A fractional-order Wilson-Cowan formulation of cortical disinhibition.

This work presents a fractional-order Wilson-Cowan model derivation under Caputo's formalism, considering an order of 0 < α ≤ 1 . To that end, we propose memory-dependent response functions and average neuronal excitation functions that permit us to naturally arrive at a fractional-order model that incorporates past dynamics into the description of synaptically coupled neuronal populations' activity. We then shift our focus on a particular example, aiming to analyze the fractional-order dynamics of the disinhibited cortex. This system mimics cortical activity observed during neurological disorders such as epileptic seizures, where an imbalance between excitation and inhibition is present, which allows brain dynamics to transition to a hyperexcited activity state. In the context of the first-order mathematical model, we recover traditional results showing a transition from a low-level activity state to a potentially pathological high-level activity state as an external factor modifies cortical inhibition. On the other hand, under the fractional-order formulation, we establish novel results showing that the system resists such transition as the order is decreased, permitting the possibility of staying in the low-activity state even with increased disinhibition. Furthermore, considering the memory index interpretation of the fractional-order model motivation here developed, our results establish that by increasing the memory index, the system becomes more resistant to transitioning towards the high-level activity state. That is, one possible effect of the memory index is to stabilize neuronal activity. Noticeably, this neuronal stabilizing effect is similar to homeostatic plasticity mechanisms. To summarize our results, we present a two-parameter structural portrait describing the system's dynamics dependent on a proposed disinhibition parameter and the order. We also explore numerical model simulations to validate our results.

Study protocol for a randomized, controlled trial using a novel, family-centered diet treatment to prevent nonalcoholic fatty liver disease in Hispanic children.

BACKGROUND: Non-alcoholic fatty liver disease (NAFLD) is the leading liver disorder among U.S. children and is most prevalent among Hispanic children with obesity. Previous research has shown that reducing the consumption of free sugars (added sugars + naturally occurring sugars in fruit juice) can reverse liver steatosis in adolescents with NAFLD. This study aims to determine if a low-free sugar diet (LFSD) can prevent liver fat accumulation and NAFLD in high-risk children. METHODS: In this randomized controlled trial, we will enroll 140 Hispanic children aged 6 to 9 years who are ≥50th percentile BMI and without a previous diagnosis of NAFLD. Participants will be randomly assigned to either an experimental (LFSD) or a control (usual diet + educational materials) group. The one-year intervention includes removal of foods high in free sugars from the home at baseline, provision of LFSD household groceries for the entire family (weeks 1-4, 12, 24, and 36), dietitian-guided family grocery shopping sessions (weeks 12, 24, and 36), and ongoing education and motivational interviewing to promote LFSD. Both groups complete assessment measures at baseline, 6, 12, 18, and 24 months. Primary study outcomes are percent hepatic fat at 12 months and incidence of clinically significant hepatic steatosis (>5%) + elevated liver enzymes at 24 months. Secondary outcomes include metabolic markers potentially mediating or moderating NAFLD pathogenesis. DISCUSSION: This protocol describes the rationale, eligibility criteria, recruitment strategies, analysis plan as well as a novel dietary intervention design. Study results will inform future dietary guidelines for pediatric NAFLD prevention. TRIAL REGISTRATION: ClinicalTrials.gov, NCT05292352.

[COVID-19 in orthopedics]. / COVID-19 en ortopedia.

STUDY DESIGN: This is a systematic literature review for COVID-19, SARS-CoV-2 with Orthopedic and Spine Surgery relevance. OBJECTIVES: It is to determine in Orthopedic surgery and Spine Surgery and its branches the new required safety protocols when attending patients with risk of infection, or transmission for COVID-19 and comorbidities in the outpatient and inpatient hospital setting. METHODS: A systematic literature review. RESULTS: Recent knowledge for this disease has changed the Virus affects ORF-8 protein of the Hemoglobin destroying B-Hemoglobin, and IDC (intravascular disseminated coagulation) is found to happen in many patients, together with its capsular capability to adhere to metallic and plastic surfaces, pneumonic pattern associated with ventilator use, and the relapse in some patients, changes the view, preventative measures and treatment of this disease. Publication of global statistics show that patients with hypertension tend to have a higher rate of suffering the disease. Some new measures are proposed. CONCLUSIONS: New care guidelines for COVID-19 patients are proposed based on the new research on SARS-CoV-2 clinical pathologic findings are necessary.

DISEÑO DEL ESTUDIO: La presente es una revisión sistemática de la literatura de COVID-19, SARS-CoV-2 con relevancia para la cirugía ortopédica y de columna. OBJETIVOS: Determinar en cirugía ortopédica y cirugía de columna y ramificar los nuevos protocolos de seguridad requeridos cuando se atiende a pacientes con riesgo de infección o transmisión de COVID-19 y comorbilidades en el entorno hospitalario y ambulatorio. MÉTODOS: Una revisión sistemática de la literatura. RESULTADOS: El conocimiento reciente de esta enfermedad ha cambiado el virus que afecta a la proteína ORF-8 de la hemoglobina destruyendo la hemoglobina B y se ha descubierto que la IDC (coagulación diseminada intravascular) ocurre en muchos pacientes. Junto con su capacidad capsular para adherirse al metal y a las superficies plásticas, el patrón neumónico asociado con el uso del ventilador y la recaída en algunos pacientes cambia la visión, las medidas preventivas y el tratamiento de esta enfermedad. La publicación de estadísticas globales muestra que los pacientes con hipertensión tienden a tener mayor tasa de padecer la enfermedad. Se proponen algunas nuevas medidas. CONCLUSIONES: Se proponen nuevas pautas de atención para pacientes con COVID-19 con base en la nueva investigación sobre los hallazgos patológicos clínicos de SARS-CoV-2.

The effect of inhibition on the existence of traveling wave solutions for a neural field model of human seizure termination.

In this paper we study the influence of inhibition on an activity-based neural field model consisting of an excitatory population with a linear adaptation term that directly regulates the activity of the excitatory population. Such a model has been used to replicate traveling wave data as observed in high density local field potential recordings (González-Ramírez et al. PLoS Computational Biology, 11(2), e1004065, 2015). In this work, we show that by adding an inhibitory population to this model we can still replicate wave properties as observed in human clinical data preceding seizure termination, but the parameter range over which such waves exist becomes more restricted. This restriction depends on the strength of the inhibition and the timescale at which the inhibition acts. In particular, if inhibition acts on a slower timescale relative to excitation then it is possible to still replicate traveling wave patterns as observed in the clinical data even with a relatively strong effect of inhibition. However, if inhibition acts on the same timescale as the excitation, or faster, then traveling wave patterns with the desired characteristics cease to exist when the inhibition becomes sufficiently strong.

Motion deficit in nodal interphalangeal joint osteoarthritis by digital goniometer in housewives.

Range of motion (ROM) measured objectively in nodal hand osteoarthritis (NHOA) is missing. Evaluation of collateral ligaments by ultrasound (US) is unknown in NHOA also. To compare ROM in interphalangeal joints in housewives with nodal OA, with a control group by a digital system using angle to voltage (Multielgon). The second objective was to assess correlation between collateral radial and ulnar ligaments thickness and ROM. For this cross-sectional observational study, we assessed 60 hands with symptomatic NHOA and 30 hands of healthy housewives matched for age. We obtained clinical and demographic characteristics (a complete standardized physical examination of hand joints, DASH questionnaire, pain surveys, gross grasp hand goniometer, and ROM measurements by Multielgon. Presence of synovitis, power Doppler signal, osteophytes, and collateral ligaments thickness was evaluated by US. We used descriptive statistics, Spearman correlation, X2 test, t test and odds ratio. Significant less gross grasp and ROM in the right hand were observed in NHOA (p = 0.01 for both). Presence of OA, painful joints, disease duration, and score DASH were significant correlated with reduced ROM (OR 4.12, 4.12, 1.04 and 1.09, respectively). Reduced ROM was statistical significant in thumb MCP and IP joints, second and third DIP in dominant hand. There was no association between collateral radial and ulnar ligaments and reduced ROM. Synovitis and osteophytes were more prevalent in OA group. Multielgon demonstrated the pattern of reduced ROM in nodal OA of housewives particularly in MCP and IP thumb joints, second and third distal interphalangeal joints.

Structure of the mexicain-E-64 complex and comparison with other cysteine proteases of the papain family.

Mexicain is a 23.8 kDa cysteine protease from the tropical plant Jacaratia mexicana. It is isolated as the most abundant product after cation-exchange chromatography of the mix of proteases extracted from the latex of the fruit. The purified enzyme inhibited with E-64 [N-(3-carboxyoxirane-2-carbonyl)-leucyl-amino(4-guanido)butane] was crystallized by sitting-drop vapour diffusion and the structure was solved by molecular replacement at 2.1 A resolution and refined to an R factor of 17.7% (R(free) = 23.8%). The enzyme belongs to the alpha+beta class of proteins and the structure shows the typical papain-like fold composed of two domains, the alpha-helix-rich (L) domain and the beta-barrel-like (R) domain, separated by a groove containing the active site formed by residues Cys25 and His159, one from each domain. The four monomers in the asymmetric unit show one E-64 molecule covalently bound to Cys25 in the active site and differences have been found in the placement of E-64 in each monomer.

Purification, crystallization and preliminary X-ray analysis of mexicain.

Mexicain is a 23.7 kDa papain-like cysteine protease from the tropical plant Jacaratia mexicana. Extracted as a mix of proteases from the latex of the fruit, mexicain is isolated after cation-exchange chromatography as the most abundant product. The purified product inhibited with E-64 was crystallized by sitting-drop vapour diffusion in the presence of ethanolamine. Cryoprotected crystals diffracted X-rays from a home source to 1.98 A and belong to the monoclinic space group P2(1), with unit-cell parameters a = 57.36, b = 90.45, c = 80.39 A, beta = 92.64 degrees . The asymmetric unit contains four molecules of mexicain, with a corresponding crystal volume per protein weight (V(M)) of 2.24 A(3) Da(-1) and a solvent content of 45% by volume. A molecular-replacement model has been determined and refinement is in progress.

Structure of concanavalin A at pH 8: bound solvent and crystal contacts.

Concanavalin A has been crystallized in the presence of the ligand (6-S-beta-D-galactopyranosyl-6-thio)-cyclomaltoheptaose. The crystals are isomorphous to those reported for ConA complexed with peptides at low resolution (3.00-2.75 angstroms). The structure was solved at 1.9 angstroms, with free R and R values of 0.201 and 0.184, respectively. As expected, no molecules of the ligand were bound to the protein. Soaking in the cryobuffer left its fingerprint as 25 molecules of glycerol in the bound solvent, most of them at specific positions. The fact that a glycerol molecule is located in the sugar-binding pocket of each of the four subunits in the asymmetric unit and another is located in two of the peptide-binding sites suggests a recognition phenomenon rather than a displacement of water molecules by glycerol. Crystal contact analysis shows that a relation exists between the residues that form hydrogen bonds to other asymmetric units and the space group: contact Asp58-Ser62 is a universal feature of ConA crystals, while Ser66-His121, Asn69-Asn118 and Tyr100-His205 contacts are general features of the C222(1) crystal form.

Structural study of the type II 3-dehydroquinate dehydratase from Actinobacillus pleuropneumoniae.

The structure of the type II dehydroquinate dehydratase (DHQase) from Actinobacillus pleuropneumoniae, the third enzyme of the shikimate pathway, has been determined. Crystals diffracting to 1.7 A were obtained in space and on earth using the counter-diffusion technique. The structure was solved using molecular replacement and refined to high resolution. The overall structure of the dodecameric enzyme is described and compared with structures of DHQases from other bacteria. DHQases contain a flexible loop that presumably closes over the active site upon substrate binding. The enzyme can exist in an open or closed conformation. The present structure displays the open conformation, with a sulfate anion bound in the active site. The availability of this structure opens a route to structure-based antibiotics targetting this pathogenic bacterium.

Soaking: the effect of osmotic shock on tetragonal lysozyme crystals.

Protein crystals crack when they are soaked in a solution with ionic strength sufficiently different from the environment in which they grew. It is demonstrated for the case of tetragonal lysozyme that the forces involved and the mechanisms that lead to the formation of cracks are different for hypertonic and hypotonic soaking. Tetragonal lysozyme crystals are very sensitive to hypotonic shocks and, after a certain waiting time, cracks always appear with a characteristic pattern perpendicular to the crystallographic c axis. Conversely, a hypertonic shock is better withstood: cracks do not display any deterministic pattern, are only visible at higher differences in ionic strength and after a certain time a phenomenon of crystal reconstruction occurs and the cracks vanish. At the lattice level, the unit-cell volume expands in hypotonic shock and shrinks under hypertonic conditions. However, the compression of the unit cell is anisotropic: the c axis is compressed to a minimum, beyond which it expands despite the unit-cell volume continuing to shrink. This behaviour is a direct consequence of the positive charge that the crystals bear and the existence of channels along the crystallographic c axis. Both features are responsible for the Gibbs-Donnan effect which limits the free exchange of ions and affects the movement of water inside the channels and bound to the protein.