A 7-year follow-up of sacral anterior root stimulation for bladder control in patients with a spinal cord injury: quality of life and users' experiences\ud

Study design: Cross-sectional descriptive study.\ud \ud Objectives: To assess long-term effects and quality of life (QoL) of using sacral anterior root stimulation (SARS) in spinal cord injured patients.\ud \ud Setting: Neurosurgical and Urological Departments of a large teaching hospital and a large rehabilitation centre in the Netherlands.\ud \ud Methods: In all, 42 patients with complete spinal cord injury (SCI) implanted between 1987 and 2000 were included. A questionnaire was constructed to determine complications, technical failures and personal experiences of the patients. The Qualiveen questionnaire was used and the outcome was compared with data obtained from a reference group of 400 SCI patients with neurogenic bladder problems not using the bladder controller. The Qualiveen questionnaire measures disease-specific aspects in four domains with respect to limitations, constraints, fears and feelings and general QoL aspects, suitable for use in SCI patients with urinary disorders.\ud \ud Results: The results of 37 patients are presented. Our results with the bladder controller with respect to medical and technical complications and infection rates are similar to the results presented by others. From users' experiences, the most important advantages reported were a decreased infection rate (68%), improved social life (54%) and continence (54%). Comparison of the obtained results of our patient group with the Qualiveen questionnaire with a reference group not using the bladder controller indicates that the specific impact of urinary disorders in the four domains on QoL is reduced and that general QoL is improved.\ud \ud Conclusion: SARS is effective and safe for neurogenic bladder management in patients with complete SCI. Users' experiences are positive. Furthermore, this therapy seems to reduce the effects of urinary-disorder-specific QoL aspects, and to increase the QoL in general\u

Multi-Scalar-Singlet Extension of the Standard Model - the Case for Dark Matter and an Invisible Higgs Boson

We consider a simple extension of the Standard Model by the addition of N real scalar gauge singlets \vp that are candidates for Dark Matter. By collecting theoretical and experimental constraints we determine the space of allowed parameters of the model. The possibility of ameliorating the little hierarchy problem within the multi-singlet model is discussed. The Spergel-Steinhardt solution of the Dark Matter density cusp problem is revisited. It is shown that fitting the recent CRESST-II data for Dark Matter nucleus scattering implies that the standard Higgs boson decays predominantly into pairs of Dark Matter scalars. It that case discovery of the Higgs boson at LHC and Tevatron is impossible. The most likely mass of the dark scalars is in the range 15 GeV \lsim \mvp \lsim 50 GeV with BR(h \to \vp\vp) up to 96%.Comment: 18 pages, 15 figure

Trends in quality of care and dying perceived by family caregivers of nursing home residents with dementia 2005-2019

BACKGROUND: Dementia palliative care is increasingly subject of research and practice improvement initiatives. AIM: To assess any changes over time in the evaluation of quality of care and quality of dying with dementia by family caregivers. DESIGN: Combined analysis of eight studies with bereaved family caregivers’ evaluations 2005–2019. SETTING/PARTICIPANTS: Family caregivers of nursing home residents with dementia in the Netherlands (n = 1189) completed the End-of-Life in Dementia Satisfaction With Care (EOLD-SWC; quality of care) and Comfort Assessment in Dying (EOLD-CAD, four subscales; quality of dying) instruments. Changes in scores over time were analysed using mixed models with random effects for season and facility and adjustment for demographics, prospective design and urbanised region. RESULTS: The mean total EOLD-SWC score was 33.40 (SD 5.08) and increased by 0.148 points per year (95% CI, 0.052–0.244; adjusted 0.170 points 95% CI, 0.055–0.258). The mean total EOLD-CAD score was 30.80 (SD 5.76) and, unadjusted, there was a trend of decreasing quality of dying over time of −0.175 points (95% CI, −0.291 to −0.058) per year increment. With adjustment, the trend was not significant (−0.070 EOLD-CAD total score points, 95% CI, −0.205 to 0.065) and only the EOLD-CAD subscale ‘Well being’ decreased. CONCLUSION: We identified divergent trends over 14 years of increased quality of care, while quality of dying did not increase and well-being in dying decreased. Further research is needed on what well-being in dying means to family. Quality improvement requires continued efforts to treat symptoms in dying with dementia

Increased Mast Cell Density and Airway Responses to Allergic and Non-Allergic Stimuli in a Sheep Model of Chronic Asthma

BACKGROUND: Increased mast cell (MC) density and changes in their distribution in airway tissues is thought to contribute significantly to the pathophysiology of asthma. However, the time sequence for these changes and how they impact small airway function in asthma is not fully understood. The aim of the current study was to characterise temporal changes in airway MC density and correlate these changes with functional airway responses in sheep chronically challenged with house dust mite (HDM) allergen. METHODOLOGY/PRINCIPAL FINDINGS: MC density was examined on lung tissue from four spatially separate lung segments of allergic sheep which received weekly challenges with HDM allergen for 0, 8, 16 or 24 weeks. Lung tissue was collected from each segment 7 days following the final challenge. The density of tryptase-positive and chymase-positive MCs (MC(T) and MC(TC) respectively) was assessed by morphometric analysis of airway sections immunohistochemically stained with antibodies against MC tryptase and chymase. MC(T) and MC(TC) density was increased in small bronchi following 24 weeks of HDM challenges compared with controls (P<0.05). The MC(TC)/MC(T) ratio was significantly increased in HDM challenged sheep compared to controls (P<0.05). MC(T) and MC(TC) density was inversely correlated with allergen-induced increases in peripheral airway resistance after 24 weeks of allergen exposure (P<0.05). MC(T) density was also negatively correlated with airway responsiveness after 24 challenges (P<0.01). CONCLUSIONS: MC(T) and MC(TC) density in the small airways correlates with better lung function in this sheep model of chronic asthma. Whether this finding indicates that under some conditions mast cells have protective activities in asthma, or that other explanations are to be considered requires further investigation

Breast cancer oestrogen independence mediated by BCAR1 or BCAR3 genes is transmitted through mechanisms distinct from the oestrogen receptor signalling pathway or the epidermal growth factor receptor signalling pathway

INTRODUCTION: Tamoxifen is effective for endocrine treatment of oestrogen receptor-positive breast cancers but ultimately fails due to the development of resistance. A functional screen in human breast cancer cells identified two BCAR genes causing oestrogen-independent proliferation. The BCAR1 and BCAR3 genes both encode components of intracellular signal transduction, but their direct effect on breast cancer cell proliferation is not known. The aim of this study was to investigate the growth control mediated by these BCAR genes by gene expression profiling. METHODS: We have measured the expression changes induced by overexpression of the BCAR1 or BCAR3 gene in ZR-75-1 cells and have made direct comparisons with the expression changes after cell stimulation with oestrogen or epidermal growth factor (EGF). A comparison with published gene expression data of cell models and breast tumours is made. RESULTS: Relatively few changes in gene expression were detected in the BCAR-transfected cells, in comparison with the extensive and distinct differences in gene expression induced by oestrogen or EGF. Both BCAR1 and BCAR3 regulate discrete sets of genes in these ZR-75-1-derived cells, indicating that the proliferation signalling proceeds along distinct pathways. Oestrogen-regulated genes in our cell model showed general concordance with reported data of cell models and gene expression association with oestrogen receptor status of breast tumours. CONCLUSIONS: The direct comparison of the expression profiles of BCAR transfectants and oestrogen or EGF-stimulated cells strongly suggests that anti-oestrogen-resistant cell proliferation is not caused by alternative activation of the oestrogen receptor or by the epidermal growth factor receptor signalling pathway

Interplant Communication of Tomato Plants through Underground Common Mycorrhizal Networks

Plants can defend themselves to pathogen and herbivore attack by responding to chemical signals that are emitted by attacked plants. It is well established that such signals can be transferred through the air. In theory, plants can also communicate with each other through underground common mycorrhizal networks (CMNs) that interconnect roots of multiple plants. However, until now research focused on plant-to-plant carbon nutrient movement and there is no evidence that defense signals can be exchanged through such mycorrhizal hyphal networks. Here, we show that CMNs mediate plant-plant communication between healthy plants and pathogen-infected tomato plants (Lycopersicon esculentum Mill.). After establishment of CMNs with the arbuscular mycorrhizal fungus Glomus mosseae between tomato plants, inoculation of ‘donor’ plants with the pathogen Alternaria solani led to increases in disease resistance and activities of the putative defensive enzymes, peroxidase, polyphenol oxidase, chitinase, β-1,3-glucanase, phenylalanine ammonia-lyase and lipoxygenase in healthy neighbouring ‘receiver’ plants. The uninfected ‘receiver’ plants also activated six defence-related genes when CMNs connected ‘donor’ plants challenged with A. solani. This finding indicates that CMNs may function as a plant-plant underground communication conduit whereby disease resistance and induced defence signals can be transferred between the healthy and pathogen-infected neighbouring plants, suggesting that plants can ‘eavesdrop’ on defence signals from the pathogen-challenged neighbours through CMNs to activate defences before being attacked themselves

Living with a Crucial Decision: A Qualitative Study of Parental Narratives Three Years after the Loss of Their Newborn in the NICU

BACKGROUND: The importance of involving parents in the end-of-life decision-making-process (EOL DMP) for their child in the neonatal intensive care unit (NICU) is recognised by ethical guidelines in numerous countries. However, studies exploring parents' opinions on the type of involvement report conflicting results. This study sought to explore parents' experience of the EOL DMP for their child in the NICU. METHODS: The study used a retrospective longitudinal design with a qualitative analysis of parental experience 3 years after the death of their child in four NICUs in France. 53 face-to-face interviews and 80 telephone interviews were conducted with 164 individuals. Semi-structured interviews were conducted to explore how parents perceived their role in the decision process, what they valued about physicians' attitudes in this situation and whether their long-term emotional well being varied according to their perceived role in the EOL DMP. FINDINGS: Qualitative analysis identified four types of perceived role in the DMP: shared, medical, informed parental decision, and no decision. Shared DM was the most appreciated by parents. Medical DM was experienced as positive only when it was associated with communication. Informed parental DM was associated with feelings of anxiousness and abandonment. The physicians' attitudes that were perceived as helpful in the long term were explicit sharing of responsibility, clear expression of staff preferences, and respectful care and language toward the child. INTERPRETATION: Parents find it valuable to express their opinion in the EOL DMP of their child. Nonetheless, they do need continuous emotional support and an explicit share of the responsibility for the decision. As involvement preferences and associated feelings can vary, parents should be able to decide what role they want to play. However, our study suggests that fully autonomous decisions should be misadvised in these types of tragic choices

Increased variability in ApcMin/+ intestinal tissue can be measured with microultrasound

Altered tissue structure is a feature of many disease states and is usually measured by microscopic methods, limiting analysis to small areas. Means to rapidly and quantitatively measure the structure and organisation of large tissue areas would represent a major advance not just for research but also in the clinic. Here, changes in tissue organisation that result from heterozygosity in Apc, a precancerous situation, are comprehensively measured using microultrasound and three-dimensional high-resolution microscopy. Despite its normal appearance in conventionally examined cross-sections, both approaches revealed a significant increase in the variability of tissue organisation in Apc heterozygous tissue. These changes preceded the formation of aberrant crypt foci or adenoma. Measuring these premalignant changes using microultrasound provides a potential means to detect microscopically abnormal regions in large tissue samples, independent of visual examination or biopsies. Not only does this provide a powerful tool for studying tissue structure in experimental settings, the ability to detect and monitor tissue changes by microultrasound could be developed into a powerful adjunct to screening endoscopy in the clinic