In Vitro and In Vivo Evidence towards Fibronectin's Protective Effects against Prion Infection.

A distinctive signature of the prion diseases is the accumulation of the pathogenic isoform of the prion protein, PrPSc, in the central nervous system of prion-affected humans and animals. PrPSc is also found in peripheral tissues, raising concerns about the potential transmission of pathogenic prions through human food supplies and posing a significant risk to public health. Although muscle tissues are considered to contain levels of low prion infectivity, it has been shown that myotubes in culture efficiently propagate PrPSc. Given the high consumption of muscle tissue, it is important to understand what factors could influence the establishment of a prion infection in muscle tissue. Here we used in vitro myotube cultures, differentiated from the C2C12 myoblast cell line (dC2C12), to identify factors affecting prion replication. A range of experimental conditions revealed that PrPSc is tightly associated with proteins found in the systemic extracellular matrix, mostly fibronectin (FN). The interaction of PrPSc with FN decreased prion infectivity, as determined by standard scrapie cell assay. Interestingly, the prion-resistant reserve cells in dC2C12 cultures displayed a FN-rich extracellular matrix while the prion-susceptible myotubes expressed FN at a low level. In agreement with the in vitro results, immunohistopathological analyses of tissues from sheep infected with natural scrapie demonstrated a prion susceptibility phenotype linked to an extracellular matrix with undetectable levels of FN. Conversely, PrPSc deposits were not observed in tissues expressing FN. These data indicate that extracellular FN may act as a natural barrier against prion replication and that the extracellular matrix composition may be a crucial feature determining prion tropism in different tissues.

Performance in Kahoot! activities as predictive of exam performance.

BACKGROUND: Game-based learning (GBL) is effective for increasing participation, creativity, and student motivation. However, the discriminative value of GBL for knowledge acquisition has not yet been proven. The aim of this study is to assess the value of Kahoot! as a discriminative tool for formative assessment in medical education in two different subjects. METHODS: A prospective experimental study was conducted on a sample of 173 students enrolled in neuroanatomy (2021-2022). One hundred twenty-five students individually completed the Kahoot! prior to the final exam. In addition, students enrolled in human histology during two academic courses were included in the study. The control group course (2018-2019) received a traditional teaching methodology (N = 211), while Kahoot! was implemented during 2020-2021 (N = 200). All students completed similar final exams for neuroanatomy and human histology based on theory tests and image exams. RESULTS: The correlation between the Kahoot score and the final grade was analyzed for all students enrolled in neuroanatomy who completed both exercises. The correlation between the Kahoot exercise and the theory test, image exam and final grade was significantly positive in all cases (r = 0.334 p < 0.001, r = 0.278 p = 0.002 and r = 0.355 p < 0.001, respectively). Moreover, students who completed the Kahoot! exercise obtained significantly higher grades in all parts of the exam. Regarding human histology, the theory tests, image exams and final grades were significantly higher when using Kahoot! versus the "traditional" methodology (p < 0.001, p < 0.001 and p = 0.014, respectively). CONCLUSIONS: Our study demonstrates for the first time that Kahoot! can be used to improve and predict the final grade in medical education subjects.

Reduced Th1 response is associated with lower glycolytic activity in activated peripheral blood mononuclear cells after metabolic and bariatric surgery.

BACKGROUND: Obesity promotes cellular immunometabolism changes that trigger the activation of macrophages and lymphocytes, leading to systemic inflammation. Activated leukocytes undergo metabolic reprogramming, increasing glycolytic activity. OBJECTIVE: To examine whether the reduction in the inflammatory state associated with bariatric surgery is associated with decreased glycolytic activity in leukocytes. Setting Single-center, prospective observational study. METHODS: This study involved 18 patients with obesity undergoing bariatric surgery. All measurements were performed preoperatively and six months postoperatively. Peripheral blood mononuclear cells and plasma were obtained to determine the glycolytic rate and mitochondrial membrane potential as surrogates of the metabolic switching and high-sensitivity C-reactive protein, adipokines, and CD69 expression as inflammatory and activation markers. RESULTS: Glycolytic activity engaged by CD3/CD28 activation was reduced six months after bariatric surgery, associated with decreased levels of T helper (Th) 1 and Th17 signature cytokines. An overall reduction in inflammatory markers was observed, which correlated with a higher adiponectin/leptin ratio. CONCLUSIONS: Metabolic and bariatric surgery-induced weight loss leads to reprogramming in T cells' metabolic machinery, resulting in reduced stimulation of glycolysis after activation, which may explain the decrease in systemic inflammation mediated by cytokines such as interferon-γ and interleukin-17A.

Prevalence and pattern of cardiovascular magnetic resonance late gadolinium enhancement in highly trained endurance athletes.

BACKGROUND: Intensive endurance exercise may induce a broad spectrum of right ventricular (RV) adaptation/remodelling patterns. Late gadolinium enhancement (LGE) has also been described in cardiovascular magnetic resonance (CMR) of some endurance athletes and its clinical meaning remains controversial. Our aim was to characterize the features of contrast CMR and the observed patterns of the LGE distribution in a cohort of highly trained endurance athletes. METHODS: Ninety-three highly trained endurance athletes (> 12 h training/week at least during the last 5 years; 36 ± 6 years old; 53% male) and 72 age and gender-matched controls underwent a resting contrast CMR. In a subgroup of 28 athletes, T1 mapping was also performed. RESULTS: High endurance training load was associated with larger bi-ventricular and bi-atrial sizes and a slight reduction of biventricular ejection fraction, as compared to controls in both genders (p < 0.05). Focal LGE was significantly more prevalent in athletes than in healthy subjects (37.6% vs 2.8%; p < 0.001), with a typical pattern in the RV insertion points. In T1 mapping, those athletes who had focal LGE had higher extracellular volume (ECV) at the remote myocardium than those without (27 ± 2.2% vs 25.2 ± 2.1%; p < 0.05). CONCLUSIONS: Highly trained endurance athletes showed a ten-fold increase in the prevalence of focal LGE as compared to control subjects, always confined to the hinge points. Additionally, those athletes with focal LGE demonstrated globally higher myocardial ECV values. This matrix remodelling and potential presence of myocardial fibrosis may be another feature of the athlete's heart, of which the clinical and prognostic significance remains to be determined.

Topographic synthesis of arbitrary surfaces with vortex Jinc functions.

When a circular aperture is uniformly illuminated, it is possible to observe in the far field an image of a bright circle surrounded by faint rings known as the Airy pattern or Airy disk. This pattern is described by the first-order Bessel function of the first type divided by its argument expressed in circular coordinates. We introduce the higher-order Bessel functions with a vortex azimuthal factor to propose a family of functions to generalize the function defining the Airy pattern. These functions, which we call vortex Jinc functions, happen to form an orthogonal set. We use this property to investigate their usefulness in fitting various surfaces in a circular domain, with applications in precision optical manufacturing, wavefront optics, and visual optics, among others. We compare them with other well-known sets of orthogonal functions, and our findings show that they are suitable for these tasks and can pose an advantage when dealing with surfaces that concentrate a considerable amount of their information near the center of a circular domain, making them suitable applications in visual optics or analysis of aberrations of optical systems, for instance, to analyze the point spread function.

Three-dimensional regional bi-ventricular shape remodeling is associated with exercise capacity in endurance athletes.

AIMS: Endurance athletes develop cardiac remodeling to cope with increased cardiac output during exercise. This remodeling is both anatomical and functional and shows large interindividual variability. In this study, we quantify local geometric ventricular remodeling related to long-standing endurance training and assess its relationship with cardiovascular performance during exercise. METHODS: We extracted 3D models of the biventricular shape from end-diastolic cine magnetic resonance images acquired from a cohort of 89 triathlon athletes and 77 healthy sedentary subjects. Additionally, the athletes underwent cardio-pulmonary exercise testing, together with an echocardiographic study at baseline and few minutes after maximal exercise. We used statistical shape analysis to identify regional bi-ventricular shape differences between athletes and non-athletes. RESULTS: The ventricular shape was significantly different between athletes and controls (p < 1e-6). The observed regional remodeling in the right heart was mainly a shift of the right ventricle (RV) volume distribution towards the right ventricular infundibulum, increasing the overall right ventricular volume. In the left heart, there was an increment of left ventricular mass and a dilation of the left ventricle. Within athletes, the amount of such remodeling was independently associated to higher peak oxygen pulse (p < 0.001) and weakly with greater post-exercise RV free wall longitudinal strain (p = 0.03). CONCLUSIONS: We were able to identify specific bi-ventricular regional remodeling induced by long-lasting endurance training. The amount of remodeling was associated with better cardiopulmonary performance during an exercise test.

Increased cerebrospinal fluid levels of cytokines monocyte chemoattractant protein-1 (MCP-1) and macrophage inflammatory protein-1ß (MIP-1ß) in patients with amyotrophic lateral sclerosis. / Incremento de las citoquinas proteína quimiotáctica de monocitos-1 (MCP-1) y proteína inflamatoria macrofágica-1ß (MIP-1ß) en líquido cefalorraquídeo de pacientes con esclerosis lateral amiotrófica.

INTRODUCTION: Neuroinflammation has recently been described in amyotrophic lateral sclerosis (ALS). However, the precise role of such proinflammatory cytokines as monocyte chemoattractant protein-1 (MCP-1) and macrophage inflammatory protein-1ß (MIP-1ß) in ALS has not yet been determined. In this study, we determined cerebrospinal fluid (CSF) MCP-1 and MIP-1ß levels and assessed their association with the duration and severity of ALS. METHODS: Concentrations of MCP-1 and MIP-1ß were determined in the CSF of 77 patients diagnosed with ALS and 13 controls. Cytokine levels were analysed in relation to ALS duration (<12months vs. >12months) and severity (<30points vs. >30points on the ALS Functional Rating Scale administered at hospital admission). RESULTS: Higher CSF MIP-1ß (10.68pg/mL vs. 4.69pg/mL, P<.0001) and MCP-1 (234.89pg/mL vs. 160.95pg/mL, P=.011) levels were found in the 77 patients with ALS compared to controls. There were no differences in levels of either cytokine in relation to disease duration or severity. However, we did observe a significant positive correlation between MIP-1ß and MCP-1 in patients with ALS. CONCLUSIONS: The increase in MIP-1ß and MCP-1 levels suggests that these cytokines may have a synergistic effect on ALS pathogenesis. However, in our cohort, no association was found with either the duration or the clinical severity of the disease.

An Alternative Treatment Against Acanthocephala ( Prosthenorchis elegans) in Captive Squirrel Monkeys ( Saimiri sciureus) in Mexico.

We provide the first report of Acanthocephala ( Prosthenorchis elegans) in Mexican non-human primates. There has been no known treatment against this parasite except for surgical removal, and this has been relatively ineffective because of the small juveniles. We report the presence of P. elegans in a captive breeding colony of squirrel monkeys ( Saimiri sciureus) in Mexico, and we describe a successful treatment protocol. Treatment involved 2 steps: oral administration of the drugs loperamide chlorhydrate (0.5 mg/0.9 kg/3 days) and niclosamide (0.2 mg/0.9 kg/3 days) followed by surgical removal of adult worms from the intestine. Fecal examination during treatment revealed live adults but no living juveniles and no eggs. Surgery after 1 wk of treatment revealed the presence of adults and an absence of juvenile parasites. All adults were physically extracted during the surgery. All subjects recovered from surgery within 1 wk.

High-frequency burst vagal nerve simulation therapy in a natural primate model of genetic generalized epilepsy.

PURPOSE: Since the approval of Vagal Nerve Stimulation (VNS) Therapy for medically refractory focal epilepsies in 1997, it has been also reported to be effective for a wide range of generalized seizures types and epilepsy syndromes. Instead of conventional VNS Therapy delivered at 20-30Hz signal frequencies, this study evaluates efficacy and tolerability of high-frequency burst VNS in a natural animal model for genetic generalized epilepsy (GGE), the epileptic baboon. METHODS: Two female baboons (B1 P.h. Hamadryas and B2 P.h. Anubis x Cynocephalus) were selected because of frequently witnessed generalized tonic-clonic seizures (GTCS) for VNS implantation. High-frequency burst VNS Therapy was initiated after a 4-5 week baseline; different VNS settings (0.25, 2 or 2.5mA, 300Hz, 4 vs 7 pulses, 0.5-2.5s interburst interval, and intermittent stimulation for 1-2 vs for 24h per day) were tested over the subsequent 19 weeks, which included a 4-6 week wash-out period. GTCS frequencies were quantified for each setting, while seizure duration and postictal recovery times were compared to baseline. Scalp EEG studies were performed at almost every setting, including intermittent light stimulation (ILS) to evaluate photosensitivity. Pre-ILS ictal and interictal discharge rates, as well as ILS responses were compared between trials. The Novel Object test was used to assess potential treatment effects on behavior. RESULTS: High-frequency burst VNS Therapy reduced GTCS frequencies at all treatment settings in both baboons, except when output currents were reduced (0.25mA) or intermittent stimulation was restricted (to 1-2h/day). Seizure duration and postictal recovery times were unchanged. Scalp EEG studies did not demonstrate treatment-related decrease of ictal or interictal epileptic discharges or photosensitivity, but continuous treatment for 120-180s during ILS appeared to reduce photoparoxysmal responses. High-frequency burst VNS Therapy was well-tolerated by both baboons, without cardiac or behavioral changes. Repetitive muscle contractions involving the neck and left shoulder girdle were observed intermittently, most commonly at 0.5 interburst intervals, but these were transient, resolving with a few cycles of stimulation and not noted in wakefulness. CONCLUSIONS: This preclinical pilot study demonstrates efficacy and tolerability of high-frequency burst VNS Therapy in the baboon model of GGE. The muscle contractions may be due to aberrant propagation of the stimulus along the vagal nerve or to the ansa cervicalis, but can be reduced by minimal adjustment of current output or stimulus duration.

Multiple pulmonary embolisms in a male marathon athlete: Is intense endurance exercise a real thrombogenic risk?

Intense endurance exercise could be associated with multiple thrombogenic risk factors, including dehydration, hemoconcentration, inflammation, and injuries. Despite an increasing number of reported cases of deep venous thrombosis (DVT) in athletes that is raising awareness in the medical community, the prevalence is not well established and evidenced-based guidelines for management of this clinical scenario are lacking. We present an episode of unprovoked DVT and multiple pulmonary embolisms with severe right ventricular dysfunction in a male runner. We highlight the challenge of diagnosing DVT and pulmonary embolism in athletes due to frequently atypical symptomatology and the emergent need for longitudinal studies to evaluate their thrombogenic risk and develop specific guidelines in this field.

Stroop Color-Word Interference Test: Normative data for the Latin American Spanish speaking adult population.

OBJECTIVE: To generate normative data on the Stroop Test across 11 countries in Latin America, with country-specific adjustments for gender, age, and education, where appropriate. METHOD: The sample consisted of 3,977 healthy adults who were recruited from Argentina, Bolivia, Chile, Cuba, El Salvador, Guatemala, Honduras, Mexico, Paraguay, Peru, and, Puerto Rico. Each subject was administered the Stroop Test, as part of a larger neuropsychological battery. A standardized five-step statistical procedure was used to generate the norms. RESULTS: The final multiple linear regression models explained 14-36% of the variance in Stroop Word scores, 12-41% of the variance in the Stoop Color, 14-36% of the variance in the Stroop Word-Color scores, and 4-15% of variance in Stroop Interference scores. Although t-tests showed significant differences between men and women on the Stroop test, none of the countries had an effect size larger than 0.3. As a result, gender-adjusted norms were not generated. CONCLUSIONS: This is the first normative multicenter study conducted in Latin America to create norms for the Stoop Test in a Spanish-Speaking sample. This study will therefore have important implications for the future of neuropsychology research and practice throughout the region.

Standard form of the Boston Naming Test: Normative data for the Latin American Spanish speaking adult population.

OBJECTIVE: To generate normative data on the Boston Naming Test (BNT) across 10 countries in Latin America, with country-specific adjustments for gender, age, and education, where appropriate. METHOD: The sample consisted of 3,779 healthy adults who were recruited from Argentina, Bolivia, Chile, Cuba, El Salvador, Guatemala, Mexico, Paraguay, Peru, and, Puerto Rico. Each subject was administered the BNT as part of a larger neuropsychological battery. A standardized five-step statistical procedure was used to generate the norms. RESULTS: The final multiple linear regression models explained between 3-32% of the variance in BNT scores. Although t-tests showed significant differences between men and women for Mexico, Argentina, Chile, Cuba, Guatemala, and Bolivia on the BNT, none of the six countries had an effect size larger than 0.3. As a result, gender-adjusted norms were not generated. CONCLUSIONS: This is the first normative multicenter study conducted in Latin America to generate norms for the BNT; this study will have substantial repercussions for the practice of neuropsychology throughout the global region.

Symbol Digit Modalities Test: Normative data for the Latin American Spanish speaking adult population.

OBJECTIVE: To generate normative data on the Symbol Digit Modalities Test (SDMT) across 11 countries in Latin America, with country-specific adjustments for gender, age, and education, where appropriate. METHOD: The sample consisted of 3,977 healthy adults who were recruited from Argentina, Bolivia, Chile, Cuba, El Salvador, Guatemala, Honduras, Mexico, Paraguay, Peru, and, Puerto Rico. Each subject was administered the SDMT as part of a larger neuropsychological battery. A standardized five-step statistical procedure was used to generate the norms. RESULTS: The final multiple linear regression models explained 29-56% of the variance in SDMT scores. Although there were gender differences on the SDMT in Mexico, Honduras, Paraguay, and Guatemala, none of the four countries had an effect size greater than 0.3. As a result, gender-adjusted norms were not generated. CONCLUSIONS: This is the first normative multicenter study conducted in Latin America to create norms for the SDMT; this study will have an impact on the future practice of neuropsychology throughout the global region.

Brief Test of Attention: Normative data for the Latin American Spanish speaking adult population.

OBJECTIVE: To generate normative data on the Brief Test of Attention (BTA) across 11 countries in Latin America, with country-specific adjustments for gender, age, and education, where appropriate. METHOD: The sample consisted of 3,977 healthy adults who were recruited from Mexico, Argentina, Peru, Paraguay, Honduras, Chile, Cuba, Puerto Rico, Guatemala, El Salvador, and Bolivia. Each subject was administered the BTA as part of a larger neuropsychological battery. A standardized five-step statistical procedure was used to generate the norms. RESULTS: The final multiple linear regression models explained between 11-41% of the variance in BTA scores. Although men had higher scores on the BTA in Honduras, there were no other significant gender differences, and this one effect size was small. As a result, gender-adjusted norms were not generated. CONCLUSIONS: This is the first normative multicenter study conducted in Latin America to create norms for the BTA; this study will have an impact on the future practice of neuropsychology throughout Latin America.

Rey-Osterrieth Complex Figure - copy and immediate recall: Normative data for the Latin American Spanish speaking adult population.

OBJECTIVE: To generate normative data on the Rey-Osterrieth Complex Figure Test (ROCF) across 11 countries in Latin America, with country-specific adjustments for gender, age, and education, where appropriate. METHOD: The sample consisted of 3,977 healthy adults who were recruited from Argentina, Bolivia, Chile, Cuba, El Salvador, Guatemala, Honduras, Mexico, Paraguay, Peru, and, Puerto Rico. Each subject was administered the ROCF as part of a larger neuropsychological battery. A standardized five-step statistical procedure was used to generate the norms. RESULTS: The final multiple linear regression models explained 7-34% of the variance in ROCF copy scores and 21-41% of the variance in immediate recall scores. Although t-tests showed significant differences between men and women on ROCF copy and immediate recall scores, none of the countries had an effect size larger than 0.3. As a result, gender-adjusted norms were not generated. CONCLUSIONS: The present study is the first to create norms for the ROCF in Latin America. As a result, this study will have important implications for the formation and practice of neuropsychology in this region.

Verbal fluency tests: Normative data for the Latin American Spanish speaking adult population.

OBJECTIVE: To generate normative data for the Verbal Fluency Tests across 11 countries in Latin America, with country-specific adjustments for gender, age, and education, where appropriate. METHOD: The sample consisted of 3,977 healthy adults who were recruited from Argentina, Bolivia, Chile, Cuba, El Salvador, Guatemala, Honduras, Mexico, Paraguay, Peru, and, Puerto Rico. Each subject was administered the Verbal Fluency Test as part of a larger neuropsychological battery. A standardized five-step statistical procedure was used to generate the norms. RESULTS: The final multiple linear regression models for the letter F explained 8-30% of the variance, 7-32% for letter A, 8-32% for the letter S, and 16-43% for the animal category in Verbal Fluency Test scores. Although t-tests showed significant differences between men and women on the Verbal Fluency Test, they did not have an effect size larger than 0.3. As a result, gender-adjusted norms were not generated. CONCLUSIONS: This is the first normative multicenter study conducted in Latin America aiming to create norms for the Verbal Fluency Test; this study will have important outcomes for the future of neuropsychology in the region.

Trail Making Test: Normative data for the Latin American Spanish speaking adult population.

OBJECTIVE: To generate normative data on the Trail Making Test (TMT) across 11 countries in Latin America, with country-specific adjustments for gender, age, and education, where appropriate. METHOD: The sample consisted of 3,977 healthy adults who were recruited from Mexico, Argentina, Peru, Paraguay, Honduras, Chile, Cuba, Puerto Rico, Guatemala, El Salvador, and Bolivia. Each subject was administered the TMT as part of a larger neuropsychological battery. A standardized five-step statistical procedure was used to generate the norms. RESULTS: The final multiple linear regression models for the TMT-A explained 23- 50% of the variance, and the final multiple linear models for the TMT-B explained 22- 49% of the variance. Although there were gender differences on the TMT in Mexico, Peru, Paraguay, and Honduras, only Honduras had an effect size greater than 0.3. As a result, gender-adjusted norms were generated for the Trail Making Test-A, but not B, in this country. CONCLUSIONS: The present study is the first to create norms for the TMT in Latin America. As a result, this study will have important implications for the practice of neuropsychology in the future.