A multi-perspective evaluation of specialist mental health clinical pharmacist prescribers practising withing general practices in NHS Highland.

Mental health issues are a common feature of primary care consultations and around a third of GP consultations have a mental health element. The Scottish Government’s 10 year Mental Health Strategy has ambitions to transform services so every GP practice has multi-disciplinary teams (MDTs) who can support and treat patients with mental health issues while ensuring good communication with community mental health teams (CMHT) and secondary care services. Despite these strategic plans, there is currently a lack of specialist mental health clinical pharmacist prescriber input to the care of patients with mental health issues within general practice in NHS Highland. A 12 month pilot, funded by the Scottish Government’s Primary Care Transformation Fund, has been conducted during which two specialist mental health clinical pharmacist prescribers consulted with patients with depression and anxiety by appointment at one of two GP Practices in NHS Highland

Influence of forest-to-silvopasture conversion and drought on components of evapotranspiration

The northeastern U.S. is projected to experience more frequent short-term (1-2 month) droughts interspersed among larger precipitation events. Agroforestry practices such as silvopasture may mitigate these impacts of climate change while maintaining economic benefits of both agricultural and forestry practices. This study evaluated the effects of forest-to-silvopasture (i.e., 50% thinning) conversion on the components of evapotranspiration (transpiration, rainfall interception, and soil evaporation) during the growing season of 2016. The study coincided with a late-summer drought throughout the northeastern U.S., which allowed us to also evaluate the effects of forest-to-silvopasture conversion on drought responses of multiple tree species, including Pinus strobus, Tsuga canadensis, and Quercus rubra. In the reference forest and silvopasture, we observed declining soil moisture and tree water use during the drought for all three tree species. However, the decline in P. strobus water use in response to declining soil moisture in the silvopasture was not as steep as compared with the reference forest, resulting in greater water use in the silvopasture for this species. In contrast, we did not detect different water-use responses between forest and silvopasture in T. canadensis or Q. rubra. This suggests that forest-to-silvopasture conversion via thinning can alleviate drought stress for P. strobus and that this species may be more sensitive to moisture stress when competition for water is high in denser stands. Evapotranspiration was 35% lower in the silvopasture compared with the reference forest, primarily a result of lower transpiration and rainfall interception. While soil evaporation was greater in the silvopasture, this was not enough to offset the considerably lower transpiration and interception. We observed greater radial tree growth 1-3 years following conversion in the silvopasture as compared with the reference forest for T. canadensis and Q. rubra, but not for P. strobus. Overall, our results suggest that forest conversion to silvopasture (in lieu of clearcutting for new pasture) may mitigate the impacts of agricultural land use intensification and climate change on ecosystem services, especially in terms of sustaining hydrologic regulation functions. Further study is required to determine the generality of these results and whether these benefits extend beyond the first few years post-conversion

The Development of Ovine Gastric and Intestinal Organoids for Studying Ruminant Host-Pathogen Interactions

Gastrointestinal (GI) infections in sheep have significant implications for animal health, welfare and productivity, as well as being a source of zoonotic pathogens. Interactions between pathogens and epithelial cells at the mucosal surface play a key role in determining the outcome of GI infections; however, the inaccessibility of the GI tract in vivo significantly limits the ability to study such interactions in detail. We therefore developed ovine epithelial organoids representing physiologically important gastric and intestinal sites of infection, specifically the abomasum (analogous to the stomach in monogastrics) and ileum. We show that both abomasal and ileal organoids form self-organising three-dimensional structures with a single epithelial layer and a central lumen that are stable in culture over serial passage. We performed RNA-seq analysis on abomasal and ileal tissue from multiple animals and on organoids across multiple passages and show the transcript profile of both abomasal and ileal organoids cultured under identical conditions are reflective of the tissue from which they were derived and that the transcript profile in organoids is stable over at least five serial passages. In addition, we demonstrate that the organoids can be successfully cryopreserved and resuscitated, allowing long-term storage of organoid lines, thereby reducing the number of animals required as a source of tissue. We also report the first published observations of a helminth infecting gastric and intestinal organoids by challenge with the sheep parasitic nematode Teladorsagia circumcincta, demonstrating the utility of these organoids for pathogen co-culture experiments. Finally, the polarity in the abomasal and ileal organoids can be inverted to make the apical surface directly accessible to pathogens or their products, here shown by infection of apical-out organoids with the zoonotic enteric bacterial pathogen Salmonella enterica serovar Typhimurium. In summary, we report a simple and reliable in vitro culture system for generation and maintenance of small ruminant intestinal and gastric organoids. In line with 3Rs principals, use of such organoids will reduce and replace animals in host-pathogen research

General public awareness and views of community pharmacy in Scotland: the 'first port of call' study.

The recently published ‘Achieving Excellence in Pharmaceutical Care: a Strategy for Scotland’ urges community pharmacy (CP) to make itself the ‘first port of call’ for healthcare advice. The aim of this research is to explore the Scottish general public's awareness of CP services and their openness to consider CP their ‘first port of call’ for healthcare advice

The Effect of Dietary Carbohydrate and Fat Manipulation on the Metabolome and Markers of Glucose and Insulin Metabolism: A Randomised Parallel Trial.

From Europe PMC via Jisc Publications RouterHistory: ppub 2022-09-01, epub 2022-09-07Publication status: PublishedHigh carbohydrate, lower fat (HCLF) diets are recommended to reduce cardiometabolic disease (CMD) but low carbohydrate high fat (LCHF) diets can be just as effective. The effect of LCHF on novel insulin resistance biomarkers and the metabolome has not been fully explored. The aim of this study was to investigate the impact of an ad libitum 8-week LCHF diet compared with a HCLF diet on CMD markers, the metabolome, and insulin resistance markers. n = 16 adults were randomly assigned to either LCHF (n = 8, <50 g CHO p/day) or HCLF diet (n = 8) for 8 weeks. At weeks 0, 4 and 8, participants provided fasted blood samples, measures of body composition, blood pressure and dietary intake. Samples were analysed for markers of cardiometabolic disease and underwent non-targeted metabolomic profiling. Both a LCHF and HCLF diet significantly (p < 0.01) improved fasting insulin, HOMA IR, rQUICKI and leptin/adiponectin ratio (p < 0.05) levels. Metabolomic profiling detected 3489 metabolites with 78 metabolites being differentially regulated, for example, an upregulation in lipid metabolites following the LCHF diet may indicate an increase in lipid transport and oxidation, improving insulin sensitivity. In conclusion, both diets may reduce type 2 diabetes risk albeit, a LCHF diet may enhance insulin sensitivity by increasing lipid oxidation

Atomic Details of the Interactions of Glycosaminoglycans with Amyloid-β Fibrils

The amyloid plaques associated with Alzheimer's disease (AD) comprise fibrillar amyloid-β (Aβ) peptides as well as non-protein factors including glycosaminoglycan (GAG) polysaccharides. GAGs affect the kinetics and pathway of Aβ self-assembly and can impede fibril clearance; thus, they may be accessory molecules in AD. Here we report the first high-resolution details of GAG-Aβ fibril interactions from the perspective of the saccharide. Binding analysis indicated that the GAG proxy heparin has a remarkably high affinity for Aβ fibrils with 3-fold cross-sectional symmetry (3Q). Chemical synthesis of a uniformly 13C-labeled octasaccharide heparin analogue enabled magic-angle spinning solid-state NMR of the GAG bound to 3Q fibrils, and measurements of dynamics revealed a tight complex in which all saccharide residues are restrained without undergoing substantial conformational changes. Intramolecular 13C-15N dipolar dephasing is consistent with close (<5 Å) contact between GAG anomeric position(s) and one or more histidine residues in the fibrils. These data provide a detailed model for the interaction between 3Q-seeded Aβ40 fibrils and a major non-protein component of AD plaques, and they reveal that GAG-amyloid interactions display a range of affinities that critically depend on the precise details of the fibril architecture

The Intersection of Massage Practice and Research: Community Massage Therapists as Research Personnel on an NIH-funded Effectiveness Study

Introduction: Few NIH funded studies give community massage therapists the opportunity to become study personnel. A recent NIH/NCCAMfunded study investigating chronic low back pain (CLBP) recruited, trained, and utilized community massage practitioners (CMPs) as study personnel. This study’s aim was to determine whether health-related outcomes for CLBP improve when patients are referred from primary care to select CAM modalities including massage therapy (MT). The purpose of this paper is to report the results of the study’s three massage practice-driven study objectives which were to: 1) identify challenges and solutions to recruiting and retaining ample CMPs, 2) develop a practice-informed protocol reflecting real-world MT, and 3) determine the extent to which CMPs comply with rigorous research methodology in their clinical practices as study personnel.Methods: Eligible CMPs in urban and rural Kentucky counties were identified through licensure board records, professional organizations, and personal contact opportunities. Interested CMPs completed 6 CE hours of research and Human Subjects Protection training and agreed to comply with a study protocol reflecting MT as practiced. Once trained, study CMPs were matched with study participants to provide and document up to 10 MT sessions per participant.Results: Utilizing prominent MT community members proved invaluable to CMP recruitment and protocol development. CMP recruitment challenges included mixed interest, low number of available rural CMPs, busy clinic schedules, and compensation. Ethics CE credits were offered to encourage CMP interest. A total of 28 Kentucky licensed massage therapists with 5–32 years of experience completed study training. A total of 127 CLBP patients consented to participate (n = 104 for MT). Twenty-five CMPs were assigned CLBP patients and provided 1–10 treatments for 94 study participants. Treatment documentation was provided by CMPs for 97% of treatments provided.Conclusions: When recruitment, retention, and protocol compliance challenges are met, CMPs are valuable study personnel for practice-based research reflecting real-world MT practice

The Effect of Carbohydrate Restriction on Lipids, Lipoproteins, and Nuclear Magnetic Resonance-Based Metabolites: CALIBER, a Randomised Parallel Trial

Low-carbohydrate high-fat (LCHF) diets can be just as effective as high-carbohydrate, lower-fat (HCLF) diets for improving cardiovascular disease risk markers. Few studies have compared the effects of the UK HCLF dietary guidelines with an LCHF diet on lipids and lipoprotein metabolism using high-throughput NMR spectroscopy. This study aimed to explore the effect of an ad libitum 8-week LCHF diet compared to an HCLF diet on lipids and lipoprotein metabolism and CVD risk factors. For 8 weeks, n = 16 adults were randomly assigned to follow either an LCHF (n = 8, <50 g CHO p/day) or an HCLF diet (n = 8). Fasted blood samples at weeks 0, 4, and 8 were collected and analysed for lipids, lipoprotein subclasses, and energy-related metabolism markers via NMR spectroscopy. The LCHF diet increased (p < 0.05) very small VLDL, IDL, and large HDL cholesterol levels, whereas the HCLF diet increased (p < 0.05) IDL and large LDL cholesterol levels. Following the LCHF diet alone, triglycerides in VLDL and HDL lipoproteins significantly (p < 0.05) decreased, and HDL phospholipids significantly (p < 0.05) increased. Furthermore, the LCHF diet significantly (p < 0.05) increased the large and small HDL particle concentrations compared to the HCLF diet. In conclusion, the LCHF diet may reduce CVD risk factors by reducing triglyceride-rich lipoproteins and improving HDL functionality

The Effect of Dietary Carbohydrate and Fat Manipulation on the Metabolome and Markers of Glucose and Insulin Metabolism: A Randomised Parallel Trial

From MDPI via Jisc Publications RouterHistory: received 2022-07-22, accepted 2022-08-24, collection 2022-09, epub 2022-09-07Peer reviewed: TrueArticle version: VoRPublication status: PublishedFunder: Liverpool John Moores UniversityHigh carbohydrate, lower fat (HCLF) diets are recommended to reduce cardiometabolic disease (CMD) but low carbohydrate high fat (LCHF) diets can be just as effective. The effect of LCHF on novel insulin resistance biomarkers and the metabolome has not been fully explored. The aim of this study was to investigate the impact of an ad libitum 8-week LCHF diet compared with a HCLF diet on CMD markers, the metabolome, and insulin resistance markers. n = 16 adults were randomly assigned to either LCHF (n = 8, <50 g CHO p/day) or HCLF diet (n = 8) for 8 weeks. At weeks 0, 4 and 8, participants provided fasted blood samples, measures of body composition, blood pressure and dietary intake. Samples were analysed for markers of cardiometabolic disease and underwent non-targeted metabolomic profiling. Both a LCHF and HCLF diet significantly (p < 0.01) improved fasting insulin, HOMA IR, rQUICKI and leptin/adiponectin ratio (p < 0.05) levels. Metabolomic profiling detected 3489 metabolites with 78 metabolites being differentially regulated, for example, an upregulation in lipid metabolites following the LCHF diet may indicate an increase in lipid transport and oxidation, improving insulin sensitivity. In conclusion, both diets may reduce type 2 diabetes risk albeit, a LCHF diet may enhance insulin sensitivity by increasing lipid oxidation

Opportunities for improving animal welfare in rodent models of epilepsy and seizures

Animal models of epilepsy and seizures, mostly involving mice and rats, are used to understand the pathophysiology of the different forms of epilepsy and their comorbidities, to identify biomarkers, and to discover new antiepileptic drugs and treatments for comorbidities. Such models represent an important area for application of the 3Rs (replacement, reduction and refinement of animal use). This report provides background information and recommendations aimed at minimising pain, suffering and distress in rodent models of epilepsy and seizures in order to improve animal welfare and optimise the quality of studies in this area. The report includes practical guidance on principles of choosing a model, induction procedures, in vivo recordings, perioperative care, welfare assessment, humane endpoints, social housing, environmental enrichment, reporting of studies and data sharing. In addition, some model-specific welfare considerations are discussed, and data gaps and areas for further research are identified. The guidance is based upon a systematic review of the scientific literature, survey of the international epilepsy research community, consultation with veterinarians and animal care and welfare officers, and the expert opinion and practical experience of the members of a Working Group convened by the United Kingdom's National Centre for the Replacement, Refinement and Reduction of Animals in Research (NC3Rs)