Co-infections and superinfections complicating COVID-19 in cancer patients: A multicentre, international study

Background: We aimed to describe the epidemiology, risk factors, and clinical outcomes of co-infections and superinfections in onco-hematological patients with COVID-19. Methods: International, multicentre cohort study of cancer patients with COVID-19. All patients were included in the analysis of co-infections at diagnosis, while only patients admitted at least 48 h were included in the analysis of superinfections. Results: 684 patients were included (384 with solid tumors and 300 with hematological malignancies). Co-infections and superinfections were documented in 7.8% (54/684) and 19.1% (113/590) of patients, respectively. Lower respiratory tract infections were the most frequent infectious complications, most often caused by Streptococcus pneumoniae and Pseudomonas aeruginosa. Only seven patients developed opportunistic infections. Compared to patients without infectious complications, those with infections had worse outcomes, with high rates of acute respiratory distress syndrome, intensive care unit (ICU) admission, and case-fatality rates. Neutropenia, ICU admission and high levels of C-reactive protein (CRP) were independent risk factors for infections. Conclusions: Infectious complications in cancer patients with COVID-19 were lower than expected, affecting mainly neutropenic patients with high levels of CRP and/or ICU admission. The rate of opportunistic infections was unexpectedly low. The use of empiric antimicrobials in cancer patients with COVID-19 needs to be optimized

Subcortical brain alterations in major depressive disorder:findings from the ENIGMA Major Depressive Disorder working group

The pattern of structural brain alterations associated with major depressive disorder (MDD) remains unresolved. This is in part due to small sample sizes of neuroimaging studies resulting in limited statistical power, disease heterogeneity and the complex interactions between clinical characteristics and brain morphology. To address this, we meta-analyzed three-dimensional brain magnetic resonance imaging data from 1728 MDD patients and 7199 controls from 15 research samples worldwide, to identify subcortical brain volumes that robustly discriminate MDD patients from healthy controls. Relative to controls, patients had significantly lower hippocampal volumes (Cohen's d=-0.14, % difference=-1.24). This effect was driven by patients with recurrent MDD (Cohen's d=-0.17, % difference=-1.44), and we detected no differences between first episode patients and controls. Age of onset <= 21 was associated with a smaller hippocampus (Cohen's d=-0.20, % difference=-1.85) and a trend toward smaller amygdala (Cohen's d=-0.11, % difference=-1.23) and larger lateral ventricles (Cohen's d=0.12, % difference=5.11). Symptom severity at study inclusion was not associated with any regional brain volumes. Sample characteristics such as mean age, proportion of antidepressant users and proportion of remitted patients, and methodological characteristics did not significantly moderate alterations in brain volumes in MDD. Samples with a higher proportion of antipsychotic medication users showed larger caudate volumes in MDD patients compared with controls. This currently largest worldwide effort to identify subcortical brain alterations showed robust smaller hippocampal volumes in MDD patients, moderated by age of onset and first episode versus recurrent episode status

RNAi-mediated serotonin transporter suppression rapidly increases serotonergic neurotransmission and hippocampal neurogenesis

Open Access: This work is licensed under the Creative Commons Attribution-NonCommercial-No Derivative Works 3.0 Unported License.-- et al.Current antidepressants, which inhibit the serotonin transporter (SERT), display limited efficacy and slow onset of action. Here, we show that partial reduction of SERT expression by small interference RNA (SERT-siRNA) decreased immobility in the tail suspension test, displaying an antidepressant potential. Moreover, short-term SERT-siRNA treatment modified mouse brain variables considered to be key markers of antidepressant action: reduced expression and function of 5-HT(1A)-autoreceptors, elevated extracellular serotonin in forebrain and increased neurogenesis and expression of plasticity-related genes (BDNF, VEGF, Arc) in hippocampus. Remarkably, these effects occurred much earlier and were of greater magnitude than those evoked by long-term fluoxetine treatment. These findings highlight the critical role of SERT in serotonergic function and show that the reduction of SERT expression regulates serotonergic neurotransmission more potently than pharmacological blockade of SERT. The use of siRNA-targeting genes in serotonin neurons (SERT, 5-HT(1A)-autoreceptor) may be a novel therapeutic strategy to develop fast-acting antidepressants.This research was supported by grants from Spanish Ministry of Science and Innovation-CDTI, with the participation of the DENDRIA Consortium; from Instituto de Salud Carlos III PI10/00290 and Centro de Investigación Biomédica en Red de Salud Mental (CIBERSAM, P91C). Structural funds of the European Union, through the National Applied Research Projects (R+D+I 2008/11) and from the Catalan Government (grant 2009SGR220) are also acknowledged.Peer Reviewe

PERFIL CLÍNICO DE NIÑOS CON ESCLERODERMIA SISTÉMICA JUVENIL EN CALI – COLOMBIA

Introduccion: La esclerosis sistémica juvenil (ESj) es una enfermedad autoinmune, crónica, de inicio antes de los 16 años, con repercusión sistémica, cuyo nombre significa “piel dura”, con un inicio menor del 2% antes de los 10 años (1). Autoinmunidad, genoma, polimorfismo poblacional se involucran en su génesis. El objetivo es describir el perfil clínico de la ESj. Metodología: Estudio descriptivo, retrospectivo, de cinco niños con ESj en la consulta de reumatología pediátrica, entre 2012 y 2017, en Cali. Resultados: Se analizaron 5 pacientes, 3/5 mujeres. Edad promedio al diagnóstico 7.6 años, tiempo promedio al diagnóstico 1.8 años. Todos cumplían el criterio mayor de esclerodermia. La calcinosis y la disnea fueron las manifestaciones sistémicas más frecuentes. Las manifestaciones clínicas se describen en la tabla 1. Los anticuerpos positivos fueron, anticuerpos antinucleares 4/5, anti-Scl 70 3/5, anti-centrómero 1/5. El diagnóstico previo en dos pacientes era de artritis reumatoidea juvenil y lupus eritematoso sistémico. El manejo se describe en la tabla 2, todos los pacientes iniciaron esteroide sistémico y metotrexate. Por persistencia de manifestaciones sistémicas otros inmunosupresores fueron administrados (ciclofosfamida, micofenolato y rituximab). Conclusiones: El curso crónico y multisistémico de la ESj condicionó un deterioro progresivo en su estado funcional a pesar del tratamiento médico. El diagnóstico inicial puede ser tardío y confundirse con otras enfermedades reumatológicas. El perfil clínico de los niños con ESj estudiados guarda similitud con lo reportado en diferentes series de otras poblaciones

Surface motility regulation of Sinorhizobium fredii HH103 by plant flavonoids and the NodD1, TtsI, NolR, and MucR1 symbiotic bacterial regulators

Bacteria can spread on surfaces to colonize new environments and access more resources. Rhizobia, a group of α- and β-Proteobacteria, establish nitrogen-fixing symbioses with legumes that rely on a complex signal interchange between the partners. Flavonoids exuded by plant roots and the bacterial transcriptional activator NodD control the transcription of different rhizobial genes (the so-called nod regulon) and, together with additional bacterial regulatory proteins (such as TtsI, MucR or NolR), influence the production of different rhizobial molecular signals. In Sinorhizobium fredii HH103, flavonoids and NodD have a negative effect on exopolysaccharide production and biofilm production. Since biofilm formation and motility are often inversely regulated, we have analysed whether flavonoids may influence the translocation of S. fredii HH103 on surfaces. We show that the presence of nod gene-inducing flavonoids does not affect swimming but promotes a mode of surface translocation, which involves both flagella-dependent and -independent mechanisms. This surface motility is regulated in a flavonoid-NodD1-TtsI-dependent manner, relies on the assembly of the symbiotic type 3 secretion system (T3SS), and involves the participation of additional modulators of the nod regulon (NolR and MucR1). To our knowledge, this is the first evidence indicating the participation of T3SS in surface motility in a plant-interacting bacterium. Interestingly, flavonoids acting as nod-gene inducers also participate in the inverse regulation of surface motility and biofilm formation, which could contribute to a more efficient plant colonisation.This research was funded by the projects PID2019-107634RB-I00 from the Spanish “Ministerio de Ciencia, Innovación y Universidades” and by Grant PGC2018-096477-B-I00 from MCIN/AEI/10.13039/501100011033 and “ERDF A way of making Europe”. P.N.-G. was recipient of a Ph.D. grant from the VPPI of the University of Seville. F.F.-R. is recipient of a Ph.D. grant from the “Consejería de Transformación Económica, Industria, Conocimiento y Universidades” of the Andalusian Government

Sinorhizobium fredii HH103 surface motility is induced by symbiotic conditions

1 página.- Presentación oral en el Congreso FEMS online Conference on Microbiology. Celebrado en Serbia. 28-31 octubre 2020This work has been funded by the Spanish Ministry of Science and Innovation, grants BIO2016-78409R and PID2019-107634RB-I00