Functional Connectivity and Temporal Variability of Brain Connections in Adults with Attention Deficit/Hyperactivity Disorder and Bipolar Disorder

Objectives: To assess brain functional connectivity and variability in adults with attention deficit/hyperactivity disorder (ADHD) or euthymic bipolar disorder (BD) relative to a control (CT) group. Methods: Electroencephalography (EEG) was measured in 35 participants (BD = 11; ADHD = 9; CT = 15) during an eyes-closed 10-min rest period, and connectivity and graph theory metrics were computed. A coefficient of variation (CV) computed also the connectivity’s temporal variability of EEG. Multivariate associations between functional connectivity and clinical and neuropsychological profiles were evaluated. Results: An enhancement of functional connectivity was observed in the ADHD (fronto-occipital connections) and BD (diffuse connections) groups. However, compared with CTs, intrinsic variability (CV) was enhanced in the ADHD group and reduced in the BD group. Graph theory metrics confirmed the existence of several abnormal network features in both affected groups. Significant associations of connectivity with symptoms were also observed. In the ADHD group, temporal variability of functional connections was associated with executive function and memory deficits. Depression, hyperactivity and impulsivity levels in the ADHD group were associated with abnormal intrinsic connectivity. In the BD group, levels of anxiety and depression were related to abnormal frontotemporal connectivity. Conclusions: In the ADHD group, we found that intrinsic variability was associated with deficits in cognitive performance and that connectivity abnormalities were related to ADHD symptomatology. The BD group exhibited less intrinsic variability and more diffuse long-range brain connections, and those abnormalities were related to interindividual differences in depression and anxiety. These preliminary results are relevant for neurocognitive models of abnormal brain connectivity in both disorders.Fil: Barttfeld, Pablo. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Departamento de Física. Laboratorio de Neurociencia Integrativa; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Petroni, Agustín. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Departamento de Física. Laboratorio de Neurociencia Integrativa; Argentina. Universidad Diego Portales; Chile. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Báez Buitrago, Sandra Jimena. Universidad Favaloro; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Urquina, Hugo. Universidad Favaloro; ArgentinaFil: Sigman, Mariano. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Departamento de Física. Laboratorio de Neurociencia Integrativa; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Cetkovich, Marcelo. Universidad Favaloro; ArgentinaFil: Torralva, Teresa. Universidad Favaloro; ArgentinaFil: Torrente, Fernando. Universidad Favaloro; ArgentinaFil: Lischinsky, Alicia. Universidad Favaloro; ArgentinaFil: Castellanos, Xavier. New York University. School of Medicine; Estados UnidosFil: Manes, Facundo Francisco. Universidad Favaloro; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Ibáñez Barassi, Agustín Mariano. Universidad Favaloro; Argentina. Universidad Autónoma del Caribe; Colombia. Universidad Diego Portales; Chile. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentin

Macronutrient supply, uptake and recycling in the coastal ocean of the west Antarctic Peninsula

Nutrient supply, uptake and cycling underpin high primary productivity over the continental shelf of the west Antarctic Peninsula (WAP). Here we use a suite of biogeochemical and isotopic data collected over five years in northern Marguerite Bay to examine these macronutrient dynamics and their controlling biological and physical processes in the WAP coastal ocean. We show pronounced nutrient drawdown over the summer months by primary production which drives a net seasonal nitrate uptake of 1.83 mol N m-2 yr-1, equivalent to net carbon uptake of 146 g C m-2 yr-1. High primary production fuelled primarily by deep-sourced macronutrients is diatom-dominated, but non-siliceous phytoplankton also play a role. Strong nutrient drawdown in the uppermost surface ocean has the potential to cause transient nitrogen limitation before nutrient resupply and/or regeneration. Interannual variability in nutrient utilisation corresponds to winter sea ice duration and the degree of upper ocean mixing, implying susceptibility to physical climate change. The nitrogen isotope composition of nitrate (δ15NNO3) shows a utilisation signal during the growing seasons with a community-level net isotope effect of 4.19 ± 0.29‰. We also observe significant deviation of our data from modelled and observed utilisation trends, and argue that this is driven primarily by water column nitrification and meltwater dilution of surface nitrate. This study is important because it provides a detailed description of the nutrient biogeochemistry underlying high primary productivity at the WAP, and shows that surface ocean nutrient inventories in the Antarctic sea ice zone can be affected by intense recycling in the water column, meltwater dilution and sea ice processes, in addition to utilisation in the upper ocean

CIGB-300, a synthetic peptide-based drug that targets the CK2 phosphoaceptor domain. Translational and clinical research

CK2 represents an oncology target scientifically validated. However, clinical research with inhibitors of the CK2-mediated phosphorylation event is still insufficient to recognize it as a clinically validated target. CIGB-300, an investigational peptide-based drug that targets the phosphoaceptor site, binds to a CK2 substrate array in vitro but mainly to B23/nucleophosmin in vivo. The CIGB-300 proapoptotic effect is preceded by its nucleolar localization, inhibition of the CK2-mediated phosphorylation on B23/nucleophosmin and nucleolar disassembly. Importantly, CIGB-300 shifted a protein array linked to apoptosis, ribosome biogenesis, cell proliferation, glycolisis, and cell motility in proteomic studies which helped to understand its mechanism of action. In the clinical ground, CIGB-300 has proved to be safe and well tolerated in a First-in-Human trial in women with cervical malignancies who also experienced signs of clinical benefit. In a second Phase 1 clinical trial in women with cervical cancer stage IB2/II, the MTD and DLT have been also identified in the clinical setting. Interestingly, in cervical tumors the B23/nucleophosmin protein levels were significantly reduced after CIGB-300 treatment at the nucleus compartment. In addition, expanded use of CIGB-300 in case studies has evidenced antitumor activity when administered as compassional option. Collectively, our data outline important clues on translational and clinical research from this novel peptide-based drug reinforcing its perspectives to treat cancer and paving the way to validate CK2 as a promising target in oncology.Fil: Perea, Silvio E.. Center for Genetic Engineering and Biotechnology; CubaFil: Baladron, Idania. Center for Genetic Engineering and Biotechnology; CubaFil: Garcia, Yanelda. Center for Genetic Engineering and Biotechnology; CubaFil: Perera, Yasser. Center for Genetic Engineering and Biotechnology; CubaFil: Lopez, Adlin. Center for Genetic Engineering and Biotechnology; CubaFil: Soriano, Jorge L.. Center for Genetic Engineering and Biotechnology; Cuba. General Hospital ‘‘Hermanos Ameijeiras’; CubaFil: Batista, Noyde. Center for Genetic Engineering and Biotechnology; Cuba. General Hospital ‘‘Hermanos Ameijeiras’; CubaFil: Palau, Aley. Center for Genetic Engineering and Biotechnology; Cuba. General Hospital ‘‘Hermanos Ameijeiras’; CubaFil: Hernández, Ignacio. Center for Genetic Engineering and Biotechnology; CubaFil: Farina, Hernán Gabriel. Universidad Nacional de Quilmes; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Garcia, Idrian. Center for Genetic Engineering and Biotechnology; CubaFil: Gonzalez, Lidia. Center for Genetic Engineering and Biotechnology; CubaFil: Gil, Jeovanis. Center for Genetic Engineering and Biotechnology; CubaFil: Rodriguez, Arielis. Center for Genetic Engineering and Biotechnology; CubaFil: Solares, Margarita. Center for Genetic Engineering and Biotechnology; CubaFil: Santana, Agueda. Center for Genetic Engineering and Biotechnology; CubaFil: Cruz, Marisol. Center for Genetic Engineering and Biotechnology; CubaFil: Lopez, Matilde. Center for Genetic Engineering and Biotechnology; CubaFil: Valenzuela, Carmen. Center for Genetic Engineering and Biotechnology; CubaFil: Reyes, Osvaldo. Center for Genetic Engineering and Biotechnology; CubaFil: López Saura, Pedro A.. Center for Genetic Engineering and Biotechnology; CubaFil: González, Carlos A.. Center for Genetic Engineering and Biotechnology; CubaFil: Diaz, Alina. Center for Genetic Engineering and Biotechnology; CubaFil: Castellanos, Lila. Center for Genetic Engineering and Biotechnology; CubaFil: Sanchez, Aniel. Center for Genetic Engineering and Biotechnology; CubaFil: Betancourt, Lazaro. Center for Genetic Engineering and Biotechnology; CubaFil: Besada, Vladimir. Center for Genetic Engineering and Biotechnology; CubaFil: González, Luis J.. Center for Genetic Engineering and Biotechnology; CubaFil: Garay, Hilda. Center for Genetic Engineering and Biotechnology; CubaFil: Gómez, Roberto. Center for Genetic Engineering and Biotechnology; CubaFil: Gomez, Daniel Eduardo. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad Nacional de Quilmes; ArgentinaFil: Alonso, Daniel Fernando. Universidad Nacional de Quilmes; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Perrin, Phillipe. No especifíca;Fil: Renualt, Jean Yves. No especifíca;Fil: Sigman, Hugo. No especifíca;Fil: Herrera, Luis. Center for Genetic Engineering and Biotechnology; CubaFil: Acevedo, Boris. Center for Genetic Engineering and Biotechnology; Cub

Safety and preliminary efficacy data of a novel Casein Kinase 2 (CK2) peptide inhibitor administered intralesionally at four dose levels in patients with cervical malignancies

<p>Abstract</p> <p>Background</p> <p>Cervical cancer is now considered the second leading cause of death among women worldwide, and its incidence has reached alarming levels, especially in developing countries. Similarly, high grade squamous intraepithelial lesion (HSIL), the precursor stage for cervical cancer, represents a growing health problem among younger women as the HSIL management regimes that have been developed are not fully effective. From the etiological point of view, the presence of Human Papillomavirus (HPV) has been demonstrated to play a crucial role for developing cervical malignancies, and viral DNA has been detected in 99.7% of cervical tumors at the later stages. CIGB-300 is a novel cyclic synthetic peptide that induces apoptosis in malignant cells and elicits antitumor activity in cancer animal models. CIGB-300 impairs the Casein Kinase (CK2) phosphorylation, by targeting the substrate's phosphoaceptor domain. Based on the perspectives of CIGB-300 to treat cancer, this "first-in-human" study investigated its safety and tolerability in patients with cervical malignancies.</p> <p>Methods</p> <p>Thirty-one women with colposcopically and histologically diagnosed microinvasive or pre-invasive cervical cancer were enrolled in a dose escalating study. CIGB-300 was administered sequentially at 14, 70, 245 and 490 mg by intralesional injections during 5 consecutive days to groups of 7 – 10 patients. Toxicity was monitored daily until fifteen days after the end of treatment, when patients underwent conization. Digital colposcopy, histology, and HPV status were also evaluated.</p> <p>Results</p> <p>No maximum-tolerated dose or dose-limiting toxicity was achieved. The most frequent local events were pain, bleeding, hematoma and erythema at the injection site. The systemic adverse events were rash, facial edema, itching, hot flashes, and localized cramps. 75% of the patients experienced a significant lesion reduction at colposcopy and 19% exhibited full histological regression. HPV DNA was negative in 48% of the previously positive patients. Long term follow-up did not reveal recurrences or adverse events.</p> <p>Conclusion</p> <p>CIGB 300 was safe and well tolerated. This is the first clinical trial where a drug has been used to target the CK2 phosphoaceptor domain providing an early proof-of-principle of a possible clinical benefit.</p

The Neural Basis of Decision-Making and Reward Processing in Adults with Euthymic Bipolar Disorder or Attention-Deficit/Hyperactivity Disorder (ADHD)

Attention-deficit/hyperactivity disorder (ADHD) and bipolar disorder (BD) share DSM-IV criteria in adults and cause problems in decision-making. Nevertheless, no previous report has assessed a decision-making task that includes the examination of the neural correlates of reward and gambling in adults with ADHD and those with BD

Vaccine breakthrough hypoxemic COVID-19 pneumonia in patients with auto-Abs neutralizing type I IFNs

Life-threatening `breakthrough' cases of critical COVID-19 are attributed to poor or waning antibody response to the SARS- CoV-2 vaccine in individuals already at risk. Pre-existing autoantibodies (auto-Abs) neutralizing type I IFNs underlie at least 15% of critical COVID-19 pneumonia cases in unvaccinated individuals; however, their contribution to hypoxemic breakthrough cases in vaccinated people remains unknown. Here, we studied a cohort of 48 individuals ( age 20-86 years) who received 2 doses of an mRNA vaccine and developed a breakthrough infection with hypoxemic COVID-19 pneumonia 2 weeks to 4 months later. Antibody levels to the vaccine, neutralization of the virus, and auto- Abs to type I IFNs were measured in the plasma. Forty-two individuals had no known deficiency of B cell immunity and a normal antibody response to the vaccine. Among them, ten (24%) had auto-Abs neutralizing type I IFNs (aged 43-86 years). Eight of these ten patients had auto-Abs neutralizing both IFN-a2 and IFN-., while two neutralized IFN-omega only. No patient neutralized IFN-ss. Seven neutralized 10 ng/mL of type I IFNs, and three 100 pg/mL only. Seven patients neutralized SARS-CoV-2 D614G and the Delta variant (B.1.617.2) efficiently, while one patient neutralized Delta slightly less efficiently. Two of the three patients neutralizing only 100 pg/mL of type I IFNs neutralized both D61G and Delta less efficiently. Despite two mRNA vaccine inoculations and the presence of circulating antibodies capable of neutralizing SARS-CoV-2, auto-Abs neutralizing type I IFNs may underlie a significant proportion of hypoxemic COVID-19 pneumonia cases, highlighting the importance of this particularly vulnerable population

Hugo Sigman, Fundador y CEO del Grupo ISUD, Nuevo Embajador de Buena Voluntad del IICA para el desarrollo sostenible

Participantes: Hugo Sigman, CEO del Grupo Insud. Manuel Otero, director IICA. Daniel Scioli, nuevo Embajador de la República Argentina en Brasil.Hugo Sigman, CEO del Grupo Insud, fue designado nuevo Embajador de Buena Voluntad del Instituto Interamericano de Cooperación para la Agricultura (IICA) para temas de desarrollo sostenible, un reconocimiento a sus contribuciones a la investigación e innovación científica y a su compromiso con el desarrollo humano, el sector agropecuario y las zonas rurales de América

Rol del sector privado para la reactivación de la agricultura en la post pandemia

Se toma como punto base el tema el rol del sector privado en la post-pandemia por el coronavirus, ya que existen fragilidades con las cadenas de valor, ante el rol que cada persona tiene ante la situación se necesita identificar el rol de los distintos actores para el progreso de la agricultura de manera eficiente

The cortical processing of facial emotional expression is associated with social cognition skills and executive functioning: a preliminary study

Several lines of experimental evidence support an association between facial processing and social cognition, but no direct link between cortical markers of facial processing and complex cognitive processes has been reported until now. In the current study, we tested the hypothesis that cortical electrophysiological markers for the processing of facial emotion are associated with individual differences in executive and social cognition skills. We tested for correlations between the amplitude of event-related potentials (N170) in a dual valence task and participants' scores on three neuropsychological assessments (general neuropsychology, executive functioning, and social cognition). N170 was modulated by the stimulus type (face versus word) and the valence of faces (positive versus negative). The neural source of N170 was estimated to be the fusiform gyrus. Robust correlations were found between neuropsychological markers and measures of facial processing. Social cognition skills (as measured by three tests: the Reading the Mind in the Eyes test, the Faux Pas test, and the Iowa Gambling Task) correlated with cortical measures of emotional discrimination. Executive functioning ability also correlated with the cortical discrimination of complex emotional stimuli. Our findings suggest that the cortical processing of facial emotional expression is associated with social cognition skills