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Mucopolysaccharidoses (MPSs) are childhood diseases caused by inherited deficiencies in glycosaminoglycan degradation. Most MPSs involve neurodegeneration, which to date is untreatable. Currently, most therapeutic strategies aim at correcting the primary genetic defect. Among these strategies, gene therapy has shown great potential, although its clinical application is challenging. We have shown previously in an MPS-IIIA mouse model that the molecular tweezer (MT) CLR01, a potent, broad-spectrum anti-amyloid small molecule, inhibits secondary amyloid storage, facilitates amyloid clearance, and protects against neurodegeneration. Here, we demonstrate that combining CLR01 with adeno-associated virus (AAV)-mediated gene therapy, targeting both the primary and secondary pathologic storage in MPS-IIIA mice, results in a synergistic effect that improves multiple therapeutic outcomes compared to each monotherapy. Moreover, we demonstrate that CLR01 is effective therapeutically in mouse models of other forms of neuronopathic MPS, MPS-I, and MPS-IIIC. These strongly support developing MTs as an effective treatment option for neuronopathic MPSs, both on their own and in combination with gene therapy, to improve therapeutic efficacy and translation into clinical application.

Graphical AbstractInhibition of platelet reactivity following ticagrelor 60 mg vs. 90 mg in elderly patients (≥75 years) undergoing PCI for ACS.A total of 50 older patients with ACS undergoing PCI were randomized to ticagrelor 60 mg vs. 90 mg twice daily. Platelet reactivity was similar and non-inferior between the two ticagrelor maintenance doses, although plasma drug concentrations were significantly lower during treatment with ticagrelor 60 mg. ACS, acute coronary syndrome; LTA, light transmittance aggregometry; MEA, multiple electrode aggregometry; PCI, percutaneous coronary intervention; PRU, P2Y12reaction units.

The Chihuahua Chub Gila nigrescensis a species of conservation concern throughout its distribution. The species is threatened by habitat degradation, nonnative species, and stochastic events (e.g., wildfire and drought). Although conservation efforts are ongoing, it is unclear how Chihuahua Chub in the Mimbres River, New Mexico, respond to conservation actions and stochastic events. To address these uncertainties, we collected population demographic and dynamics data on Chihuahua Chub in the Mimbres River and used the data to construct an age‐structured, female‐based population model. The model was used to evaluate the response of Chihuahua Chub to (1) habitat improvement, (2) conservation stocking, and (3) stochastic events. Habitat improvements were modeled as a 50% increase in current abundance. Conservation stocking was represented by two stocking regimes: annual “maintenance” stocking of 200 fish or “catastrophe” stocking of 400–1500 fish for two consecutive years after a stochastic event. The effects of stochastic events were represented by 20–95% reductions in annual survival. Each scenario was simulated for 5000 iterations over 25 years. In the absence of conservation actions, the Chihuahua Chub population was projected to decline due to stochastic events. However, stocking and habitat improvement decreased the risk of extirpation. When stochastic events resulted in a 95% decline in annual survival, catastrophe stocking reduced population declines in abundance by 47–58% relative to no conservation stocking. When stochastic events caused a 20% reduction in annual survival, habitat improvement increased the median population size after 25 years by almost 50% relative to no habitat improvements. Collectively, our results suggest that an increase in habitat and conservation stocking efforts is likely the most effective approach for conserving Chihuahua Chub in the face of future stochastic events. Impact statementThe Chihuahua Chub population in the Mimbres River is threatened by drought and wildfire. Habitat improvement and supplemental stocking improve the long‐term viability of the population. The Chihuahua Chub population in the Mimbres River is threatened by drought and wildfire. Habitat improvement and supplemental stocking improve the long‐term viability of the population.

Background: Severe hematoma expansion (sHE) has the strongest impact on intracerebral hemorrhage (ICH) outcome. We investigated the predictors of sHE.Methods: Retrospective analysis of ICH patients admitted at nine sites in Italy, Germany, China, and Canada. The following imaging features were analyzed: non-contrast CT (NCCT) hypodensities, heterogeneous density, blend sign, irregular shape, and CT angiography (CTA) spot sign. The outcome of interest was sHE, defined as volume increase >66% and/or >12.5 from baseline to follow-up NCCT. Predictors of sHE were explored with logistic regression.Results: A total of 1472 patients were included (median age 73, 56.6% males) of whom 223 (15.2%) had sHE. Age (odds ratio (OR) per year, 95% confidence interval (CI), 1.02 (1.01–1.04)), Anticoagulant treatment (OR 3.00, 95% CI 2.09–4.31), Glasgow Coma Scale (OR 0.93, 95% CI 0.89–0.98), time from onset/last known well to imaging, (OR per h 0.96, 95% CI 0.93–0.99), and baseline ICH volume, (OR per mL 1.02, 95% CI 1.02–1.03) were independently associated with sHE. Ultra-early hematoma growth (baseline volume/baseline imaging time) was also a predictor of sHE (OR per mL/h 1.01, 95% CI 1.00–1.02). All NCCT and CTA imaging markers were also predictors of sHE. Amongst imaging features NCCT hypodensities had the highest sensitivity (0.79) whereas the CTA spot sign had the highest positive predictive value (0.51).Conclusions: sHE is common in the natural history of ICH and can be predicted with few clinical and imaging variables. These findings might inform clinical practice and future trials targeting active bleeding in ICH.

Purpose: Improved resistive plate chambers (iRPCs) will be installed in the challenging forward region of the compact muon solenoid (CMS) during its Phase-2 upgrade. The design target of iRPC time resolution is 1.5 ns. It will help the Level-1 trigger system distinguish the muons from high backgrounds and improve the trigger efficiency. Studying the time resolution after integrating the new backend electronics boards (BEB) is essential for ensuring timely performance. In this system, a time reference (Tref) signal is distributed by the BEB to several frontend electronics boards (FEB) to reset the time-to-digital converters (TDC). In the CMS experiment, the arrangement of the iRPC chambers and on-chamber FEBs is at different positions, resulting in varying Tref arrival times on the FEB side. This paper describes the measures taken to ensure the time resolution of the single path and adjust the time base for multi-paths. Method: Unique designs were implemented in the chamber, FEB, and BEB to ensure a satisfactory time resolution. Tref adjustments for different paths were performed in bunch crossing steps (24.950 ns) in the BEB using shift registers. And the sub-bunch crossing adjustment steps were performed in the FEB using the TDC correction module. Finally, the arrival time differences of Tref on different FEBs were less than 1.25 ns after adjustment. Results: The time resolution of the FEB–BEB system was observed to be 32 ps. The time resolution of the chamber FEB–BEB system was first measured and is 554 ps at an iRPC working point of 7200 V. In addition, the Tref arrival time differences of different paths were adjusted from − 99.923 (− 90.113) ns to 0.073 (− 0.141) ns. Conclusion: The test results revealed that the system time resolution and Tref adjustment performed by the BEB met the Phase-2 upgrade goals.

In this study, we synthesized novel Pd(II)-indenyl complexes using various N-heterocyclic carbene (NHC) ligands, including chelating NHC-picolyl, NHC-thioether, and diNHC ligands, and two monodentate NHCs. Transmetalation reactions between a Pd(II)-indenyl precursor and silver-NHC complexes were generally employed, except for chelating diNHC derivatives, which required direct reaction with bisimidazolium salts and potassium carbonate. Characterization included NMR, HRMS analysis, and single-crystal X-ray diffraction. In vitroon five ovarian cancer cell lines showed notable cytotoxicity, with IC50values in the micro- and submicromolar range. Some compounds exhibited intriguing selectivity for cancer cells due to higher tumor cell uptake. Mechanistic studies revealed that monodentate NHCs induced mitochondrial damage while chelating ligands caused DNA damage. One chelating NHC-picolyl ligand showed promising cytotoxicity and selectivity in high-grade serous ovarian cancer models, supporting its consideration for preclinical study.

The widespread and irrational use of azole antifungal agents has led to an increase of azole-resistant Candida albicansstrains with an urgent need for combination drug therapy, enhancing the treatment efficacy. Here, we report the discovery of a first-in-class pyrazole-isoxazole, namely, 5b, that showed remarkable growth inhibition against the C. albicansATCC 10231 strain in combination with voriconazole, acting as a downregulator of ERG 11 (Cyp51) gene expression with a significant reduction of the yeast-to-hypha morphological transition. Furthermore, C. albicansCYP51 enzyme assay and in-depth molecular docking studies unveiled the unique ability of the combination of 5band voriconazole to completely fill the CYP51 binding sites. In vivostudies using a Galleria mellonellamodel confirmed the previously in vitroobserved synergistic effect of 5bwith voriconazole. Also considering its biocompatibility in a cellular model of human keratinocytes, these results indicate that 5brepresents a promising compound for a further optimization campaign.

The paper aims to analyse the opportunity to promote the scholastic inclusion of pupils, through physical education. In the first instance, the historical process that has seen the transition from the concept of school integration of pupils with disabilities to that of inclusion through the introduction of regulations suitable for protecting the educational needs of each one will be explored. The potential of physical education will be explored through the structuring of new ways of designing and managing educational practice as an exercise of active and inclusive citizenship. Attention will also be focused on the mind-body binomial, with a view to the potential of the Embodied Cognition paradigm, which can take on a formative and pedagogically significant value, both by soliciting all those components of an expressive-communicative nature that support the union between body, mind, emotion, cognition and environment, and to further qualify inclusive processes in the context of ordinary teaching. [ABSTRACT FROM AUTHOR]

The present work describes the development of an improved synthesis of the pharmaceutically relevant building block 2-butylbenzofuran (BBF). The telescoped hybrid batch–flow process is composed of three steps and affords the final product in high yield and purity. The key cyclization step is performed in continuous mode with integrated workup: this approach is more efficient compared to the standard batch conditions. The high quality of the product makes crude BBF suitable to be used in the downstream process of production of amiodarone without purification. The optimization was realized using the Design of Experiments approach and afforded a sustainable process suitable for industrial application.

Pt/CeO2catalysts are promising for the low-temperature water gas shift (LT-WGS) reaction, which is an important step to produce H2from syngas. When prepared by impregnation of platinum salt and calcination at 500 °C, they contain Pt2+single atoms (SAs) and/or PtOxclusters which need to be converted into Pt0nanoparticles (NPs) to obtain higher activity for the LT-WGS reaction. In this work, it was shown that reducing pretreatments at 250 °C under H2promote the molar activity of catalysts containing from 0.10 to 1.06 wt% Pt by increasing the number of Pt0NPs formed during reaction at 230 °C. An improvement was also obtained viapretreatment at 500 °C but only for low-Pt-content catalysts, underlying the importance of the pretreatment temperature. Furthermore, it was shown that all prepared Pt/CeO2catalysts which slowly deactivate over reaction time can be regenerated by oxidative post-treatment at only 230 °C, which is industrially interesting. Even more original, a strong improvement in activity of the low-Pt-content catalysts was observed after a 12 h oxidative post-treatment at 500 °C. This treatment was shown to redisperse and reoxidize Pt atoms into PtOxspecies different from the initial ones. Such species are highly reducible on the surface of CeO2and easily transformed into active Pt0NPs.

The novel awareness of humic matter as supramolecular associations of relatively small heterogeneous molecules has gained a consensus following the progressively larger number of experimental evidence present in the literature. This new understanding has implied that the humic molecules may be separated from each other by a sequential fractionation and be analytically identified one by one, thereby increasing our knowledge on their molecular structure. A method called Humeomics was thus conceived to solubilize not only unbound small molecules but also those bound in ester and ether linkages and allow to separate less chemically complex fractions easier to characterize. Humeomics was first successfully applied to humic extracts from soil, and then, directly to cropped and uncropped soils to reach a more detailed understanding of the soil Humeome, that is the molecular composition of the totality of soil humic molecules.

Hydrogenated amorphous silicon (a-Si:H) is a material having an intrinsically high radiation hardness that can be deposited on flexible substrates such as polyimide (PI). For these properties, a-Si:H can be used for the production of flexible sensors. a-Si:H sensors can be successfully utilized in dosimetry, beam monitoring for particle physics (X-ray, electron, gamma ray, and proton detection) and radiotherapy, radiation flux measurement for space applications (study of solar energetic particles and stellar events), and neutron flux measurements. In this article, we have studied the dosimetric X-ray response of n-i-p diodes deposited on PI. We measured the linearity of the photocurrent response to X-rays versus dose rate from which we have extracted the dosimetric X-ray sensitivity at various bias voltages. In particular, low bias voltage operation has been studied to assess the high energy efficiency of these kinds of sensors. A measurement of stability of X-ray response versus time has been shown. The effect of detectors annealing has been studied. Operation under bending at various bending radii is also shown.

Single lithium-ion conducting polymer electrolytes are promising candidates for next generation safer lithium batteries. In this work, Li+-conducting Nafion membranes have been synthesized by using a novel single-step procedure. The Li-Nafion membranes were characterized by means of small-wide angle X-ray scattering, infrared spectroscopy and thermal analysis, for validating the proposed lithiation method. The obtained membranes were swollen in different organic aprotic solvent mixtures and characterized in terms of ionic conductivity, electrochemical stability window, lithium stripping-deposition ability and their interface properties versus lithium metal. The membrane swollen in ethylene carbonate:propylene carbonate (EC:PC, 1:1 w/w) displays good temperature-activated ionic conductivities (σ≈ 5.5 × 10–4S cm−1at 60 °C) and a more stable Li-electrolyte interface with respect to the other samples. This Li-Nafion membrane was tested in a lithium-metal cell adopting LiFePO4as cathode material. A specific capacity of 140 mAhg−1, after 50 cycles, was achieved at 30 °C, demonstrating the feasibility of the proposed Li-Nafion membrane.

Observers of North American Indigenous life and scholarship still struggle to understand Indigenous ideas and how they are politically relevant, especially regarding the relationship between humans and nonhuman nature. Even when Indigenous claims are warmly received, scholars gloss over how these accounts understand nature to be politically relevant. By looking to a range of contemporary Native American thinkers, I argue they indeed have a coherent account of the natural world differing from dominant modern Western philosophy. In four parts, I argue Indigenous thought rejects the idea that morality is solely a product of human relationships, Indigenous thinkers do not accept the is/ought distinction pervasive in modern Western philosophy, Indigenous thinkers insist meaning can be located in the existence of specific beings that in themselves constitute wholes with identifiable purposes, and the concept of “relationality” means that one of the political community’s roles is to build relationships with the nonhuman world.

Antithrombotic therapy represents the cornerstone of the pharmacological treatment in patients with acute coronary syndrome (ACS). The optimal combination and duration of antithrombotic therapy is still matter of debate requiring a critical assessment of patient comorbidities, clinical presentation, revascularization modality, and/or optimization of medical treatment. The 2023 European Society of Cardiology (ESC) guidelines for the management of patients with ACS encompassing both patients with and without ST segment elevation ACS have been recently published. Shortly before, a European expert consensus task force produced guidance for clinicians on the management of antithrombotic therapy in patients with ACS as well as chronic coronary syndrome. The scope of this manuscript is to provide a critical appraisal of differences and similarities between the European consensus paper and the latest ESC recommendations on oral antithrombotic regimens in ACS patients.

Purpose: Metabolic dysfunction-associated steatotic liver disease (MASLD) may have distinctive pathophysiological features in type 1 diabetes (T1D). We evaluated the independent role of blood glucose control on MASLD in T1D. Methods: In a cross-sectional study on 659 T1D adult patients, MASLD was assessed by the Fatty Liver Index (FLI) and the Hepatic Steatosis Index (HSI). Anthropometric, biochemical, and clinical parameters were retrieved from electronic records. Blood glucose control status was evaluated by dividing participants into subgroups according to the median value of HbA1c [7.6% (60 mmol/mol)], and this analysis was repeated excluding overweight/obese patients. Results: Patients with HbA1c above 7.6% (60 mmol/mol) showed significantly higher MASLD indices (HSI 38 ± 6 vs. 36 ± 5, p < 0.001; FLI 26 ± 26 vs.19 ± 19, p < 0.001), and higher proportions of MASLD identified by HSI (57 vs. 44%, p < 0.001) and FLI (14 vs. 7%, p < 0.001) than patients with HbA1c below 7.6% (60 mmol/mol). Similar results were obtained for HSI after the exclusion of overweight/obese patients. Stepwise linear regression analysis confirmed that HbA1c was independently associated with HSI (r = 0.496, p = 0.009) and FLI (r = 0.722, p = 0.007); waist circumference with HSI (r = 0.492, p < 0.001); and waist circumference (r = 0.700, p < 0.001), HDL cholesterol (r = 0.719, p < 0.001), and LDL cholesterol (r = 0.712, p < 0.001) with FLI. Conclusions: Blood glucose control is a main factor associated with MASLD in adults with T1D, also independently of overweight and obesity. Appropriate therapeutic strategies focused on tight blood glucose control may also be needed for the prevention and treatment of MASLD in T1D.

Official data about consumers’ qualitative expectation and perception of inflation are derived from repeated surveys conducted by national statistical institutes. In EU, these data are published in aggregate form, and cannot be described by means of classical methods based on cumulative models for ordinal data. This article illustrates an integrated approach that locates CUB mixture models for ratings in a time series perspective in order to investigate the joint evolution of inflation judgments and expectations in Italy. In order to measure the common sentiment of interviewees through the feeling component of the model, net of possible uncertainty and nuisance effects, its estimation is pursued through profile likelihood methods given the empirical frequency distributions of consumers’ opinions observed over time. Then, the relationship between the time series of the estimated feeling parameters is modelled using a dynamic regression model and the results are compared in three periods marked by different economic conditions. Results indicate that each series has a substantial inertial component, and thus it is characterized by a slow variation over time, and that both judgments about past price levels and previous expectations affect current expectations about the future in fairly different ways for the three time periods.

Video Abstract1_e1y74gxsKaltura

Disorder of consciousness (DOC) can be either an acute and reversible condition or a chronic condition, including vegetative state or minimally conscious state. Herein, we describe a patient who has unexpectedly recovered consciousness after being in a misdiagnosed vegetative state for a long period. A 63-year-old woman was admitted to our rehabilitation center in vegetative state (Coma Recovery Scale-Revised score, 6) and treated with a standard rehabilitation program, including physical therapy and multisensory stimulation, besides psychoactive drugs. After 26 months of such training, she progressively presented with unexpected signs of awareness. Thus, she was submitted to an intensive cognitive rehabilitation with a significant improvement of her performance (Coma Recovery Scale-Revised score, 19). With this report, we want to underline that the early use of paraclinical methods, including neuroimaging and neurophysiological paradigms, is mandatory in DOC to reach a more accurate diagnosis and perform the most appropriate neurorehabilitation. Moreover, diagnosis of functional locked-in syndrome should be considered because some patients with DOC may have covert awareness with the impossibility to display consistent and reproducible behaviors due to a 'motor-cognitive dissociation.' Keywords: cognitive rehabilitation, consciousness, DOC, Consciousness is a multifaceted concept consisting of 2 aspects: wakefulness (ie, eyes opening, vigilance) and awareness (of the environment and of the self). (1) Both of these functions could be [...]

Multiple guidelines and consensus papers have addressed the role of antithrombotic strategies in patients with established coronary artery disease (CAD). Since evidence and terminology continue to evolve, the authors undertook a consensus initiative to guide clinicians to select the optimal antithrombotic regimen for each patient. The aim of this document is to provide an update for clinicians on best antithrombotic strategies in patients with established CAD, classifying each treatment option in relation to the number of antithrombotic drugs irrespective of whether the traditional mechanism of action is expected to mainly inhibit platelets or coagulation cascade. With the aim to reach comprehensiveness of available evidence, we systematically reviewed and performed meta-analyses by means of both direct and indirect comparisons to inform the present consensus document.Graphical AbstractAlgorithm for antithrombotic treatment in patients with established CAD. Treatment preferences within each box are shown from above to below, whereas treatments within the same line are sorted in alphabetical order. Panels A and B refer to non-high bleeding risk (HBR) and HBR patients, respectively. HBR is defined according to the ARC-HBR criteria or a PRECISE-DAPT score ≥25. * for patients at high ischaemic risk and very low bleeding risk. § if the patient is not eligible for above shown treatment options. Box colours indicate composition of antithrombotic regimens (light blue: SAPT; grey: DAPT; and red: DAT). Abbreviations: ARC, Academic Research Consortium; CABG, coronary artery bypass grafting; CAD, coronary artery disease; DAPT, dual antiplatelet therapy; DAT, dual antithrombotic therapy; MI, myocardial infarction; PCI, percutaneous coronary intervention; SAPT, single antiplatelet therapy.

The social, cultural and economic changes of this century have inevitably also affected the world of education and training, which, therefore, have renewed paths, objectives and goals.

Background Indocyanine green fluorescence (ICG) is one of the first fluorophore that found a clinical application in medicine. In the liver, ICG fluorescence is due to the preserved uptake but impaired washout of the dye from hepatocellular cells into the bile ducts. Therefore, some hepatobiliary surgeons proposed the technique of intravenous ICG injection before surgery for the detection of superficial hepatocarcinomas (HCCs) and colorectal liver metastases (CRLMs). Little evidence exists regarding the use of ICG to identify other hepatic tumors, such as intrahepatic cholangiocarcinoma (ICC). We report two patients affected by ICC who underwent laparoscopic liver resection with lymphadenectomy, the ICG staining was routinely performed not only to evaluate the site of the hepatic lesions but also to guide the extension of liver resection.Methods It was injected intravenously a single dose of ICG dye (0.5 mg/kg) during liver function tests 5 days before scheduled surgery. All patients underwent laparoscopic staging with both laparoscopic ultrasound and ICG fluorescence imaging.Results It was identified two different patter of ICG imaging: rim and segmental fluorescence for mass forming and mixed ICC subtype respectively.Conclusions Identification of the ICC subtype before definitive histological examination may have an impact on the surgical plan.

Reading Ben Hewitt's essay 'Rules of the Dirt Road' [March/April] reminds me that I have come full circle. I grew up on a dirt road in Arlington, Massachusetts, back in [...]

Arterial hypertension is a condition with a high prevalence in the global population and represents a major risk factor for adverse cardiovascular events, including stroke and death. Non-pharmacological and pharmacological interventions, with combination therapy as a standard strategy, are very effective in achieving optimal blood pressure (BP) goals. Nevertheless, in a non-negligible proportion of patients, drug therapy is ineffective at achieving BP targets or there is intolerance to specific anti-hypertensive medications. In this context, the use of invasive treatments for BP control, including renal denervation, represents a valuable therapeutic option. Renal denervation has experienced ups and downs over the years, with an initial growth period and a decline mainly linked to the initial negative results of a large, randomized trial. However, recent data from new trials and long-term follow-up of initial trials have confirmed the benefit and safety of the procedure by relaunching it in daily clinical practice. Additional research evaluating ablation methods other than radiofrequency are needed to be able to more clearly define the role of this procedure and the type of patients that can benefit most from it.

Graphical AbstractThe two best-in-class treatments for each outcome. Number needed to treat (NNT) and number needed to harm (NNH) with 95% confidence intervals were generated from the within and beyond 12 months network meta-analyses (NMAs) and adjusted according to baseline risk profile (low and high risks). Best-in-class antithrombotic regimens for patients at high and low risk of all-cause mortality, myocardial infarction, stroke, or major bleeding are presented in hierarchical order in terms of net benefit (NNH/NNT ratio). The average follow-up for the within and beyond 12 months NMA was 12 and 30 months, respectively. * denotes statistically significant differences in the NMA.

Background: Altered serum magnesium (Mg) levels in older persons have been hypothesized to have a role in predicting hospitalization and mortality. Hypomagnesemia and delirium are frequent problems in older patients, but no study has evaluated such an association in acute geriatric setting. Aims: We investigated the impact of hypomagnesemia on the incidence of delirium in an acute geriatric setting. Methods: This retrospective study was conducted on 209 older hospitalized patients. All subjects underwent a comprehensive geriatric assessment. Mg was measured in serum by routine laboratory methods. The presence of incident delirium was determined by the 4AT screening tool. A logistic regression model was used to assess the association between serum Mg and delirium controlling for multiple covariates. Results: 209 patients (77.9% women) were included in the study. The mean age of the participants was 85.7 ± 6.50 years (range 65–100). 27 subjects (12.9%) developed delirium during the hospitalization, with no difference between genders. Subjects with delirium had lower serum magnesium levels than those without (1.88 ± 0.34 versus 2.04 ± 0.28; p= 0.009). Delirium risk was significantly higher in patients with lower serum magnesium levels (OR 5.80 95% CI 1.450–23.222; p= 0.013), independent of multiple covariates. Conclusion: Our data show that low serum Mg level is a good predictor of incident delirium in acute geriatric settings. Present findings have relevant implications for clinical management, highlighting the need for analyzing Mg concentration carefully. Whether Mg supplementation in patients with hypomagnesemia could lead to delirium prevention and/or control needs further investigation.

The oilseed pressing process for the production of vegetable oils creates large amounts of cakes as by-products that contain high-added-value substances such as proteins and lipids. This work targets the chemical characterization of flax cake (FC), camelina cake (CC), and sunflower cake (SC) in order to evaluate the composition of proteins and residual oil, which are two of the main components, and to assess further technological applications of these biowastes. The use of a deep eutectic solvent (DES) was developed for protein extraction as a green alternative to conventional organic solvents. The lipid component, on the contrary, was extracted with n-hexane, which is typically used in oil industries. Several analytical techniques were used to characterize the cakes and the extracts (thermogravimetric analysis, attenuated total reflectance-Fourier transform infrared spectroscopy, elemental analysis; HPLC-ESI-Q-TOF/MS). In general, proteins were extracted with DES and precipitated with water, obtaining a higher yield for FC and CC. An improvement in extraction was obtained by increasing the temperature of the treatment. Different acyl glycerides profiles were identified in the residual oils obtained by solvent extraction from the cakes.

BRAT1biallelic variants are associated with rigidity and multifocal seizure syndrome, lethal neonatal (RMFSL), and neurodevelopmental disorder associating cerebellar atrophy with or without seizures syndrome (NEDCAS). To date, forty individuals have been reported in the literature. We collected clinical and molecular data from 57 additional cases allowing us to study a large cohort of 97 individuals and draw phenotype-genotype correlations. Fifty-nine individuals presented with BRAT1-related RMFSL phenotype. Most of them had no psychomotor acquisition (100%), epilepsy (100%), microcephaly (91%), limb rigidity (93%), and died prematurely (93%). Thirty-eight individuals presented a non-lethal phenotype of BRAT1-related NEDCAS phenotype. Seventy-six percent of the patients in this group were able to walk and 68% were able to say at least a few words. Most of them had cerebellar ataxia (82%), axial hypotonia (79%) and cerebellar atrophy (100%). Genotype-phenotype correlations in our cohort revealed that biallelic nonsense, frameshift or inframe deletion/insertion variants result in the severe BRAT1-related RMFSL phenotype (46/46; 100%). In contrast, genotypes with at least one missense were more likely associated with NEDCAS (28/34; 82%). The phenotype of patients carrying splice variants was variable: 41% presented with RMFSL (7/17) and 59% with NEDCAS (10/17).

In this study, Russo et al. describe the functional synergy between the adaptor protein Symplekin, the protein phosphatase 1 (PP1) regulatory subunit (PNUTS), and the Restrictor complex in controlling extragenic transcription termination in yeast. Their findings show that Symplekin is competitively recruited by Restrictor- or CPSF-containing transcription termination machineries and has a role in CPSF- and cleavage-independent transcriptional repression of noncoding RNAs and endogenous retroviral elements.

Purpose: Childhood overweight and obesity associated with insulin resistance and metabolic syndrome represent the new global pandemic and the main causative factors for dysglycemia, prediabetes, and Type 2 Diabetes Mellitus (T2DM). Predictors, such as HOMA-IR, HOMA-β%, and QUICKI lack specific reference values in children. OGTT is a gold standard for glycometabolic assessment. Recently, a glycemic level higher than 155 mg/dl at + 60′ after glucose ingestion has been defined as a risk factor for T2DM in obese adolescents. We aim to analyze and correlate fasting insulin-resistance markers with OGTT results in overweight/obese children and adolescents. Methods: We retrospectively evaluated glucose and insulin values during a 2-h OGTT every 30 min in 236 overweight/obese patients. Glucose values and insulin sum during OGTT were compared to glycometabolic indexes and different cut-off values for insulin sum. Results: A 1-h glucose > 155 mg/dl and insulin sum > 535 microU/ml at all times during OGTT are the best predictors of diabetes risk in obese youths. A1-h glucose > 155 mg/dl is significantly associated with HbA1c > 5.7%, while no association was observed between HbA1c > 5.7% and glucose levels at baseline and 2 h. The ability of the standardized HOMA-IR to predict the prediabetes status is clearly lower than the total insulin sum at OGTT. Conclusion: Our study demonstrates that also 1-h post-OGTT glucose, together with HbA1c, is an effective diabetes predictor.

Endometrial carcinomas (ECs) exhibit well-recognized characteristics on MRI sequences. In T2-weighted imaging (T2WI), the tumor presents as a diffuse or well-delineated soft tissue mass with an epicenter in the endometrial cavity and a heterogeneous intermediate signal relative to the hyperintense normal endometrium and hypointense myometrium. In diffusion-weighted imaging (DWI), tumors are hyperintense at a high b value in correspondence with the hypointense signal in the apparent diffusion coefficient (ADC) map. In dynamic contrast-enhanced MRI (DCE-MRI), endometrial tumors can show slower enhancement than the myometrium in the early phases and a hypointense signal in the later phases. In summary, dynamic sequences assist in the evaluation of continuous enhancement of the subendometrial zone (best evaluated approximately 35–40 seconds after the injection of gadolinium) and the estimated degree of myometrial invasion (best evaluated during the equilibrium phase—2.5 minutes after the injection of the contrast) and permit an adequate evaluation of the presence of infiltration of the cervical stroma (CSI), ideally evaluated 4 to 5 minutes after the injection of the contrast.1

This article has supplementary material on the web site: www.jdbp.org.