690 research outputs found
Beyond the Brain:Systematic Review of Extra-Cerebral Phenotypes associated with Monogenic Cerebral Small Vessel Disease
Does device matter? Impacts of food-specific inhibition training on food choice, liking and approach bias when delivered by smartphone or computer.
Food-specific inhibition training (FSIT) requires users to inhibit responses to energy-dense (ED) food stimuli within a reaction time game. FSIT reduces choice and liking of ED foods. Research with the public shows larger effects when FSIT is delivered by computer versus smartphone. This pre-registered study is the first to compare computer-FSIT versus smartphone-FSIT in a controlled setting. Three-hundred-and-thirty-one adults were randomised to computer-FSIT, smartphone-FSIT or non-food control training (computer-delivered). In session 1, participants completed baseline measures of impulsive food choice, food approach bias (approach/avoid implicit association test), and food liking ratings, before completing eight minutes of FSIT/control training. In session 2, participants repeated the same training task, followed by the same measures of food choice, approach bias and liking. We hypothesised that FSIT groups would show healthier food choices, lower ED food liking, and reduced ED food approach bias at post-training compared to control. We expected no statistically significant differences between the two FSIT groups. Post-exclusions, data for 259 participants was analysed. Contrary to predictions, there was no evidence of significant group differences on any of the outcome measures. Baseline measures suggest participants already showed high approach to healthy foods, which may explain these null results
Common clonal origin of chronic myelomonocytic leukemia and B-cell acute lymphoblastic leukemia in a patient with a germline CHEK2 variant
Hematological malignancies are broadly divided into myeloid and lymphoid neoplasms, reflecting the two major cellular lineages of the hematopoietic system. It is generally rare for hematological malignancies to spontaneously progress with a switch from myeloid to lymphoid lineage. We describe the exceptional case of a patient who sequentially developed myelodysplastic syndrome (MDS), chronic myelomonocytic leukemia (CMML), and B-cell acute lymphoblastic leukemia (B-ALL), as well as our investigation into the underlying pathogenesis. Using whole-exome sequencing (WES) performed on sorted CMML and B-ALL cell fractions, we identified both common and unique potential driver mutations, suggesting a branching clonal evolution giving rise to both diseases. Interestingly, we also identified a germline variant in the cancer susceptibility gene CHEK2 We validated that this variant (c.475T > C; p.Y159H), located in the forkhead-associated (FHA) domain, impairs its capacity to bind BRCA1 in cellulo. This unique case provides novel insight into the genetics of complex hematological diseases and highlights the possibility that such patients may carry inherited predispositions
Impact of valve morphology, hypertension and age on aortic wall properties in patients with coarctation: a two-centre cross-sectional study
Objective: We aimed to investigate the combined effects of arterial hypertension, bicuspid aortic valve disease (BAVD) and age on the distensibility of the ascending and descending aortas in patients with aortic coarctation.
Design: Cross-sectional study.
Setting: The study was conducted at two university medical centres, located in Berlin and London.
Participants: A total of 121 patients with aortic coarctation (ages 1-71 years) underwent cardiac MRI, echocardiography and blood pressure measurements.
Outcome measures: Cross-sectional diameters of the ascending and descending aortas were assessed to compute aortic area distensibility. Findings were compared with age-specific reference values. The study complied with the Strengthening the Reporting of Observational Studies in Epidemiology statement and reporting guidelines.
Results: Impaired distensibility (below fifth percentile) was seen in 37% of all patients with coarctation in the ascending aorta and in 43% in the descending aorta. BAVD (43%) and arterial hypertension (72%) were present across all ages. In patients >10 years distensibility impairment of the ascending aorta was predominantly associated with BAVD (OR 3.1, 95% CI 1.33 to 7.22, p=0.009). Distensibility impairment of the descending aorta was predominantly associated with arterial hypertension (OR 2.8, 95% CI 1.08 to 7.2, p=0.033) and was most pronounced in patients with uncontrolled hypertension despite antihypertensive treatment.
Conclusion: From early adolescence on, both arterial hypertension and BAVD have a major impact on aortic distensibility. Their specific effects differ in strength and localisation (descending vs ascending aorta). Moreover, adequate blood pressure control is associated with improved distensibility. These findings could contribute to the understanding of cardiovascular complications and the management of patients with aortic coarctation
Hepatitis E in England and Wales
In 2005, 329 cases of hepatitis E virus infection were confirmed in England and Wales; 33 were confirmed indigenous infections, and a further 67 were estimated to be indigenous infections. Hepatitis E should be considered in the investigation of patients with hepatitis even if they have no history of travel
A General Black String and its Microscopics
Using G2(2) dualities we construct the most general black string solution of
minimal five-dimensional ungauged supergravity. The black string has five
independent parameters, namely, the magnetic one-brane charge, smeared electric
zero-brane charge, boost along the string direction, energy above the BPS
bound, and rotation in the transverse space. In one extremal limit it reduces
to the three parameter supersymmetric string of five-dimensional minimal
supergravity; in another extremal limit it reduces to the three parameter
non-supersymmetric extremal string of five-dimensional minimal supergravity. It
also admits an extremal limit when it has maximal rotation in the
four-dimensional transverse space. The decoupling limit of our general black
string is a BTZ black hole times a two sphere. The macroscopic entropy of the
string is reproduced by the Maldacena-Strominger-Witten CFT in appropriate
ranges of the parameters. When the pressureless condition is imposed, our
string describes the infinite radius limit of the most general class of black
rings of minimal supergravity. We discuss implications our solution has for
extremal and non-extremal black rings of minimal supergravity.Comment: 35 pages; 3 figures; v2 section 4.1.1 rewritten + minor changes + ref
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Integrating NGS-derived mutational profiling in the diagnosis of multiple lung adenocarcinomas
MICROABSTRACT: Integration of Next Generation Sequencing (NGS) information for use in distinguishing between Multiple Primary Lung Cancer and intrapulmonary metastasis was evaluated. We used a probabilistic model, comprehensive histologic assessment and NGS to classify patients. Integrating NGS data confirmed initial diagnosis (n = 41), revised the diagnosis (n = 12), while resulted in non-informative data (n = 8). Accuracy of diagnosis can be significantly improved with integration of NGS data. BACKGROUND: Distinguishing between multiple primary lung cancers (MPLC) and intrapulmonary metastases (IPM) is challenging. The goal of this study was to evaluate how Next Generation Sequencing (NGS) information may be integrated in the diagnostic strategy. PATIENTS AND METHODS: Patients with multiple lung adenocarcinomas were classified using both the comprehensive histologic assessment and NGS. We computed the joint probability of each pair having independent mutations by chance (thus being classified as MPLC). These probabilities were computed using the marginal mutation rates of each mutation, and the known negative dependencies between driver genes and different gene loci. With these NGS-driven data, cases were re-classified as MPLC or IPM. RESULTS: We analyzed 61 patients with a total of 131 tumors. The most frequent mutation was KRAS (57.3%) which occured at a rate higher than expected (p < 0.001) in lung cancer. No mutation was detected in 25/131 tumors (19.1%). Discordant molecular findings between tumor sites were found in 46 patients (75.4%); 11 patients (18.0%) had concordant molecular findings, and 4 patients (6.6%) had concordant molecular findings at 2 of the 3 sites. After integration of the NGS data, the initial diagnosis was confirmed for 41 patients (67.2%), the diagnosis was revised for 12 patients (19.7%) or was considered as non-informative for 8 patients (13.1%). CONCLUSION: Integrating the information of NGS data may significantly improve accuracy of diagnosis and staging
A qualitative examination of apathy and physical activity in Huntington's and Parkinson's disease
Aim: In Huntington's disease (HD) and Parkinson's disease (PD), apathy is a frequently cited barrier to participation in physical activity. Current diagnostic criteria emphasize dissociable variants of apathy that differentially affect goal-directed behavior. How these dimensions present and affect physical activity in HD and PD is unknown. Methods: Using a qualitative approach, we examined the experience of apathy and its impact on physical activity in 20 people with early-manifest HD or idiopathic PD. Results: Two major themes emerged: the multidimensionality of apathy, including initiation or goal-identification difficulties, and the interplay of apathy and fatigue; and facilitators of physical activity, including routines, safe environments and education. Conclusion: Physical activity interventions tailored to apathy phenotypes may maximize participant engagement
Epilepsy due to PNPO mutations: genotype, environment and treatment affect presentation and outcome
Mutations in PNPO are a known cause of neonatal onset seizures that are resistant to pyridoxine but responsive to pyridoxal phosphate (PLP). Mills etal. show that PNPO mutations can also cause neonatal onset seizures that respond to pyridoxine but worsen with PLP, as well as PLP-responsive infantile spasm
VvNPR1.1 est lâorthologue dâAtNPR1 et sa surexpression provoque lâactivation constitutive des gĂšnes PR et la rĂ©sistance Ă Erysiphe necator chez Vitis vinifera
La comprĂ©hension des bases molĂ©culaires des mĂ©canismes de rĂ©sistance de la Vigne aux agresseurs biotiques constitue un prĂ©requis Ă la recherche de moyens de lutte alternatifs aux pesticides. Chez Arabidopsis, NPR1 (Non expressor of PR genes 1) joue un rĂŽle clĂ© dans la voie de signalisation rĂ©gulĂ©e par lâacide salicylique et responsable de la mise en place de la rĂ©sistance aux agents pathogĂšnes biotrophes et de la rĂ©sistance systĂ©mique acquise (SAR). Nous avons identifiĂ© deux gĂšnes homologues dâAtNPR1 chez la Vigne : VvNPR1.1 et VvNPR1.2. La caractĂ©risation fonctionnelle de ces deux gĂšnes montre que la surexpression de VvNPR1.1 dans le mutant npr1-2 dâArabidopsis permet, contrairement `a VvNPR1.2, de restaurer lâexpression de PR1 aprĂšs traitement par du SA ou inoculation bactĂ©rienne, ainsi que la rĂ©sistance Ă Pseudomonas syringae pv. maculicola, un
agent pathogĂšne virulent. VvNPR1.1 apparaĂźt donc comme lâorthologue fonctionnel dâAtNPR1, alors que VvNPR1.2 assure vraisemblablement une fonction diffĂ©rente. La surexpression stable de VvNPR1.1 en fusion avec la GFP a Ă©galement pu ĂȘtre rĂ©alisĂ©e chez V. vinifera cv. Chardonnay, grĂące Ă une technique de transformation par A. tumefaciens de cals embryogĂšnes de Vigne. Les rĂ©sultats obtenus sur les plantules transformĂ©es montrent une localisation constitutive de VvNPR1-GFP dans
le noyau, ainsi quâune expression Ă©levĂ©e des protĂ©ines PR en lâabsence dâinfection. De plus, les vignes surexprimant VvNPR1-GFP montrent clairement une augmentation de la rÂŽesistance vis-Ă -vis de lâinfection par Erysiphe necator, lâagent de lâoĂŻdium. La forte conservation de sĂ©quence des gĂšnes VvNPR1 chez les Vitaceae ainsi que lâensemble de ces rĂ©sultats souligne lâimportance de la voie rĂ©gulĂ©e par le SA et NPR1 pour la rĂ©sistance aux agents pathogĂšnes biotrophes chez la Vigne
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