Neurofilament Light Chain in Adult and Pediatric Multiple Sclerosis:A Promising Biomarker to Better Characterize Disease Activity and Personalize MS Treatment

Many biological markers have been explored in multiple sclerosis (MS) to better quantify disease burden and better evaluate response to treatments, beyond clinical and MRI data. Among these, neurofilament light chain (Nf-L), although non-specific for this disease and found to be increased in other neurological conditions, has been shown to be the most promising biomarker for assessing axonal damage in MS, with a definite role in predicting the development of MS in patients at the first neurological episode suggestive of MS, and also in a preclinical phase. There is strong evidence that Nf-L levels are increased more in relapsing versus stable MS patients, and that they predict future disease evolution (relapses, progression, MRI measures of activity/progression) in MS patients, providing information on response to therapy, helping to anticipate clinical decisions in patients with an apparently stable evolution, and identifying patient non-responders to disease-modifying treatments. Moreover, Nf-L can contribute to the better understanding of the mechanisms of demyelination and axonal damage in adult and pediatric MS. A fundamental requirement for its clinical use is the accurate standardization of normal values, corrected for confounding factors, in particular age, sex, body mass index, and presence of comorbidities. In this review, a guide is provided to update clinicians on the use of Nf-L in clinical activity.</p

Attractions between charged colloids at water interfaces

The effective potential between charged colloids trapped at water interfaces is analyzed. It consists of a repulsive electrostatic and an attractive capillary part which asymptotically both show dipole--like behavior. For sufficiently large colloid charges, the capillary attraction dominates at large separations. The total effective potential exhibits a minimum at intermediate separations if the Debye screening length of water and the colloid radius are of comparable size.Comment: 8 pages, 1 figure, revised version (one paragraph added) accepted in JPC

Inhibitor binding mode and allosteric regulation of Na+-glucose symporters.

Sodium-dependent glucose transporters (SGLTs) exploit sodium gradients to transport sugars across the plasma membrane. Due to their role in renal sugar reabsorption, SGLTs are targets for the treatment of type 2 diabetes. Current therapeutics are phlorizin derivatives that contain a sugar moiety bound to an aromatic aglycon tail. Here, we develop structural models of human SGLT1/2 in complex with inhibitors by combining computational and functional studies. Inhibitors bind with the sugar moiety in the sugar pocket and the aglycon tail in the extracellular vestibule. The binding poses corroborate mutagenesis studies and suggest a partial closure of the outer gate upon binding. The models also reveal a putative Na+ binding site in hSGLT1 whose disruption reduces the transport stoichiometry to the value observed in hSGLT2 and increases inhibition by aglycon tails. Our work demonstrates that subtype selectivity arises from Na+-regulated outer gate closure and a variable region in extracellular loop EL5

A Spectroscopic Analysis of the California-Kepler Survey Sample. I. Stellar Parameters, Planetary Radii, and a Slope in the Radius Gap

We present results from a quantitative spectroscopic analysis conducted on archival Keck/HIRES high-resolution spectra from the California-Kepler Survey (CKS) sample of transiting planetary host stars identified from the Kepler mission. The spectroscopic analysis was based on a carefully selected set of Fe i and Fe ii lines, resulting in precise values for the stellar parameters of effective temperature (Teff) and surface gravity (log g). Combining the stellar parameters with Gaia DR2 parallaxes and precise distances, we derived both stellar and planetary radii for our sample, with a median internal uncertainty of 2.8% in the stellar radii and 3.7% in the planetary radii. An investigation into the distribution of planetary radii confirmed the bimodal nature of this distribution for the small-radius planets found in previous studies, with peaks at ~1.47 ± 0.05 and ~2.72 ± 0.10 R⊕ with a gap at ~1.9 R⊕. Previous studies that modeled planetary formation that is dominated by photoevaporation predicted this bimodal radii distribution and the presence of a radius gap, or photoevaporation valley. Our results are in overall agreement with these models, as well as core powered mass-loss models. The high internal precision achieved here in the derived planetary radii clearly reveal the presence of a slope in the photoevaporation valley for the CKS sample, indicating that the position of the radius gap decreases with orbital period; this decrease was fit by a power law of the form Rpl ∝ P−0.11, which is consistent with both photoevaporation and core powered mass-loss models of planet formation, with Earth-like core compositions.Conselho Nacional de Desenvolvimento Cientifico e Tecnologico (CNPq); National Aeronautics and Space Administration [16-XRP16 2-0004]; Coordenacao de Aperfeicoamento de Pessoal de Nivel Superior (CAPES)This item from the UA Faculty Publications collection is made available by the University of Arizona with support from the University of Arizona Libraries. If you have questions, please contact us at [email protected]

Longitudinal umbilical vein blood flow changes in normal and growth-retarded fetuses

Objective. To explore whether the umbilical vein blood flow of growth-retarded fetuses with normal Doppler parameters changes over time differently to that of normally grown fetuses. Methods. Fifteen consecutive women whose fetus was diagnosed to be growth restricted were compared with 30 women whose fetus was normally grown. Two ultrasonographic evaluations were conducted at 2-weekly intervals (± 2 days) in all cases. At each sonographic evaluation, umbilical vein blood flow parameters were obtained by digital color Doppler velocity profile integration. To allow comparisons among fetuses, the umbilical vein blood flow per minute was normalized for abdominal circumference. Results. The absolute vein blood flow was lower in growth-retarded than in normally grown fetuses (209 ml/min ± 73 vs. 313 ml/min ± 72, p &lt; 0.01). The median (range) umbilical vein blood flow normalized for abdominal circumference was significantly lower in growth-retarded than in normally grown fetuses at the first [0.70 (0.32; 1.15) vs. 1.11 (0.65; 2.07), p &lt; 0.05] and at the second [0.71(0.30; 1.09) vs. 1.14 (0.69; 2.05), p &lt; 0.05] sonographic evaluation. The difference in umbilical vein blood flow normalized for abdominal circumference between the second and the first examination was significantly lower in growth-retarded than in appropriate for gestational age fetuses [-0.005 (-0.08; 0.06) vs. 0.02 (-0.08; 0.1), p &lt; 0.05]. Conclusion. This study demonstrates that umbilical vein blood flow normalized for biometric parameters is lower in growth-retarded fetuses than in healthy fetuses even in the absence of umbilical artery Doppler abnormalities

Asymmetric core combustion in neutron stars and a potential mechanism for gamma ray bursts

We study the transition of nuclear matter to strange quark matter (SQM) inside neutron stars (NSs). It is shown that the influence of the magnetic field expected to be present in NS interiors has a dramatic effect on the propagation of a laminar deflagration (widely studied so far), generating a strong acceleration of the flame in the polar direction. This results in a strong asymmetry in the geometry of the just formed core of hot SQM which resembles a cylinder orientated in the direction of the magnetic poles of the NS. This geometrical asymmetry gives rise to a bipolar emission of the thermal neutrino-antineutrino pairs produced in the process of SQM formation. The neutrino-antineutrino pairs annihilate into electron-positron pairs just above the polar caps of the NS giving rise to a relativistic fireball, thus providing a suitable form of energy transport and conversion to gamma emission that may be associated to short gamma ray bursts (GRBs).Comment: 2 figure

Transumbilical versus transvaginal retrieval of surgical specimens at laparoscopy: a randomized trial.

Objective We sought to compare transumbilical (TU) and transvaginal (TV) route for retrieval of surgical specimens at laparoscopy. Study design Women scheduled for a laparoscopic resection of an adnexal mass were randomized to have their surgical specimen removed either through a posterior colpotomy (n = 34) or the umbilical port site (n = 32). Group allocation was concealed from patients and bedside clinicians. The primary outcome was postoperative incisional pain assessed by a 10-cm visual analog scale at 1, 3, and 24 hours after surgery. Results TV retrieval caused less postoperative pain than TU specimen extraction at each time point (visual analog scale score at 1 hour: 2.6 \ub1 2.9 vs 1.2 \ub1 2.0, P = .03; at 3 hours: 2.4 \ub1 2.0 vs 1.4 \ub1 2.0, P = .02; and at 24 hours: 1.1 \ub1 1.5 vs 0.5 \ub1 1.4, P = .02). A higher proportion of women in the TU group than in the TV group indicated the umbilicus as the most painful area at 1 and 3 hours postoperatively. Two months after surgery, the participants scored similarly as to their overall satisfaction, cosmetic outcome, and dyspareunia upon resumption of intercourse. Conclusion A TV approach for specimen removal after laparoscopic resection of adnexal masses offers the advantage of less postoperative pain than TU retrieva

The implicit component of moral disengagement: applying the relational responding task to investigate its relationship with cheating behavior

This article aims to conceptualize, for the first time, an implicit form of moral disengagement and investigate its role in relation to cheating behavior. In line with the implicit social-cognition models, we argue that the implicit moral disengagement would represent an unintentional, automatic, and less accessible form of the mechanisms bypassing the moral self-regulatory system. We anticipate that in situations implying on-the-spot decisions and where individuals might suffer no consequences for the misconduct, the implicit moral disengagement would predict the actual behavior while the explicit moral disengagement would predict self-reported conduct. The results of three empirical studies provide support for the theorization of an implicit moral disengagement and its assessment through a newly developed implicit measurement procedure using the relational responding task. Results of the structural equation models, including both implicit and explicit moral disengagement, demonstrated that only the implicit one was associated with the actual misconduct