Proton block and voltage gating are potassium-dependent in the cardiac leak channel Kcnk3.

Potassium leak conductances were recently revealed to exist as independent molecular entities. Here, the genomic structure, cardiac localization, and biophysical properties of a murine example are considered. Kcnk3 subunits have two pore-forming P domains and unique functional attributes. At steady state, Kcnk3 channels behave like open, potassium-selective, transmembrane holes that are inhibited by physiological levels of proton. With voltage steps, Kcnk3 channels open and close in two phases, one appears to be immediate and one is time-dependent (tau = approximately 5 ms). Both proton block and gating are potassium-sensitive; this produces an anomalous increase in outward flux as external potassium levels rise because of decreased proton block. Single Kcnk3 channels open across the physiological voltage range; hence they are "leak" conductances; however, they open only briefly and rarely even after exposure to agents that activate other potassium channels

Patient transfers in Australia: Implications for nursing workload and patient outcomes

Aim To discuss the impact of patient transfers on patient outcomes and nursing workload. Background Many patient transfers are essential and occur in response to patients' clinical changes. However, increasingly within Australia transfers are performed in response to reductions in bed numbers, resulting in 'bed block'. Evaluation A discussion of the literature related to inpatient transfers, nursing workload and patient safety. Key issues Measures to increase patient flow such as short-stay units may result in an increase in patient transfers and nursing workload. Frequent patient transfers may also increase the risk of medication incidents, health-care acquired infections and patient falls. Conclusions The continuing demand for health care has led to a reactionary bed management system that, in an attempt to accommodate patients, has resulted in increased transfers between wards. This can have a negative effect on nursing workload and affect patient outcomes. Implications for nursing management High nursing workload is cited as one reason for nurses leaving the profession. Reductions in non-essential transfers may reduce nurse workload, improve patient outcomes and enhance continuity of patient care. © 2011 Blackwell Publishing Ltd

Concentric lamellae - novel microanatomical structures in the articular calcified cartilage of mice.

The structure, ultrastructure and function of hyaline articular cartilage (HAC) and subchondral bone (SCB), and their involvement in the pathogenesis of osteoarthritis (OA) have been extensively researched. However, much less attention has been focused on the intervening tissue, articular calcified cartilage (ACC) and its role in the initiation and progression of OA. Using both light microscopy (LM) and transmission electron microscopy (TEM), a study of ACC in wild type (WT) mice, and mice with genetic osteoarthropathies (AKU) was undertaken to further understand the role played by ACC in the early stages of OA.Tibio-femoral joints were obtained from BALB/c WT and BALB/c AKU mice aged between 7 and 69 weeks. One joint was processed for routine histological analysis. The tip of the medial femoral condyle (MFC), which contained HAC, ACC, and SCB, was dissected from the contra-lateral joint and processed for TEM.In WT and AKU mice novel microanatomical structures, designated concentric lamellae, were identified surrounding chondrocytes in the ACC. The lamellae appeared to be laid down in association with advancement of the tidemark indicating they may be formed during calcification of cartilage matrix. The lamellae were associated with hypertrophic chondrocytes throughout the ACC.Novel microanatomical structures, termed concentric lamellae, which were present around hypertrophic chondrocytes in the ACC are described for the first time. Their apparent association with mineralisation, advancement of the tidemark, and greater abundance in a model of osteoarthropathy indicate their formation could be important in the pathogenesis of OA and AKU

Exploring women's sensory experiences of undergoing colposcopy and related procedures: implications for preparatory sensory information provision

INTRODUCTION: Some women experience distress during colposcopy examinations which is partly related to women's fear, or experience, of pain during the procedure. However, little is known about women's sensory experiences of colposcopy (other than pain) or what might impact on these experiences. The aim of this study was to explore women's sensory experiences of colposcopy and related procedures and identify factors which influenced negative sensory experiences. METHODS: In-depth interviews were conducted with 23 women who had undergone, for the first time, a colposcopy (some with related procedures, including punch biopsies and loop excision) as part of follow-up for abnormal cervical cytology. Interviews were analysed thematically using the Framework Approach to organise the data and identify emerging higher-order themes. RESULTS: Women described a range of sensory experiences including pain or discomfort, cramping, stinging and cold sensations (due to the application of acetic acid to the cervix). Four key themes emerged as important aspects of the overall sensory experience: levels of pain, treatment-specific sensations, anaesthetic-specific sensations and solution-specific sensations. Factors that may influence women having a negative sensory experience were sensory expectations of the procedure(s) and lack of preparatory sensory information. DISCUSSION: Our study provides unique in-depth insight into women's sensory experiences of colposcopy and related procedures and suggests women require more preparatory sensory information. The issues identified as contributing to women having a negative sensory experience may help inform the development of pre-colposcopy information which may better prepare women with abnormal cervical cytology for follow-up examinations

Socio-economic variations in anticipated adverse reactions to testing HPV positive: Implications for the introduction of primary HPV-based cervical screening

Some cervical cancer screening programmes are replacing cytology with human papillomavirus (HPV) DNA testing as the primary screening test. Concerns have been previously raised around the potential psychosocial impact of testing positive for HPV. We analysed socio-economic variations in anticipated adverse reactions to testing positive for HPV in women of screening age in the general population. A questionnaire was mailed to a random sample of 5553 women aged 20-64 in 2010, selected through primary care in Ireland. This included questions on: socio-economics; HPV knowledge; and women's anticipated adverse psychosocial responses to testing HPV positive (shame, anxiety, stigma and worry). Multivariable linear regression was used to identify socio-economic factors significantly associated with each anticipated adverse reaction. The response rate was 62% (n = 3470). In multivariate analyses, having only attained primary level education were significantly associated with higher mean scores for all four adverse outcomes. Religion was significantly associated with all four adverse outcomes. Age was associated with anxiety and worry; younger women (<30 years) had the highest mean scores. Being married/cohabiting was significantly associated with significantly lower shame and worry scores. Not working was significantly associated with higher mean anxiety and worry scores. Our large population-based survey found significant socio-economic variations in anticipated adverse reactions to testing HPV positive. In order to minimise possible negative impacts on screening uptake and alleviate potential adverse psychological effects of HPV-based screening on women, screening programmes may need to develop specific messages around HPV infection and HPV screening that target certain subgroups of women

Systemic juvenile idiopathic arthritis: The Great Ormond Street Hospital experience (2005–2021)

Systemic juvenile idiopathic arthritis (sJIA) is a complex, systemic inflammatory disorder driven by both innate and adaptive immunity. Improved understanding of sJIA pathophysiology has led to recent therapeutic advances including a growing evidence base for the earlier use of IL-1 or IL-6 blockade as first-line treatment. We conducted a retrospective case notes review of patients diagnosed with sJIA over a 16-year period (October 2005-October 2021) at Great Ormond Street Hospital for Children. We describe the clinical presentation, therapeutic interventions, complications, and remission rates at different timepoints over the disease course. We examined our data, which spanned a period of changing therapeutic landscape, to try and identify potential therapeutic signals in patients who received biologic treatment early in the disease course compared to those who did not. A total of 76-children (female n = 40, 53%) were diagnosed with sJIA, median age 4.5 years (range 0.6-14.1); 36% (27/76) presented with suspected or confirmed macrophage activation syndrome. A biologic disease-modifying anti-rheumatic drug (bDMARD) alone was commenced as first-line treatment in 28% (n = 21/76) of the cohort; however, at last review, 84% (n = 64/76) had received treatment with a bDMARD. Clinically inactive disease (CID) was achieved by 88% (n = 67/76) of the cohort at last review; however, only 32% (24/76) achieved treatment-free CID. At 1-year follow-up, CID was achieved in a significantly greater proportion of children who received treatment with a bDMARD within 3 months of diagnosis compared to those who did not (90% vs. 53%, p = 0.002). Based on an ever-increasing evidence base for the earlier use of bDMARD in sJIA and our experience of the largest UK single-centre case series described to date, we now propose a new therapeutic pathway for children diagnosed with sJIA in the UK based on early use of bDMARDs. Reappraisal of the current National Health Service commissioning pathway for sJIA is now urgently required

Age-Related Tau Burden and Cognitive Deficits Are Attenuated in KLOTHO KL-VS Heterozygotes

Background: Identification of new genetic variants that modify Alzheimer’s disease (AD) risk will elucidate novel targets for curbing the disease progression or delaying symptom onset. Objective: To examine whether the functionally advantageous KLOTHO gene KL-VS variant attenuates age-related alteration in cerebrospinal fluid (CSF) biomarkers or cognitive function in middle-aged and older adults enriched for AD risk. Methods: Sample included non-demented adults (N = 225, mean age = 63±8, 68% women) from the Wisconsin Registry for Alzheimer’s Prevention and the Wisconsin Alzheimer’s Disease Research Center who were genotyped for KL-VS, underwent CSF sampling and had neuropsychological testing data available proximal to CSF draw. Covariate-adjusted multivariate regression examined relationships between age group (Younger versus Older; mean split at 63 years), AD biomarkers, and neuropsychological performance tapping memory and executive function, and whether these relationships differed between KL-VS non-carriers (KL-VSNC) and heterozygote (KL-VSHET). Results: In the pooled analyses, older age was associated with higher levels of total tau (tTau), phosphorylated tau (pTau), and their respective ratios to amyloid-β (Aβ)42 (ps ≤ 0.002), and with poorer performance on neuropsychological tests (ps ≤ 0.001). In the stratified analyses, KL-VSNC exhibited this age-related pattern of associations with CSF biomarkers (all ps ≤ 0.001), and memory and executive function (ps ≤ 0.003), which were attenuated in KL-VSHET (ps ≥ 0.14). Conclusion: Worse memory and executive function, and higher tau burden with age were attenuated in carriers of a functionally advantageous KLOTHO variant. KL-VS heterozygosity seems to be protective against age-related cognitive and biomolecular alterations that confer risk for AD

Patient-Specific Prosthetic Fingers by Remote Collaboration - A Case Study

The concealment of amputation through prosthesis usage can shield an amputee from social stigma and help improve the emotional healing process especially at the early stages of hand or finger loss. However, the traditional techniques in prosthesis fabrication defy this as the patients need numerous visits to the clinics for measurements, fitting and follow-ups. This paper presents a method for constructing a prosthetic finger through online collaboration with the designer. The main input from the amputee comes from the Computer Tomography (CT) data in the region of the affected and the non-affected fingers. These data are sent over the internet and the prosthesis is constructed using visualization, computer-aided design and manufacturing tools. The finished product is then shipped to the patient. A case study with a single patient having an amputated ring finger at the proximal interphalangeal joint shows that the proposed method has a potential to address the patient's psychosocial concerns and minimize the exposure of the finger loss to the public.Comment: Open Access articl

Trends in, and predictors of, anxiety and specific worries following colposcopy: a 12-month longitudinal study

Objective Little is known about which women are at greatest risk of adverse psychological after-effects following colposcopy. This study examined time trends in, and identified predictors of, anxiety and specific worries over 12 months. Methods Women attending two hospital-based colposcopy clinics for abnormal cervical cytology were invited to complete psychosocial questionnaires at 4, 8 and 12 months following colposcopy. General anxiety and screening-specific worries (about cervical cancer, having sex and future fertility) were measured. Generalised estimating equations were used to assess associations between socio-demographic, lifestyle and clinical variables and risk of psychological outcomes. Results Of 584 women initially recruited, 429, 343 and 303 completed questionnaires at 4, 8 and 12 months, respectively. Screening-specific worries declined significantly over time but were still relatively high at 12 months: 23%, 39% and 18% for worries about cervical cancer, fertility and having sex, respectively. Anxiety remained stable (20%) over time. Risks of cervical cancer worry and anxiety were both almost double in women without private health insurance (cervical cancer worry: OR = 1.80, 95% CI 1.25–2.61; anxiety: OR = 1.84, 95% CI 1.20–2.84). Younger women (<40 years) had higher risk of fertility worries. Non-Irish women had higher risk of anxiety (OR = 2.13, 95% CI 1.13–4.01). Conclusions Screening-specific worries declined over time but anxiety remained stable. Notable proportions of women still reported adverse outcomes 12 months following colposcopy, with predictors varying between outcomes. Women in socio-demographically vulnerable groups were at greatest risk of adverse psychological outcomes. This information could inform development of interventions to alleviate psychological distress post-colposcopy. Copyright © 2015 John Wiley & Sons, Ltd