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Objective: Physicians vary in their computed tomography (CT) scan usage. It remains unclear how physician gender relates to clinical practice or patient outcomes. The aim of this study was to assess the association between physician gender and decision to order head CT scans for older emergency patients who had fallen. Methods: This was a secondary analysis of a prospective observational cohort study conducted in 11 hospital emergency departments (EDs) in Canada and the United States. The primary study enrolled patients who were 65 years and older who presented to the ED after a fall. The analysis evaluated treating physician gender adjusted for multiple clinical variables. Primary analysis used a hierarchical logistic regression model to evaluate the association between treating physician gender and the patient receiving a head CT scan. Secondary analysis reported the adjusted odds ratio (OR) for diagnosing intracranial bleeding by physician gender. Results: There were 3663 patients and 256 physicians included in the primary analysis. In the adjusted analysis, women physicians were no more likely to order a head CT than men (OR 1.26, 95% confidence interval 0.98–1.61). In the secondary analysis of 2294 patients who received a head CT, physician gender was not associated with finding a clinically important intracranial bleed. Conclusions: There was no significant association between physician gender and ordering head CT scans for older emergency patients who had fallen. For patients where CT scans were ordered, there was no significant relationship between physician gender and the diagnosis of clinically important intracranial bleeding. [ABSTRACT FROM AUTHOR]

Signalling by the Unfolded Protein Response (UPR) or by the Death Receptors (DR) are frequently activated towards pro-tumoral outputs in cancer. Herein, we demonstrate that the UPR sensor IRE1 controls the expression of the DR CD95/Fas, and its cell death-inducing ability. Both genetic and pharmacologic blunting of IRE1 activity increased CD95 expression and exacerbated CD95L-induced cell death in glioblastoma (GB) and Triple-Negative Breast Cancer (TNBC) cell lines. In accordance, CD95 mRNA was identified as a target of Regulated IRE1-Dependent Decay of RNA (RIDD). Whilst CD95 expression is elevated in TNBC and GB human tumours exhibiting low RIDD activity, it is surprisingly lower in XBP1s-low human tumour samples. We show that IRE1 RNase inhibition limited CD95 expression and reduced CD95-mediated hepatic toxicity in mice. In addition, overexpression of XBP1s increased CD95 expression and sensitized GB and TNBC cells to CD95L-induced cell death. Overall, these results demonstrate the tight IRE1-mediated control of CD95-dependent cell death in a dual manner through both RIDD and XBP1s, and they identify a novel link between IRE1 and CD95 signalling. Synopsis: Dual regulation of Cell Death Receptor CD95 signalling by ER stress sensor IRE1. IRE1, a mediator of the unfolded protein response (UPR), governs CD95/Fas expression and CD95L-induced cell death in opposing ways. IRE1 can induce CD95 expression to promote CD95L-induced cell death via the transcription factor XBP1s in triple-negative breast cancer (TNBC) and glioblastoma (GB) cells. IRE1 can also repress CD95 expression to limit CD95L-induced cell death through RIDD activity, which cleaves CD95 mRNA in both TNBC and GB cells. The net effect of these opposing mechanisms depends on the cellular context. IRE1 controls CD95 signalling in vivo. Activation of RIDD or XBP1s downstream of IRE1 dually correlates with CD95 mRNA expression in human TNBC and GB tumours. Dual regulation of Cell Death Receptor CD95 signaling by ER stress sensor IRE1. IRE1, a mediator of the unfolded protein response (UPR), governs CD95/Fas expression and CD95L-induced cell death in opposing ways. [ABSTRACT FROM AUTHOR]

Background: Constant exposure of health professionals to the pain and suffering of patients can adversely affect their emotional wellbeing. Aim: The study aimed to investigate the prevalence and the factors affecting the levels of secondary traumatic stress/compassion fatigue (STS/CF), burnout (BO) and compassion satisfaction (CS) of health professionals working in adult and paediatric Intensive Care Units (ICU) as well as in departments treating patients with serious illness in five hospitals in Crete. Study Design: A descriptive cross‐sectional survey with the use of the Professional Quality of Life Scale (ProQOL‐CSF‐R‐IV) questionnaire. Methods: We enrolled medical, nursing and support staff working in the adult and paediatric ICU, emergency, oncology, haematology and neurosurgical departments, haemodialysis unit and operating theatre. Results: 598 health professionals completed the questionnaire (response rate 73.2%). Significantly increased levels of STS/CF were observed in non – ICU as compared to ICU staff (p =.009) females compared to males (p <.001), those who have previously experienced a traumatic event (p <.004), nurses and support staff compared to doctors (p =.007 and p =.028 respectively), and people not working in a department by choice (p <.001). CS was higher for older professionals, personnel subjected to stress reduction techniques (p <.019) and professionals working with children or mixed adults and children population (p =.009). Rolling schedule and bad working conditions negatively affected CS (p =.02, p =.001). Increased BO levels were associated with younger age (p =.029) and showed a positive correlation with STS/CF (r =.356, p <.001). Conclusions: STS/CF is common in health professionals regardless of their profession, working department or hospital level. Non‐ICU staff displayed higher STS/CF levels. Working in a department by choice ameliorates CS, BO and STS/CF. Relevance to Clinical Practice: Health professionals need to be informed about the risks of projecting patients' suffering on themselves. Hospital managers and department heads are responsible to provide appropriate support. [ABSTRACT FROM AUTHOR]

The endoplasmic reticulum (ER) is a membranous intracellular organelle and the first compartment of the secretory pathway. As such, the ER contributes to the production and folding of approximately one‐third of cellular proteins, and is thus inextricably linked to the maintenance of cellular homeostasis and the fine balance between health and disease. Specific ER stress signalling pathways, collectively known as the unfolded protein response (UPR), are required for maintaining ER homeostasis. The UPR is triggered when ER protein folding capacity is overwhelmed by cellular demand and the UPR initially aims to restore ER homeostasis and normal cellular functions. However, if this fails, then the UPR triggers cell death. In this review, we provide a UPR signalling‐centric view of ER functions, from the ER's discovery to the latest advancements in the understanding of ER and UPR biology. Our review provides a synthesis of intracellular ER signalling revolving around proteostasis and the UPR, its impact on other organelles and cellular behaviour, its multifaceted and dynamic response to stress and its role in physiology, before finally exploring the potential exploitation of this knowledge to tackle unresolved biological questions and address unmet biomedical needs. Thus, we provide an integrated and global view of existing literature on ER signalling pathways and their use for therapeutic purposes. The current article reviews the most up‐to‐date literature on Endoplasmic Reticulum (ER) biology and articulates this information from a signalling perspective. Not only do we cover the basic cell biology aspects of adaptive ER signalling but also provide information about the latest discoveries on ER stress targeting drugs and their potential use in the clinic. [ABSTRACT FROM AUTHOR]

Activating transcription factor 6 alpha (referred to as ATF6 hereafter) is an endoplasmic reticulum (ER)‐resident glycoprotein and one of the three sensors of the unfolded protein response (UPR). Upon ER stress, ATF6 is exported to the Golgi complex where it is cleaved by the S1P and S2P proteases thus releasing ATF6 cytosolic fragment and leading to the transcription of ATF6 target genes. In this study, we performed a phenotypic small‐interfering RNA (siRNA) screening to better characterize the ER mechanisms involved in ATF6 activation upon ER stress. This revealed that silencing of ER‐degradation‐enhancing alpha‐mannosidase‐like protein‐1 (EDEM1) increased the bioavailability of ER stress‐induced ATF6 export to the Golgi complex through the stabilization of the natively unstable ATF6 protein. Moreover, we characterized a somatic variant of EDEM1 (N198I) found in hepatocellular carcinoma that alters ATF6 signaling and might provide a selective advantage to the transforming cells. Hence, our work confirms the natively unstable nature of ATF6 and links this property to potentially associated pro‐oncogenic functions. The unfolded protein response (UPR) is a cellular stress response that is triggered by protein misfolding in the ER. A key protein involved in 'sensing' ER stress and activating UPR genes is the transcription factor ATF6. The molecular mechanisms underpinning this role remain largely elusive. Here, Chevet and co‐authors used an siRNA‐based screen to uncover functional relationships between ATF6 and mediators of ER protein quality control (ERQC). They show that silencing of an ERQC component, EDEM1, leads to enhanced activation of ATF6, providing new insight into its regulation in the ER. Intriguingly, characterisation of a mutant variant of EDEM1 linked to hepatocellular carcinoma indicates that alteration of ATF6 signalling could promote oncogenesis. [ABSTRACT FROM AUTHOR]

The collected works of Hippocrates describe for the first time in a systematic way a large number of oral diseases, such as ulcers, inflammations, abscesses and tumours from the epiglottis, mouth, tongue, palate, uvula and the sublingual area. Several of these case reports are remarkable for the accurate observation of clinical symptoms and signs, the aetiology, the pathogenesis and their therapeutic approach in relation to prognosis. The Hippocratic authors report cases of aphthae as part of a polysystemic disease, described many centuries later by Behçet and Adamantiades, while they associate features of splenomegaly from endemic malaria with gingivitis (ulitis). Benign lip ulcers, caused by sharp teeth bites, were distinguished from the difficult to treat herpes labialis (herpes) and from the necrotising nomae. Although staphylitis and angina (kynanche) were attributed to phlegm accumulation, they were recognised as true emergencies when they were associated with a swollen tongue and uvula. Several cases of kynanche with forward displacement of the first cervical vertebrae, atrophy of the uvula and oedema of the jaws are illustrated. A fatal outcome was anticipated in cases of phagedaenic ulcers of the teeth, causing necrosis and abscess formation. The therapeutic approach of oral diseases proceeded step by step, starting with simple regimens and progressing to invasive techniques, such as phlebotomy, surgical incisions for fluid drainage, and cauterisation. With the aim to avoid adverse events, special attention was paid to the correct timing of surgery and the maintenance of a patent airway with the insertion of small pharyngeal tubes. [ABSTRACT FROM AUTHOR]

Objective Adults with type 2 diabetes mellitus (DM) have an elevated fracture risk despite normal areal bone mineral density (aBMD). The study objective was to compare trabecular bone microarchitecture of postmenopausal women with type 2 DM and women without type 2 DM. Methods An extremity 1T magnetic resonance imaging system was used to acquire axial images (195 × 195 × 1,000 μm3 voxel size) of the distal radius of women recruited from outpatient clinics or by community advertisement. Image segmentation yielded geometric, topologic, and stereologic outcomes, i.e., number and size of trabecular bone network holes (marrow spaces), endosteal area, trabecular bone volume fraction, nodal and branch density, and apparent trabecular thickness, separation, and number. Lumbar spine (LS) and proximal femur BMD were measured with dual x-ray absorptiometry. Microarchitectural differences were assessed using linear regression and adjusted for percent body fat, ethnicity, timed up-and-go test, Charlson Index, and calcium and vitamin D intake; aBMD differences were adjusted for body mass index (BMI). Results Women with type 2 DM (n = 30, mean ± SD age 71.0 ± 4.8 years) had larger holes (+13.3%; P = 0.001) within the trabecular bone network than women without type 2 DM (n = 30, mean ± SD age 70.7 ± 4.9 years). LS aBMD was greater in women with type 2 DM; however, after adjustment for BMI, LS aBMD did not differ between groups. Conclusion In women with type 2 DM, the average hole size within the trabecular bone network at the distal radius is greater compared to controls. This may explain the elevated fracture risk in this population. [ABSTRACT FROM AUTHOR]

kaasalainen s, dolovich l, papaioannou a, holbrook a, lau e, ploeg j, levine m, cosby j & emily a ( 2011) Journal of Nursing and Healthcare of Chronic Illness 3, 407-418 The process of medication management for older adults with dementia Aim. The purpose of this study was to explore the personal experiences related to medication management of community-dwelling older adults diagnosed with dementia, their informal caregivers, as well as healthcare professionals who assist them. Background. Older adults who have dementia face many challenges in managing their medications while living in the community. Medication regimens used to treat a variety of conditions in older adults with dementia are usually overseen and coordinated by healthcare professionals such as community nurses, physicians and pharmacists, but often, more supports are needed. However, little research has been conducted to study the barriers and facilitators to medication adherence in this unique population. Methods. Using a grounded theory approach, 57 interviews were completed (10 nurses, 10 pharmacists, 6 physicians, 20 caregivers and 11 patients) in southern Ontario, Canada, in 2007. Findings. The findings indicate that the processes of medication management differ according to the level of dementia. A number of corresponding facilitators and barriers to medication management were identified. Medication management in early stage dementia is characterised by patients' desire to maintain independence, denial of issues or disease, and a refusal to take medications owing to feeling angry. In late-stage dementia, older adults often refuse medications owing to delusional or suspicious thinking, which results in caregivers assuming responsibility for managing their medications. Conclusions. Older adults with dementia, their informal caregivers and the healthcare professionals who assist them are faced with the challenges of declining cognitive function and memory while trying to manage medications at home. However, a number of adherence strategies appear to be helpful and should be considered. Relevance to clinical practice. Healthcare professionals struggle with helping older adults who have dementia manage medications safely and therapeutically, often with little resources to draw from. Future work is needed to design, implement and evaluate supportive networks and interventions with the goal of helping older adults with dementia manage their medications better while living in the community. [ABSTRACT FROM AUTHOR]

Background: Mild cognitive impairment (MCI) is highly prevalent in older adults aged 60+ with prevalence rates of 16‐20% and one of the first cognitive expressions of Alzheimer's Disease and other dementias. Dance activates many brain regions to integrate complex movement patterns with musical and emotional expression and may lower the risk of dementia over time. We investigated the effect of 12‐weeks of GERAS DANcing for Cognition and Exercise (DANCE) on cognitive function in older adults (aged 60+) with and without cognitive impairment. Methods: GERAS DANCE is a specialised program tailored for older adults with early memory or mobility problems. It was offered across 12 YMCAs in Southern Ontario, Canada with in‐person classes 2x weekly (1‐hour each) and homework (10‐minutes daily) for a period of 12 weeks. Cognitive function was assessed with the Montreal Cognitive Assessment [MOCA]. Changes in cognitive function from baseline to 12 weeks were evaluated using ANOVA [2 (Time: pre‐ post‐intervention) x 2 (Group: cognitive impairment, no cognitive impairment)]. Result: A total of 106 older adults participated in the analysis (mean age = 76.12 ± 7.03, range 61 to 93 years, 81% female). Overall GERAS DANCE improved cognitive function [F(1,105) = 4.928, p = 0.029]. In older adults with cognitive impairment, the mean difference of MOCA total scores improved by 1.04 points (pre = 21.71 ± 3.34, post = 22.74 ± 4,12). Conclusion: GERAS DANCE has the potential to improve or maintain cognitive function in older adults with and without dementia. Next steps include testing for efficacy of GERAS DANCE as a part of an overall approach for cognitive health and to inform clinical practice guidelines. [ABSTRACT FROM AUTHOR]

OBJECTIVES: To describe an older patient with delirium attributed to systemic lupus erythematosus (SLE) and to review the literature on neuropsychiatric manifestations of SLE in older people. DESIGN: Case report and literature review. MEDLINE search using terms systemic lupus erythematosus, neurologic, psychiatric, neuropsychiatric, autoantibodies (antinuclear antibody (ANA), antiphospholipid, anticardiolipin, anti-double stranded deoxyribonucleic acid (anti-dsDNA), anti-Smith), and elderly. Additional articles obtained from hand-searched references and through experts. SETTING: Hospital (case report). PARTICIPANTS: Case report and literature cases. MEASUREMENTS: None. RESULTS: SLE is increasingly diagnosed in older adults. Onset is insidious and diagnosis is delayed because of a different clinical spectrum and immunological profile than in younger adults. Autoantibodies have an important role in the pathogenesis of neuropsychiatric manifestations, while vasculitis is less common. Aggressive immunosuppressive therapy is typically indicated, although recent case reports suggest that lower doses may suffice. The American College of Rheumatology 1982 revised criteria may be inadequate to diagnose neuropsychiatric lupus in older persons. CONCLUSION: Neuropsychiatric symptoms can be prominent in older people, presenting features of SLE. This case illustrates the lowest dose of corticosteroids shown to be effective in an older patient with delirium due to SLE. [ABSTRACT FROM AUTHOR]

A letter to the editor is presented which is concerned with research which investigated the association between vitamin D3 supplementation and serum 25-hydroxyvitamin D levels in nursing home patients.

A letter to the editor is presented which is concerned with a renal drug alert system for prescribing drugs to residents in long term care facilities.