Analysis of the question–answer service of the Emma Children’s Hospital information centre

The information centre of the Emma Children’s Hospital AMC (EKZ AMC) is a specialised information centre where paediatric patients and persons involved with the patient can ask questions about all aspects of disease and its social implications. The aim of the study was to evaluate the question–answer service of this information centre in order to determine the role of a specialised information centre in an academic children’s hospital, identify the appropriate resources for the service and potential positive effects. For this purpose, a case management system was developed in MS ACCESS. The characteristics of the requester and the question, the time it took to answer questions, the information sources used and the extent to which we were able to answer the questions were registered. The costs of the service were determined. We analysed all questions that were asked in the year 2007. Fourteen hundred thirty-four questions were asked. Most questions were asked by parents (23.3%), healthcare workers (other than nurses; 16.5%) and nurses (15.3%). The scope of the most frequently asked questions include disease (20.2%) and treatment (13.0%). Information on paper was the main information source used. Most questions could be solved within 15 min. Twelve percent to 28% of total working hours are used for the question–answer service. Total costs including staff salary are rather large. In conclusions, taking over the task of providing additional medical information and by providing readily available, good quality information that healthcare professionals can use to inform their patients will lead to less time investment of these more expensive staff members. A specialised information service can anticipate on the information need of parents and persons involved with the paediatric patient. It improves information by providing with relatively simple resources that has the potential to improve patient and parent satisfaction, coping and medical results. A specialised information centre is therefore a valuable and affordable asset to an academic children’s hospital

Cytokinesis in bloodstream stage Trypanosoma brucei requires a family of katanins and spastin

Microtubule severing enzymes regulate microtubule dynamics in a wide range of organisms and are implicated in important cell cycle processes such as mitotic spindle assembly and disassembly, chromosome movement and cytokinesis. Here we explore the function of several microtubule severing enzyme homologues, the katanins (KAT80, KAT60a, KAT60b and KAT60c), spastin (SPA) and fidgetin (FID) in the bloodstream stage of the African trypanosome parasite, Trypanosoma brucei. The trypanosome cytoskeleton is microtubule based and remains assembled throughout the cell cycle, necessitating its remodelling during cytokinesis. Using RNA interference to deplete individual proteins, we show that the trypanosome katanin and spastin homologues are non-redundant and essential for bloodstream form proliferation. Further, cell cycle analysis revealed that these proteins play essential but discrete roles in cytokinesis. The KAT60 proteins each appear to be important during the early stages of cytokinesis, while downregulation of KAT80 specifically inhibited furrow ingression and SPA depletion prevented completion of abscission. In contrast, RNA interference of FID did not result in any discernible effects. We propose that the stable microtubule cytoskeleton of T. brucei necessitates the coordinated action of a family of katanins and spastin to bring about the cytoskeletal remodelling necessary to complete cell divisio

Mycobacterial infections in a large Virginia hospital, 2001-2009

<p>Abstract</p> <p>Background</p> <p>In areas where both tuberculosis (TB) and nontuberculous mycobacteria (NTM) are prevalent, descriptive studies of the clinical features of individual mycobacteria are needed to inform clinical triage.</p> <p>Methods</p> <p>We queried the University of Virginia Clinical Data Repository for all mycobacterial infections from 2001-2009.</p> <p>Results</p> <p>Of 494 mycobacterial infections in 467 patients there were 22 species. Patients with pulmonary Tb were more likely to be reported as immigrants (p < 0.001) and less likely to have a predisposing risk factor for NTM (pre-existing lung disease or host predisposition; p = 0.002). Review of chest CT scans revealed that TB infection was more likely to exhibit cavities and pleural effusion than NTM infection (p < 0.05). Among NTM infections <it>M. kansasii</it>, <it>M. xenopi</it>, and <it>M. fortuitum </it>were more likely than MAC to have cavities. There were at least 83 patients that met criteria for NTM lung disease and these were caused by 9 species. <it>M. abscessus </it>infection was associated with cystic fibrosis and <it>M. xenopi </it>infection was associated with male gender.</p> <p>Conclusions</p> <p>In our center mycobacterial infections were common and of diverse species. Immigrant status, cavities, and effusion were associated with TB vs. NTM.</p

A rocky planet transiting a nearby low-mass star

M-dwarf stars -- hydrogen-burning stars that are smaller than 60 per cent of the size of the Sun -- are the most common class of star in our Galaxy and outnumber Sun-like stars by a ratio of 12:1. Recent results have shown that M dwarfs host Earth-sized planets in great numbers: the average number of M-dwarf planets that are between 0.5 to 1.5 times the size of Earth is at least 1.4 per star. The nearest such planets known to transit their star are 39 parsecs away, too distant for detailed follow-up observations to measure the planetary masses or to study their atmospheres. Here we report observations of GJ 1132b, a planet with a size of 1.2 Earth radii that is transiting a small star 12 parsecs away. Our Doppler mass measurement of GJ 1132b yields a density consistent with an Earth-like bulk composition, similar to the compositions of the six known exoplanets with masses less than six times that of the Earth and precisely measured densities. Receiving 19 times more stellar radiation than the Earth, the planet is too hot to be habitable but is cool enough to support a substantial atmosphere, one that has probably been considerably depleted of hydrogen. Because the host star is nearby and only 21 per cent the radius of the Sun, existing and upcoming telescopes will be able to observe the composition and dynamics of the planetary atmosphere.Comment: Published in Nature on 12 November 2015, available at http://dx.doi.org/10.1038/nature15762. This is the authors' version of the manuscrip

“Medically unexplained” symptoms and symptom disorders in primary care: prognosis-based recognition and classification

Background: Many patients consult their GP because they experience bodily symptoms. In a substantial proportion of cases, the clinical picture does not meet the existing diagnostic criteria for diseases or disorders. This may be because symptoms are recent and evolving or because symptoms are persistent but, either by their character or the negative results of clinical investigation cannot be attributed to disease: so-called “medically unexplained symptoms” (MUS). MUS are inconsistently recognised, diagnosed and managed in primary care. The specialist classification systems for MUS pose several problems in a primary care setting. The systems generally require great certainty about presence or absence of physical disease, they tend to be mind-body dualistic, and they view symptoms from a narrow specialty determined perspective. We need a new classification of MUS in primary care; a classification that better supports clinical decision-making, creates clearer communication and provides scientific underpinning of research to ensure effective interventions. Discussion: We propose a classification of symptoms that places greater emphasis on prognostic factors. Prognosis-based classification aims to categorise the patient’s risk of ongoing symptoms, complications, increased healthcare use or disability because of the symptoms. Current evidence suggests several factors which may be used: symptom characteristics such as: number, multi-system pattern, frequency, severity. Other factors are: concurrent mental disorders, psychological features and demographic data. We discuss how these characteristics may be used to classify symptoms into three groups: self-limiting symptoms, recurrent and persistent symptoms, and symptom disorders. The middle group is especially relevant in primary care; as these patients generally have reduced quality of life but often go unrecognised and are at risk of iatrogenic harm. The presented characteristics do not contain immediately obvious cut-points, and the assessment of prognosis depends on a combination of several factors. Conclusion: Three criteria (multiple symptoms, multiple systems, multiple times) may support the classification into good, intermediate and poor prognosis when dealing with symptoms in primary care. The proposed new classification specifically targets the patient population in primary care and may provide a rational framework for decision-making in clinical practice and for epidemiologic and clinical research of symptoms

Is the Rehbein procedure obsolete in the treatment of Hirschsprung’s disease?

Contains fulltext : 87916.pdf (publisher's version ) (Closed access)PURPOSE: After 25 years of practice and positive results of the Rehbein-procedure (RB) for children with Hirschsprung Disease (HD), we changed to the less invasive transanal endorectal pull through (TERPT). The aim of this study was to compare short- and mid-term complications of these two procedures in our patients with HD. METHODS: Retrospective data of 50 HD patients were analyzed. Of these patients, 25 underwent RB (2000-2006) and in 25 the TERPT was performed (2005-2009). Medical records were reviewed to score complications and outcomes. Differences were analyzed using Chi-Square and Mann-Whitney U tests. RESULTS: All RB patients (100%) were given a colostomy compared with four patients (16%) in the TERPT group (p < 0.001). The average age at surgery in the RB group was 191 days whereas this was 72 days in the TERPT group (p < 0.01). The mean length of time of surgery in the RB group (158 min) was not significantly different from that in the TERPT group (183 min). Ganglion cells were located in all specimens at the proximal end of the specimens. The median time to first feeding significantly decreased from 2 days (range 1-11) in the RB group to 1 day (range 1-3) in the TERPT group (p < 0.01). The median length of hospital stay decreased in the TERPT group (8 days) compared with the RB group (10 days) (p < 0.001). There was a significant reduction in postoperative obstructive symptoms during the first 6 months in the TERPT group (48%) compared with the RB group (84%) (p = 0.016). Postoperative enterocolitis decreased from 40% in the RB group to 24% in the TERPT group although this was not statistically significant. CONCLUSIONS: The introduction of TERPT reduced the need for colostomies; it shortened days to first feeding after surgery and reduced hospital stay. It also improved short-term outcome with less obstructive symptoms. We recommend TERPT surgery as a first choice in children with HD. we consider the RB now to be obsolete.1 november 201

Impact of weight loss on cancer-related proteins in serum: results from a cluster randomised controlled trial of individuals with type 2 diabetes

\ua9 2024 The Author(s)Background: Type 2 diabetes is associated with higher risk of several cancer types. However, the biological intermediates driving this relationship are not fully understood. As novel interventions for treating and managing type 2 diabetes become increasingly available, whether they also disrupt the pathways leading to increased cancer risk is currently unknown. We investigated the effect of a type 2 diabetes intervention, in the form of intentional weight loss, on circulating proteins associated with cancer risk to gain insight into potential mechanisms linking type 2 diabetes and adiposity with cancer development. Methods: Fasting serum samples from participants with diabetes enrolled in the Diabetes Remission Clinical Trial (DiRECT) receiving the Counterweight-Plus weight-loss programme (intervention, N = 117, mean weight-loss 10 kg, 46% diabetes remission) or best-practice care by guidelines (control, N = 143, mean weight-loss 1 kg, 4% diabetes remission) were subject to proteomic analysis using the Olink Oncology-II platform (48% of participants were female; 52% male). To identify proteins which may be altered by the weight-loss intervention, the difference in protein levels between groups at baseline and 1 year was examined using linear regression. Mendelian randomization (MR) was performed to extend these results to evaluate cancer risk and elucidate possible biological mechanisms linking type 2 diabetes and cancer development. MR analyses were conducted using independent datasets, including large cancer meta-analyses, UK Biobank, and FinnGen, to estimate potential causal relationships between proteins modified during intentional weight loss and the risk of colorectal, breast, endometrial, gallbladder, liver, and pancreatic cancers. Findings: Nine proteins were modified by the intervention: glycoprotein Nmb; furin; Wnt inhibitory factor 1; toll-like receptor 3; pancreatic prohormone; erb-b2 receptor tyrosine kinase 2; hepatocyte growth factor; endothelial cell specific molecule 1 and Ret proto-oncogene (Holm corrected P-value &lt;0.05). Mendelian randomization analyses indicated a causal relationship between predicted circulating furin and glycoprotein Nmb on breast cancer risk (odds ratio (OR) = 0.81, 95% confidence interval (CI) = 0.67–0.99, P-value = 0.03; and OR = 0.88, 95% CI = 0.78–0.99, P-value = 0.04 respectively), though these results were not supported in sensitivity analyses examining violations of MR assumptions. Interpretation: Intentional weight loss among individuals with recently diagnosed diabetes may modify levels of cancer-related proteins in serum. Further evaluation of the proteins identified in this analysis could reveal molecular pathways that mediate the effect of adiposity and type 2 diabetes on cancer risk. Funding: The main sources of funding for this work were Diabetes UK, Cancer Research UK, World Cancer Research Fund, and Wellcome

Parent-of-origin-specific allelic associations among 106 genomic loci for age at menarche.

Age at menarche is a marker of timing of puberty in females. It varies widely between individuals, is a heritable trait and is associated with risks for obesity, type 2 diabetes, cardiovascular disease, breast cancer and all-cause mortality. Studies of rare human disorders of puberty and animal models point to a complex hypothalamic-pituitary-hormonal regulation, but the mechanisms that determine pubertal timing and underlie its links to disease risk remain unclear. Here, using genome-wide and custom-genotyping arrays in up to 182,416 women of European descent from 57 studies, we found robust evidence (P < 5 × 10(-8)) for 123 signals at 106 genomic loci associated with age at menarche. Many loci were associated with other pubertal traits in both sexes, and there was substantial overlap with genes implicated in body mass index and various diseases, including rare disorders of puberty. Menarche signals were enriched in imprinted regions, with three loci (DLK1-WDR25, MKRN3-MAGEL2 and KCNK9) demonstrating parent-of-origin-specific associations concordant with known parental expression patterns. Pathway analyses implicated nuclear hormone receptors, particularly retinoic acid and γ-aminobutyric acid-B2 receptor signalling, among novel mechanisms that regulate pubertal timing in humans. Our findings suggest a genetic architecture involving at least hundreds of common variants in the coordinated timing of the pubertal transition