Real-life analysis on safety and efficacy of asciminib for ponatinib pretreated patients with chronic myeloid leukemia.

Failure of second-generation tyrosine kinase inhibitors (2GTKI) is a challenging situation in patients with chronic myeloid leukemia (CML). Asciminib, recently approved by the US Federal Drug Administration, has demonstrated in clinical trials a good efficacy and safety profile after failure of 2GTKI. However, no study has specifically addressed response rates to asciminib in ponatinib pretreated patients (PPT). Here, we present data on responses to asciminib from 52 patients in clinical practice, 20 of them (38%) with prior ponatinib exposure. We analyzed retrospectively responses and toxicities under asciminib and compared results between PPT and non-PPT patients.After a median follow-up of 30 months, 34 patients (65%) switched to asciminib due to intolerance and 18 (35%) due to resistance to prior TKIs. Forty-six patients (88%) had received at least 3 prior TKIs. Regarding responses, complete cytogenetic response was achieved or maintained in 74% and 53% for non-PPT and PPT patients, respectively. Deeper responses such as major molecular response and molecular response 4.5 were achieved in 65% and 19% in non-PPT versus 32% and 11% in PPT, respectively. Two patients (4%) harbored the T315I mutation, both PPT.In terms of toxicities, non-PPT displayed 22% grade 3-4 TEAE versus 20% in PPT. Four patients (20% of PPT) suffered from cross-intolerance with asciminib as they did under ponatinib.Our data supports asciminib as a promising alternative in resistant and intolerant non-PPT patients, as well as in intolerant PPT patients; the resistant PPT subset remains as a challenging group in need of further therapeutic options.

Cold sensing by NaV1.8-positive and NaV1.8-negative sensory neurons.

The ability to detect environmental cold serves as an important survival tool. The sodium channels NaV1.8 and NaV1.9, as well as the TRP channel Trpm8, have been shown to contribute to cold sensation in mice. Surprisingly, transcriptional profiling shows that NaV1.8/NaV1.9 and Trpm8 are expressed in nonoverlapping neuronal populations. Here we have used in vivo GCaMP3 imaging to identify cold-sensing populations of sensory neurons in live mice. We find that ∼80% of neurons responsive to cold down to 1 °C do not express NaV1.8, and that the genetic deletion of NaV1.8 does not affect the relative number, distribution, or maximal response of cold-sensitive neurons. Furthermore, the deletion of NaV1.8 had no observable effect on transient cold-induced (≥5 °C) behaviors in mice, as measured by the cold-plantar, cold-plate (5 and 10 °C), or acetone tests. In contrast, nocifensive-like behavior to extreme cold-plate stimulation (-5 °C) was completely absent in mice lacking NaV1.8. Fluorescence-activated cell sorting (FACS) and subsequent microarray analysis of sensory neurons activated at 4 °C identified an enriched repertoire of ion channels, which include the Trp channel Trpm8 and potassium channel Kcnk9, that are potentially required for cold sensing above freezing temperatures in mouse DRG neurons. These data demonstrate the complexity of cold-sensing mechanisms in mouse sensory neurons, revealing a principal role for NaV1.8-negative neurons in sensing both innocuous and acute noxious cooling down to 1 °C, while NaV1.8-positive neurons are likely responsible for the transduction of prolonged extreme cold temperatures, where tissue damage causes pan-nociceptor activation.

Short telomeres drive pessimistic judgement bias in zebrafish.

The role of telomerase reverse transcriptase has been widely investigated in the contexts of ageing and age-related diseases. Interestingly, decreased telomerase activities (and accelerated telomere shortening) have also been reported in patients with emotion-related disorders, opening the possibility for subjective appraisal of stressful stimuli playing a key role in stress-driven telomere shortening. In fact, patients showing a pessimistic judgement bias have shorter telomeres. However, in humans the evidence for this is correlational and the causal directionality between pessimism and telomere shortening has not been established experimentally yet. We have developed and validated a judgement bias experimental paradigm to measure subjective evaluations of ambiguous stimuli in zebrafish. This behavioural assay allows classification of individuals in an optimistic-pessimistic dimension (i.e. from individuals that consistently evaluate ambiguous stimuli as negative to others that perceive them as positive). Using this behavioural paradigm we found that telomerase-deficient zebrafish (tert-/-) were more pessimistic in response to ambiguous stimuli than wild-type zebrafish. The fact that individuals with constitutive shorter telomeres have pessimistic behaviours demonstrates for the first time in a vertebrate model a genetic basis of judgement bias.

Osteoarthritis-related nociceptive behaviour following mechanical joint loading correlates with cartilage damage.

OBJECTIVE: In osteoarthritis (OA), the pain-structure relationship remains complex and poorly understood. Here, we used the mechanical joint loading (MJL) model of OA to investigate both knee pathology and nociceptive behaviour. DESIGN: MJL was used to induce OA in the right knees of 12-week-old male C57BL/6 mice (40 cycles, 9N, 3x/week for 2 weeks). Mechanical sensitivity thresholds and weight-bearing ratios were measured before loading and at weeks one, three and six post-loading. At these time points, separate groups of loaded and non-loaded mice (n = 12/group) were sacrificed, joints collected, and fur corticosterone levels measured. µCT analyses of subchondral bone integrity was performed before joint sections were prepared for nerve quantification, cartilage or synovium grading (scoring system from 0 to 6). RESULTS: Loaded mice showed increased mechanical hypersensitivity paired with altered weight-bearing. Initial ipsilateral cartilage lesions 1-week post-loading (1.8 ± 0.4) had worsened at weeks three (3.0 ± 0.6, CI = -1.8-0.6) and six (2.8 ± 0.4, CI = -1.6-0.4). This increase in lesion severity correlated with mechanical hypersensitivity development (correlation; 0.729, P = 0.0071). Loaded mice displayed increased synovitis (3.6 ± 0.5) compared to non-loaded mice (1.5 ± 0.5, CI = -2.2-0.3) 1-week post-loading which returned to normal by weeks three and six. Similarly, corticosterone levels were only increased at week one post-loading (0.21 ± 0.04 ng/mg) compared to non-loaded controls (0.14 ± 0.01 ng/mg, CI = -1.8-0.1). Subchondral bone integrity and nerve volume remained unchanged. CONCLUSIONS: Our data indicates that although the loading induces an initial stress reaction and local inflammation, these processes are not directly responsible for the nociceptive phenotype observed. Instead, MJL-induced allodynia is mainly associated with OA-like progression of cartilage lesions.

Intrinsic Rashba coupling due to hydrogen bonding in DNA.

We present an analytical model for the role of hydrogen bonding on the spin-orbit coupling of a model DNA molecule. Here, we analyze in detail the electric fields due to the polarization of the hydrogen bond on the DNA base pairs and derive, within a tight binding analytical band folding approach, an intrinsic Rashba coupling which should dictate the order of the spin active effects in the chiral-induced spin selectivity effect. The coupling found is ten times larger than the intrinsic coupling estimated previously and points out to the predominant role of hydrogen bonding in addition to chirality in the case of biological molecules. We expect similar dominant effects in oligopeptides, where the chiral structure is supported by hydrogen-bonding and bears on orbital carrying transport electrons.

Obstetrical providers' preferred mode of delivery and attitude towards non-medically indicated caesarean sections: a cross-sectional study.

OBJECTIVE: To describe obstetrical providers' delivery preferences and attitudes towards caesarean section without medical indication, including on maternal request, and to examine the association between provider characteristics and preferences/attitudes. DESIGN: Cross-sectional study. SETTING: Two public and two private hospitals in Argentina. POPULATION: Obstetrician-gynaecologists and midwives who provide prenatal care and/or labour/delivery services. METHODS: Providers in hospitals with at least 1000 births per year completed a self-administered, anonymous survey. MAIN OUTCOME MEASURES: Provider delivery preference for low-risk women, perception of women's preferred delivery method, support for a woman's right to choose her delivery method and willingness to perform caesarean section on maternal request. RESULTS: 168 providers participated (89.8% coverage rate). Providers (93.2%) preferred a vaginal delivery for their patients in the absence of a medical indication for caesarean section. Whereas 74.4% of providers supported their patient's right to choose a delivery method in the absence of a medical indication for caesarean section and 66.7% would perform a caesarean section upon maternal request, only 30.4% would consider a non-medically indicated caesarean section for their own personal delivery or that of their partner. In multivariate adjusted analysis, providers in the private sector [odds ratio (OR) 4.70, 95% CI 1.19-18.62] and obstetrician-gynaecologists (OR 4.37, 95% CI 1.58-12.09) were more willing than either providers working in the public/both settings or midwives to perform a caesarean section on maternal request. CONCLUSIONS: Despite the ethical debate surrounding non-medically indicated caesarean sections, we observe very high levels of support, especially by providers in the private sector and obstetrician-gynaecologists, as aligned with the high caesarean section rates in Argentina. TWEETABLE ABSTRACT: Non-medically indicated c-section? 74% of sampled Argentine OB providers support women's right to choose.

Numerical activities of daily living in adults with neurofibromatosis type 1.

BACKGROUND: This study aimed to identify the mathematical domains affected in adults with neurofibromatosis 1 (NF1) and the impact of the numerical difficulties on the patients' activities of daily living. METHODS: We assessed 28 adult patients with NF1 and 28 healthy control participants. All participants completed the standardised battery of numerical activities of daily living along with clinical batteries of cognitive (Mini-Mental State Examination) and daily functioning (instrumental activities of daily living). The group comparisons of the performance on numerical activities of daily living were carried out using t-test correcting for multiple comparisons. RESULTS: The results showed that the NF1 group performed worse than controls in written subtractions, written multiplication, multiplication principles and digit comprehension (dot counting) tasks. Importantly, no significant differences in numerical ecological tasks were found between patients and controls, suggesting a possible use of compensatory strategies in daily living abilities in spite of calculation deficits. CONCLUSION: The findings indicate that NF1 affects calculation but not the basic comprehension or representation of numbers in adult patients. These data have important implications for designing cognitive interventions tailored to the cognitive profile of individuals with NF1.

Influence of cognitive impairment on fall risk among elderly nursing home residents.

BACKGROUND: Information relating the severity of cognitive decline to the fall risk in institutionalized older adults is still scarce. This study aims to identify potential fall risk factors (medications, behavior, motor function, and neuropsychological disturbances) depending on the severity of cognitive impairment in nursing home residents. METHODS: A total of 1,167 nursing home residents (mean age 81.44 ± 8.26 years; 66.4% women) participated in the study. According to the MEC, (the Spanish version of the Mini-Mental State Examination) three levels of cognitive impairment were established: mild (20-24) "MCI", moderate (14-19) "MOCI", and severe (≤14) "SCI". Scores above 24 points indicated the absence cognitive impairment (NCI). Information regarding fall history and fall risk during the previous year was collected using standardized questionnaires and tests. RESULTS: Sixty falls (34%) were registered among NCI participants and 417 (43%) among people with cognitive impairment (MCI: 35%; MOCI: 40%; SCI: 50%). A different fall risk model was observed for MCI, MOCI, SCI, and NCI patients. The results imply that the higher the level of cognitive impairment, the greater the number of falls (F1,481 = 113.852; Sig = 0.015), although the level of significance was not maintained when MOCI and SCI participants were compared. Depression, neuropsychiatric disturbances, autonomy constraints in daily life activity performance, and low functional mobility were factors closely associated with fall risk. CONCLUSION: This study provides evidence indicating that fall risk factors do not hold a direct correlation with the level of cognitive impairment among elderly nursing home care residents.

[Multidose treatment of methotrexate in cornual ectopic pregnancy]. / Protocolo de tratamiento multidosis con metotrexato a pacientes con embarazo-ectópico cornual.

BACKROUND: Ectopic pregnancy represents a common entity when the differential diagnosis of first trimester pathologies is performed. Extratubal location, nonetheless, is an in unfrequent situation that delays and difficults the diagnoses. CASE REPORT: 41-year-old women who goes to clinic for a pregnancy test, which proved positive done. During normal ultrasonographic we observed attached with endometrial 8 mm thick, without gestational sac inside, no free liquid in the bottom of the pouch of Douglas. In the left cornual region had a suggestive image of ectopic pregnancy, of 2.8 cm, with embryo without cardiac activity, tested with Doppler color, according to 6 weeks of amenorrhea was observed. The level of ß-HCG was 17,656 mU/mL, which confirmed the diagnosis of corneal ectopic pregnancy. Multidose protocol of methotrexate and folinic acid was prescribed at a dose of 50 mg on days 1, 3, 5 and 7, and 5 mg in the days 2, 4, 6 and 8, respectively. After 14 days of treatment a new ß-HCG study control was made, which results was 2,519 mU/mL. From that time we take a weekly control studies of the ß-HCG until was negative (six months later). The multidose protocol of methotrexate and folinic acid is an effective treatment in patients with cornual ectopic pregnancy.

[Gatrointestinal stromal tumor: a case report]. / Tumor del estroma gastrointestinal: reporte de un caso.

Gastrointestinal stromal tumors are the most common mesenquimal neoplasms of the gastrointestinal tract. A preoperative diagnose of GIST it is very difficult to make, but up to 5% of the cases initially appear as a pelvic mass. Clinical case: 45-year-old patient attended in medical service by unspecific pain in the lower abdomen of several weeks of evolution. The abdominopelvic tomography evidence collection of 9×8 cm above of the uterus and sigma's right with air in the cavity, it is was compatible with pelvic abscess. Due to increased pain, we realized emergency exploratory laparotomy, which showed a 14 cm tumor, dependent of the small intestine, without ascites or involvement other organs of the digestive or reproductive tract. The excision of the tumor was successfully (non intraoperative rupture). The pathological study reported a bowel piece of 20 cm, in which a tumor of 14 cm with large central cavitation was identified. Histologically showed diffuse growth pattern and neoplastic epithelioid cells with low rate of mitosis (mitosis 1-2/5 mm2). The immunohistochemistry test reports strong expression of DOG-1 and focal expression in CD117 (c-kit), with very low proliferation index (Ki67). The molecular pathology study identified a mutation in exon 11, codon 557-558, the c-kit gene in the p.W557_K558del position. We use imatinib (400 mg/24 h) from the second month after surgery. Today keep in treatment, and clinical and laboratories following every month: in addition, to CT scans scheduled every 6 months.

Enantiospecificity in NMR enabled by chirality-induced spin selectivity.

Spin polarization in chiral molecules is a magnetic molecular response associated with electron transport and enantioselective bond polarization that occurs even in the absence of an external magnetic field. An unexpected finding by Santos and co-workers reported enantiospecific NMR responses in solid-state cross-polarization (CP) experiments, suggesting a possible additional contribution to the indirect nuclear spin-spin coupling in chiral molecules induced by bond polarization in the presence of spin-orbit coupling. Herein we provide a theoretical treatment for this phenomenon, presenting an effective spin-Hamiltonian for helical molecules like DNA and density functional theory (DFT) results on amino acids that confirm the dependence of J-couplings on the choice of enantiomer. The connection between nuclear spin dynamics and chirality could offer insights for molecular sensing and quantum information sciences. These results establish NMR as a potential tool for chiral discrimination without external agents.

Single-nucleus and spatial landscape of the sub-ventricular zone in human glioblastoma.

The sub-ventricular zone (SVZ) is the most well-characterized neurogenic area in the mammalian brain. We previously showed that in 65% of patients with glioblastoma (GBM), the SVZ is a reservoir of cancer stem-like cells that contribute to treatment resistance and emergence of recurrence. Here, we built a single-nucleus RNA-sequencing-based microenvironment landscape of the tumor mass (T_Mass) and the SVZ (T_SVZ) of 15 GBM patients and 2 histologically normal SVZ (N_SVZ) samples as controls. We identified a mesenchymal signature in the T_SVZ of GBM patients: tumor cells from the T_SVZ relied on the ZEB1 regulatory network, whereas tumor cells in the T_Mass relied on the TEAD1 regulatory network. Moreover, the T_SVZ microenvironment was predominantly characterized by tumor-supportive microglia, which spatially co-exist and establish heterotypic interactions with tumor cells. Lastly, differential gene expression analyses, predictions of ligand-receptor and incoming/outgoing interactions, and functional assays revealed that the IL-1ß/IL-1RAcP and Wnt-5a/Frizzled-3 pathways are therapeutic targets in the T_SVZ microenvironment. Our data provide insights into the biology of the SVZ in GBM patients and identify specific targets of this microenvironment.

[Neonatal pyloroduodenal duplication cyst. A case report].

Intestinal duplications located in the duodenum are rare conditions that generally affect the first or second duodenal portion. It is extremely unusual for this condition to be located in the pyloroduodenal area, accounting for less than ten documented cases. This research presents a case of a female newborn who showed on the second day of life signs of upper intestinal obstruction which required exploratory laparotomy. The surgery revealed a pyloroduodenal cyst that was successfully excised. This is an extremely rare congenital anomaly that encompasses challenging symptoms and signs, and the purpose of the surgery should be the complete resection of the lesion. If the complete excision endangers the surrounding organs, partial resection through mucosectomy is a valid alternative to prevent the complications of more invasive surgery.

[Reliability and validity of the SAPF questionnaire and the Stunkard rating scale amongst elderly Spanish people].

BACKGROUND: The aim of the study was to identify the reliability and validity of the SAPF questionnaire and the Stunkard rating scale in determining self-perceived physical appearance and the degree of body dissatisfaction in a group of elderly Spanish people. METHODS: Both instruments were adapted to Spanish people and were administered twice to a group of 86 elderly people. Their reliability and validity were assessed by means of the intraclass correlation coefficient (ICC), Cronbach's alpha and Spearman's rho coefficient, from the physical fitness level of the participants and their body mass index (BMI). ANOVA test was carried out to compare the variables with normal distribution. RESULTS: The questionnaire and the Stunkard rating scale showed a good test-retest reliability (ICC=0.78 and ICC=0.8, respectively). SAPF and fitness level showed a significant, albeit weak, association (rho=0.424), while the association between self-perception of body composition and BMI was moderately strong (rho=0.727). The self-perceived physical appearance of 59.5% of the sample was acknowledged to be normal, 11.4% perceived it as bad and 29.1% as good. Only 27.1% were satisfied with their body image, while the other participants showed a desire to lose the equivalent weight of one (47.06%), two (22.35%) or three or more (3.5%) points in the Stunkard scale. CONCLUSION: The versions of both instruments adapted to Spanish persons showed reliability and validity, and showed that it was possible to determine that a large part of the sample was dissatisfied with their body image. BMI had a significant influence in this regard.

Magnetoencephalography reveals differences in brain activations for fast and slow responses to simple multiplications.

Despite decades of studies, it is still an open question on how and where simple multiplications are solved by the brain. This fragmented picture is mostly related to the different tasks employed. While in neuropsychological studies patients are asked to perform and report simple oral calculations, neuroimaging and neurophysiological studies often use verification tasks, in which the result is shown, and the participant must verify the correctness. This MEG study aims to unify the sources of evidence, investigating how brain activation unfolds in time using a single-digit multiplication production task. We compared the participants' brain activity-focusing on the parietal lobes-based on response efficiency, dividing their responses in fast and slow. Results showed higher activation for fast, as compared to slow, responses in the left angular gyrus starting after the first operand, and in the right supramarginal gyrus only after the second operand. A whole-brain analysis showed that fast responses had higher activation in the right dorsolateral prefrontal cortex. We show a timing difference of both hemispheres during simple multiplications. Results suggest that while the left parietal lobe may allow an initial retrieval of several possible solutions, the right one may be engaged later, helping to identify the solution based on magnitude checking.

[Analysis of the convergent validity of the Spanish short version of the Minnesota Leisure Time Physical Activity Questionnaire (VREM) and the Spanish version of the International Physical Activity Questionnaire in elderly people (IPAQ-E)]. / Análisis de la validez convergente de la Versión reducida en español del cuestionario de actividad física en el tiempo libre de Minnesota (VREM) y de la versión española del Cuestionario internacional de actividad física en personas mayores (IPAQ-E).

BACKGROUND: In our country the Spanish short version of the Minnesota Leisure Time Physical Activity Questionnaire (VREM) and the International Physical Activity Questionnaire in elderly people (IPAQ-E) are considered useful tools for estimating the amount of physical activity (PA) performed by the geriatric population. However, few studies have been carried out on their psychometric properties. Therefore, this research aims to provide information on their convergent validity by analysing the degree of association that both questionnaires show with physical fitness level. MATERIAL AND METHODS: A total of 105 people (mean age: 76.77 (SD=6.01) years; 84.8% women), answered both questionnaires and performed the Senior Fitness Test (SFT), in order to assess their physical fitness level. RESULTS: Significant correlations were found between the SFT and the VREM items related to energy expenditure derived from walking (r=0.227) or from performing sports activities or dancing (r=0.235), and the estimated total energy expenditure (r=0.314). The IPAQ-E did not establish significant associations with any of the variables analysed. Although a certain a priori correlation was observed between the VREM and the IPAQ-E (r=0.447, p<0.001) and the mean difference between both parameters was nil (p=0.553), it was considered that the questionnaires showed a lack of agreement due to the great width found in the range of differences. CONCLUSIONS: The use of the VREM questionnaire is recommended for estimating the amount of PA performed by the geriatric population, as it shows a certain degree of association, albeit weak, with the level of physical fitness.

Sleep disorders and cognitive dysfunction in acromegaly.

PURPOSE: In the general population, sleep disorders are associated with an increased risk of cognitive impairment. The prevalence of sleep disorders, such as sleep apnea, in acromegalic patients is higher than in the general population, and they may have additional risk of cognitive impairment due to acromegaly treatment and comorbidities. We aim to study the relationship between sleep disturbances and cognitive dysfunction in a group of acromegalic patients. METHODS: We studied 67 consecutive acromegalic patients. We performed a neurocognitive assessment and patients completed the Acromegaly Quality of Life Questionnaire (AcroQoL), Epworth Sleepiness Scale, and Pittsburgh Sleep Quality Index. RESULTS: Of the 67 acromegaly patients in the study, 38.8% were male and median age at the neurological examination was 56 (IQR 48, 65). Approximately 6-10% of patients had impaired cognitive assessment, depending on the test. In linear regression models adjusted for age, sex, BMI, disease duration, and disease activity, poorer sleep quality was associated with lower global cognitive z-score (B = -0.03, 95% CI -0.06, -0.002). Daytime somnolence was associated with poorer physical AcroQoL sub-score (B = -0.04, 95% CI -0.08, -0.002). Sleep quality was associated with poorer overall AcroQoL (B = -0.03, 95% CI -0.05, -0.006), physical AcroQoL (B = -0.04, 95% CI -0.07, -0.005), psychological AcroQoL (B = -0.02, 95% CI -0.04, -0.001), and social AcroQoL (B = -0.02, 95% CI -0.04, -0.0009). CONCLUSIONS: In acromegaly patients, we found robust evidence that poor sleep quality is associated with poorer quality of life, and some evidence that it is associated with poorer cognitive function.

Influence of cognitive impairment on the freezing of gait in non demented people with Parkinson's disease. / Influencia del deterioro cognitivo en la congelacion de la marcha en pacientes con enfermedad de Parkinson sin demencia.

INTRODUCTION: Freezing of gait (FOG) is a motor disturbance usually appearing in advanced Parkinson's disease (PD). Cognitive and executive function seems to play an important role in this phenomenon. AIM: To investigate if cognitive and kinematic parameters correlate with FOG in PD patients without dementia. PATIENTS AND METHODS: We conducted an observational cross-sectional study. Participants were classified in two groups: freezers and non-freezers. Clinical information was obtained by Hoehn and Yahr scale, Unified Parkinson's Disease Rating Scale and balance test of Short Physical Performance Battery. Cognitive function was evaluated using Minimental Examination and the Fuld Object Memory Evaluation; executive function was assessed with the Frontal Assessment Battery test. Battery kinematic parameters were assessed by means of gait speed, cadence, stride length and stride time. RESULTS: Twenty-five participants with PD without dementia completed the evaluation. Statistical significant differences between freezers and non-freezers were found in global cognition (p = 0,02), memory (p = 0,04), executive function (p = 0,04), cadence (p = 0,02), stride length (p = 0,04) and stride time (p = 0,01). CONCLUSION: Cognitive parameters may have an important contribution to the manifestation of freezing of gait in PD. These results may have important clinical implications for developing future non-pharmacological and cognitive interventions strategies targeted to PD patients with FOG.

TITLE: Influencia del deterioro cognitivo en la congelacion de la marcha en pacientes con enfermedad de Parkinson sin demencia.Introduccion. La congelacion de la marcha (CDM) es una alteracion motora que suele aparecer en estadios avanzados de la enfermedad de Parkinson (EP). Las funciones cognitivas y ejecutivas parecen tener un papel importante en la aparicion de este fenomeno. Objetivo. Investigar si los parametros cognitivos y cinematicos se correlacionan con la CDM en pacientes con EP sin demencia. Pacientes y metodos. Estudio observacional y transversal. Los participantes se clasificaron en dos grupos: con y sin CDM. La informacion clinica se obtuvo mediante la escala de Hoehn y Yahr, la Unified Parkinson's Disease Rating Scale y la prueba de equilibrio de la Short Physical Performance Battery. La funcion cognitiva se valoro con el miniexamen cognitivo y la Fuld Object Memory Evaluation, y la funcion ejecutiva, con la Frontal Assessment Battery. Los parametros cinematicos se valoraron mediante la velocidad de la marcha, la cadencia, la longitud del paso y el tiempo del paso. Resultados. Veinticinco participantes con EP sin demencia completaron el programa. Se encontraron diferencias estadisticamente significativas entre individuos con y sin CDM en cognicion global (p = 0,02), memoria (p = 0,04), funcion ejecutiva (p = 0,04), cadencia (p = 0,02), longitud del paso (p = 0,04) y tiempo del paso (p = 0,01). Conclusion. Diversos parametros cognitivos pueden contribuir de forma importante en la aparicion de la CDM en la EP. Estos resultados pueden tener implicaciones clinicas relevantes para el desarrollo de estrategias e intervenciones no farmacologicas y cognitivas dirigidas a pacientes con EP y con CDM.

N2pc reflects two modes for coding the number of visual targets.

Humans share with a variety of animal species the spontaneous ability to detect the numerical correspondence between limited quantities of visual objects and discrete auditory events. Here, we explored how such mental representation is generated in the visual modality by monitoring a parieto-occipital ERP component, N2pc, whose amplitude covaries with the number of visual targets in explicit enumeration. Participants listened to an auditory sequence of one to three tones followed by a visual search display containing one to three targets. In Experiment 1, participants were asked to respond based on the numerical correspondence between tones and visual targets. In Experiment 2, participants were asked to ignore the tones and detect a target presence in the search display. The results of Experiment 1 showed an N2pc amplitude increase determined by the number of visual targets followed by a centroparietal ERP component modulated by the numerical correspondence between tones and visual targets. The results of Experiment 2 did not show an N2pc amplitude increase as a function of the number of visual targets. However, the numerical correspondence between tones and visual targets influenced N2pc amplitude. By comparing a subset of amplitude/latency parameters between Experiment 1 and 2, the present results suggest N2pc reflects two modes for representing the number of visual targets. One mode, susceptible to subjective control, relies on visual target segregation for exact target individuation, whereas a different mode, likely enabling spontaneous cross-modal matching, relies on the extraction of rough information about number of targets from visual input.