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The sleeping brain retains some residual information processing capacity. Although direct evidence is scarce, a substantial literature suggests the phase of slow oscillations during deep sleep to be an important determinant for stimulus processing. Here, we introduce an algorithm for predicting slow oscillations in real-time. Using this approach to present stimuli directed at both oscillatory up and down states, we show neural stimulus processing depends importantly on the slow oscillation phase. During ensuing wakefulness, however, we did not observe differential brain or behavioral responses to these stimulus categories, suggesting no enduring memories were formed. We speculate that while simpler forms of learning may occur during sleep, neocortically based memories are not readily established during deep sleep.

Alpha band power, particularly at the 10 Hz frequency, is significantly involved in sensory inhibition, attention modulation, and working memory. However, the interactions between cortical areas and their relationship to the different functional roles of the alpha band oscillations are still poorly understood. Here we examined alpha band power and the cortico-cortical interregional phase synchrony in a psychophysical task involving the detection of an object moving in depth by an observer in forward self-motion. Wavelet filtering at the 10 Hz frequency revealed differences in the profile of cortical activation in the visual processing regions (occipital and parietal lobes) and in the frontoparietal regions. The alpha rhythm driving the visual processing areas was found to be asynchronous with the frontoparietal regions. These findings suggest a decoupling of the 10 Hz frequency into separate functional roles: sensory inhibition in the visual processing regions and spatial attention in the frontoparietal regions.

Traumatic brain injury (TBI) is an important public health problem, comparable to stroke in incidence and prevalence. Few interventions have proven efficacy in TBI, and clinical trials are, therefore, necessary to advance management in TBI. We describe the current clinical trial landscape in traumatic brain injury and compare it with the trial efforts for stroke. For this, we analysed all stroke and TBI studies registered on the US Clinical Trials (www.clinicaltrials.gov) database over a 10-year period (01/01/2000 to 01/31/2013). This methodology has been previously used to analyse clinical trial efforts in other specialties. We describe the research profile in each area: total number of studies, total number of participants and change in number of research studies over time. We also analysed key study characteristics, such as enrolment number and scope of recruitment. We found a mismatch between relative public health burden and relative research effort in each disease. Despite TBI having comparable prevalence and higher incidence than stroke, it has around one fifth of the number of clinical trials and participant recruitment. Both stroke and TBI have experienced an increase in the number of studies over the examined time period, but the rate of growth for TBI is one third that for stroke. Small-scale (

Las contradicciones en el desarrollo urbano post-industrial, sobre todo en las metrópolis del llamado Tercer Mundo en una economía globalizada, acentúan viejas desigualdades sociales y abren las puertas para nuevas espacializaciones, tanto entre los estratos ricos como entre los pobres. El presente trabajo presenta una primera visión de la segregación socioespacial. La estructura intraurbana del municipio de São Paulo concentra sus estratos más ricos en los anillos más centrales, dejando que la pobreza domine la periferia. Es el retrato de una metrópolis excluyente, sin urbanidad, un tejido urbano donde se perciben enclaves de riqueza y de pobreza, en el medio de una malla indistinta, tejido fragmentadoThe contradictions in post-industrial urban development, mainly regarding the so-called third world metropolis in a globalized economy, enhance old social disparities and welcome new "spacial structures", both in rich and poor fractions. The present paper shows an initial view of the socio-spacial segregation. The intra-urban structure of the city of Sao Paulo concentrates the wealthy in central rings, thus making the periphery the domain of the poor. It is the picture of a divided metropolis, with no civility, an urban patchwork quilt where rich and poor enclaves are placed on an indistinct frame

Recent findings suggest that sleep might serve a role in emotional coping. However, most findings are based on subjective reports of sleep quality, while the relation with underlying sleep physiology is still largely unknown. In this study, the impact of an emotionally distressing experience on the EEG correlates of sleep was assessed. In addition, the association between sleep physiological parameters and the extent of emotional attenuation over sleep was determined. The experimental set up involved presentation of an emotionally neutral or distressing film fragment in the evening, followed by polysomnographic registration of undisturbed, whole-night sleep and assessment of emotional reactivity to film cues on the next evening. We found that emotional distress induced mild sleep deterioration, but also an increase in the proportion of slow wave sleep (SWS) and altered patterning of rapid eye movement (REM) sleep. Indeed, while REM sleep occurrence normally increases over the course of the night, emotional distress flattened this distribution and correlated with an increased number of REM periods. While sleep deterioration was negatively associated to emotional attenuation over sleep, the SWS response was positively related to such attenuation and may form part of a compensatory response to the stressor. Interestingly, trait-like SWS characteristics also correlated positively with the extent of emotion attenuation over sleep. The combined results provide strong evidence for an intimate reciprocal relation between sleep physiology and emotional processing. Moreover, individual differences in subjects' emotional and sleep responses suggest there may be a coupling of certain emotion and sleep traits into distinct emotional sleep types.

This study evaluated the Propolis product (LLOS) effects on feed intake, dry matter (DM) and nutrients total digestibility, rumen characteristics and microbial efficiency in buffaloes fed a roughage based diet (70% Cynodon spp hay and 30% concentrate). Using a 4¥4 latin square design, four crossbred buffalo (Murrah x Jafarabadi) steers (519.0±13.0 kg body weight - BW), were fed four treatments with three LLOS concentrations: Control (no LLOS), LLOS B3+ (0.272 mg/g flavonoid chrysin equivalents), LLOS C1 (0.092 mg/g flavonoid chrysin equivalents), and LLOS C1+ (0.184 mg/g flavonoid chrysin equivalents). Diet formulation was 60% total digestible nutrient (TDN) and 11% crude protein (CP). No difference was observed in DM intake among experimental diets (P>0.05). Steers fed LLOS C1 had greater (Pvs 62.7%), organic matter (OM) (68.1 vs 63.7%), neutral detergent fibre (NDF) (61.7 vs 56.6%), total carbohydrates (TCHO) (67.7 vs 63.2%) and TDN (66.1 vs 62.8%) compared to animals fed the control diet. LLOS C1 provided greatest (Pvs 14.05 μM/mL) compared to control. The lowest rumen pH (6.65; P0.05) was observed for ammoniacal nitrogen (N-NH3), solid and liquid passage rate and microbial efficiency among treatments. In this study LLOS C1 improved forage diet efficiency in buffalo steers.

Following anterior cruciate ligament reconstruction (ACLR), patients exhibit abnormal walking mechanics and quadriceps dysfunction. Quadriceps dysfunction has been largely attributed to muscle atrophy and weakness. While important, these factors do not capture intrinsic properties of muscle that govern its ability to generate force and withstand load. While fascicle abnormalities after ACLR have been documented in early stages of recovery (<12 mo), long-term effects of ACLR on fascicle mechanics remain unexplored. We evaluated quadriceps fascicle mechanics during walking 3 years post-ACLR and examined the relationship with knee mechanics. Participants included 24 individuals with ACLR and 24 Controls. Linear mixed models compared the ACLR, Contralateral, and Controls limbs for (1) quadriceps strength, (2) fascicle architecture and mechanics, and (3) knee mechanics. No difference in strength or overall fascicle length excursions was found between limbs. The ACLR limb exhibited longer fascicles at heel strike and peak knee extension moment (P <.001–.004), and smaller fascicle angles at heel strike, peak knee extension moment, and overall suppressed fascicle angle excursions (P <.001–.049) relative to the Contralateral and/or Control limb. This indicates an abnormality in fascicle architecture and mechanics following ACLR and suggests abnormalities in contractile function that cannot be explained by muscle weakness and may contribute to long-term gait irregularities. [ABSTRACT FROM AUTHOR]

This paper pursues the idea that event-internal pluractional verbs are morphologically complex forms that describe non-canonical events and denote in the domain of events constituted by pluralities of phases [Tovena 2010b]. Non-canonicity is understood in comparative terms with respect to the description of the events provided by the corresponding simplex verb forms. The leading question is what is the source of the multiplicative meaning component in verb forms such as tagliuzzare and tossicchiare in Italian, and it is answered by arguing that it arises from the use of diminutive morphology specifically to build verb forms that describe modified events. Parallelisms with the nominal domain strengthen the case for a characterisation of the word formation process as involving diminutive morphology. It is also shown that the type of modification of an event description allowed by forming pluractional verbs is generally more complex that by simple adverbial or PP adjunction, as it involves at least two dimensions of the event. Furthermore, languages may use morphological distinctions to mark different binary oppositions within Cusic’s three level system.

BACKGROUND: Endothelial dysfunction in widely diffuse disorders, such as atherosclerosis, hypertension, diabetes and senescence, is associated with nitric oxide (NO) deficiency. Here, the behavioural and molecular consequences deriving from NO deficiency in human umbilical vein endothelial cells (HUVECs) were investigated. RESULTS: Endothelial nitric oxide synthase (eNOS) was chronically inhibited either by N(G)-Nitro-L-arginine methyl ester (L-NAME) treatment or its expression was down-regulated by RNA interference. After long-term L-NAME treatment, HUVECs displayed a higher migratory capability accompanied by an increased Vascular Endothelial Growth Factor (VEGF) and VEGF receptor-2 (kinase insert domain receptor, KDR) expression. Moreover, both pharmacological and genetic inhibition of eNOS induced a state of pseudohypoxia, revealed by the stabilization of hypoxia-inducible factor-1α (HIF-1α). Furthermore, NO loss induced a significant decrease in mitochondrial mass and energy production accompanied by a lower O(2) consumption. Notably, very low doses of chronically administered DETA/NO reverted the HIF-1α accumulation, the increased VEGF expression and the stimulated migratory behaviour detected in NO deficient cells. CONCLUSION: Based on our results, we propose that basal release of NO may act as a negative controller of HIF-1α levels with important consequences for endothelial cell physiology. Moreover, we suggest that our experimental model where eNOS activity was impaired by pharmacological and genetic inhibition may represent a good in vitro system to study endothelial dysfunction.

BACKGROUND: A recent modeling study by the authors predicted that contextual information is poorly integrated into episodic representations in schizophrenia, and that this is a main cause of the retrieval deficits seen in schizophrenia. METHODOLOGY/PRINCIPAL FINDINGS: We have tested this prediction in patients with first-episode schizophrenia and matched controls. The benefit from contextual cues in retrieval was strongly reduced in patients. On the other hand, retrieval based on item cues was spared. CONCLUSIONS/SIGNIFICANCE: These results suggest that reduced integration of context information into episodic representations is a core deficit in schizophrenia and one of the main causes of episodic memory impairment.

A citomegalia é considerada a mais frequente das infecções congênitas, sendo responsável por numerosos casos de deficiência mental e surdez. No Brasil, as publicações sobre este assunto prendem-se, mais especificamente, aos aspectos patológico e epidemiológico. Este estudo preocupa-se em mostrar a importância desta infecção na origem da paralisia cerebral, dando ênfase aos aspectos clínico e laboratorial.

BACKGROUND:A large body of evidence suggests impaired context processing in schizophrenia. Here we propose that this impairment arises from defective integration of mediotemporal 'what' and 'where' routes, carrying object and spatial information to the hippocampus. METHODOLOGY AND FINDINGS:We have previously shown, in a mediotemporal lobe (MTL) model, that the abnormal connectivity between MTL regions observed in schizophrenia can explain the episodic memory deficits associated with the disorder. Here we show that the same neuropathology leads to several context processing deficits observed in patients with schizophrenia: 1) failure to choose subordinate stimuli over dominant ones when the former fit the context, 2) decreased contextual constraints in memory retrieval, as reflected in increased false alarm rates and 3) impaired retrieval of contextual information in source monitoring. Model analyses show that these deficits occur because the 'schizophrenic MTL' forms fragmented episodic representations, in which objects are overrepresented at the expense of spatial contextual information. CONCLUSIONS AND SIGNIFICANCE:These findings highlight the importance of MTL neuropathology in schizophrenia, demonstrating that it may underlie a broad spectrum of deficits, including context processing and memory impairments. It is argued that these processing deficits may contribute to central schizophrenia symptoms such as contextually inappropriate behavior, associative abnormalities, conversational drift, concreteness and delusions.

This paper reviews data published between 1990 and 2006 regarding smoking prevalence as well as individual and contextual influences on the smoking behavior among Romanian young adults. Highlights include a consideration of multiple levels of influence, from intra-individual factors, such as demographic and cognitive factors, to social influences, such as families and peers, to the more macro, societal/cultural levels of influence, including advertising and tobacco-related policies The source of data is represented by articles and short information published in journals or in electronic format, legislation, statistics and are illustrated with pictures. Based on these data, recommendations for future smoking prevention and reduction actions for Romanian youth are taken.Se revisan datos publicados entre 1990 y 2006 sobre prevalencia de tabaquismo, así como influencias individuales y contextuales respecto al hábito de fumar entre adultos jóvenes rumanos. Los hallazgos incluyen una consideración de múltiples niveles de influencia, desde factores intraindividuales (por ejemplo, demográficos y cognitivos), influencias sociales (como familia y pares), hasta niveles de influencia macro sociales/culturales (publicidad y políticas relacionadas con el tabaco, entre otros). La fuente de datos incluye artículos y notas breves publicadas en revistas científicas o en formato electrónico, leyes, estadísticas, y se ilustran con imágenes. Con base en estos datos, se establecen recomendaciones para acciones futuras de prevención y reducción del consumo de tabaco en jóvenes rumanos.

In response to the COVID-19 pandemic, many medical schools suspended clinical clerkships and implemented newly adapted curricula to facilitate continued educational progress. While the implementation of these new curricula has been described, an understanding of the impact on student learning outcomes is lacking. In 2020, the authors followed Kern's 6-step approach to curricular development to create and evaluate a novel COVID-19 curriculum for medical students at the University of California San Francisco School of Medicine and evaluate its learning outcomes. The primary goal of the curriculum was to provide third- and fourth-year medical students an opportunity for workplace learning in the absence of clinical clerkships, specifically for students to develop clerkship-level milestones in the competency domains of practice-based learning and improvement, professionalism, and systems-based practice. The curriculum was designed to match students with faculty-mentored projects occurring primarily in virtual formats. A total of 126 students enrolled in the curriculum and completed a survey about their learning outcomes (100% response rate). Of 35 possible clerkship-level milestones, there were 12 milestones for which over half of students reported development in competency domains including practice-based learning and improvement, professionalism, and interpersonal and communication skills. Thematic analysis of students' qualitative survey responses demonstrated 2 central motivations for participating in the curriculum: identity as physicians-in-training and patient engagement. Six central learning areas were developed during the curriculum: interprofessional teamwork, community resources, technology in medicine, skill-building, quality improvement, and specialty-specific learning. This analysis demonstrates that students can develop competencies and achieve rich workplace learning through project-based experiential learning, even in virtual clinical workplaces. Furthermore, knowledge of community resources, technology in medicine, and quality improvement was developed through the curriculum more readily than in traditional clerkships. These could be considered as integral learning objectives in future curricular design.

Alfred Agache, french urbanist, has put forward to Rio de Janeiro a monumental civic square which he named "Gateway to Brazil". This square would be placed at Gauanabara Bay ' shoreline, and it was designed as part of the city's master plan, during 1927-1930. This paper brings a brief analysis of this square, understanding the urban landscape as a cultural construction

Prostate cancer genomic subtypes that stratify aggressive disease and inform treatment decisions at the primary stage are currently limited. Previously, we functionally validated an aggressive subtype present in 15% of prostate cancer characterized by dual deletion of MAP3K7 and CHD1. Recent studies in the field have focused on deletion of CHD1 and its role in androgen receptor (AR) chromatin distribution and resistance to AR-targeted therapy; however, CHD1 is rarely lost without codeletion of MAP3K7. Here, we show that in the clinically relevant context of co-loss of MAP3K7 and CHD1 there are significant, collective changes to aspects of AR signaling. Although CHD1 loss mainly impacts the expansion of the AR cistrome, loss of MAP3K7 drives increased AR target gene expression. Prostate cancer cell line models engineered to cosuppress MAP3K7 and CHD1 also demonstrated increased AR-v7 expression and resistance to the AR-targeting drug enzalutamide. Furthermore, we determined that low protein expression of both genes is significantly associated with biochemical recurrence (BCR) in a clinical cohort of radical prostatectomy specimens. Low MAP3K7 expression, however, was the strongest independent predictor for risk of BCR over all other tested clinicopathologic factors including CHD1 expression. Collectively, these findings illustrate the importance of MAP3K7 loss in a molecular subtype of prostate cancer that poses challenges to conventional therapeutic approaches. IMPLICATIONS: These findings strongly implicate MAP3K7 loss as a biomarker for aggressive prostate cancer with significant risk for recurrence that poses challenges for conventional androgen receptor-targeted therapies.

The global burden of mortality and morbidity caused by traumatic brain injury (TBI) is significant, and the heterogeneity of TBI patients and the relatively small sample sizes of most current neuroimaging studies is a major challenge for scientific advances and clinical translation. The ENIGMA (Enhancing NeuroImaging Genetics through Meta-Analysis) Adult moderate/severe TBI (AMS-TBI) working group aims to be a driving force for new discoveries in AMS-TBI by providing researchers world-wide with an effective framework and platform for large-scale cross-border collaboration and data sharing. Based on the principles of transparency, rigor, reproducibility and collaboration, we will facilitate the development and dissemination of multiscale and big data analysis pipelines for harmonized analyses in AMS-TBI using structural and functional neuroimaging in combination with non-imaging biomarkers, genetics, as well as clinical and behavioral measures. Ultimately, we will offer investigators an unprecedented opportunity to test important hypotheses about recovery and morbidity in AMS-TBI by taking advantage of our robust methods for large-scale neuroimaging data analysis. In this consensus statement we outline the working group's short-term, intermediate, and long-term goals.

Abstract Introduction Urethral carcinoid tumors are very rare tumors with only four cases described in the literature. Case presentation We present the case of a 61-year-old man with a primary carcinoid tumor of the verumontanum (colliculis seminalis) portion of the prostatic urethra with a coexisting prostatic adenocarcinoma. In addition to whole mount hematoxylin and eosin staining, special immunoperoxidase staining specific for chromogranin A, neuron specific enolase, synaptophysin, pan-cytokeratin and PSA, and a special combined staining for racemase (α-methyl CoA) antigen and p63 antigen were performed. A review of the literature is included. A single focus of invasive prostatic adenocarcinoma was identified in the periphery of the mid-left, posterior quadrant of the prostate. Approximately 17 mm from this adenocarcinoma, within the verumontanum of the prostatic urethra, there was a 3 mm maximal dimension carcinoid tumor. Conclusion Based on different histological features and antigenic profiles, we concluded that the two tumors were distinct.