Effect of body position on intra-abdominal pressures and abdominal perfusion pressures measured at three sites in horses anesthetized with short-term total intravenous anesthesia.

OBJECTIVE: To assess effects of body position on direct measurements of intra-abdominal pressure (IAP) and abdominal perfusion pressure (APP) in horses anesthetized with total intravenous anesthesia (TIVA). ANIMALS: 9 healthy adult horses. PROCEDURES: Instrumentation in unsedated standing horses involved insertion of an arterial catheter for blood pressure measurements and 3 intraperitoneal cannulas (left flank, right flank, and ventral abdomen) for IAP measurements. Baseline values were measured for heart rate, respiratory rate, systolic arterial blood pressure, mean arterial blood pressure (MAP), diastolic arterial blood pressure, and IAP. Horses were medicated with xylazine, and pressures were measured again. Anesthesia was induced with ketamine-diazepam and maintained with a ketamine-guaifenesin infusion. Horses were positioned twice into left lateral recumbency, right lateral recumbency, or dorsal recumbency. Hemodynamic pressures and accessible abdominal pressures were measured for each recumbency position. The APP was calculated as MAP - IAP. Differences in IAP, MAP, APP and sedation (standing horses) or body position (anesthetized horses) were compared by means of repeated-measures ANOVA or paired t tests. RESULTS: Baseline hemodynamic and IAPs were not different after xylazine administration. Ventral abdomen IAP and MAP were lower for horses in dorsal recumbency than in right or left lateral recumbency. Ventral abdomen APP remained unchanged. For lateral recumbencies, flank IAP was lower and APP was higher than pressure measurements at the same sites during dorsal recumbency. CONCLUSIONS AND CLINICAL RELEVANCE: Body position affected IAP and APP in healthy anesthetized horses. These effects should be considered when developing IAP acquisition methods for use in horses with abdominal disease

SCN1A overexpression, associated with a genomic region marked by a risk variant for a common epilepsy, raises seizure susceptibility

Mesial temporal lobe epilepsy with hippocampal sclerosis and a history of febrile seizures is associated with common variation at rs7587026, located in the promoter region of SCN1A. We sought to explore possible underlying mechanisms. SCN1A expression was analysed in hippocampal biopsy specimens of individuals with mesial temporal lobe epilepsy with hippocampal sclerosis who underwent surgical treatment, and hippocampal neuronal cell loss was quantitatively assessed using immunohistochemistry. In healthy individuals, hippocampal volume was measured using MRI. Analyses were performed stratified by rs7587026 type. To study the functional consequences of increased SCN1A expression, we generated, using transposon-mediated bacterial artificial chromosome transgenesis, a zebrafish line expressing exogenous scn1a, and performed EEG analysis on larval optic tecta at 4 day post-fertilization. Finally, we used an in vitro promoter analysis to study whether the genetic motif containing rs7587026 influences promoter activity. Hippocampal SCN1A expression differed by rs7587026 genotype (Kruskal-Wallis test P = 0.004). Individuals homozygous for the minor allele showed significantly increased expression compared to those homozygous for the major allele (Dunn's test P = 0.003), and to heterozygotes (Dunn's test P = 0.035). No statistically significant differences in hippocampal neuronal cell loss were observed between the three genotypes. Among 597 healthy participants, individuals homozygous for the minor allele at rs7587026 displayed significantly reduced mean hippocampal volume compared to major allele homozygotes (Cohen's D = - 0.28, P = 0.02), and to heterozygotes (Cohen's D = - 0.36, P = 0.009). Compared to wild type, scn1lab-overexpressing zebrafish larvae exhibited more frequent spontaneous seizures [one-way ANOVA F(4,54) = 6.95 (P < 0.001)]. The number of EEG discharges correlated with the level of scn1lab overexpression [one-way ANOVA F(4,15) = 10.75 (P < 0.001]. Finally, we showed that a 50 bp promoter motif containing rs7587026 exerts a strong regulatory role on SCN1A expression, though we could not directly link this to rs7587026 itself. Our results develop the mechanistic link between rs7587026 and mesial temporal lobe epilepsy with hippocampal sclerosis and a history of febrile seizures. Furthermore, we propose that quantitative precision may be important when increasing SCN1A expression in current strategies aiming to treat seizures in conditions involving SCN1A haploinsufficiency, such as Dravet syndrome

Systematic assessment of long-read RNA-seq methods for transcript identification and quantification

The Long-read RNA-Seq Genome Annotation Assessment Project (LRGASP) Consortium was formed to evaluate the effectiveness of long-read approaches for transcriptome analysis. The consortium generated over 427 million long-read sequences from cDNA and direct RNA datasets, encompassing human, mouse, and manatee species, using different protocols and sequencing platforms. These data were utilized by developers to address challenges in transcript isoform detection and quantification, as well as de novo transcript isoform identification. The study revealed that libraries with longer, more accurate sequences produce more accurate transcripts than those with increased read depth, whereas greater read depth improved quantification accuracy. In well-annotated genomes, tools based on reference sequences demonstrated the best performance. When aiming to detect rare and novel transcripts or when using reference-free approaches, incorporating additional orthogonal data and replicate samples are advised. This collaborative study offers a benchmark for current practices and provides direction for future method development in transcriptome analysis

Safety of intravenous ferric carboxymaltose versus oral iron in patients with nondialysis-dependent CKD: an analysis of the 1-year FIND-CKD trial.

Background: The evidence base regarding the safety of intravenous (IV) iron therapy in patients with chronic kidney disease (CKD) is incomplete and largely based on small studies of relatively short duration. Methods: FIND-CKD (ClinicalTrials.gov number NCT00994318) was a 1-year, open-label, multicenter, prospective study of patients with nondialysis-dependent CKD, anemia and iron deficiency randomized (1:1:2) to IV ferric carboxymaltose (FCM), targeting higher (400-600 µg/L) or lower (100-200 µg/L) ferritin, or oral iron. A post hoc analysis of adverse event rates per 100 patient-years was performed to assess the safety of FCM versus oral iron over an extended period. Results: The safety population included 616 patients. The incidence of one or more adverse events was 91.0, 100.0 and 105.0 per 100 patient-years in the high ferritin FCM, low ferritin FCM and oral iron groups, respectively. The incidence of adverse events with a suspected relation to study drug was 15.9, 17.8 and 36.7 per 100 patient-years in the three groups; for serious adverse events, the incidence was 28.2, 27.9 and 24.3 per 100 patient-years. The incidence of cardiac disorders and infections was similar between groups. At least one ferritin level ≥800 µg/L occurred in 26.6% of high ferritin FCM patients, with no associated increase in adverse events. No patient with ferritin ≥800 µg/L discontinued the study drug due to adverse events. Estimated glomerular filtration rate remained the stable in all groups. Conclusions: These results further support the conclusion that correction of iron deficiency anemia with IV FCM is safe in patients with nondialysis-dependent CKD

The genetic architecture of the human cerebral cortex

The cerebral cortex underlies our complex cognitive capabilities, yet little is known about the specific genetic loci that influence human cortical structure. To identify genetic variants that affect cortical structure, we conducted a genome-wide association meta-analysis of brain magnetic resonance imaging data from 51,665 individuals. We analyzed the surface area and average thickness of the whole cortex and 34 regions with known functional specializations. We identified 199 significant loci and found significant enrichment for loci influencing total surface area within regulatory elements that are active during prenatal cortical development, supporting the radial unit hypothesis. Loci that affect regional surface area cluster near genes in Wnt signaling pathways, which influence progenitor expansion and areal identity. Variation in cortical structure is genetically correlated with cognitive function, Parkinson's disease, insomnia, depression, neuroticism, and attention deficit hyperactivity disorder

Chemometrics and metabolomics of Cannabis sativa L.

Cannabis is a domesticated crop that has a long history of medical and recreational use. Strains have been selected through informal breeding programs with undisclosed parentage and criteria. The term ‘strain’ refers to minor morphological differences and grower branding rather than distinct stabilized varieties. Anecdotal evidence suggests that there are significant variations in pharmacological effects of different strains, for which the phytochemicals responsible are unknown. The overall objective of this research was to develop analytical methodologies and metabolomic tools to characterize the phytochemical diversity of Cannabis strains within the Canadian marketplace. The expected outcomes were to understand phytochemical relationships caused by domestication and the varying pharmacological effects of the strains. A method was optimized and validated for the quantitation of ten cannabinoids in Cannabis flowers. With nine test materials, the relative standard deviations ranged from 0.78 to 10.08 % with intermediate precision HorRat values of 0.3 to 2.0. In the thirty-three Canadian market samples, the two cannabinoids Δ9-tetrahydrocannabinolic acid and cannabidiolic acid contents ranged from 0.76 to 20.71% and <MDL to 18.11%, respectively. Five clusters of strains were identified based on the ranges of total THC/CBD in the strains. Using targeted-untargeted metabolomics, the relationships between known and unknown cannabinoids were evaluated to identify CBD correlated cannabinoids, and losses in the phytochemical diversity of strains based on the distribution of cannabinoids across strain clusters. Terpenes were determined by headspace profiling in the strains. In total, 67 terpenes were detected and grouped according to their cannabinoid clusters. There were several terpenes identified in unique clusters, which highlights the impacts of aroma and breeding practices on the losses of phytochemical diversity. A data fusion model and post hoc algorithms were used to identify relationships between all cannabinoids and terpenes. There was a strong indication of a unique biosynthetic pathway for the synthesis of terpinolene, nine additional monoterpenes and three unidentified cannabinoids. Isolation and characterization of the most prominent cannabinoid was identified as THCA-C4 with a butyl sidechain. Another correlated cannabinoid was identified as THCVA. These two cannabinoids are present in higher quantities in the presence of terpinolene suggesting that breeding for increased cannabinoid production, switches on the biosynthesis of terpinolene in some strains. This research provides novel insight into the impacts of breeding, selection and domestication syndrome in Cannabis. There is a loss of phytochemical diversity in many strains that can potentially impact pharmacological activities.Arts and Sciences, Irving K. Barber School of (Okanagan)Chemistry, Department of (Okanagan)Graduat

Exploring hospital mealtime experiences of older inpatients, caregivers and staff using photovoice methods

Aim: To gather and understand the experience of hospital mealtimes from the perspectives of those receiving and delivering mealtime care (older inpatients, caregivers and staff) using photovoice methods to identify touchpoints and themes to inform the co-design of new mealtime interventions.Methods: This study was undertaken on acute care wards within a single metropolitan hospital in Brisbane, Australia in 2019. Photovoice methods involved a researcher accompanying 21 participants (10 older patients, 5 caregivers, 4 nurses and 2 food service officers) during a mealtime and documenting meaningful elements using photographs and field notes. Photo-elicitation interviews were then undertaken with participants to gain insight into their experience. Data were analysed using inductive thematic analysis, involving a multidisciplinary research team including a consumer.Results: Themes were identified across the three touchpoints: (1) preparing for the meal (the juggle, the anticipation), (2) delivering/receiving the meal (the rush, the clutter and the wait) and (3) experiencing the meal (the ideal, pulled away and acceptance). Despite a shared understanding of the importance of meals and shared vision of 'the ideal' mealtime, generally this was a time of tension, missed cares and dissatisfaction for staff, patients and caregivers. There was stark contrast in some aspects of mealtime experience, with simultaneous experiences of 'the rush' (staff) and 'the wait' (patients and caregivers). There was an overwhelming sense of acceptance and lack of control over change from all.Conclusions: This study identified themes during hospital mealtimes which have largely gone unaddressed in the design of mealtime interventions to date. This research may provide a framework to inform the future co-design of mealtime interventions involving patients, caregivers and multidisciplinary staff, centred around these key touchpoints.Practice implications: Mealtimes are experienced differently by patients, caregivers, nurses and food service officers across three key touchpoints: preparing for, delivering/receiving and experiencing the meal. Improving mealtime experiences therefore necessitates a collaborative approach, with co-designed mealtime improvement programs that include specific interventions focusing each touchpoint. Our data suggest that improvements could focus on reducing clutter, clarifying mealtime roles and workflows and supporting caregiver involvement.Impact: What problem did the study address? Mealtimes are the central mechanism to meet patients' nutritional needs in hospital; however, research consistently shows that many patients do not eat enough to meet their nutritional requirements and that they often do not receive the mealtime assistance they require. Interventions to improve hospital mealtimes have, at best, shown only modest improvements in nutritional intake and mealtime care practices. Gaining deeper insight into the mealtime experience from multiple perspectives may identify new opportunities for improvement. What were the main findings? Patients, caregivers and staff have shared ideals of comfort, autonomy and conviviality at mealtimes, but challenges of complex teamwork and re-prioritisation of mealtimes in the face of prevailing power hierarchies make it difficult to achieve this ideal. There are three discrete touchpoints (preparing for, delivering/receiving and experiencing the meal) that require different approaches to improvement. Our data suggests a need to focus improvement on reducing clutter, clarifying mealtime roles and workflows and supporting caregivers. Where and on whom will the research have an impact? The research provides a framework for multidisciplinary teams to begin co-designing improvements to mealtime care to benefit patients, caregivers and staff, while also providing a method for researchers to understand other complex care situations in hospital.Reporting method: This manuscript is written in adherence with the Standards for Reporting Qualitative Research.Patient or public contribution: Patients and caregivers were involved in the conception and design of the study through their membership of the hospital mealtime reference group. A consumer researcher (GP) was involved in the team to advise on study conduct (i.e. recruitment methods and information), data analysis (i.e. coding transcripts), data interpretation (i.e. review and refinement of themes) and manuscript writing (i.e. review and approval of final manuscript)

Pressure ulcers: Effectiveness of risk-assessment tools. A randomised controlled trial (the ULCER trial)

Objective: To evaluate the effectiveness of two pressure-ulcer screening tools against clinical judgement in preventing pressure ulcers. Design: A single blind randomised controlled trial. Setting: A large metropolitan tertiary hospital. Participants: 1231 patients admitted to internal medicine or oncology wards. Patients were excluded if their hospital stay was expected to be 2 days or less. Interventions: Participants allocated to either a Waterlow (n=410) or Ramstadius (n=411) screening tool group or to a clinical judgement group (n=410) where no formal risk screening instrument was used. Main outcome measure: Incidence of hospital acquired pressure ulcers ascertained by regular direct observation. Use of any devices for the prevention of pressure ulcers, documentation of a pressure plan and any dietetic or specialist skin integrity review were recorded. Results: On admission, 71 (5.8%) patients had an existing pressure ulcer. The incidence of hospital-acquired pressure ulcers was similar between groups (clinical judgement 28/410 (6.8%); Waterlow 31/411 (7.5%); Ramstadius 22/410 (5.4%), p=0.44). Significant associations with pressure injury in regression modelling included requiring a dietetic referral, being admitted from a location other than home and age over 65 years. Conclusion: The authors found no evidence to show that two common pressure-ulcer risk-assessment tools are superior to clinical judgement to prevent pressure injury. Resources associated with use of these tools might be better spent on careful daily skin inspection and improving management targetted at specific risks. Study registration: The trial was registered with the Australian and New Zealand Clinicat Trials Registry (ACTRN 12608000541303)

Using a general theory of implementation to plan the introduction of delirium prevention for older people in hospital

To develop an implementation plan for delirium prevention.The use of non-pharmacological interventions to prevent hospital-acquired delirium is well established but their implementation has been notoriously difficult to achieve. Systematic analysis of context as part of implementation planning is critical.Ethnographic study was conducted in a 24-bed general medical ward. Eleven patients and family members and 15 health service staff participated through observations, individual interviews and document review. Inductive analysis was used to generate themes that described enablers and barriers.Enablers included a ward culture that embraced safety and placing the person at the centre of care. Barriers were in tension with the enablers and included limited staff knowledge, specialist forms exclusive to the nursing discipline, inflexible ward routines and frequent disruptions.In addition to standard implementation strategies such as individual education and leadership, implementing delirium prevention requires consideration of team practices, review of policy document design and identification of outcomes data than can support collaborative reflexive practice.The use of a theory-informed ethnographic approach exposed tensions that may be otherwise invisible. Understanding the tensions increases the likelihood of implementation success. Using a systematic assessment approach can create a comprehensive implementation plan