Offspring sex modifies the association between early-pregnancy adiposity and 2-year-old physical activity-The Glowing Study.

BACKGROUND: Rodent models suggest that in utero exposure to under and overnutrition programs offspring physical activity (PA) behaviors. Such nexus has not been established in humans. This study evaluated the association of early pregnancy maternal adiposity with offspring PA at age 2 years (2-yo-PA) taking into consideration prenatal and postnatal factors. METHODS: Women (n = 153) were enrolled early in pregnancy (<10 weeks). At enrollment, maternal adiposity [air displacement plethysmography, fat mass index (FMI, kg/m2)] and PA (accelerometers, activity counts) were measured, and age, race, and education self-reported. Gestational weight gain was measured at the research facility. Offspring birthweight and sex were self-reported. At age 2 years, parental feeding practices (child feeding questionnaire) were assessed, whereas anthropometrics (length and weight) and physical activity (accelerometers) were objectively measured. Offspring body mass index z-scores were calculated. Generalized linear regression analysis modeled the association of maternal FMI and 2-yo-PA [average activity counts (AC)4/day]. RESULTS: In bivariate associations, 2-yo-PA did not associate with maternal FMI (ß = -0.22, CI = -0.73 to 0.29, p = 0.398). However, maternal FMI interacted with offspring sex in association with 2-yo-PA. Specifically, 2-yo-PA was lower in girls (ß = -1.14, CI = -2.1 to -0.18, p = 0.02) compared to boys when maternal FMI was ≥7 kg/m2. When stratified by sex, 2-yo-PA of girls negatively associated with maternal FMI (ß = -0.82, CI = -1.43 to 0.29, p = 0.009) while no association was found between maternal FMI and boy's PA (ß = 0.32, CI = -0.38 to 1.01, p = 0.376). CONCLUSIONS: The association of 2-yo-PA and early pregnancy maternal adiposity was modified by offspring sex. Offspring's physical activity decreased with increasing early pregnancy adiposity maternal in girls but not boys in second parity dyads.

Mapping the spatial dynamics of the CD4+ T cell spectrum in classical Hodgkin lymphoma.

As around 25-30% of classical Hodgkin Lymphoma (cHL) patients with advanced stages do not respond to standard therapies, the tumor microenvironment (TME) of cHL is one avenue that may be explored with the aim of improving risk stratification. CD4+ T cells are thought to be one of the main cell types in the TME. However, few immune signatures have been studied, and many of these lack related spatial data. Thus, our aim is to spatially resolve the CD4+ T cell subtypes that influence cHL outcome, depicting new immune signatures or transcriptional patterns that are in crosstalk with the tumor cells. This study was conducted using the Nanostring GeoMx DSP technology, based on the selection of distinct functional areas of patients' tissues followed by the gene-expression profiling. The goals were to assess the differences in CD4+ T cell populations between tumor-rich and immune-predominant areas defined by different CD30 and PD-L1 expression levels and to seek correlations with clinical metadata. Our results depict a complex map of CD4+ T cells with different functions and differentiation states that are enriched at distinct locations, the flux of cytokines and chemokines that could be related to these, and the specific relationships with the clinical outcome.

Optically induced ultrafast magnetization switching in ferromagnetic spin valves.

The discovery of spin-transfer torque (STT) enabled the control of the magnetization direction in magnetic devices in nanoseconds using an electrical current. Ultrashort optical pulses have also been used to manipulate the magnetization of ferrimagnets at picosecond timescales by bringing the system out of equilibrium. So far, these methods of magnetization manipulation have mostly been developed independently within the fields of spintronics and ultrafast magnetism. Here we show optically induced ultrafast magnetization reversal taking place within less than a picosecond in rare-earth-free archetypal spin valves of [Pt/Co]/Cu/[Co/Pt] commonly used for current-induced STT switching. We find that the magnetization of the free layer can be switched from a parallel to an antiparallel alignment, as in STT, indicating the presence of an unexpected, intense and ultrafast source of opposite angular momentum in our structures. Our findings provide a route to ultrafast magnetization control by bridging concepts from spintronics and ultrafast magnetism.

Tumor-intrinsic perinuclear LOXL2: Prognostic relevance and relationship with YAP1 activation status in oral squamous cell carcinoma.

INTRODUCTION: Lysyl Oxidase-Like 2 (LOXL2) expression and function is frequently altered in different cancers, but scarcely explored in oral squamous cell carcinoma (OSCC). This prompted us to investigate the clinical relevance of LOXL2 expression pattern in OSCC and also a possible crosstalk with Hippo/YAP1 pathway signaling. METHODS: Immunohistochemical analysis of LOXL2 protein expression was performed in 158 OSCC patient samples, together with Yes-associated protein 1 (YAP1) activation status. Correlations with clinicopathological parameters and patient survival were assessed. RESULTS: Tumor cell-intrinsic LOXL2 expression showed two distinct expression patterns: diffuse cytoplasmic staining (64.6%), and heterogeneous perinuclear staining (35.4%). Remarkably, perinuclear LOXL2 staining was significantly associated with lymph node metastasis, advanced clinical stage and perineural invasion. Moreover, patients harboring tumors with perinuclear LOXL2 expression exhibited significantly poorer disease-specific survival (DSS) rates. Strikingly, we also found that perinuclear LOXL2 positivity gradually increased in relation to YAP1 activation, and patients harboring tumors with concomitant perinuclear LOXL2 and fully active YAP1 exhibited the worst DSS. Multivariate Cox analysis further revealed combined perinuclear LOXL2 and fully active YAP1 as a significant independent predictor of poor DSS. CONCLUSION: Tumor-intrinsic perinuclear LOXL2 emerges as a clinically and biologically relevant feature associated with advanced disease, tumor aggressiveness, and poor prognosis in OSCC. Moreover, this study unprecedentedly uncovers a functional relationship between perinuclear LOXL2 and YAP1 activation with major prognostic implications. Notably, combined perinuclear LOXL2 and fully active YAP1 was revealed as independent predictor of poor prognosis. These findings encourage targeting oncogenic LOXL2 functions for personalized treatment regimens.

BET inhibitors induce NF-κB and E2F downregulation in Hodgkin and Reed-Sternberg cells.

The prognosis of patients with relapsed and/or refractory classic Hodgkin lymphoma (cHL) continues to be poor. Therefore, there is a continuing need to develop novel therapies and to rationalize the use of target combinations. In recent years there has been growing interest in epigenetic targets for hematological malignancies under the rationale of the presence of common alterations in epigenetic transcriptional regulation. Since Hodgkin and Reed-Sternberg (HRS) cells have frequent inactivating mutations of the CREBBP and EP300 acetyltransferases, bromodomain and extra-terminal (BET) inhibitors can be a rational therapy for cHL. Here we aimed to confirm the efficacy of BET inhibitors (iBETs) using representative cell models and functional experiments, and to further explore biological mechanisms under iBET treatment using whole-transcriptome analyses. Our results reveal cytostatic rather than cytotoxic activity through the induction of G1/S and G2/M cell-cycle arrest, in addition to variable MYC downregulation. Additionally, massive changes in the transcriptome induced by the treatment include downregulation of relevant pathways in cHL disease: NF-kB and E2F, among others. Our findings support the therapeutic use of iBETs in selected cHL patients and reveal previously unknown biological mechanisms and consequences of pan-BET inhibition.

Novel neuroactive steroids as positive allosteric modulators of NMDA receptors: mechanism, site of action, and rescue pharmacology on GRIN variants associated with neurological conditions.

N-methyl-D-aspartate receptors (NMDARs) play vital roles in normal brain functions (i.e., learning, memory, and neuronal development) and various neuropathological conditions, such as epilepsy, autism, Parkinson's disease, Alzheimer's disease, and traumatic brain injury. Endogenous neuroactive steroids such as 24(S)-hydroxycholesterol (24(S)-HC) have been shown to influence NMDAR activity, and positive allosteric modulators (PAMs) derived from 24(S)-hydroxycholesterol scaffold can also enhance NMDAR function. This study describes the structural determinants and mechanism of action for 24(S)-hydroxycholesterol and two novel synthetic analogs (SGE-550 and SGE-301) on NMDAR function. We also show that these agents can mitigate the altered function caused by a set of loss-of-function missense variants in NMDAR GluN subunit-encoding GRIN genes associated with neurological and neuropsychiatric disorders. We anticipate that the evaluation of novel neuroactive steroid NMDAR PAMs may catalyze the development of new treatment strategies for GRIN-related neuropsychiatric conditions.

Biodiesel production from sewage sludge using supported heteropolyacid as heterogeneous acid catalyst.

Phosphotungstic acid (HPW) and silicotungstic acid (HSiW) were tested as homogeneous and as heterogeneous catalysts (after immobilized on different supports as high surface area graphite -HSAG500-, montmorillonite -MMT- and alumina -Al2O3-) for the in situ transesterification of sewage sludge lipids. Both catalysts exhibited similar performance in homogeneous phase, with slightly higher biodiesel yield for HPW. When the different supports were tested with HPW, the maximum yield obtained follow the trend: MMT > HSAG500 > Al2O3, but a greater leaching of the heteropolyacid (HPA) was observed with MMT. Therefore, HSAG500 showed the best results with a good FAMEs profile. The percentage of active phase was optimized from 1 to 40%, reaching the optimum at 10%. A more heterogeneous surface is obtained with larger quantities, also favouring the HPA leaching. The reaction temperature and the use of sonication as pre-treatment were also optimized. The best results were obtained after sonication with HPW-HSAG500 (10%) as catalyst, catalyst/sludge ratio 1:2, MeOH/sludge ratio 33:1, 120 °C and 21 h of reaction time with a maximum biodiesel yield of 31.1 % (FAMEs/lipids). In view of the results obtained HPW supports on HSAG500 offers a novel alternative as heterogeneous acid catalyst for in situ transesterification using sewage sludge as raw material.

Noninvasive detection of microsatellite instability in patients with endometrial cancer.

The analysis of mismatch repair proteins in solid tissue is the standard of care (SoC) for the microsatellite instability (MSI) characterization in endometrial cancer (EC). Uterine aspirates (UAs) or circulating-DNA (cfDNA) samples capture the intratumor heterogeneity and provide a more comprehensive and dynamic molecular diagnosis. Thus, MSI analysis by droplet-digital PCR (ddPCR) in UAs and cfDNA can provide a reliable tool to characterize and follow-up the disease. The UAs, paraffin-embedded tumor tissue (FFPE) and longitudinal plasma samples from a cohort of 90 EC patients were analyzed using ddPCR panel and compared to the SoC. A high concordance (96.67%) was obtained between the analysis of MSI markers in UAs and the SoC. Three discordant cases were validated as unstable by ddPCR on FFPE samples. Besides, a good overall concordance (70.27%) was obtained when comparing the performance of the ddPCR assay on UAs and cfDNA in high-risk tumors. Importantly, our results also evidenced the value of MSI analysis to monitor the disease evolution. MSI evaluation in minimally invasive samples shows great accuracy and sensitivity and provides a valuable tool for the molecular characterization and follow-up of endometrial tumors, opening new opportunities for personalized management of EC.

Improving the Management of Endometrial Cancer Patients through the Use of Liquid Biopsy Analyses: A Case Report.

Endometrial cancer (EC) is the 4th most common neoplasm of the female genital tract, with 15-20% of patients being of high risk of recurrence which leads to a significant decrease in patient survival. Current therapeutic options for patients with EC are poor, being the combined therapy of carboplatin and paclitaxel the standard of care, with limited efficacy. Therefore, new therapeutic options and better monitoring tools are needed to improve the management of the disease. In the current case report, we showcase the value of liquid biopsy analyses in a microsatellite instability EC patient with initially good prognosis that however underwent rapid progression disease within 6 months post-surgery; through the study of plasma cfDNA/ctDNA dynamics to assess the tumour evolution during treatment, as well as the study of the uterine aspirate as a valuable sample that captures the intra-tumour heterogeneity that allows a comprehensive genomic profiling of the disease to identify potential therapeutic options. Furthermore, preclinical models were generated at the time of tumour progression to assess the efficacy of the identified targeted therapies.

Divergent Changes in Serum Branched-Chain Amino Acid Concentrations and Estimates of Insulin Resistance throughout Gestation in Healthy Women.

BACKGROUND: Branched-chain amino acid (BCAA) concentrations in the blood have been correlated with insulin resistance, but this relation throughout gestation (period in which insulin resistance typically increases) is unclear. OBJECTIVE: The objective of this study was to determine the associations between changes in BCAA concentrations and estimates of insulin resistance throughout gestation. METHODS: Serum BCAA (Leu, Ile, Val) concentrations and insulin resistance/sensitivity [i.e., homeostatic model assessment-2 of insulin resistance (HOMA2-IR), estimated metabolic clearance rate (MCR) of glucose, and estimated first- and second-phase insulin responses] were assessed at early (EP; 8.5 ± 0.2 wk) and/or late (LP; 29.2 ± 0.8 wk) pregnancy in 53 healthy women from the Glowing cohort. Adjusted Spearman correlations were used to evaluate the association between BCAA and insulin resistance/sensitivity measures at EP and LP, adjusted for body fat percentage and gestational weight gain (GWG). A multiple linear regression analysis was used to assess the association between changes in HOMA2-IR and BCAAs throughout gestation. Groups were made post hoc based on the mean percentage change (10% decrease) in Leu throughout gestation, creating a group with a ≥10% decrease in LeuLP-EP (BELOW) and a <10% decrease in LeuLP-EP (ABOVE), and Student's t tests were performed to assess differences between groups. RESULTS: Leu and Ile concentrations positively correlated with HOMA2-IR at both time points, but these relations at EP disappeared/weakened when adjusted for body fat percentage. From EP to LP, the change in Leu (LeuLP-EP) was negatively associated with the change in HOMA2-IR (HOMA2-IRLP-EP) (ß = -0.037, P = 0.006). MCR was lower in the BELOW group compared with the ABOVE group, whereas there was no difference in HOMA2-IR between groups. CONCLUSIONS: In this pregnancy cohort, BCAA concentrations decreased throughout gestation, whereas the mean insulin resistance did not change. These data do not support a connection between changes in blood BCAA concentrations and estimates of insulin resistance in pregnant women. This trial is registered at clinicaltrials.gov as NCT01131117.

A comparative study of mitochondrial respiration in circulating blood cells and skeletal muscle fibers in women.

Skeletal muscle mitochondrial respiration is thought to be altered in obesity, insulin resistance, and type 2 diabetes; however, the invasive nature of tissue biopsies is an important limiting factor for studying mitochondrial function. Recent findings suggest that bioenergetics profiling of circulating cells may inform on mitochondrial function in other tissues in lieu of biopsies. Thus, we sought to determine whether mitochondrial respiration in circulating cells [peripheral blood mononuclear cells (PBMCs) and platelets] reflects that of skeletal muscle fibers derived from the same subjects. PBMCs, platelets, and skeletal muscle (vastus lateralis) samples were obtained from 32 young (25-35 yr) women of varying body mass indexes. With the use of extracellular flux analysis and high-resolution respirometry, mitochondrial respiration was measured in intact blood cells as well as in permeabilized cells and permeabilized muscle fibers. Respiratory parameters were not correlated between permeabilized muscle fibers and intact PBMCs or platelets. In a subset of samples (n = 12-13) with permeabilized blood cells available, raw measures of substrate (pyruvate, malate, glutamate, and succinate)-driven respiration did not correlate between permeabilized muscle (per mg tissue) and permeabilized PBMCs (per 106 cells); however, complex I leak and oxidative phosphorylation coupling efficiency correlated between permeabilized platelets and muscle (Spearman's ρ = 0.64, P = 0.030; Spearman's ρ = 0.72, P = 0.010, respectively). Our data indicate that bioenergetics phenotypes in circulating cells cannot recapitulate muscle mitochondrial function. Select circulating cell bioenergetics phenotypes may possibly inform on overall metabolic health, but this postulate awaits validation in cohorts spanning a larger range of insulin resistance and type 2 diabetes status.

Electrochemical degradation of naproxen from water by anodic oxidation with multiwall carbon nanotubes glassy carbon electrode.

Naproxen (NPX) degradation was investigated by anodic oxidation both at constant potential and by cyclic voltammetry, using this last technique for optimizing reaction conditions and catalyst properties. Three multiwall carbon nanotubes (MWCNTs)-promoted electrodes were used (MWCNT, MWCNT-COOH and MWCNT-NH2) and a two steps oxidation process was observed in all the cases. At the optimized conditions (volume of MWCNT = 15 µL), the influence of the scan rate indicates the diffusion-adsorption control of the process. Likewise, the kinetic study of NPX degradation at fix potential, considering two different stirring speeds (250 and 500 rpm), indicates that degradation rate increases with the stirring speed. After 20 h, NPX is degraded even an 82.5%, whereas the mineralization reaches almost 70%, as it was obtained from total organic carbon analysis. The pH effect was also analysed, in the range 5-11, observing a positive effect at low pH. Concerning the surface chemistry of the electrode, MWCNT-NH2, with the highest isoelectric point (4.70), is the most promising material due to the improved interactions with the reactant. From these observations, a pathway is proposed, which includes two steps of electrochemical oxidation followed by subsequent oxidation steps, until mineralization of the NPX, attributed mainly to active chlorine species and ·OH.

Carbon nanotube modified glassy carbon electrode for electrochemical oxidation of alkylphenol ethoxylate.

Electrochemical oxidation of an emerging pollutant, 2-(4-methylphenoxy)ethanol (MPET), from water has been studied by cyclic voltammetry (CV). Multiwall carbon nanotubes glassy carbon electrodes (MWCNT-GCE) were used as working electrode due to their extraordinary properties. The oxidation process is irreversible, since no reduction peaks were observed in the reverse scan. The electrocatalytic effect of MWCNT was confirmed as the oxidation peak intensity increases in comparison to bare-GCE. The effect of functional groups on MWCNT was also studied by MWCNT functionalized with NH2 (MWCNT-NH2) and COOH (MWCNT-COOH) groups. The oxidation peak current decreases in the following order: MWCNT > MWCNT-NH2 > MWCNT-COOH. Taking into account the normalized peak current, MWCNT-NH2 exhibits the best results due to its strong interaction with MPET. Under optimal conditions (pH = 5.0 and volume of MWCNT = 10 µL), degradation was studied for MWCNT-GCE and MWCNT-NH2-GCE. A complete MPET removal was observed using MWCNT-GCE after four CV cycles, for a volume/area (V/A) ratio equal to 19. In the case of MWCNT-NH2-GCE, the maximum MPET removal was close to 90% for V/A = 37, higher than that obtained for MWCNT-GCE at the same conditions (≈80%). In both cases, no organic by-products were detected.

Clinical Outcome of Mechanical Thrombectomy for Stroke in the Elderly.

BACKGROUND: Endovascular revascularization with mechanical devices has proven an effective treatment for proximal occlusions of the major intracranial arteries in stroke patients, but there is only limited information as to whether there should be an age limit for its use. We aimed to evaluate the safety and effectiveness of endovascular revascularization in stroke patients aged 80 years and older, and compare the results with younger patients. METHODS: We prospectively collected 81 consecutive patients subjected to mechanical thrombectomy for proximal occlusion of the anterior circulation during a period of 27 months. According to age, patients were divided into those aged less than 80 years (younger group) and those aged 80 years and older (elderly group). We analyzed favorable outcome, successful and futile recanalization, neurological improvement, in-hospital complications, and mortality in both groups. RESULTS: A favorable outcome (modified Rankin Scale score ≤2 at 3 months) was reached by 51.6% in the elderly group and 64% of younger patients, and neurological improvement (improvement of ≥4 points on National Institutes of Health Stroke Scale) was present in 77.4% of the elderly group. Overall, successful recanalization rates were 95.1% and futile recanalization reached 39% without statistically significant differences between both groups. Elderly patients presented more in-hospital complications (61.3% versus 38%) and higher mortality rates (16.1% versus 8%). CONCLUSIONS: Clinical independence was reached in over half of elderly stroke patients treated with mechanical thrombectomy, supporting the use of this treatment without age restriction.

Circulating tumor DNA for monitoring classic Hodgkin lymphoma patients: Correlation with FDG-PET/CT.

The value of circulating tumor DNA (ctDNA) as a biomarker of disease activity in classic Hodgkin lymphoma (cHL) patients has not yet been well established. By profiling primary tumors and ctDNA, we identified common variants between primary tumors and longitudinal plasma samples in most of the cases, confirming high spatial and temporal heterogeneity. Although ctDNA analyses mirrored HRS cell genetics overall, the prevalence of variants shows that none of them can be used as a single biomarker. Conversely, the estimation of hGE/mL, based on measures of total ctDNA, reflects disease activity and is almost perfectly correlated with standard parameters such as PET/CT that are associated with refractoriness.

Immune and stromal transcriptional patterns that influence the outcome of classic Hodgkin lymphoma.

Classic Hodgkin lymphoma (cHL) is characterized by a rich immune microenvironment as the main tumor component. It involves a broad range of cell populations, which are largely unexplored, even though they are known to be essential for growth and survival of Hodgkin and Reed-Sternberg cells. We profiled the gene expression of 25 FFPE cHL samples using NanoString technology and resolved their microenvironment compositions using cell-deconvolution tools, thereby generating patient-specific signatures. The results confirm individual immune fingerprints and recognize multiple clusters enriched in refractory patients, highlighting the relevance of: (1) the composition of immune cells and their functional status, including myeloid cell populations (M1-like, M2-like, plasmacytoid dendritic cells, myeloid-derived suppressor cells, etc.), CD4-positive T cells (exhausted, regulatory, Th17, etc.), cytotoxic CD8 T and natural killer cells; (2) the balance between inflammatory signatures (such as IL6, TNF, IFN-γ/TGF-ß) and MHC-I/MHC-II molecules; and (3) several cells, pathways and genes related to the stroma and extracellular matrix remodeling. A validation model combining relevant immune and stromal signatures identifies patients with unfavorable outcomes, producing the same results in an independent cHL series. Our results reveal the heterogeneity of immune responses among patients, confirm previous findings, and identify new functional phenotypes of prognostic and predictive utility.

Decisional Conflict Regarding Disease-Modifying Treatment Choices Among Patients with Mid-Stage Relapsing-Remitting Multiple Sclerosis.

Purpose: Shared decision-making is critical in multiple sclerosis (MS) due to the uncertainty of the disease trajectory over time and the large number of treatment options with differing efficacy, safety and administration characteristics. The aim of this study was to assess patients' decisional conflict regarding the choice of a disease-modifying therapy and its associated factors in patients with mid-stage relapsing-remitting multiple sclerosis (RRMS). Methods: A multicenter, non-interventional study was conducted. Adult patients with a diagnosis of RRMS (2017 revised McDonald criteria) and disease duration of 3 to 8 years were included. The level of uncertainty experienced by a patient when faced with making a treatment choice was assessed using the 4-item Decisional Conflict Scale. A battery of patient-reported and clinician-rated measures was administered to obtain information on symptom severity, illness perception, illness-related uncertainty, regret, MS knowledge, risk taking behavior, preferred role in the decision-making process, cognition, and self-management. Patients were recruited during routine follow-up visits and completed all questionnaires online using electronic tablets at the hospital. A multivariate logistic regression analysis was conducted. Results: A total of 201 patients were studied. Mean age (Standard deviation) was 38.7 (8.4) years and 74.1% were female. Median disease duration (Interquartile range) was 6.0 (4.0-7.0) years. Median EDSS score was 1.0 (0-2.0). Sixty-seven (33.3%) patients reported a decisional conflict. These patients had lower MS knowledge and more illness uncertainty, anxiety, depressive symptoms, fatigue, subjective symptom severity, a threatening illness perception, and poorer quality of life than their counterparts. Lack of decisional conflict was associated with MS knowledge (Odds ratio [OR]=1.195, 95% CI 1.045, 1.383, p=0.013), self-management (OR=1.049, 95% CI 1.013, 1.093, p=0.018), and regret after a healthcare decision (OR=0.860, 95% CI 0.756, 0.973, p=0.018) in the multivariate analysis. Conclusion: Decisional conflict regarding the selection of a disease-modifying therapy was a common phenomenon in patients with mid-stage RRMS. Identifying factors associated with decisional conflict may be useful to implement preventive strategies that help patients better understand their condition and strengthen their self-management resources.

Assessing illness-related uncertainty in relapsing-remitting multiple sclerosis: A psychometric analysis of the Mishel Uncertainty of Illness Scale.

A multicenter study involving 204 adults with relapsing-remitting multiple sclerosis (RRMS) assessed the dimensionality and item characteristics of the Mishel-Uncertainty of Illness Scale (MUIS), a generic self-assessment tool. Mokken analysis identified two dimensions in the MUIS with an appropriate item and overall scale scalability after excluding nonclassifiable items. A refined 12-item MUIS, employing a grade response model, effectively discriminated uncertainty levels among RRMS patients (likelihood ratio test p-value = .03). These findings suggest the potential value of the 12-item MUIS as a reliable measure for assessing uncertainty associated with the course of illness in RRMS.

Statistical analysis plan for the multicenter, open, randomized controlled clinical trial to assess the efficacy and safety of intravenous tirofiban vs aspirin in acute ischemic stroke due to tandem lesion, undergoing recanalization therapy by endovascular treatment (ATILA trial).

RATIONALE: In-stent reocclusion after endovascular therapy has a negative impact on outcomes in acute ischemic stroke (AIS) due to tandem lesions (TL). Optimal antiplatelet therapy approach in these patients to avoid in-stent reocclusion is yet to be elucidated. AIMS: To assess efficacy and safety of intravenous tirofiban versus intravenous aspirin in patients undergoing MT plus carotid stenting in the setting of AIS due to TL. SAMPLE SIZE ESTIMATES: Two hundred forty patients will be enrolled, 120 in every treatment arm. METHODS AND DESIGN: A multicenter, prospective, randomized, controlled (aspirin group), assessor-blinded clinical trial will be conducted. Patients fulfilling the inclusion criteria will be randomized at MT onset to the experimental or control group (1:1). Intravenous aspirin will be administered at a 500-mg single dose and tirofiban at a 500-mcg bolus followed by a 200-mcg/h infusion during the first 24 h. All patients will be followed for up to 3 months. STUDY OUTCOMES: Primary efficacy outcome will be the proportion of patients with carotid in-stent thrombosis within the first 24 h after MT. Primary safety outcome will be the rate of symptomatic intracranial hemorrhage. DISCUSSION: This will be the first clinical trial to assess the best antiplatelet therapy to avoid in-stent thrombosis after MT in patients with TL. TRIAL REGISTRATION: The trial is registered as NCT05225961. February, 7th, 2022.

Effect of Water and Carbon Dioxide on the Performance of Basolite Metal-Organic Frameworks for Methane Adsorption.

MOFs are potential adsorbents for methane separation from nitrogen, including recovery in diluted streams. However, water and carbon dioxide can seriously affect the adsorption performance. Three commercial MOFs, basolite C300, F300, and A100, were studied under similar conditions to fugitive methane streams, such as water (75 and 100% relative humidity) and carbon dioxide (0.33%) presence in a fixed bed. The presence of available open metal sites of copper (Cu2+) and aluminum (Al3+) in the case of basolite C300 and A100, respectively, constitutes a clear drawback under humid conditions, since water adsorbs on them, leading to significant methane capacity losses. Surprisingly, basolite F300 is the most resistant material due to its amorphous structure, which hinders water access. The combination of carbon dioxide and water creates a synergy that seriously affects basolite A100, closely related to its breathing effect, but does not constitute an important issue for basolite C300 and F300.