An exploration of visuomotor and perceptual mechanisms in humans and rats.

Neuropsychological, neurophysiological and psychophysical evidence support the notion of two separate and largely independent cortical visual systems: a dorsal system mediating visually guided action and a ventral system mediating object perception and recognition (Goodale & Milner, 1992). This thesis is divided into three parts that explore questions related to the two-visual-systems model, two in humans and one in rats. The first part explores whether dorsal representations are based on the veridical properties of the stimuli or whether they include information produced by filling-in mechanisms of cortical visual areas. All human experiments were carried out with the ELITE and SMART motion tracking systems. Kinematic analysis showed that grasping Kanizsa illusory squares and partly-occluded objects was as accurate as grasping luminance-defined targets and it is concluded that information about interpolated regions is available to the dorsal system for the calibration of the movement parameters. A Vernier acuity task confirmed that the perceptual localization of Kanizsa and luminance-defined contours is not equally accurate in the ventral visual system. The second part explores the effect of target dimensionality on grasping, focusing on the possibility that actions aimed at targets that contain two-dimensional information could be modulated by ventral visual mechanisms. The Diagonal Illusion (DI) was chosen to investigate this possibility because it is entirely the product of three- dimensional objects. The DI exerted an effect on both perception and action, although the latter was smaller, suggesting that the effects of illusions on action previously reported are not attributable to the presence of 2D information and, by implication, that 2D information in the target array does not elicit modulation by the ventral visual system. These conclusions were confirmed by a study that found similar kinematic profiles from grasps aimed at 3D, 2D and 2D-enhanced targets. Control studies ruled out potential confounding effects resulting from curvatures of the stimuli that could have acted as obstacles and from differences in haptic feedback. It is concluded that object-directed action is mediated by dorsal visual mechanisms, irrespective of target dimensionality. The third part seeks to find evidence of ventral visual processing in rats by measuring the perception of visual illusions and object recognition in this species. The aim is to establish whether rats could provide a suitable model to further investigate the dorsal and ventral visual systems. An automated apparatus with a touch-screen and computer generated stimuli was developed to train the animals. The results from the illusion studies are not conclusive as only one out of three groups of rats was able to solve a discrimination with Kanizsa illusory figures. The preliminary results from the object recognition studies are however clearer. Rats were able to use aspect ratio to solve a discrimination with stimuli that varied in size and location suggesting that size- and location-independent object recognition occurs in this species. Probe trials confirmed these results. It is concluded that rats may have visual processes comparable to those occurring in the ventral visual system of humans and primates

Chronic exertional compartment syndrome of the forearm: a systematic review

The aim of this systematic review is to understand which surgical procedure provides better results in terms of pain relief and function in the treatment of chronic exertional compartment syndrome (CECS) of the forearm. We searched Medline (PubMed), Web of Science, Embase and Scopus databases on 8 July 2020. Twelve studies were included in this review. We assessed the quality of the studies using the Coleman Methodological Score. Data on demographic features, operative readings, diagnostic methods, follow-up periods, type and rates of complications, survivorship of the procedure, return to sport activity, and outcome measures were recorded. In conclusion, compared to the other techniques, endoscopic fasciotomy delivers similar success rates and lower incidence of complications

Normal and five-fingered hand: comparative X-ray morphometry in the post-natal age

Background: Five-fingered hand (5-FH) with completely developed phalanges is a rare phenotype observed so far only in humans and characterised by three phalanges of the 1st ray. A long-lasting, debated question is if the missing element of the normal hand 1st ray is the metacarpal or the phalanx. In this study, comparative X-rays morphometry of long bones in normal and 5-FH is carried out with the aim to face this question through homology analysis of long bone segments in the transverse and longitudinal line of normal hand and 5-FH. Materials and methods: In the normal hand X-rays (n =20) and in a 5-FH X-rays series (n = 9) the relative length of each segment on the ray total length and the index of growth rate (IGR) were assessed. The calculation of the first parameter in normal hand bi-phalangeal thumb was carried out on the 3rd ray total length in the same hand. Results: The parameters of relative length and the proximal/distal growth rate asymmetry in the post-natal period (assessed through the IGR) confirmed in 5-FH the homology of all the five segment on the transverse line. In the normal control hand, the relative length assessment methodology was biased by the missing segment of the thumb, therefore, the reference to the 3rd ray total length in the same hand (instead of the 1st), allowed the homology analysis of the thumb metacarpal and 1st phalanx with the lateral segments (2nd–5th ray) of the same hand. The 5-FH analysis was used to choose the more appropriate reference ray for the normal hand group. Conclusions: The comparative analysis of relative lengths and IGRs in the two groups suggested homology of the (anatomical) 1st metacarpal with the 2nd–5th proximal phalanges in the same hand and that of the (anatomical) 1st proximal phalanx with the 2nd–5th mid phalanges. These data suggest that the missing segment of the normal hand thumb is the metacarpal

Functional Characterization of Two Mutations Located in the Ligand Binding Domain in the SF1

Purpose: Since SF1 gene mutations located in the ligand binding domain are associated with a wide phenotypic spectrum in 46,XY subjects, the functional and structural characterization of these variations is of great interest. The aim of this study is to evaluate the clinical phenotype, hormonal pattern and molecular studies (genetic, functional data and protein structural analysis) in two non-related 46,XY disorder of sex development (DSD) index patients. Methods: Clinical characteristics, genomic DNA sequencing analysis, protein prediction software study and protein structure analysis, and functional characterization of the mutations was carried out. Results: Both index DSD patients showed a similar phenotype, however several affected members of Family 1 showed variable phenotypes. While in Family 1 a previously reported heterozygous missense point mutation (p.Arg313His) was found, in Family 2 a novel heterozygous missense point mutation (p.Ser303Arg) was detected. Both mutations were predicted to be as “probably damaging”. The transcriptional activity of SF1 mutants p.Arg313His and p.Ser303Arg, studied using two different promoters in two cell lines, exhibited significant reductions of transactivation activity. Structural analysis showed differences between both mutants, such as changes in the flexibility of the receptor backbone and in the tertiary structure around the ligand and in the AF-2 domain. Conclusions: One of these ligand binding domain mutations in SF1 showed phenotypic heterogeneity among family members, while both variations showed similarities in prepubertal phenotype, as well as in damage prediction and experimental decreases in transcriptional activity, but marked differences in structural consequence predictions. Finally the present study reinforces the concept of the wide variability in the clinical phenotype in affected 46,XY DSD patients.Fil: Perez Garrido, Natalia Isabel. Gobierno de la Ciudad de Buenos Aires. Hospital de Pediatría "Juan P. Garrahan"; ArgentinaFil: Saraco, Nora Isabel. Gobierno de la Ciudad de Buenos Aires. Hospital de Pediatría "Juan P. Garrahan"; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Marino, R.. Gobierno de la Ciudad de Buenos Aires. Hospital de Pediatría "Juan P. Garrahan"; ArgentinaFil: Ramirez, P.. Gobierno de la Ciudad de Buenos Aires. Hospital de Pediatría "Juan P. Garrahan"; ArgentinaFil: Ciaccio, Marta Graciela Cristina. Gobierno de la Ciudad de Buenos Aires. Hospital de Pediatría "Juan P. Garrahan"; ArgentinaFil: Costanzo, M.. Gobierno de la Ciudad de Buenos Aires. Hospital de Pediatría "Juan P. Garrahan"; ArgentinaFil: Guercio, Gabriela Viviana. Gobierno de la Ciudad de Buenos Aires. Hospital de Pediatría "Juan P. Garrahan"; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Warman, M.. Gobierno de la Ciudad de Buenos Aires. Hospital de Pediatría "Juan P. Garrahan"; ArgentinaFil: Minini, L.. Universidad de la República. Facultad de Ciencias; UruguayFil: Portillo Ledesma, S.. Universidad de la República. Facultad de Ciencias; UruguayFil: Rivarola, Marco Aurelio. Gobierno de la Ciudad de Buenos Aires. Hospital de Pediatría "Juan P. Garrahan"; ArgentinaFil: Coitiño, E. L.. Universidad de la República. Facultad de Ciencias; UruguayFil: Belgorosky, Alicia. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Gobierno de la Ciudad de Buenos Aires. Hospital de Pediatría "Juan P. Garrahan"; Argentin

Comparison of Bioelectrical Impedance Analysis (BIA)-Derived Parameters in Healthy Volunteers and Critically Ill Patients

Objective: To compare bioelectrical impedance analysis (BIA)-derived parameters in healthy volunteers and critically ill patients and to assess its prognostic value in an ICU patient cohort. Design: Retrospective, observational data analysis. Setting: Single centre, tertiary-level ICU (Ziekenhuis Netwerk Antwerpen, ZNA Stuivenberg Hospital). Patients: 101 patients and 101 healthy subjects, participants of International Fluid Academy Days. Measurements and main results: Compared to healthy volunteers, both male and female ICU patients had significantly higher values for total body water (TBW), extracellular water (ECW), extracellular fluid (ECF), plasma, and interstitial fluid volumes. The phase angle was significantly lower and the malnutrition index was significantly higher in ICU patients, regardless of gender. Non-survivors in the ICU had significantly higher extracellular water content (ECW, 50.7 ± 5.1 vs. 48.9 ± 4.3%, p = 0.047) and accordingly significantly lower intracellular water (ICW, 49.2 ± 5.1 vs. 51.1 ± 4.3%, p = 0.047). The malnutrition index was also significantly higher in non-survivors compared to survivors (0.94 ± 0.17 vs. 0.87 ± 0.16, p = 0.048), as was the capillary leak index (ECW/ICW). Conclusions: Compared to healthy volunteers, this study observed a higher malnutrition index and TBW in ICU patients with an accumulation of fluids in the extracellular compartment. ICU non-survivors showed similar results, indicating that ICU patients and a fortiori non-survivors are generally overhydrated, with increased TBW and ECW, and more undernourished, as indicated by a higher malnutrition index

Garbage in, garbage out: how reliable training data improved a virtual screening approach against SARS-CoV-2 MPro

Introduction: The identification of chemical compounds that interfere with SARS-CoV-2 replication continues to be a priority in several academic and pharmaceutical laboratories. Computational tools and approaches have the power to integrate, process and analyze multiple data in a short time. However, these initiatives may yield unrealistic results if the applied models are not inferred from reliable data and the resulting predictions are not confirmed by experimental evidence.Methods: We undertook a drug discovery campaign against the essential major protease (MPro) from SARS-CoV-2, which relied on an in silico search strategy –performed in a large and diverse chemolibrary– complemented by experimental validation. The computational method comprises a recently reported ligand-based approach developed upon refinement/learning cycles, and structure-based approximations. Search models were applied to both retrospective (in silico) and prospective (experimentally confirmed) screening.Results: The first generation of ligand-based models were fed by data, which to a great extent, had not been published in peer-reviewed articles. The first screening campaign performed with 188 compounds (46 in silico hits and 100 analogues, and 40 unrelated compounds: flavonols and pyrazoles) yielded three hits against MPro (IC50 ≤ 25 μM): two analogues of in silico hits (one glycoside and one benzo-thiazol) and one flavonol. A second generation of ligand-based models was developed based on this negative information and newly published peer-reviewed data for MPro inhibitors. This led to 43 new hit candidates belonging to different chemical families. From 45 compounds (28 in silico hits and 17 related analogues) tested in the second screening campaign, eight inhibited MPro with IC50 = 0.12–20 μM and five of them also impaired the proliferation of SARS-CoV-2 in Vero cells (EC50 7–45 μM).Discussion: Our study provides an example of a virtuous loop between computational and experimental approaches applied to target-focused drug discovery against a major and global pathogen, reaffirming the well-known “garbage in, garbage out” machine learning principle

Do rats use shape to solve "shape discriminations"?

Visual discrimination tasks are increasingly used to explore the neurobiology of vision in rodents, but it remains unclear how the animals solve these tasks: Do they process shapes holistically, or by using low-level features such as luminance and angle acuity? In the present study we found that when discriminating triangles from squares, rats did not use shape but instead relied on local luminance differences in the lower hemifield. A second experiment prevented this strategy by using stimuli-squares and rectangles-that varied in size and location, and for which the only constant predictor of reward was aspect ratio (ratio of height to width: a simple descriptor of "shape"). Rats eventually learned to use aspect ratio but only when no other discriminand was available, and performance remained very poor even at asymptote. These results suggest that although rats can process both dimensions simultaneously, they do not naturally solve shape discrimination tasks this way. This may reflect either a failure to visually process global shape information or a failure to discover shape as the discriminative stimulus in a simultaneous discrimination. Either way, our results suggest that simultaneous shape discrimination is not a good task for studies of visual perception in rodents

Neural modulation by binocular disparity greatest in human dorsal visual stream.

Although cortical activation to binocular disparity can be demonstrated throughout occipital and parietal cortices, the relative contributions to depth perception made by different human cortical areas have not been established. To investigate whether different regions are optimized for specific disparity ranges, we have measured the responses of occipital and parietal areas to different magnitudes of binocular disparity. Using stimuli consisting of sinusoidal depth modulations, we measured cortical activation when the stimuli were located at pedestal disparities of 0, 0.1, 0.35, and 0.7 degrees from fixation. Across all areas, occipital and parietal, there was an increase in BOLD signal with increasing pedestal disparity, compared with a plane at zero disparity. However, the greatest modulation of response by the different pedestals was found in the dorsal visual areas and the parietal areas. These differences contrast with the response to the zero disparity plane, compared with fixation, which is greatest in the early visual areas, smaller in the ventral and dorsal visual areas, and absent in parietal areas. Using the simultaneously acquired psychophysical data we also measured a greater response to correct than to incorrect trials, an effect that increased with rising pedestal disparity and was greatest in dorsal visual and parietal areas. These results illustrate that the dorsal stream, along both its occipital and parietal branches, can reliably discriminate a large range of disparities