The impact of a two-year long COVID-19 public health restriction program on mechanical thrombectomy outcomes in a stroke network.

OBJECTIVE: The purpose of this study was to evaluate the impact of COVID-19 pandemic public health restrictions on our drip and ship mechanical thrombectomy program in Santiago Chile. MATERIALS AND METHODS: This was a retrospective analysis of a prospectively collected database comparing two cohorts, one during a two-year period before COVID-19 and the second during the two years of the pandemic at our metropolitan stroke program. RESULTS: A total of 100 patients were included in the pre COVID-19 cohort (cohort 1) and 121 in the COVID-19 cohort (cohort 2). There was a significant difference between cohorts, with older patients, different occlusion sites and higher door to arterial puncture time during the COVID-19 period. A non-significant trend for worse 90-day outcomes and higher mortality was present in cohort 2. There were no statistical differences in safety treatment parameters. CONCLUSIONS: COVID-19 pandemic has had a measurable impact on our mechanical thrombectomy program. Results showed similarities to other reported Latin American series, where less robust health systems could adapt less efficiently compared to developed countries. After two years of public health restrictions, there were changes in the treatment population characteristics, delay in some internal management metrics and a non-significant trend to worse 90-day outcomes and higher mortality.

Single-molecule optical tweezers reveals folding steps of the domain swapping mechanism of a protein.

Domain swapping is a mechanism of protein oligomerization by which two or more subunits exchange structural elements to generate an intertwined complex. Numerous studies support a diversity of swapping mechanisms in which structural elements can be exchanged at different stages of the folding pathway of a subunit. Here, we used single-molecule optical tweezers technique to analyze the swapping mechanism of the forkhead DNA-binding domain of human transcription factor FoxP1. FoxP1 populates folded monomers in equilibrium with a swapped dimer. We generated a fusion protein linking two FoxP1 domains in tandem to obtain repetitive mechanical folding and unfolding trajectories. Thus, by stretching the same molecule several times, we detected either the independent folding of each domain or the elusive swapping step between domains. We found that a swapped dimer can be formed directly from fully or mostly folded monomer. In this situation, the interaction between the monomers in route to the domain-swapped dimer is the rate-limiting step. This approach is a useful strategy to test the different proposed domain swapping mechanisms for proteins with relevant physiological functions.

GERO Cohort Protocol, Chile, 2017-2022: Community-based Cohort of Functional Decline in Subjective Cognitive Complaint elderly.

BACKGROUND: With the global population aging and life expectancy increasing, dementia has turned a priority in the health care system. In Chile, dementia is one of the most important causes of disability in the elderly and the most rapidly growing cause of death in the last 20 years. Cognitive complaint is considered a predictor for cognitive and functional decline, incident mild cognitive impairment, and incident dementia. The GERO cohort is the Chilean core clinical project of the Geroscience Center for Brain Health and Metabolism (GERO). The objective of the GERO cohort is to analyze the rate of functional decline and progression to clinical dementia and their associated risk factors in a community-dwelling elderly with subjective cognitive complaint, through a population-based study. We also aim to undertake clinical research on brain ageing and dementia disorders, to create data and biobanks with the appropriate infrastructure to conduct other studies and facilitate to the national and international scientific community access to the data and samples for research. METHODS: The GERO cohort aims the recruitment of 300 elderly subjects (> 70 years) from Santiago (Chile), following them up for at least 3 years. Eligible people are adults not diagnosed with dementia with subjective cognitive complaint, which are reported either by the participant, a proxy or both. Participants are identified through a household census. The protocol for evaluation is based on a multidimensional approach including socio-demographic, biomedical, psychosocial, neuropsychological, neuropsychiatric and motor assessments. Neuroimaging, blood and stool samples are also obtained. This multidimensional evaluation is carried out in a baseline and 2 follow-ups assessments, at 18 and 36 months. In addition, in months 6, 12, 24, and 30, a telephone interview is performed in order to keep contact with the participants and to assess general well-being. DISCUSSION: Our work will allow us to determine multidimensional risks factors associated with functional decline and conversion to dementia in elderly with subjective cognitive complain. The aim of our GERO group is to establish the capacity to foster cutting edge and multidisciplinary research on aging in Chile including basic and clinical research. TRIAL REGISTRATION: NCT04265482 in ClinicalTrials.gov. Registration Date: February 11, 2020. Retrospectively Registered.

Treatments used for obsessive-compulsive disorder-An international perspective.

OBJECTIVE: The objective of this study was to characterise international trends in the use of psychotropic medication, psychological therapies, and novel therapies used to treat obsessive-compulsive disorder (OCD). METHODS: Researchers in the field of OCD were invited to contribute summary statistics on the characteristics of their samples. Consistency of summary statistics across countries was evaluated. RESULTS: The study surveyed 19 expert centres from 15 countries (Argentina, Australia, Brazil, China, Germany, Greece, India, Italy, Japan, Mexico, Portugal, South Africa, Spain, the United Kingdom, and the United States) providing a total sample of 7,340 participants. Fluoxetine (n = 972; 13.2%) and fluvoxamine (n = 913; 12.4%) were the most commonly used selective serotonin reuptake inhibitor medications. Risperidone (n = 428; 7.3%) and aripiprazole (n = 415; 7.1%) were the most commonly used antipsychotic agents. Neurostimulation techniques such as transcranial magnetic stimulation, deep brain stimulation, gamma knife surgery, and psychosurgery were used in less than 1% of the sample. There was significant variation in the use and accessibility of exposure and response prevention for OCD. CONCLUSIONS: The variation between countries in treatments used for OCD needs further evaluation. Exposure and response prevention is not used as frequently as guidelines suggest and appears difficult to access in most countries. Updated treatment guidelines are recommended.

[Emergency endovascular management of ischemic stroke. Experience in 104 patients]. / Experiencia en el tratamiento endovascular del accidente cerebrovascular isquémico agudo en un centro chileno.

BACKGROUND: Recently, five randomized controlled trials confirmed the efficacy and safety of endovascular treatment with or without intravenous thrombolysis in acute ischemic stroke with large-vessel occlusion. AIM: To report patients with ischemic stroke treated with endovascular methods. MATERIAL AND METHODS: Retrospective analysis of 104 patients aged 61 ± 15 years (54% males) with ischemic stroke who received endovascular treatment at a single medical center between 2009 and 2017. RESULTS: Sixty one percent were treated with intravenous thrombolysis plus endovascular procedures and 39% with endovascular procedures alone. The median door-to needle time was 61 minutes and door-to femoral puncture was 135 minutes. The median National Institute of Health Stroke Scale (NIHSS) scores on admission, 24 hours later and at discharge were 12,4 and 1 points, respectively. Middle cerebral artery was occluded in 60% of cases. Other frequent localizations where distal carotid artery in 17% and vertebro-basilar artery in 14%. Thrombolysis in cerebral infarction (TICI) scale flow score after the procedure was 3 or 2b in 58% of cases and significantly correlated with NIHSS scores at 24 hours and discharge. Fifty percent of patients had a mRankin score < = 1 and ten patients died (9.6%). Eight percent had a symptomatic intracerebral hemorrhage. CONCLUSIONS: The clinical improvement of these patients 24 hours after the procedure and at discharge demonstrate the effectiveness of endovascular treatment in ischemic stroke. The presence neurologists able to interpret multimodal images at the emergency room, the use of local guidelines, the availability of an experienced neuro-interventional team engaged with the workflow and the use of stent retrievers are strongly associated with good outcomes.

Respirometric response and microbial succession of nitrifying sludge to m-cresol pulses in a sequencing batch reactor.

A nitrifying consortium was kinetically, stoichiometrically and molecularly characterized via the in situ pulse respirometric method and pyrosequencing analysis before and after the addition of m-cresol (25 mg C L-1) in a sequencing batch reactor (SBR). Five important kinetic and stoichiometric parameters were determined: the maximum oxygen uptake rate, the maximum nitrification rate, the oxidation yield, the biomass growth yield, and the substrate affinity constant. An inhibitory effect was observed in the nitrification process with a recovery of this by up to eight SBR cycles after m-cresol was added to the system. However, full recovery of the nitrification process was not observed, as the maximum oxygen uptake rate was 25% lower than that of the previous operation without m-cresol addition. Furthermore, the pyrosequencing analyses of the nitrifying consortium after the addition of only two pulses of 25 mg C L-1 m-cresol showed an important microbial community change represented by a decrease in the nitrifying populations and an increase in the populations degrading phenolic compounds.

Accuracy of ASGE criteria for the prediction of choledocholithiasis.

BACKGROUND/AIMS: Few studies have validated the performance of guidelines for the prediction of choledocholithiasis (CL). Our objective was to prospectively assess the accuracy of the American Society for Gastrointestinal Endoscopy (ASGE) guidelines for the identification of CL. METHODS: A two-year prospective evaluation of patients with suspected CL was performed. We evaluated the ASGE guidelines and its component variables in predicting CL. RESULTS: A total of 256 patients with suspected CL were analyzed. Of the 208 patients with high-probability criteria for CL, 124 (59.6%) were found to have a stone/sludge at endoscopic retrograde cholangiopancreatography (ERCP). Among 48 patients with intermediate-probability criteria, 21 (43.8%) had a stone/sludge. The performance of ASGE high- and intermediate-probability criteria in our population had an accuracy of 59.0% (85.5% sensitivity, 24.3% specificity) and 41.0% (14.4% sensitivity, 75.6% specificity), respectively. The mean ERCP delay time was 6.1 days in the CL group and 6.4 days in the group without CL, p = 0.638. The presence of a common bile duct (CBD) > 6 mm (OR 2.21; 95% CI, 1.20-4.10), ascending cholangitis (OR 2.37; 95% CI, 1.01-5.55) and a CBD stone visualized on transabdominal US (OR 3.33; 95% CI, 1.48-7.52) were stronger predictors of CL. The occurrence of biliary pancreatitis was a strong protective factor for the presence of a retained CBD stone (OR 0.30; 95% CI, 0.17-0.55). CONCLUSIONS: Irrespective of a patient's ASGE probability for CL, the application of current guidelines in our population led to unnecessary performance of ERCPs in nearly half of cases.

Unusual origin of the left ophthalmic artery from the basilar trunk.

The formation of the ophthalmic artery (OA) is a complex process with two different proposed embryological steps for its development. Several anatomical variants have been described. We present a very unusual origin of the ophthalmic artery from the basilar trunk, in a 45-year-old male with a history of pontine hemorrhagic stroke. MRI and CTA showed evidence of previous hemorrhage in the pons and several intracranial arterial dysplastic dilatations. DSA confirmed several fusiform dilatations of the basilar trunk. In the left ICA, no ophthalmic artery was seen arising from the carotid siphon. The left ophthalmic artery arises from the basilar trunk and runs lateral to the cavernous sinus through the middle cranial fossa, entering the left orbit at the superior orbital fissure. The patient was treated conservatively. Two main theories for this anomaly are known, one from Lasjaunias and the other from Paget. To our knowledge, this basilar origin of the OA has only been described three times in the literature. For its origin, we propose a partial persistence of the trigeminal artery together with a dominance of the dorsal ophthalmic artery.

[Changes in cerebral blood flow velocity in supine and sitting position in patients with aneurysmal subarachnoid hemorrhage]. / Descripción de los cambios en la velocidad media de flujo sanguíneo cerebral en posición supino y sedente, en pacientes con hemorragia subaracnoidea aneurismática con vasoespasmo asintomático o sin vasoespasmo. Serie de casos.

BACKGROUND: Early mobilization in intensive care units (ICU) provides respiratory, neurological and cardiovascular benefits in hospitalized patients. However, the orthostatic effects of changing from a supine to a sitting position may interfere with cerebral hemodynamics of patients with aneurysmal subarachnoid hemorrhage (aSAH). AIM: To describe the changes in mean cerebral blood flow velocity (MCBFV) in supine and sitting position, in adult patients with aSAH, with asymptomatic vasospasm (AVS) or without vasospasm (VS) at a neurosurgical ICU. MATERIAL AND METHODS: Descriptive case series study in 21 patients with aSAH, both with and without VS. They were positioned in a supine 30° position and then seated at the edge of bed for six minutes. MCBFV was measured by transcranial Doppler (TCD), and hemodynamic variables in both positions were registered. After this basal assessment and for 21 days after the episode of SAH, patients were seated once a day and signs of VS were recorded. RESULTS: No significant changes in MCBFV or hemodynamic variables were detected during position changes, except for an increase in heart rate in the sitting position. No patient with AVS at the onset, had symptomatic VS during the 21 days of follow up when patients were seated. Among patients with a normal MCBFV at baseline, five patients (24%) had VS at a mean of three days after the first time that they were seated on the edge of bed. CONCLUSIONS: Sitting patients at the edge of the bed is a safe mobilization alternative for patients who suffered aSAH who did not have VS or had AVS.

Brain Arteriovenous Malformation In Vitro Model for Transvenous Embolization Using 3D Printing and Real Patient Data.

BACKGROUND AND PURPOSE: Transvenous embolization has emerged as a novel technique for treating selected brain AVMs with high reported occlusion rates. However, it requires anatomic and technical skills to be successful and to ensure patient safety. Therefore, training and testing are essential for preparing clinicians to perform these procedures. Our aim was to develop and test a novel, patient-specific brain AVM in vitro model for transvenous embolization by using 3D printing technology. MATERIALS AND METHODS: We developed a brain AVM in vitro model based on real patient data by using stereolithography resin 3D printing. We created a closed pulsed circuit with flow passing from the arterial side to the venous side, and we tested the effect of mean arterial pressure on retrograde nidal filling with contrast injections. Transvenous embolization simulations were conducted for each of the 12 identical models divided into 2 groups (2×6). This involved the use of an ethylene-vinyl alcohol liquid embolic agent injected through microcatheters either without or with a coil in the vein (groups 1 and 2, respectively). RESULTS: Retrograde contrast advance to nidus was directly related to lower mean arterial pressure. Transvenous embolization tests with a liquid embolic agent adequately reproduced the usual embolization plug and push technique. We found no differences between the 2 group conditions, and additional venous coil neither increased nidus penetration nor reduced injection time in the model (57.6 versus 61.2% nidus occlusion rate, respectively). CONCLUSIONS: We were able to develop and test a functional in vitro brain AVM model for transvenous embolization by using 3D printing to emulate its conditions and characteristics. Better contrast penetration was achieved with less mean arterial pressure, and no embolization advantage was found by adding coil to the vein in this model.

A clinical mutation in glucokinase causing maturity-onset diabetes in the young type 2 increases enzyme activity.

Glucokinase (GCK) is the pancreatic ß-cell glucose sensor, and its kinetics are key to that purpose. A slow transition step, displayed as non-hyperbolic kinetics, and a low affinity for glucose characterize GCK. Mutations in GCK associated with maturity-onset diabetes of the young type 2 (MODY2) previously described reduce the functionality of the human pancreatic ß-cell, leading to diabetic clinical phenotypes. We present a kinetic characterization of the G448D mutation identified in a MODY2 patient, which is one of the first mutations to exhibit increased functionality. This mutant displays increased activity, high affinity for both Mg2+ -ATP and glucose, hyperbolic kinetics and increased phosphorylation potential. Hyperbolic kinetics and assays in the presence of glycerol indicate that G448D lacks the slow transition step crucial for the pancreatic ß-cell glucose sensor function.

A novel self-expanding shape memory polymer coil for intracranial aneurysm embolization: 1 year follow-up in Chile.

BACKGROUND: Aneurysm recurrence remains a challenge when coiling cerebral aneurysms. Development of next generation coils has focused on accelerating thrombus maturation and increasing coil packing density. Ultra low density shape memory polymer is a novel embolic material designed for this purpose. The polymer is crimped over a platinum-tungsten coil for catheter delivery and self-expands to a predefined volume on contact with blood. METHODS: This prospective study in humans evaluated aneurysms 5-16 mm (inclusive) in diameter that were indicated for endovascular coil embolization. At least 70% coil volume was required to be shape memory polymer coils. Patients were followed-up according to standard of care for 12 months. RESULTS: Nine patients (89% women, mean age 55.8±11.7 years) were treated with shape memory polymer coils and completed 12 months of follow-up. Aneurysms were all unruptured and were in the ophthalmic segment of the internal carotid artery (n=7), posterior communicating artery, and anterior cerebral artery A1-A2 segment. Aneurysms were a mean of 7.8±2.9 mm in diameter (range 5.2-14.9 mm). The mean packing density based on unexpanded polymer was 17±6%. Packing density based on expanded polymer was 43±13%. At 12 months, no recurrence had occurred, and a Raymond-Roy occlusion classification of 1 (n=5) or 2 (n=4) was observed. No serious adverse events related to the study device occurred over the 12 months after the procedure. CONCLUSIONS: Shape memory polymer coils were safe and effective in treating intracranial aneurysms over 12 months in this first study in human subjects.

Endovascular treatment simulations using a novel in vitro brain arteriovenous malformation model based on three-dimensional printing millifluidic technology.

BACKGROUND: Brain arteriovenous malformations (bAVM) are complex vascular diseases. Several models have been used to simulate endovascular treatments; thus in vitro models have not been widely employed because it has been difficult to recreate realistic phantoms of this disease. OBJECTIVE: To describe the development and evaluate the preliminary experience of a novel bAVM in vitro model for endovascular embolization using millifluidic three-dimensional (3D) printing technology. METHODS: We designed a bAVM phantom starting from simple to more complex designs, composed of a nidus, feeding arteries and draining vein. We recreate the design by using millifluidic technology with stereolithography 3D printing. Structural and functional tests were performed using angiographic images and computer flow dynamics. Treatment simulations with ethylene vinyl alcohol were tested using two different microcatheter position techniques. A Likert-scale questionnaire was applied to perform a qualitative evaluation of the model. RESULTS: We developed a realistic model of a bAVM with hollow channels. The structural evaluation showed a high precision of the 3D printing process. Embolization tests with the liquid agent gave similar sensations and material behaviour as in vivo cases. There were no significant differences between microcatheter position techniques, thus we observed a trend for better nidus filling with a deeper in-nidus position technique. CONCLUSIONS: We were able to create and test a novel bAVM in vitro model with stereolithography 3D printing in resin. It showed a high capacity for simulating endovascular embolization characteristics, with an excellent user experience. It could be potentially used for training and testing of bAVM embolizations.

A high throughput bispecific antibody discovery pipeline.

Bispecific antibodies (BsAbs) represent an emerging class of immunotherapy, but inefficiency in the current discovery has limited their broad clinical availability. Here we report a high throughput, agnostic, single-cell-based functional screening pipeline, comprising molecular and cell engineering for efficient generation of BsAb library cells, followed by functional interrogation at the single-cell level to identify and sort positive clones and downstream sequence identification and functionality characterization. Using a CD19xCD3 bispecific T cell engager (BiTE) as a model, we demonstrate that our single-cell platform possesses a high throughput screening efficiency of up to one and a half million variant library cells per run and can isolate rare functional clones at a low abundance of 0.008%. Using a complex CD19xCD3 BiTE-expressing cell library with approximately 22,300 unique variants comprising combinatorially varied scFvs, connecting linkers and VL/VH orientations, we have identified 98 unique clones, including extremely rare ones (~ 0.001% abundance). We also discovered BiTEs that exhibit novel properties and insights to design variable preferences for functionality. We expect our single-cell platform to not only increase the discovery efficiency of new immunotherapeutics, but also enable identifying generalizable design principles based on an in-depth understanding of the inter-relationships between sequence, structure, and function.

Basilar artery occlusion management: Specialist perspectives from an international survey.

BACKGROUND AND PURPOSE: Two early basilar artery occlusion (BAO) randomized controlled trials did not establish the superiority of endovascular thrombectomy (EVT) over medical management. While many providers continue to recommend EVT for acute BAO, perceptions of equipoise in randomizing patients with BAO to EVT versus medical management may differ between clinician specialties. METHODS: We conducted an international survey (January 18, 2022 to March 31, 2022) regarding management strategies in acute BAO prior to the announcement of two trials indicating the superiority of EVT, and compared responses between interventionalists (INTs) and non-interventionalists (nINTs). Selection practices for routine EVT and perceptions of equipoise regarding randomizing to medical management based on neuroimaging and clinical features were compared between the two groups using descriptive statistics. RESULTS: Among the 1245 respondents (nINTs = 702), INTs more commonly believed that EVT was superior to medical management in acute BAO (98.5% vs. 95.1%, p < .01). A similar proportion of INTs and nINTs responded that they would not randomize a patient with BAO to EVT (29.4% vs. 26.7%), or that they would only under specific clinical circumstances (p = .45). Among respondents who would recommend EVT for BAO, there was no difference in the maximum prestroke disability, minimum stroke severity, or infarct burden on computed tomography between the two groups (p > .05), although nINTs more commonly preferred perfusion imaging (24.2% vs. 19.7%, p = .04). Among respondents who indicated they would randomize to medical management, INTs were more likely to randomize when the National Institutes of Health Stroke Scale was ≥10 (15.9% vs. 6.9%, p < .01). CONCLUSIONS: Following the publication of two neutral clinical trials in BAO EVT, most stroke providers believed EVT to be superior to medical management in carefully selected patients, with most indicating they would not randomize a BAO patient to medical treatment. There were small differences in preference for advanced neuroimaging for patient selection, although these preferences were unsupported by clinical trial data at the time of the survey.

Soluble RAGE as a severity marker in community acquired pneumonia associated sepsis.

BACKGROUND: Community-acquired pneumonia (CAP) is considered the most important cause of death from infectious disease in developed countries. Severity assessment scores partially address the difficulties in identifying high-risk patients. A lack of specific and valid pathophysiologic severity markers affect early and effective sepsis therapy. HMGB-1, sRAGE and RAGE have been involved in sepsis and their potential as severity markers has been proposed. The aim of this study was to evaluate HMGB-1, RAGE and sRAGE levels in patients with CAP-associated sepsis and determine their possible association with clinical outcome. METHOD: We evaluated 33 patients with CAP-associated sepsis admitted to the emergency room and followed in the medical wards. Severity assessment scores (CURB-65, PSI, APACHE II, SOFA) and serologic markers (HMGB-1, RAGE, sRAGE) were evaluated on admission. RESULTS: Thirty patients with a diagnosis of CAP-associated sepsis were enrolled in the study within 24 hours after admission. Fourteen (46.6%) had pandemic (H1N1) influenza A virus, 2 (6.6%) had seasonal influenza A and 14 other diagnoses. Of the patients in the study group, 16 (53.3%) had a fatal outcome. ARDS was observed in 17 (56.6%) and a total of 22 patients had severe sepsis on admission (73%). The SOFA score showed the greatest difference between surviving and non-surviving groups (P = .003) with similar results in ARDS patients (P = .005). sRAGE levels tended to be higher in non-surviving (P = .058) and ARDS patients (P = .058). Logistic regression modeling demonstrated that SOFA (P = .013) and sRAGE (P = .05) were the only variables that modified the probability of a fatal outcome. CONCLUSION: The association of elevated sRAGE with a fatal outcome suggests that it may have an independent causal effect in CAP. SOFA scores were the only clinical factor with the ability to identify surviving and ARDS patients.

Endovascular treatment of aneurysm arising from fenestration of the supraclinoid internal carotid artery--two case reports.

We report two cases of aneurysm located in a fenestration of the supraclinoid internal carotid artery, an extremely rare anatomical variant, and describe the feasibility of endovascular treatment using two different strategies applicable for each case. Each presented aneurysm had a particular location on the fenestration, which led to different endovascular approaches. In one case, the aneurysm arose from the proximal junction of fenestration, involving both of its limbs. For this aneurysm, the treatment strategy adopted aimed to achieve a selective exclusion. In the second case, two aneurysms arose from the minor limb of the fenestration, which could be entirely excluded, considering the absence of perforating arteries arising from that carotid segment. To our knowledge, these two cases are the first ICA fenestration aneurysms treated exclusively by endovascular approach, showing two treatment strategies using coils in association to two different endovascular devices (stent/TrisPan(®)).

Fiscal Reform in Costa Rica: Price Elasticities of Major Food Categories to Inform Decision-Making.

In the context of fiscal reform in Costa Rica (value added tax revision), the definition of a new basic tax basket, "canasta básica tributaria" (CBT) in Spanish, incorporating nutritional criteria is underway in the country. In this study, price elasticities of major food categories were analyzed using a Quadratic Almost Ideal Demand System (QUAIDS) model. Data from the 2018 National Survey of Household Income and Expenditures was used. Measuring price elasticities is essential because it allows: knowing the extent to which food demand reacts to price changes, anticipating changes in the quantities demanded as a result of fiscal policy changes, measuring potential substitution and complementary effects between food groups, and potential nutritional effects of fiscal policies. As a result, it helps providing recommendations on the content of a CBT with nutritional criteria. Results show that the food categories with the most elastic demand are "Bread and cereals," soft drinks and "Milk, cheese and eggs." Substitution effects exist between the following groups: "Fruits" and "Oils and fats," "Fruits" and "Bread and cereals," and between "Milk, cheese and eggs" and "Oils and fats." For this last food category and for the one which includes sweets and chocolates, the consumption decreases when the price of "Bread and cereals" increases. They are complementary goods. These relations between food groups need to be taken into account when defining a national CBT with nutritional criteria and with the objective of promoting the consumption of healthier food groups while disincentivizing the consumption of the unhealthy ones. Lastly, it is important that the consumption of the healthiest foods within each food group be fiscally promoted. Clinical Trial Registration: JEL codes: D12, H3, I18.

The curvature of gold nanoparticles influences the exposure of amyloid-ß and modulates its aggregation process.

Gold nanoparticles (GNP) are tunable nanomaterials that can be used to develop rational therapeutic inhibitors against the formation of pathological aggregates of proteins. In the case of the pathological aggregation of the amyloid-ß protein (Aß), the shape of the GNP can slow down or accelerate its aggregation kinetics. However, there is a lack of elementary knowledge about how the curvature of GNP alters the interaction with the Aß peptide and how this interaction modifies key molecular steps of fibril formation. In this study, we analysed the effect of flat gold nanoprisms (GNPr) and curved gold nanospheres (GNS) on in vitro Aß42 fibril formation kinetics by using the thioflavin-based kinetic assay and global fitting analysis, with several models of aggregation. Whereas GNPr accelerate the aggregation process and maintain the molecular mechanism of aggregation, GNS slow down this process and modify the molecular mechanism to one of fragmentation/secondary nucleation, with respect to controls. These results can be explained by a differential interaction between the Aß peptide and GNP observed by Raman spectroscopy. While flat GNPr expose key hydrophobic residues involved in the Aß peptide aggregation, curved GNS hide these residues from the solvent. Thus, this study provides mechanistic insights to improve the rational design of GNP nanomaterials for biomedical applications in the field of amyloid-related aggregation.

Predicting and Characterizing Neurodegenerative Subtypes with Multimodal Neurocognitive Signatures of Social and Cognitive Processes.

BACKGROUND: Social cognition is critically compromised across neurodegenerative diseases, including the behavioral variant frontotemporal dementia (bvFTD), Alzheimer's disease (AD), and Parkinson's disease (PD). However, no previous study has used social cognition and other cognitive tasks to predict diagnoses of these conditions, let alone reporting the brain correlates of prediction outcomes. OBJECTIVE: We performed a diagnostic classification analysis using social cognition, cognitive screening (CS), and executive function (EF) measures, and explored which anatomical and functional networks were associated with main predictors. METHODS: Multiple group discriminant function analyses (MDAs) and ROC analyses of social cognition (facial emotional recognition, theory of mind), CS, and EF were implemented in 223 participants (bvFTD, AD, PD, controls). Gray matter volume and functional connectivity correlates of top discriminant scores were investigated. RESULTS: Although all patient groups revealed deficits in social cognition, CS, and EF, our classification approach provided robust discriminatory characterizations. Regarding controls, probabilistic social cognition outcomes provided the best characterization for bvFTD (together with CS) and PD, but not AD (for which CS alone was the best predictor). Within patient groups, the best MDA probabilities scores yielded high classification rates for bvFTD versus PD (98.3%, social cognition), AD versus PD (98.6%, social cognition + CS), and bvFTD versus AD (71.7%, social cognition + CS). Top MDA scores were associated with specific patterns of atrophy and functional networks across neurodegenerative conditions. CONCLUSION: Standardized validated measures of social cognition, in combination with CS, can provide a dimensional classification with specific pathophysiological markers of neurodegeneration diagnoses.