 16-residue region of long-type GATA-6.

Human GATA-6 mRNA utilizes two Met-codons in frame as translational initiation codons in cultured mammalian cells. An internal ribosome entry site (IRES) is not present in front of the coding region for short-type GATA-6. The 5'-upstream sequence with a short upstream open reading frame (uORF) did not affect the production of either long- or short-type GATA-6. Introduction of a canonical Kozak sequence around the upstream Met-codon resulted in predominant synthesis of long-type GATA-6, suggesting that the translation of short-type GATA-6 could be due to leaky scanning of the Met-codon by ribosomes. We found that at least the sequence comprising the 90th to 139th nucleotide bases from the first letter of the upstream Met-codon plays a positive role in the expression of long-type GATA-6. This was confirmed by insertion of the corresponding sequence in frame at the site of deletion (the 38th to 304th nucleotide residues). However, insertion of the sequence comprising the 92nd to 141st bases did not suppress the negative effect of the deletion. These results suggest that the translation of this region (Glu-31-Cys-46) could be critical for the apparent production of long-type GATA-6. We also demonstrated that long-type GATA-6 is potentially more active than the short-type.