Cognitive decline in adult-onset temporal lobe epilepsy: Insights from aetiology.

PURPOSE: To identify patients with adult-onset temporal lobe epilepsy (TLE) at risk of developing cognitive decline. Detecting which patients, aetiologies, or factors are most closely related with memory decline would allow us to identify patients that would eventually benefit from more specific treatment. METHODS: Single centre, retrospective analysis of a prospectively followed-up cohort study, including all patients with the diagnosis of adult-onset TLE during 2013, with a minimum follow-up of five years. Memory and cognitive decline were analysed at 5 years and at last follow-up. RESULTS: Of 89 initially selected patients, 71 were included. After 5 years, 11/71 (15.5%) patients suffered cognitive decline, of which 1/71 (4%) developed dementia. At last follow-up (range 65-596 m) a total of 34/71 (47.8%) patients were diagnosed with cognitive decline, specifically either memory decline or dementia. Cognitive decline at 5 years was related to: 1. Age at onset: 62.65 years (SD 9.04) in the group with cognitive decline vs 50.33 y. (SD 13.02 in the group without cognitive decline; p=0.004); 2. Onset as status epilepticus (3/6 in patients with memory decline vs 8/65 in patients without cognitive decline; p=0.04); 3. Immune aetiology: 42% compared with unknown (10%) and structural (10%) aetiologies; p=0.036; 4. Hippocampal sclerosis on MRI: 5/11 patients with cognitive decline vs 9/51 patients without cognitive decline; p=0.035. Cognitive decline was not related to seizure frequency, sex, or age (p=0.78; p=0.40; p=0.95, respectively). CONCLUSIONS: Older age at epilepsy onset, onset as status epilepticus, immune aetiology, and hippocampal sclerosis are risk factors for developing cognitive decline in patients with adult-onset temporal lobe epilepsy.

Measurement of the 2νßß Decay Rate and Spectral Shape of

Neutrinoless double beta decay (0νßß) is a yet unobserved nuclear process that would demonstrate Lepton number violation, a clear evidence of beyond standard model physics. The process two neutrino double beta decay (2νßß) is allowed by the standard model and has been measured in numerous experiments. In this Letter, we report a measurement of 2νßß decay half-life of ^{100}Mo to the ground state of ^{100}Ru of [7.07±0.02(stat)±0.11(syst)]×10^{18} yr by the CUPID-Mo experiment. With a relative precision of ±1.6% this is the most precise measurement to date of a 2νßß decay rate in ^{100}Mo. In addition, we constrain higher-order corrections to the spectral shape, which provides complementary nuclear structure information. We report a novel measurement of the shape factor ξ_{3,1}=0.45±0.03(stat)±0.05(syst) based on a constraint on the ratio of higher-order terms from theory, which can be reliably calculated. This is compared to theoretical predictions for different nuclear models. We also extract the first value for the effective axial vector coupling constant obtained from a spectral shape study of 2νßß decay.

Improvements in the radiochemical method for separating 226Ra in solid samples through coprecipitation with BaSO4.

The aim of this work was to improve the commonly used method for 226Ra determination in water and to establish its application in solid samples. This method is based on the coprecipitation of Ra with BaSO4 and gross alpha counting of the precipitate. An exhaustive study of the coprecipitation behaviour of the most abundant cations present in solid samples was performed to avoid incorrect radiochemical yields. As a result, it was considered necessary to introduce two new purification steps into the conventional method. Likewise, two nuclides, 241Am and 226Ra, were compared to obtain the mass efficiency curve given their different behaviour in the coprecipitation process. While Ra behaves similarly to Ba, Am coprecipitates, forming mixed crystals that may behave differently in the self-absorption process. The influence of the cations on the chemical yield with no precipitate purification was: Sr2+≫Fe3+>Mg2+≈Ca2+>K+≈Na+. The method was successfully applied to soil, sediment, and plant ash samples.

New Limit for Neutrinoless Double-Beta Decay of

The CUPID-Mo experiment at the Laboratoire Souterrain de Modane (France) is a demonstrator for CUPID, the next-generation ton-scale bolometric 0νßß experiment. It consists of a 4.2 kg array of 20 enriched Li_{2}^{100}MoO_{4} scintillating bolometers to search for the lepton-number-violating process of 0νßß decay in ^{100}Mo. With more than one year of operation (^{100}Mo exposure of 1.17 kg×yr for physics data), no event in the region of interest and, hence, no evidence for 0νßß is observed. We report a new limit on the half-life of 0νßß decay in ^{100}Mo of T_{1/2}>1.5×10^{24} yr at 90% C.I. The limit corresponds to an effective Majorana neutrino mass ⟨m_{ßß}⟩<(0.31-0.54) eV, dependent on the nuclear matrix element in the light Majorana neutrino exchange interpretation.

First Germanium-Based Constraints on Sub-MeV Dark Matter with the EDELWEISS Experiment.

We present the first Ge-based constraints on sub-MeV/c^{2} dark matter (DM) particles interacting with electrons using a 33.4 g Ge cryogenic detector with a 0.53 electron-hole pair (rms) resolution, operated underground at the Laboratoire Souterrain de Modane. Competitive constraints are set on the DM-electron scattering cross section, as well as on the kinetic mixing parameter of dark photons down to 1 eV/c^{2}. In particular, the most stringent limits are set for dark photon DM in the 6 to 9 eV/c^{2} range. These results demonstrate the high relevance of Ge cryogenic detectors for the search of DM-induced eV-scale electron signals.

Cu-BTC Functional Microdevices as Smart Tools for Capture and Preconcentration of Nerve Agents.

Cu-based metal-organic framework (MOF) microdevices are applied in sampling and preconcentration of nerve agents (NAs) diluted in gaseous streams. An in situ electrochemical-assisted synthesis of a Cu-benzene-1,3,5-tricarboxylate (BTC) thick film is carried out to functionalize a Cu-modified glass substrate. This simple, rapid, reproducible, and easy-to-integrate MOF synthesis approach enables the microfabrication of functional micro-preconcentrators with a large Brunauer-Emmett-Teller (BET) surface area (above 2000 cm2) and an active pore volume (above 90 nL) for the efficient adsorption of nerve agent molecules along the microfluidic channel 2.5 cm in length. The equilibrium adsorption capacity of the bulk material has been characterized through thermogravimetric analysis after exposure to controlled atmospheres of a sarin gas surrogate, dimethyl methylphosphonate (DMMP), in both dry and humid conditions (30% RH at 293 K). Breakthrough tests at the ppm level (162 mg/m3) reveal equilibrium adsorption capacities up to 691 mg/g. The preconcentration performance of such µ-devices when dealing with highly diluted surrogate atmosphere, i.e., 520 ppbV (2.6 mg/m3) at 298 K, leads to preconcentration coefficients up to 171 for sample volume up to 600 STP cm3. We demonstrate the potentialities of Cu-BTC micro-preconcentrators as smart first responder tools for "on-field" detection of nerve agents in the gas phase at relevant conditions.

Use of serology in a systematic screening programme for strongyloidiasis in an immigrant population.

OBJECTIVES: The aim of this cross-sectional study was to describe the results of a systematic serological screening programme for strongyloidiasis. METHODS: A prospective serological screening programme for strongyloidiasis was performed between 2009 and 2014 for all immigrant patients attending the Tropical Medicine Unit. Three formalin-ether concentrated stool samples and an ELISA for anti-Strongyloides stercoralis antibodies were used as screening tools. RESULTS: Of 659 patients screened, 79 (12%) were positive for S. stercoralis regardless of the diagnostic method used. The prevalence of infection was 42.9% in East African patients, 16.3% in Central African patients, 10.9% in those from South America, and 10% in the case of West Africa. Univariate analysis showed that infection by S. stercoralis was significantly more frequent in patients from Central Africa (p=0.026; OR 1.72, 95% CI 1.03-2.85) and East Africa (p<0.001; OR 5.88, 95% CI 1.75-19.32). Taking West Africa as the reference (as the area of lowest prevalence among the positive prevalence areas), the statistical analysis showed that the risk of infection was higher in East Africa (p=0.001; OR 6.750, 95% CI 2.127-21.423) and Central Africa (p=0.065; OR 1.747, 95% CI 0.965-3.163). CONCLUSIONS: Due to the potential complications of strongyloidiasis infection, we recommend that immigrant patients from developing countries be routinely screened for S. stercoralis, especially those from East Africa. A serological test is a highly appropriate screening tool.

Import of community-associated, methicillin-resistant Staphylococcus aureus to Europe through skin and soft-tissue infection in intercontinental travellers, 2011-2016.

OBJECTIVES: Recently, following import by travel and migration, epidemic community-associated methicillin-resistant Staphylococcus aureus (CA-MRSA) has caused nosocomial outbreaks in Europe, sometimes with a fatal outcome. We describe clinico-epidemiological characteristics of CA-MRSA detected by the European Network for the Surveillance of imported S. aureus (www.staphtrav.eu) from May 2011 to November 2016. METHODS: Sentinel surveillance at 13 travel clinics enrolling patients with travel-associated skin and soft-tissue infection (SSTI) and analysing lesion and nose swabs at one central laboratory. RESULTS: A total of 564 independent case-patients with SSTI were enrolled and had 374 (67%) S. aureus-positive lesions, of which 14% (51/374) were MRSA. The majority of CA-MRSA isolates from SSTI were Panton-Valentine leucocidin (PVL) -positive (43/51, 84%). The risk of methicillin-resistance in imported S. aureus varied by travel region (p <0.001) and was highest in Latin America (16/57, 28%, 95% CI 17.0-41.5) and lowest in Sub-Saharan Africa (4/121, 3%, 95% CI 0.9-8.3). Major epidemic clones (USA300 / USA300 Latin-American Variant, Bengal Bay, South Pacific) accounted for more than one-third (19/51, 37%) of CA-MRSA imports. CA-MRSA SSTI in returnees was complicated (31/51 multiple lesions, 61%; 22/50 recurrences, 44%), led to health-care contact (22/51 surgical drainage, 43%; 7/50 hospitalization, 14%), was transmissible (13/47 reported similar SSTI in non-travelling contacts, 28%), and associated with S. aureus nasal colonization (28 of 51 CA-MRSA cases, 55%; 24 of 28 colonized with identical spa-type in nose and lesion, 85%). CONCLUSIONS: Travel-associated CA-MRSA SSTI is a transmissible condition that leads to medical consultations and colonization of the infected host.

Social Interactions and Social Activities After Burn Injury: A Life Impact Burn Recovery Evaluation (LIBRE) Study.

Social interactions and activities are key components of social recovery following burn injuries. The objective of this study is to determine the predictors of these areas of social recovery. This study provides a secondary analysis of a cross-sectional survey of adult burn survivors. The Life Impact Burn Recovery Evaluation-192 was administered to 601 burn survivors for the field-testing of the Life Impact Burn Recovery Evaluation Profile. Survivors aged 18 years and older with injuries ≥5% total BSA or burns to critical areas (hands, feet, face, or genitals) were eligible to participate. Multivariate linear regression analyses were used to determine predictors of the Social Activities and Social Interactions scale scores. A total of 599 people completed the Social Interactions and Social Activities scales. Of these, 77% identified as White Non-Hispanic, 55% were female, 55% were unmarried, and 80% had burns to critical areas. Participants had a mean age of 45 years, a mean time since burn injury of 15 years, and a mean burn size of 41% total BSA. Younger age (P < .01) and being married/living with a significant other (P ≤ .01) were associated with higher Social Activities and Social Interactions scale scores. Individual item responses reveal that survivors had lower scores on items related to participating in outdoor activities (30.4%) or feeling uncomfortable with their appearance (32.4% report dressing to avoid stares). Social interactions and activities are long-term challenges for burn survivors. It is important for clinicians to identify patients who may struggle with social recovery in order to focus on future community-based interventions.

Blackwater fever in a non-immune patient with Plasmodium falciparum malaria after intravenous artesunate.

Blackwater fever was typically reported after quinine administration, although it is poor recognized in patients receiving artesunate. This case describes a blackwater fever in a non-immune patient after artesunate for severe malaria. It highlights the importance of monitoring haemolytic parameters in severe malaria to avoid renal impairment or severe anaemia.

What to expect and when: benznidazole toxicity in chronic Chagas' disease treatment.

Background: Benznidazole is one of the two most effective antiparasitic drugs for Chagas' disease treatment. However, knowledge about its toxicity profile is mostly based on post-marketing observational studies. Objectives: Our study combines data from two prospective clinical trials designed to assess the safety of the drug newly produced by ELEA Laboratories (Abarax®). Methods: Eligible participants were selected using a consecutive sampling strategy in the CINEBENZ and BIOMARCHA studies between 2013 and 2016 (EUDRACT 2011-002900-34 and 2012-002645-38, respectively, and clinicaltrials.gov NCT01755403 and NCT01755377, respectively). Enrolled subjects received treatment with 5 mg/kg/day benznidazole orally in two divided doses for 8 weeks and were followed up fortnightly. Results: We observed 305 adverse reactions in 85 of 99 participants (85.9%). Each patient had a median of three adverse reactions, 89.5% were mild and the median duration was 12 days. Most adverse reactions appeared in the first month of treatment except arthritis and peripheral neuropathy. Twenty-six patients did not complete treatment: 2 were withdrawn, 1 for ectopic pregnancy and 1 for epilepsy relapse due to cysticercosis; 2 were lost to follow-up; and 22 were owing to adverse reactions, two of them severe. We observed some unexpected adverse reactions that have not been described previously, such as psychiatric symptoms, erectile dysfunction, menstrual cycle alterations and lung infiltration. Conclusions: There is a very high frequency of adverse reactions to benznidazole. Most adverse reactions are mild, but the treatment burden is significant and unexpected reactions are not rare. Severe reactions are uncommon, but they can be life-threatening. Further studies are necessary to optimize treatment.

Unidad del paciente crónico - Programa PRINCEP / Chronic patient unit - PRINCEP program

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Harvesting the photoexcited holes on a photocatalytic proton reduction metal-organic framework.

The highly porous titanium based metal-organic framework NH2-MIL-125(Ti) has recently attracted significant attention in the field of photocatalysis as a promising material for H+ reduction. This work reveals charge transfer upon visible light illumination from this MOF to two different charge acceptors, as an alternative to sacrificial electron donors. Charge transfer is demonstrated through a combined spectroscopic study between this MOF and: (1) 2-(1H-pyrazol-3-yl)phenol, a molecule that functionally mimics the tyrosine-histidine pair, responsible for shuttling the holes to the oxygen evolving centre in natural photosynthesis, and (2) TEMPO, a well known and stable radical. Charge transfer of the holes from the MOF to these occluded molecules takes place on the picosecond time scale. This work suggests that, by coupling a stable and recyclable charge acceptor to the photogenerated holes, the charges can be utilised for oxidation reactions and, thus, link the reduction to the oxidation reactions in water splitting.

Metal-organic and covalent organic frameworks as single-site catalysts.

Heterogeneous single-site catalysts consist of isolated, well-defined, active sites that are spatially separated in a given solid and, ideally, structurally identical. In this review, the potential of metal-organic frameworks (MOFs) and covalent organic frameworks (COFs) as platforms for the development of heterogeneous single-site catalysts is reviewed thoroughly. In the first part of this article, synthetic strategies and progress in the implementation of such sites in these two classes of materials are discussed. Because these solids are excellent playgrounds to allow a better understanding of catalytic functions, we highlight the most important recent advances in the modelling and spectroscopic characterization of single-site catalysts based on these materials. Finally, we discuss the potential of MOFs as materials in which several single-site catalytic functions can be combined within one framework along with their potential as powerful enzyme-mimicking materials. The review is wrapped up with our personal vision on future research directions.

Separation of nuclear isomers for cancer therapeutic radionuclides based on nuclear decay after-effects.

177Lu has sprung as a promising radionuclide for targeted therapy. The low soft tissue penetration of its ß- emission results in very efficient energy deposition in small-size tumours. Because of this, 177Lu is used in the treatment of neuroendocrine tumours and is also clinically approved for prostate cancer therapy. In this work, we report a separation method that achieves the challenging separation of the physically and chemically identical nuclear isomers, 177mLu and 177Lu. The separation method combines the nuclear after-effects of the nuclear decay, the use of a very stable chemical complex and a chromatographic separation. Based on this separation concept, a new type of radionuclide generator has been devised, in which the parent and the daughter radionuclides are the same elements. The 177mLu/177Lu radionuclide generator provides a new production route for the therapeutic radionuclide 177Lu and can bring significant growth in the research and development of 177Lu based pharmaceuticals.

Determination of early warning signs for photocatalytic degradation of titanium white oil paints by means of surface analysis.

Titanium white (TiO2) has been widely used as a pigment in the 20th century. However, its most photocatalytic form (anatase) can cause severe degradation of the oil paint in which it is contained. UV light initiates TiO2-photocatalyzed processes in the paint film, degrading the oil binder into volatile components resulting in chalking of the paint. This will eventually lead to severe changes in the appearance of a painting. To date, limited examples of degraded works of art containing titanium white are known due to the relatively short existence of the paintings in question and the slow progress of the degradation process. However, UV light will inevitably cause degradation of paint in works of art containing photocatalytic titanium white. In this work, a method to detect early warning signs of photocatalytic degradation of unvarnished oil paint is proposed, using atomic force microscopy (AFM) and X-ray photoelectron spectroscopy (XPS). Consequently, a four-stage degradation model was developed through in-depth study of TiO2-containing paint films in various stages of degradation. The XPS surface analysis proved very valuable for detecting early warning signs of paint degradation, whereas the AFM results provide additional confirmation and are in good agreement with bulk gloss reduction.

Development of 100 Mo -containing scintillating bolometers for a high-sensitivity neutrinoless double-beta decay search.

This paper reports on the development of a technology involving 100 Mo -enriched scintillating bolometers, compatible with the goals of CUPID, a proposed next-generation bolometric experiment to search for neutrinoless double-beta decay. Large mass ( ∼ 1 kg ), high optical quality, radiopure 100 Mo -containing zinc and lithium molybdate crystals have been produced and used to develop high performance single detector modules based on 0.2-0.4 kg scintillating bolometers. In particular, the energy resolution of the lithium molybdate detectors near the Q-value of the double-beta transition of 100 Mo (3034 keV) is 4-6 keV FWHM. The rejection of the α -induced dominant background above 2.6 MeV is better than 8 σ . Less than 10 µ Bq/kg activity of 232 Th ( 228 Th ) and 226 Ra in the crystals is ensured by boule recrystallization. The potential of 100 Mo -enriched scintillating bolometers to perform high sensitivity double-beta decay searches has been demonstrated with only 10 kg × d exposure: the two neutrino double-beta decay half-life of 100 Mo has been measured with the up-to-date highest accuracy as T 1 / 2 = [6.90 ± 0.15(stat.) ± 0.37(syst.)] × 10 18 years . Both crystallization and detector technologies favor lithium molybdate, which has been selected for the ongoing construction of the CUPID-0/Mo demonstrator, containing several kg of 100 Mo .

The MOD-QM/MM Method: Applications to Studies of Photosystem II and DNA G-Quadruplexes.

Quantum mechanics/molecular mechanics (QM/MM) hybrid methods are currently the most powerful computational tools for studies of structure/function relations and catalytic sites embedded in macrobiomolecules (eg, proteins and nucleic acids). QM/MM methodologies are highly efficient since they implement quantum chemistry methods for modeling only the portion of the system involving bond-breaking/forming processes (QM layer), as influenced by the surrounding molecular environment described in terms of molecular mechanics force fields (MM layer). Some of the limitations of QM/MM methods when polarization effects are not explicitly considered include the approximate treatment of electrostatic interactions between QM and MM layers. Here, we review recent advances in the development of computational protocols that allow for rigorous modeling of electrostatic interactions in biomacromolecules and structural refinement, beyond the common limitations of QM/MM hybrid methods. We focus on photosystem II (PSII) with emphasis on the description of the oxygen-evolving complex (OEC) and its high-resolution extended X-ray absorption fine structure spectra (EXAFS) in conjunction with Monte Carlo structural refinement. Furthermore, we review QM/MM structural refinement studies of DNA G4 quadruplexes with embedded monovalent cations and direct comparisons to NMR data.

Adsorption of CO2 on MIL-53(Al): FTIR evidence of the formation of dimeric CO2 species.

FTIR spectra of (12)CO2 and (12)CO2 + (13)CO2 mixtures adsorbed on MIL-53(Al) reveal the formation of highly symmetric dimeric (CO2)2 species connected to two structural OH groups.