Spatiotemporal brain hierarchies of auditory memory recognition and predictive coding.

Our brain is constantly extracting, predicting, and recognising key spatiotemporal features of the physical world in order to survive. While neural processing of visuospatial patterns has been extensively studied, the hierarchical brain mechanisms underlying conscious recognition of auditory sequences and the associated prediction errors remain elusive. Using magnetoencephalography (MEG), we describe the brain functioning of 83 participants during recognition of previously memorised musical sequences and systematic variations. The results show feedforward connections originating from auditory cortices, and extending to the hippocampus, anterior cingulate gyrus, and medial cingulate gyrus. Simultaneously, we observe backward connections operating in the opposite direction. Throughout the sequences, the hippocampus and cingulate gyrus maintain the same hierarchical level, except for the final tone, where the cingulate gyrus assumes the top position within the hierarchy. The evoked responses of memorised sequences and variations engage the same hierarchical brain network but systematically differ in terms of temporal dynamics, strength, and polarity. Furthermore, induced-response analysis shows that alpha and beta power is stronger for the variations, while gamma power is enhanced for the memorised sequences. This study expands on the predictive coding theory by providing quantitative evidence of hierarchical brain mechanisms during conscious memory and predictive processing of auditory sequences.

Prolonged-release pirfenidone in patients with pulmonary fibrosis as a phenotype of post-acute sequelae of COVID-19 pneumonia. Safety and efficacy.

INTRODUCTION: One of the major concerns with post-acute sequelae of COVID-19 (PASC) is the development of pulmonary fibrosis, for which no approved pharmacological treatment exists. Therefore, the primary aim of this open-label study was to evaluate the safety and the potential clinical efficacy of a prolonged-release pirfenidone formulation (PR-PFD) in patients having PASC-pulmonary fibrosis. METHODS: Patients with PASC-pulmonary fibrosis received PR-PFD 1800 mg/day (1200 mg in the morning after breakfast and 600 mg in the evening after dinner) for three months. Blood samples were taken to confirm the pharmacokinetics of PR-PFD, and adverse events (AEs) were evaluated monthly using a short questionnaire. Symptoms, dyspnea, and pulmonary function tests (spirometry, diffusing capacity for carbon monoxide, plethysmography, and 6-min walk test [6MWT]) were evaluated at baseline, and one and three months after having started the PR-PFD treatment. RESULTS: Seventy subjects with mild to moderate lung restriction were included. The most common AEs were diarrhea (23%), heartburn (23%), and headache (16%), for which no modifications in the drug study were needed. Two patients died within the first 30 days of enrolment, and three opted not to continue the study, events which were not associate with PR-PFD. Pulmonary function testing, 6MWT, dyspnea, symptoms, and CT scan significantly improved after three months of treatment with PR-PFD. CONCLUSION: In patients with PASC pulmonary fibrosis, three months' treatment with PR-PFD was safe and showed therapeutic efficacy. Still, it remains to be seen whether the pulmonary fibrotic process remains stable, becomes progressive or will improve.

Apathetic symptoms and white matter integrity after traumatic brain injury.

PRIMARY OBJECTIVE: The aim of the study was twofold. First, to study the relationship among apathy in the long term, initial clinical measures, and standard outcome scores after traumatic brain injury (TBI). Second, to describe white matter integrity correlates of apathy symptoms. RESEARCH DESIGN: Correlational study. Methods and Procedures: Correlation and Bayesian networks analyses were performed in a sample of 40 patients with moderate to severe TBI in order to identify the relationship among clinical variables, functionality, and apathy. A diffusion tensor imaging study was developed in 25 participants to describe correlations between fractional anisotropy (FA) measures and apathetic symptoms. MAIN OUTCOMES AND RESULTS: Correlation analysis revealed associations between pairs of variables as apathy in the long term and functional score at discharge from hospital. Bayesian network illustrated the relevant role of axonal injury mediating the relationship between apathy and initial clinical variables. FA in the superior longitudinal fasciculus, the inferior longitudinal fasciculus, and the internal capsule were negatively correlated with apathy measures. Widespread brain areas showed positive correlations between FA and apathy. CONCLUSIONS: These results highlight the relevance of white matter integrity measures in initial assessment after TBI and its relationship with apathetic manifestations in the chronic phase.

Combination of white matter hyperintensities and Aß burden is related to cognitive composites domain scores in subjective cognitive decline: the FACEHBI cohort.

BACKGROUND: To explore whether the combination of white matter hyperintensities (WMHs) and amyloid-beta (Aß) deposition is associated with worse cognitive performance on cognitive composites (CCs) domain scores in individuals with subjective cognitive decline (SCD). METHODS: Two hundred participants from the FACEHBI cohort underwent structural magnetic resonance imaging (MRI), 18F-florbetaben positron emission tomography (FBB-PET), and neuropsychological assessment. WMHs were addressed through the Fazekas scale, the Age-Related White Matter Changes (ARWMC) scale, and the FreeSurfer pipeline. Eight CCs domain scores were created using the principal component analysis (PCA). Age, sex, education, and apolipoprotein E (APOE) were used as adjusting variables. RESULTS: Adjusted multiple linear regression models showed that FreeSurfer (B - .245; 95% CI - .1.676, - .393, p = .016) and ß burden (SUVR) (B - .180; 95% CI - 2.140, - .292; p = .070) were associated with face-name associative memory CCs domain score, although the latest one was not statistically significant after correction for multiple testing (p = .070). There was non-significant interaction of these two factors on this same CCs domain score (p = .54). However, its cumulative effects on face-name associative performance indicated that those individuals with either higher WMH load or higher Aß burden showed the worst performance on the face-name associative memory CCs domain score. CONCLUSIONS: Our results suggest that increased WMH load and increased Aß are independently associated with poorer episodic memory performance in SCD individuals, indicating a cumulative effect of the combination of these two pathological conditions in promoting lower cognitive performance, an aspect that could help in terms of treatment and prevention.

Psychophysiological Correlates of Emotional- and Alcohol-Related Cues Processing in Offspring of Alcohol-Dependent Patients.

AIMS: To determinate if offspring of alcohol-dependent patients (OA) process affective stimuli and alcohol-related cues in a different manner than control subjects do. METHODS: Event-related potentials (early posterior negativity [EPN]/ late positive potential [LPP]) and event-related oscillations (Theta) were obtained by electroencephalographic (EEG) recording during the viewing of International Affective Picture System (IAPS) images with positive, negative and neutral valence, as well as alcohol-related cues. The total sample was comprised of 60 participants, divided into two groups: one group consisted of OA (30) and the control group of participants with negative family history of alcohol use disorders (30). RESULTS: Theta power analysis implies a significant interaction between condition, region and group factors. Post-hoc analysis indicates an increased theta power for the OA at different regions, during pleasant (frontal, central, parietal, occipital, right temporal); unpleasant (frontal, central, occipital); alcohol (frontal, central, parietal, occipital, right and left temporal) and neutral (occipital) cues. There are no group differences regarding any of the event-related potential measurements (EPN/LPP). CONCLUSIONS: There is evidence of alterations in the processing of affective stimuli and alcohol-related information, evidenced by changes in theta brain oscillations. These alterations are characterized by an increased emotional reactivity, evidenced by increased theta at posterior sites. There is also an increased recruitment of emotion control, which could be a compensation mechanism, evidenced by increased theta power at anterior sites during affective stimuli and alcohol cues.

Genome Wide Meta-Analysis identifies common genetic signatures shared by heart function and Alzheimer's disease.

Echocardiography has become an indispensable tool for the study of heart performance, improving the monitoring of individuals with cardiac diseases. Diverse genetic factors associated with echocardiographic measures have been previously reported. The impact of several apoptotic genes in heart development identified in experimental models prompted us to assess their potential association with human cardiac function. This study aimed at investigating the possible association of variants of apoptotic genes with echocardiographic traits and to identify new genetic markers associated with cardiac function. Genome wide data from different studies were obtained from public repositories. After quality control and imputation, a meta-analysis of individual association study results was performed. Our results confirmed the role of caspases and other apoptosis related genes with cardiac phenotypes. Moreover, enrichment analysis showed an over-representation of genes, including some apoptotic regulators, associated with Alzheimer's disease. We further explored this unexpected observation which was confirmed by genetic correlation analyses. Our findings show the association of apoptotic gene variants with echocardiographic indicators of heart function and reveal a novel potential genetic link between echocardiographic measures in healthy populations and cognitive decline later on in life. These findings may have important implications for preventative strategies combating Alzheimer's disease.

Correlations between plasma and PET beta-amyloid levels in individuals with subjective cognitive decline: the Fundació ACE Healthy Brain Initiative (FACEHBI).

BACKGROUND: Peripheral biomarkers that identify individuals at risk of developing Alzheimer's disease (AD) or predicting high amyloid beta (Aß) brain burden would be highly valuable. To facilitate clinical trials of disease-modifying therapies, plasma concentrations of Aß species are good candidates for peripheral AD biomarkers, but studies to date have generated conflicting results. METHODS: The Fundació ACE Healthy Brain Initiative (FACEHBI) study uses a convenience sample of 200 individuals diagnosed with subjective cognitive decline (SCD) at the Fundació ACE (Barcelona, Spain) who underwent amyloid florbetaben(18F) (FBB) positron emission tomography (PET) brain imaging. Baseline plasma samples from FACEHBI subjects (aged 65.9 ± 7.2 years) were analyzed using the ABtest (Araclon Biotech). This test directly determines the free plasma (FP) and total plasma (TP) levels of Aß40 and Aß42 peptides. The association between Aß40 and Aß42 plasma levels and FBB-PET global standardized uptake value ratio (SUVR) was determined using correlations and linear regression-based methods. The effect of the APOE genotype on plasma Aß levels and FBB-PET was also assessed. Finally, various models including different combinations of demographics, genetics, and Aß plasma levels were constructed using logistic regression and area under the receiver operating characteristic curve (AUROC) analyses to evaluate their ability for discriminating which subjects presented brain amyloidosis. RESULTS: FBB-PET global SUVR correlated weakly but significantly with Aß42/40 plasma ratios. For TP42/40, this observation persisted after controlling for age and APOE ε4 allele carrier status (R2 = 0.193, p = 1.01E-09). The ROC curve demonstrated that plasma Aß measurements are not superior to APOE and age in combination in predicting brain amyloidosis. It is noteworthy that using a simple preselection tool (the TP42/40 ratio with an empirical cut-off value of 0.08) optimizes the sensitivity and reduces the number of individuals subjected to Aß FBB-PET scanners to 52.8%. No significant dependency was observed between APOE genotype and plasma Aß measurements (p value for interaction = 0.105). CONCLUSION: Brain and plasma Aß levels are partially correlated in individuals diagnosed with SCD. Aß plasma measurements, particularly the TP42/40 ratio, could generate a new recruitment strategy independent of the APOE genotype that would improve identification of SCD subjects with brain amyloidosis and reduce the rate of screening failures in preclinical AD studies. Independent replication of these findings is warranted.

P3 Component as a Potential Endophenotype for Control Inhibition in Offspring of Alcoholics.

AIMS: To assess inhibitory processes and the ongoing event-related potential (ERP) activity of offspring of alcoholics (OA) during a Go/No-Go task, with the purpose of characterizing possible psychophysiological endophenotypes for alcohol-dependent vulnerability. SHORT SUMMARY: EEG recordings and ERP measurements of young adults with positive and negative family history of alcoholism where obtained while they performed a Go/No-Go task to assess inhibitory processes. Offspring of alcoholics showed a different ERP pattern compared to the control group and exerted greater effort than the control group. METHODS: ERP measurements were obtained by electroencephalogram (EEG) recordings of 65 participants divided into two groups: one group of 30 subjects with positive family history of alcoholism and a control group of 35 subjects with negative family history of alcoholism. They performed a Go/No-Go task, where each individual was required to classify visual stimuli by colour (Go) and inhibit their response to a No-Go signal. RESULTS: OA have higher P3 amplitudes during the Go condition in all of the regions analysed and higher No-Go P3 amplitudes than control subjects in the frontal region. Unlike controls, OA have no differences between the P3 amplitudes across conditions. CONCLUSIONS: The absence of differences between the P3 Go and No-Go observed in the OA group can be interpreted as a possible alteration related with inhibition, in a way that they may need to recruit similar resources for inhibitory and classificational processes for both conditions. Therefore, the P3 component may be considered as a useful endophenotype and a vulnerability marker to develop addictive behaviour.

Modified Le Fort III Osteotomy: Different Applications.

SUMMARY: Based on the new concepts of the modified Le Fort III osteotomy (MLFIIIO), Three variations of this technique are implemented: (A) the modified osteotomy Le Fort III Champy (1980) technique to be described with the use of surgical guides, and subciliary approach or an transconjunctival approach. Excellent technique for horizontal advancement no further to 6 mm, without requiring any type of graft.. (B) The modified Le Fort III osteotomy in "Z": to solve horizontal (posterior anterior) problems of more than 6 mm without bone grafting. It is itself a modification of the technique described by Champy. (C) The modified Le Fort III osteotomy ascending: modified the original technique described by Bell and Epker with interpositional grafts, was modified by the called ascendant, making it higher in cases where the patient has an acceptable nasal bridge, but exorbitism the lateral wall of the orbit. Le Fort III osteotomy combined with a Le Fort I osteotomy and a front implant. METHOD: As pointed out in Part I for the modified oblique Le Fort III osteotomy, methods for the design of the osteotomy Le Fort III property will depend on the requirements of individual patients, and this has led us to design specific techniques for the deformity. RESULTS: Patients have a right projection of the middle third, and protection of the eyeball. CONCLUSIONS: The techniques presented for the advancement of the middle third have excellent results with the ability to be tailored to each patient deformity.

Differential impact of marine debris ingestion during ontogenetic dietary shift of green turtles in Uruguayan waters.

Anthropogenic debris ingestion has been reported for green turtles in all their life stages worldwide. The aim of the present study is to evaluate the marine debris ingestion by green turtles stranded in Uruguayan coast between 2005 and 2013. Debris items were categorized and quantified by frequency of occurrence, relative weight, volume and number of items. A total of 96 dead stranded turtles were analyzed and 70% presented debris in their guts. The majority of debris found were plastic, being hard plastics the most abundant in weight. We found no differences in debris ingestion in stranded turtles a long the Uruguayan coast. However we detected a negative correlation between the presence of debris and turtle's size. Smaller turtles are new recruits to neritic grounds indicating that the early juvenile stage of this species is the most vulnerable to this threat in the Southwestern Atlantic.

Anaphylaxis caused by green tea: a case repor

No disponible

Thermolability of soybean allergen gly m bd 30K: report of a case of anaphylaxis

No disponible

Zinc Complexes with Cyanoxime: Structural, Spectroscopic, and Catalysis Studies in the Pivaloylcyanoxime-Zn System.

Reaction of 2-hydroxyimino-4,4-dimethyl-3-oxo-pentanenitrile (common abbreviation HPiCO, pivaloyl-cyanoxime) with zinc sulfate in an aqueous solution results in the formation of the two new complexes: [Zn(PiCO){H(PiCO)2}(H2O)] (I) and tetranuclear Zn complex [Zn4(µ3-OH)2(PiCO)6 (H2O)4] (II). Both complexes were characterized by elemental analysis, IR- and UV-visible spectra, DSC/TGA studies, and X-ray analysis. In complex II, the PiCO- cyanoxime anion adopts three bidentate binding modes: O-monodentate, chelating (κ2), and bridging (η2) coordinations. Also, the ligand represents the mixture of two diasteromers (cis-anti and cis-syn) that form five- and six-membered chelate rings with Zn atoms and cocrystallize in one unit cell at population of 0.57-0.43. There are two crystallographically different Zn-centers in the ASU, and two µ3-bridging hydroxo-groups arrange via inversion center the formation of an elegant tetranuclear complex. Each Zn atom has a molecule of coordinated water and is in the distorted octahedral environment. Because of the structural flexibility and multidentate propensity of the pivaloyl-cyanoxime, complex II may act as a structural model of naturally occurring Zn-containing enzymes. Indeed, compound I exhibits an efficient catalytic performance for transesterification reaction of various esters in ethanol under mild reaction conditions. Therefore, obtained results allow assignment of observed activity as green catalysis.

A randomized phase II/III study of cabazitaxel versus vinflunine in metastatic or locally advanced transitional cell carcinoma of the urothelium (SECAVIN).

BACKGROUND: Despite the advent of immunotherapy in urothelial cancer, there is still a need to find effective cytotoxic agents beyond first and second lines. Vinflunine is the only treatment approved in this setting by the European Medicines Agency and taxanes are also widely used in second line. Cabazitaxel is a taxane with activity in docetaxel-refractory cancers. A randomized study was conducted to compare its efficacy versus vinflunine. PATIENTS AND METHODS: This is a multicenter, randomized, open-label, phase II/III study, following a Simon's optimal method with stopping rules based on an interim futility analysis and a formal efficacy analysis at the end of the phase II. ECOG Performance Status, anaemia and liver metastases were stratification factors. Primary objectives were overall response rate for the phase II and overall survival for the phase III. RESULTS: Seventy patients were included in the phase II across 19 institutions in Europe. Baseline characteristics were well balanced between the two arms. Three patients (13%) obtained a partial response on cabazitaxel (95% CI 2.7-32.4) and six patients (30%) in the vinflunine arm (95% CI 11.9-54.3). Median progression-free survival for cabazitaxel was 1.9 versus 2.9 months for vinflunine (P = 0.039). The study did not proceed to phase III since the futility analysis showed a lack of efficacy of cabazitaxel. A trend for overall survival benefit was found favouring vinflunine (median 7.6 versus 5.5 months). Grade 3- to 4-related adverse events were seen in 41% patients with no difference between the two arms. CONCLUSION: This phase II/III second line bladder study comparing cabazitaxel with vinflunine was closed when the phase II showed a lack of efficacy of the cabazitaxel arm. Vinflunine results were consistent with those known previously. TRIAL NUMBER: NCT01830231.

"Modified Oblique Le Fort III Osteotomy" New Concepts.

INTRODUCTION: The purpose of this study is to demonstrate the surgical technique for the correction of midfacial deformities; vertical excess and posteroanterior hypoplasia. This situation obligates the need to move the whole osseous structure in an oblique posteroanterior movement that should correct both midfacial deformities. This should also correct the lip incompetence while improving the malar projection on a profile view of the patient. We also present a mathematical formula that gives the angulation needed for moving the midface complex in a simultaneous vertical and posteroanterior direction. Once given the correct angulation for the desired oblique movement, the surgeon can reproduce this angulation with custom made surgical guides over the stereolithographic model, that can then be used during surgery to achieve the desired movement accurately. This technique exemplified on this paper will give maxillofacial surgeons a new and affordable tool for the correction of midfacial deformities in an accurate and easily reproducible manner and amplifying the surgical repertoire. MATERIALS AND METHODS: Patients seen in the specialty hospital "Dr. Bernardo Sepulveda" National Medical Center XXI Century, IMSS, during the period from February 2013 to November 2014 with Modified Oblique Le Fort III osteotomies, with the application of two trigonometric formulas for the accuracy of the technique. CONCLUSIONS: The application of the formulas give accurate results as well as the enlargement of the upper airway and esthetic results.

Dehydroepiandrosterone increases the number and dendrite maturation of doublecortin cells in the dentate gyrus of middle age male Wistar rats exposed to chronic mild stress.

Aging increases the vulnerability to stress and risk of developing depression. These changes have been related to a reduction of dehydroepiandrosterone (DHEA) levels, an adrenal steroid with anti-stress effects. Also, adult hippocampal neurogenesis decreases during aging and its alteration or impaired is related to the development of depression. Besides, it has been hypothesized that DHEA increases the formation of new neurons. However, it is unknown whether treatment with DHEA in aging may stimulate the dendrite maturation of newborn neurons and reversing depressive-like signs evoked by chronic stress exposure. Here aged male rats (14 months old) were subjected to a scheme of chronic mild stress (CMS) during six weeks, received a treatment with DHEA from the third week of CMS. Changes in body weight and sucrose preference (SP) were measured once a week. DHEA levels were measured in serum, identification of doublecortin-(DCX)-, BrdU- and BrdU/NeuN-labeled cells was done in the dentate gyrus of the hippocampus. CMS produced a gradual reduction in the body weight, but no changes in the SP were observed. Treatment enhanced levels of DHEA, but lack of recovery on body weight of stressed rats. Aging reduced the number of DCX-, BrdU- and BrdU/NeuN- cells but DHEA just significantly increased the number of DCX-cells in rats under CMS and controls, reaching levels of young non-stressed rats (used here as a reference of an optimal status of health). In rats under CMS, DHEA facilitated dendritic maturation of immature new neurons. Our results reveal that DHEA improves neural plasticity even in conditions of CMS in middle age rats. Thus, this hormone reverted the decrement of DCX-cells caused during normal aging.

Prosexual Effect of Chrysactinia mexicana A. Gray (Asteraceae), False Damiana, in a Model of Male Sexual Behavior.

Chrysactinia mexicana A. Gray (Asteraceae) and Turnera diffusa Willd (Turneraceae) are employed in traditional medicine as aphrodisiacs; however, there is no scientific evidence supporting the prosexual properties of C. mexicana. The aim of this study was to determine whether an aqueous extract of C. mexicana (Cm) stimulates rat male sexual behavior in the sexual exhaustion paradigm. Sexually exhausted (SExh) male rats were treated with Cm (80, 160, and 320 mg/kg), an aqueous extract of T. diffusa (Td), or yohimbine. The sexual exhaustion state in the control group was characterized by a low percentage of males exhibiting mounts, intromissions, and ejaculations and no males demonstrating mating behavior after ejaculation. Cm (320 mg/kg), Td, or yohimbine significantly increased the proportion of SExh rats that ejaculated and resumed copulation after ejaculation. In males that exhibited reversal of sexual exhaustion, Cm (320 mg/kg) improved sexual performance by reducing the number of intromissions and shrinking ejaculation latency. The effects of treatments on sexual behavior were not related with alterations in general locomotion. In conclusion, the prosexual effects of Cm, as well as those of Td, are established at a central level, which supports the traditional use of C. mexicana for stimulating sexual activity.