Defining the mutational landscape of classic Hodgkin lymphoma is still a major research goal. New targeted next-generation sequencing (NGS) techniques may identify pathogenic mechanisms and new ...therapeutic opportunities related to this disease. We describe the mutational profile of a series of 57 cHL cases, enriched in Hodgkin and Reed-Sternberg (HRS) cells. Overall, the results confirm the presence of strong genomic heterogeneity. However, several variants were consistently detected in genes related to relevant signaling pathways, such as GM-CSF/IL-3, CBP/EP300, JAK/STAT, NF-kappaB, and numerous variants of genes affecting the B-cell receptor (BCR) pathway, such as
,
,
, among others. This unexpectedly high prevalence of mutations affecting the BCR pathway suggests some requirement for active BCR signaling for cHL cell viability. Additionally, incubation of a panel of cHL cellular models with selective BTK inhibitors
constrains cell proliferation and causes cell death. Our results indicate new pathogenic mechanisms and therapeutic opportunities in this disease.
We describe a community-wide outbreak of measles due to a D4 genotype virus that took place in the Region of Madrid, Spain, between February 2011 and August 2012, along with the control measures ...adopted. The following variables were collected: date of birth, sex, symptoms, complications, hospital admission, laboratory test results, link with another cases, home address, places of work or study, travel during the incubation period, ethnic group, and Mumps-Measles-Rubella (MMR) vaccination status. Incidences were calculated by 100,000 inhabitants. A total of 789 cases were identified. Of all cases, 36.0% belonged to Roma community, among which 68.7% were 16 months to 19 y old. Non-Roma cases were predominantly patients from 6 to 15 months (28.1%) and 20 to 39 y (52.3%). Most cases were unvaccinated. We found out that 3.0% of cases were healthcare workers. The first vaccination dose was brought forward to 12 months, active recruitment of unvaccinated children from 12 months to 4 y of age was performed and the vaccination of healthcare workers and of members of the Roma community was reinforced. High vaccination coverage must be reached with 2 doses of MMR vaccine, aimed at specific groups, such as young adults, Roma population and healthcare workers.
OBJECTIVETo investigate whether vitamin D, smoking, and anti-Epstein-Barr virus (EBV) antibody concentrations predict long-term cognitive status and neuroaxonal injury in multiple sclerosis (MS).
...METHODSThis study was conducted among 278 patients with clinically isolated syndrome who participated in the clinical trial BENEFIT (Betaferon/Betaseron in Newly Emerging Multiple Sclerosis for Initial Treatment) and completed the 11-year assessment (BENEFIT-11). We measured serum 25-hydroxyvitamin-D (25(OH)D), cotinine (smoking biomarker), and anti-Epstein-Barr virus nuclear antigen 1 (EBNA-1) immunoglobulin G (IgG) at baseline and at months 6, 12, and 24 and examined whether these biomarkers contributed to predict Paced Auditory Serial Addition Test (PASAT)-3 scores and serum neurofilament light chain (NfL) concentrations at 11 years. Linear and logistic regression models were adjusted for sex, baseline age, treatment allocation, steroid treatment, multifocal symptoms, T2 lesions, and body mass index.
RESULTSHigher vitamin D predicted better, whereas smoking predicted worse cognitive performance. A 50-nmol/L higher mean 25(OH)D in the first 2 years was related to 65% lower odds of poorer PASAT performance at year 11 (95% confidence intervals 95% CIs0.14–0.89). Standardized PASAT scores were lower in smokers and heavy smokers than nonsmokers (ptrend = 0.026). Baseline anti–EBNA-1 IgG levels did not predict cognitive performance (ptrend = 0.88). Associations with NfL concentrations at year 11 corroborated these findings—a 50-nmol/L higher mean 25(OH)D in the first 2 years was associated with 20% lower NfL (95% CI−36% to 0%), whereas smokers had 20% higher NfL levels than nonsmokers (95% CI2%–40%). Anti–EBNA-1 antibodies were not associated with NfL.
CONCLUSIONSLower vitamin D and smoking after clinical onset predicted worse long-term cognitive function and neuronal integrity in patients with MS.
Background
The BENEFIT study examined interferon beta (IFNB)-1b treatment in patients with clinically isolated syndrome (CIS) and ≥ 2 clinically silent brain MRI lesions.
Methods
Subgroups of 468 ...patients (IFNB-1b:
n
= 292; placebo:
n
= 176) were created for demographics, clinical, laboratory, and MRI findings at onset. The 'natural' risk of clinically definite MS (CDMS) over 2 years was estimated by Kaplan Meier statistics in placebo-treated patients; the IFNB-1b treatment effect was analysed by Cox proportional hazards regression.
Results
The risk of CDMS was increased in placebotreated patients (overall 45 %) if they were younger (< 30 years: 60%), were cerebrospinal fluid (CSF)-positive (49 %), or had received steroid treatment (48 %). MRI parameters implied a higher risk in placebo-treated patients with ≥ 9 T2-lesions (48%) or ≥ 1 gadolinium (Gd)-enhancing lesions (52 %). The CDMS risk was highest (75 %) in placebo-treated patients with monofocal disease onset displaying MRI disease activity (≥ 1 Gd-lesion) and dissemination (≥ 9 T2-lesions). Treatment effects were significant across almost all subgroups including patients with less disease dissemination/activity at onset (monofocal: 55%; < 9 T2-lesions: 60%; no Gd-lesions: 57%) and patients without steroid treatment for the CIS (62 %). Monofocal patients had greater treatment effects if they had ≥ 9 T2-lesions (61 %), Gd-lesions (58 %), or both (65 %).
Conclusions
This study confirms the impact of age of onset, CSF and MRI findings on risk of conversion from CIS to CDMS. IFNB-1b treatment effect was robust across the study population including patients without MRI disease activity and less clinical or MRI disease dissemination at onset and patients not receiving steroids for the CIS.
The forthcoming data expected from space missions such as CoRoT require the capacity of the available tools to provide accurate models whose numerical precision is well above the expected ...observational errors. In order to secure that these tools meet the specifications, a team has been established to test and, when necessary, to improve the codes available in the community. The CoRoT evolution and seismic tool activity (ESTA) has been set up with this mission. Several groups have been involved. The present paper describes the motivation and the organisation of this activity, providing the context and the basis for the presentation of the results that have been achieved so far. This is not a finished task as future even better data will continue to demand more precise and complete tools for asteroseismology.
The beneficial effects of seaweed extracts have been related to plant growth regulators present in seaweeds. However, algae extracts comprise other organic compounds such as phenols, mannitol, ...alginates, laminarins, and fucoidans that may have a relevant role regarding abiotic stress tolerance due to nutrient deficiency. Therefore, we evaluated the individual effect of these organic compounds in a range of concentrations on the mitigation of Fe deficiency in tomato plants. Germination and plant growth promotion, root morphology, chlorophyll content, and antioxidant activity were determined. Results showed that the lowest concentration of phenolics, laminarin, and fucose compounds contributed to increasing the tolerance to Fe deficiency in tomato plants.
To study vision related quality of life (VRQoL) before and after a massive cataract campaign in West Africa and the relationship with visual indicators.
All the patients who received cataract surgery ...in Burkina Faso during a blindness prevention campaign were examined. VRQoL was assessed using a modified version of the WHO/PBD VF20. The questionnaire was changed to reflect the socioeconomic and local culture. Patients were interviewed by local interviewers before and three months after surgery. A quality of life related to vision index (QoL-RVI) was calculated.
A total of 305 patients underwent cataract extraction in at least one eye, of these, a total of 196 (64%) completed the study. Mean age was 61.97 ± 14.39 years. The majority of eyes had poor visual acuity (VA<20/200, log MAR: 1.0) preoperatively (88.70%) with a mean VA of logMAR 2.17 ± 0.70 (20/2000) which improved to 0.86 ± 0.64 LogMAR (20/150) 3 months after cataract surgery. QoL-RVI improved postoperatively in 90.2% of patients, did not change in 3.1% and was worse in 6.7%. Statistically significant differences were detected (Wilcoxon test p <0.05) for all items tested before and after surgeries. Correlations for the patients after operations showed that there was a statistically significant relation between a global estimated QoL-RVI and the VA previous to the surgery (-0.196 p=0.014), regarding the same index and the VA after the procedures (-0,35 p=0,00018).
Cataract surgery increases the quality of life of patients living in a developing country such as Burkina Faso and the improvement correlates with the recovery of the visual acuity.
We present recent work undertaken by the Evolution and Seismic Tools Activity
(ESTA) team of the CoRoT Seismology Working Group. The new ESTA-Task 3 aims at
testing, comparing and optimising stellar ...evolution codes which include
microscopic diffusion of the chemical elements resulting from pressure,
temperature and concentration gradients. The results already obtained are
globally satisfactory, but some differences between the different numerical
tools appear that require further investigations.
In order to make astroseismology a powerful tool to explore stellar interiors, different numerical codes should give the same oscillation frequencies for the same input physics. This work is devoted ...to test, compare and, if needed, optimize the seismic codes used to calculate the eigenfrequencies to be finally compared with observations. The oscillation codes of nine research groups in the field have been used in this study. The same physics has been imposed for all the codes in order to isolate the non-physical dependence of any possible difference. Two equilibrium models with different grids, 2172 and 4042 mesh points, have been used, and the latter model includes an explicit modelling of semiconvection just outside the convective core. Comparing the results for these two models illustrates the effect of the number of mesh points and their distribution in particularly critical parts of the model, such as the steep composition gradient outside the convective core. A comprehensive study of the frequency differences found for the different codes is given as well. These differences are mainly due to the use of different numerical integration schemes. The use of a second-order integration scheme plus a Richardson extrapolation provides similar results to a fourth-order integration scheme. The proper numerical description of the Brunt-Vaisala frequency in the equilibrium model is also critical for some modes. An unexpected result of this study is the high sensitivity of the frequency differences to the inconsistent use of values of the gravitational constant (G) in the oscillation codes, within the range of the experimentally determined ones, which differ from the value used to compute the equilibrium model.
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