The East Lancashire Clinic Model: Supporting care homes to understand reactive behaviours (Innovative Practice)

The East Lancashire Clinic model is a consultancy-based approach to supporting care home staff to assess and respond to reactive behaviours of people with dementia and reduce the need to refer into secondary mental health services. The clinics are person centred and solution focused, aiming to promote recognition of unmet needs and early interventions implemented by staff. The pilot was able to resolve most cases and reduce referral rates into secondary care services. Through working collaboratively, it empowers staff to improve the care of all their residents, improves relationship with secondary care services and has potential to offer efficiency savings

The IL-33:ST2 axis is unlikely to play a central fibrogenic role in idiopathic pulmonary fibrosis

BACKGROUND: Idiopathic pulmonary fibrosis (IPF) is a devastating interstitial lung disease (ILD) with limited treatment options. Interleukin-33 (IL-33) is proposed to play a role in the development of IPF however the exclusive use of prophylactic dosing regimens means that the therapeutic benefit of targeting this cytokine in IPF is unclear. METHODS: IL-33 expression was assessed in ILD lung sections and human lung fibroblasts (HLFs) by immunohistochemistry and gene/protein expression and responses of HLFs to IL-33 stimulation measured by qPCR. In vivo, the fibrotic potential of IL-33:ST2 signalling was assessed using a murine model of bleomycin (BLM)-induced pulmonary fibrosis and therapeutic dosing with an ST2-Fc fusion protein. Lung and bronchoalveolar lavage fluid were collected for measurement of inflammatory and fibrotic endpoints. Human precision-cut lung slices (PCLS) were stimulated with transforming growth factor-β (TGFβ) or IL-33 and fibrotic readouts assessed. RESULTS: IL-33 was expressed by fibrotic fibroblasts in situ and was increased by TGFβ treatment in vitro. IL-33 treatment of HLFs did not induce IL6, CXCL8, ACTA2 and COL1A1 mRNA expression with these cells found to lack the IL-33 receptor ST2. Similarly, IL-33 stimulation had no effect on ACTA2, COL1A1, FN1 and fibronectin expression by PCLS. Despite having effects on inflammation suggestive of target engagement, therapeutic dosing with the ST2-Fc fusion protein failed to reduce BLM-induced fibrosis measured by hydroxyproline content or Ashcroft score. CONCLUSIONS: Together these findings suggest the IL-33:ST2 axis does not play a central fibrogenic role in the lungs with therapeutic blockade of this pathway unlikely to surpass the current standard of care for IPF

A novel homozygous UMOD mutation reveals gene dosage effects on uromodulin processing and urinary excretion

Heterozygous mutations in $\textit{UMOD}$ encoding the urinary protein uromodulin are the most common genetic cause of autosomal dominant tubulointerstitial kidney disease (ADTKD). We describe the exceptional case of a patient from a consanguineous family carrying a novel homozygous $\textit{UMOD}$ mutation (p.C120Y) affecting a conserved cysteine residue within the EGF-like domain III of uromodulin. Comparison of heterozygote and homozygote mutation carriers revealed a gene dosage effect with unprecedented low levels of uromodulin and aberrant uromodulin fragments in the urine of the homozygote proband. Despite an amplified biological effect of the homozygote mutation, the proband did not show a strikingly more severe clinical evolution nor was the near absence of urinary uromodulin associated with urinary tract infections or kidney stones.J.A.S. is supported by the Kidney Research Fund and the Medical Research Council (MR/M012212/1). S.A.R. is a Kidney Research UK Post-Doctoral Fellow. O.D. is supported by grants from the European Community’s Seventh Framework Programme (305608 EURenOmics), the Swiss National Centre of Competence in Research Kidney Control of Homeostasis (NCCR Kidney.CH) programme, the Swiss National Science Foundation (31003A_169850) and the Rare Disease Initiative Zu¨rich (Radiz), a clinical research priority program of the University of Zurich, Switzerland. E.O. is supported by the Fonds National de la Recherche Luxembourg (6903109) and the University Research Priority Programme ‘Integrative Human Physiology, ZIHP’ of the University of Zurich

Coronary artery height differences and their effect on fractional flow reserve

Background: Fractional flow reserve (FFR) uses pressure-based measurements to assess the severityof a coronary stenosis. Distal pressure (Pd) is often at a different vertical height to that of the proximalaortic pressure (Pa). The difference in pressure between Pd and Pa due to hydrostatic pressure, mayimpact FFR calculation.Methods: One hundred computed tomography coronary angiographies were used to measure heightdifferences between the coronary ostia and points in the coronary tree. Mean heights were used to calculate the hydrostatic pressure effect in each artery, using a correction factor of 0.8 mmHg/cm. Thiswas tested in a simulation of intermediate coronary stenosis to give the “corrected FFR” (cFFR) andpercentage of values, which crossed a threshold of 0.8.Results: The mean height from coronary ostium to distal left anterior descending (LAD) was +5.26 cm,distal circumflex (Cx) –3.35 cm, distal right coronary artery-posterior left ventricular artery (RCA-PLV)–5.74 cm and distal RCA-posterior descending artery (PDA) +1.83 cm. For LAD, correction resulted in a mean change in FFR of +0.042, –0.027 in the Cx, –0.046 in the PLV and +0.015 in the PDA. Using 200 random FFR values between 0.75 and 0.85, the resulting cFFR crossed the clinical treatmentthreshold of 0.8 in 43% of LAD, 27% of Cx, 47% of PLV and 15% of PDA cases.Conclusions: There are significant vertical height differences between the distal artery (Pd) and its point of normalization (Pa). This is likely to have a modest effect on FFR, and correcting for this results in a proportion of values crossing treatment thresholds. Operators should be mindful of this phenomenon when interpreting FFR values

Experiences of hospital care for people with multiple long-term conditions: a scoping review of qualitative research

Background Multiple long-term conditions—the co-existence of two or more chronic health conditions in an individual—present an increasing challenge to populations and healthcare systems worldwide. This challenge is keenly felt in hospital settings where care is oriented around specialist provision for single conditions. The aim of this scoping review was to identify and summarise published qualitative research on the experiences of hospital care for people living with multiple long-term conditions, their informal caregivers and healthcare professionals. Methods We undertook a scoping review, following established guidelines, of primary qualitative research on experiences of hospital care for people living with multiple long-term conditions published in peer-reviewed journals between Jan 2010 and June 2022. We conducted systematic electronic searches of MEDLINE, CINAHL, PsycInfo, Proquest Social Science Premium, Web of Science, Scopus and Embase, supplemented by citation tracking. Studies were selected for inclusion by two reviewers using an independent screening process. Data extraction included study populations, study design, findings and author conclusions. We took a narrative approach to reporting the findings. Results Of 8002 titles and abstracts screened, 54 papers reporting findings from 41 studies conducted in 14 countries were identified as eligible for inclusion. The perspectives of people living with multiple long-term conditions (21 studies), informal caregivers (n = 13) and healthcare professionals (n = 27) were represented, with 15 studies reporting experiences of more than one group. Findings included poor service integration and lack of person-centred care, limited confidence of healthcare professionals to treat conditions outside of their specialty, and time pressures leading to hurried care transitions. Few studies explored inequities in experiences of hospital care. Conclusions Qualitative research evidence on the experiences of hospital care for multiple long-term conditions illuminates a tension between the desire to provide and receive person-centred care and time pressures inherent within a target-driven system focussed on increasing specialisation, reduced inpatient provision and accelerated journeys through the care system. A move towards more integrated models of care may enable the needs of people living with multiple long-term conditions to be better met. Future research should address how social circumstances shape experiences of care

Use of lumpfish for sea-lice control in salmon farming: challenges and opportunities

Efficient sea-lice control remains one of the most important challenges for the salmon farming industry. The use of wrasse (Labridae) as cleaner fish offers an alternative to medicines for sea-lice control, but wrasse tend to become inactive in winter. Lumpfish (Cyclopterus lumpus) continue to feed on sea-lice at low temperatures, and commercial production has escalated from thousands of fish in 2010 to well over 30 million juveniles deployed in 2016. However, production still relies on the capture of wild broodstock, which may not be sustainable. To meet global industry needs, lumpfish production needs to increase to reach c. 50 million fish annually and this can only come from aquaculture. We review current production methods and the use of lumpfish in sea cages and identify some of the main challenges and bottlenecks facing lumpfish intensification. Our gap analysis indicates that the areas in most need of research include better control of maturation for year-round production; formulation of appropriate diets; artificial selection of elite lines with desirable traits; and development of vaccines for certified, disease-free juvenile production. The welfare of farmed lumpfish also needs to be better quantified, and more information is needed on optimal densities and tank design. Finally, the risk of farmed lumpfish escaping from net pens needs to be critically assessed, and we argue that it might be beneficial to recover cleaner fish from salmon cages after the production cycle, perhaps using them as broodstock, for export to the Asian food markets or for the production of animal feeds

Relating realist metatheory to issues of gender and mental health

This paper seeks to advance the debate that considers critical realism as an alternative approach for understanding gender and mental health and its relatedness to mental health research and practice. The knowledge base of how ‘sex’ and ‘gender’affect mental health and illness is expanding. However, the way we conceptualize gender is significant and challenging as quite often our ability to think about ‘gender’as independent of ‘sex’ is not common. The influences and interplay of how sex (biological) and gender (social) affect mental health and illness requires consideration. Critical realism suggests a shared ontology and epistemology for the natural and social sciences. While much of the debate surrounding gender is guided within a constructivist discourse, an exploration of the concept ‘gender’ is reflected on and some key realist propositions are considered for mental health research and practice. This is achieved through the works of some key realist theorists. Critical realism offers potential for research and practice in relation to gender and mental health because it facilitates changes in our understanding, while simultaneously, not discarding that which is already known. In so doing, it allows the biological (sex) and social (gender) domains of knowledge for mental health and illness to coexist,without either being reduced to or defined by the other. Arguably, greater depth and explanations for gender and mental health issues are presented within a realist metatheory

A General RNA Motif for Cellular Transfection

We have developed a selection scheme to generate nucleic acid sequences that recognize and directly internalize into mammalian cells without the aid of conventional delivery methods. To demonstrate the generality of the technology, two independent selections with different starting pools were performed against distinct target cells. Each selection yielded a single highly functional sequence, both of which folded into a common core structure. This internalization signal can be adapted for use as a general purpose reagent for transfection into a wide variety of cell types including primary cells

Impact of point-of-care pre-procedure creatinine and eGFR testing in patients with ST segment elevation myocardial infarction undergoing primary PCI: The pilot STATCREAT study

Background: Contrast-induced acute kidney injury (CI-AKI) is a recognised complication during primary PCI that affects short and long term prognosis. The aim of this study was to assess the impact of point-of-care (POC) pre-PPCI creatinine and eGFR testing in STEMI patients. Methods 160 STEMI patients (STATCREAT group) with pre-procedure POC testing of Cr and eGFR were compared with 294 consecutive retrospective STEMI patients (control group). Patients were further divided into subjects with or without pre-existing CKD. Results: The incidence of CI-AKI in the whole population was 14.5% and not different between the two overall groups. For patients with pre-procedure CKD, contrast dose was significantly reduced in the STATCREAT group (124.6 ml vs. 152.3 ml, p = 0.015). The incidence of CI-AKI was 5.9% (n = 2) in the STATCREAT group compared with 17.9% (n = 10) in the control group (p = 0.12). There was no difference in the number of lesions treated (1.118 vs. 1.196, p = 0.643) or stents used (1.176 vs. 1.250, p = 0.78). For non-CKD patients, there was no significant difference in contrast dose (172.4 ml vs. 158.4 ml, p = 0.067), CI-AKI incidence (16.7% vs. 13.4%, p = 0.4), treated lesions (1.167 vs. 1.164, p = 1.0) or stents used (1.214 vs. 1.168, p = 0.611) between the two groups. Conclusions: Pre-PPCI point-of-care renal function testing did not reduce the incidence of CI-AKI in the overall group of STEMI patients. In patients with CKD, contrast dose was significantly reduced, but a numerical reduction in CI-AKI was not found to be statistically significant. No significant differences were found in the non-CKD group

UNBOUND

Featured here, are the extraordinary works of our graduating Fanshawe Design class. This accomplishment is truly a celebration of the three years of passion, hard work, and dedication put forth by our students. It is our greatest hope that family, friends and the fashion industry will enjoy the creative endeavors of these emerging designers from the Fashion Design program at Fanshawe College in London, Ontario.https://first.fanshawec.ca/famd_design_fashiondesign_unbound/1001/thumbnail.jp