Collet Sicard syndrome secondary to granulomatosis with polyangiitis

Granulomatosis with polyangiitis (GPA) is a systemic vasculitis that affects small to medium-sized blood vessels. Although uncommon, cranial nerve (CN) involvement can result in CN palsy. We present a clinical case of a female with collet Sicard syndrome (CSS), displaying left-sided CN IX, X, XI, and XII involvement, which we determined to be caused by GPA. Our patient met 7 points on the American College of Rheumatology 2018 (ACR) criteria for GPA with positive ANCA, bilateral mastoiditis, and decreased sensorineural hearing. Early identification of GPA is crucial due to systemic CN involvement, as it can lead to dysphonia, dysphagia, and other complications. Early treatment can improve the functional prognosis of patients, requiring intensive induction immunosuppression due to frequent bilateral progression and worse prognosis. Despite its infrequency, timely diagnosis is critical for better patient outcomes

A Drosophila model of GDAP1 function reveals the involvement of insulin signalling in the mitochondria-dependent neuromuscular degeneration

[EN] Charcot-Marie-Tooth disease is a rare peripheral neuropathy for which there is no specific treatment. Some forms of Charcot-Marie-Tooth are due to mutations in the GDAP1 gene. A striking feature of mutations in GDAP1 is that they have a variable clinical manifestation, according to disease onset and progression, histology and mode of inheritance. Studies in cellular and animal models have revealed a role of GDAP1 in mitochondrial morphology and distribution, calcium homeostasis and oxidative stress. To get a better understanding of the disease mechanism we have generated models of over-expression and RNA interference of the Drosophila Gdapl gene. In order to get an overview about the changes that Gdapl mutations cause in our disease model, we have combined a comprehensive determination of the metabolic profile in the flies by nuclear magnetic resonance spectroscopy with gene expression analyses and biophysical tests. Our results revealed that both up- and down-regulation of Gdapl results in an early systemic inactivation of the insulin pathway before the onset of neuromuscular degeneration, followed by an accumulation of carbohydrates and an increase in the (3-oxidation of lipids. Our findings are in line with emerging reports of energy metabolism impairments linked to different types of neural pathologies caused by defective mitochondrial function, which is not surprising given the central role of mitochondria in the control of energy metabolism. The relationship of mitochondrial dynamics with metabolism during neurodegeneration opens new avenues to understand the cause of the disease, and for the discovery of new biomarkers and treatments.This work was supported by a project grant from the Association Francaise contre les Myopathies [AFM 18540 to M.I.G]; a collaborative grant from International Rare Diseases Research consortium (IRDiRC) and Institute de Salud Carlos III [IR11/TREAT-CMT to M.I.G. (partner 12) and F.V.P. (partner 8)]; funding from Institute de Salud Carlos III through Biomedical Network Research Center for Rare Diseases and the INGENIO 2010 program to F.V.P.; and a project grant from the Spanish Government (Secretaria de Estado de Investigacion, Desarollo e Innovacion, Ministerio de Economia y Competitividad) [SAF2014-53977-R to A.P.].Lopez Del Amo, V.; Palomino-Schätzlein, M.; Seco-Cervera, M.; Garcia-Gimenez, JL.; Pallardó-Calatayud, FV.; Pineda-Lucena, A.; Galindo-Orozco, MI. (2017). A Drosophila model of GDAP1 function reveals the involvement of insulin signalling in the mitochondria-dependent neuromuscular degeneration. Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease. 1863(3):801-809. https://doi.org/10.1016/j.bbadis.2017.01.003S8018091863

Espondilodiscitis infecciosa por abscesos de psoas secundario a infección por Burkholderia cepacia

Context: Infection by the Burkholderia cepacia complex is a clinical entity rarely reported in the literature outside the context of pneumonia in patients with cystic fibrosis or chronic granulomatosis; its appearance in soft tissues or the articular system is scarce.   Case description: We report the case of a 59-year-old man with diabetes mellitus 2 who was admitted with chronic low back pain secondary to multiple bilateral abscesses at the level of the psoas muscles associated with spondylodiscitis. After draining the abscesses, Burkholderia cepacia was isolated in culture.   Conclusions: This is the second report of deep posed abscess associated with infection by bacteria of the genus Burkholderia cepacia. The extrapulmonary and specifically musculoskeletal behavior is a fact to consider within the spectrum of clinical manifestations associated with this disease.   Key words: psoas abscess, Burkholderia cepacia, spondylodiscitisIntroducción: La infección por el complejo Burkholderia cepacia se trata de una entidad clínica raramente reportada en la literatura fuera del contexto de neumonía en pacientes con fibrosis quística o granulomatosis crónica; su aparición en tejidos blandos o del sistema articular son escasos. Caso: Reportamos el caso de un hombre de 59 años de edad con diabetes mellitus 2 quien ingresó con cuadro de dolor lumbar crónico secundario a múltiples abscesos de forma bilateral a nivel de los músculos psoas asociado a espondilodiscitis. Tras el drenaje de los abscesos se aisló en cultivo Burkholderia cepacia. Conclusiones: Este es el segundo reporte de absceso profundo de posas a nivel mundial y el primero en el continente americano asociado a infección por bacterias del género Burkholderia cepacia. El comportamiento extrapulmonar y específicamente muscoloesquelético es un hecho a considerar dentro del espectro de manifestaciones clínicas asociadas a esta enfermedad

Espondilodiscitis infecciosa por abscesos de psoas secundario a infección por Burkholderia cepacia

Context: Infection by the Burkholderia cepacia complex is a clinical entity rarely reported in the literature outside the context of pneumonia in patients with cystic fibrosis or chronic granulomatosis; its appearance in soft tissues or the articular system is scarce.   Case description: We report the case of a 59-year-old man with diabetes mellitus 2 who was admitted with chronic low back pain secondary to multiple bilateral abscesses at the level of the psoas muscles associated with spondylodiscitis. After draining the abscesses, Burkholderia cepacia was isolated in culture.   Conclusions: This is the second report of deep posed abscess associated with infection by bacteria of the genus Burkholderia cepacia. The extrapulmonary and specifically musculoskeletal behavior is a fact to consider within the spectrum of clinical manifestations associated with this disease.   Key words: psoas abscess, Burkholderia cepacia, spondylodiscitisIntroducción: La infección por el complejo Burkholderia cepacia se trata de una entidad clínica raramente reportada en la literatura fuera del contexto de neumonía en pacientes con fibrosis quística o granulomatosis crónica; su aparición en tejidos blandos o del sistema articular son escasos. Caso: Reportamos el caso de un hombre de 59 años de edad con diabetes mellitus 2 quien ingresó con cuadro de dolor lumbar crónico secundario a múltiples abscesos de forma bilateral a nivel de los músculos psoas asociado a espondilodiscitis. Tras el drenaje de los abscesos se aisló en cultivo Burkholderia cepacia. Conclusiones: Este es el segundo reporte de absceso profundo de posas a nivel mundial y el primero en el continente americano asociado a infección por bacterias del género Burkholderia cepacia. El comportamiento extrapulmonar y específicamente muscoloesquelético es un hecho a considerar dentro del espectro de manifestaciones clínicas asociadas a esta enfermedad

A global experiment on motivating social distancing during the COVID-19 pandemic

Finding communication strategies that effectively motivate social distancing continues to be a global public health priority during the COVID-19 pandemic. This cross-country, preregistered experiment (n = 25,718 from 89 countries) tested hypotheses concerning generalizable positive and negative outcomes of social distancing messages that promoted personal agency and reflective choices (i.e., an autonomy-supportive message) or were restrictive and shaming (i.e., a controlling message) compared with no message at all. Results partially supported experimental hypotheses in that the controlling message increased controlled motivation (a poorly internalized form of motivation relying on shame, guilt, and fear of social consequences) relative to no message. On the other hand, the autonomy-supportive message lowered feelings of defiance compared with the controlling message, but the controlling message did not differ from receiving no message at all. Unexpectedly, messages did not influence autonomous motivation (a highly internalized form of motivation relying on one’s core values) or behavioral intentions. Results supported hypothesized associations between people’s existing autonomous and controlled motivations and self-reported behavioral intentions to engage in social distancing. Controlled motivation was associated with more defiance and less long-term behavioral intention to engage in social distancing, whereas autonomous motivation was associated with less defiance and more short- and long-term intentions to social distance. Overall, this work highlights the potential harm of using shaming and pressuring language in public health communication, with implications for the current and future global health challenges

A multi-country test of brief reappraisal interventions on emotions during the COVID-19 pandemic.

The COVID-19 pandemic has increased negative emotions and decreased positive emotions globally. Left unchecked, these emotional changes might have a wide array of adverse impacts. To reduce negative emotions and increase positive emotions, we tested the effectiveness of reappraisal, an emotion-regulation strategy that modifies how one thinks about a situation. Participants from 87 countries and regions (n = 21,644) were randomly assigned to one of two brief reappraisal interventions (reconstrual or repurposing) or one of two control conditions (active or passive). Results revealed that both reappraisal interventions (vesus both control conditions) consistently reduced negative emotions and increased positive emotions across different measures. Reconstrual and repurposing interventions had similar effects. Importantly, planned exploratory analyses indicated that reappraisal interventions did not reduce intentions to practice preventive health behaviours. The findings demonstrate the viability of creating scalable, low-cost interventions for use around the world

Cooperative Binding of SRSF3 to Structured 3’ss-α Exon RNA during α Exon Inclusion in the ZO-1 mRNA

ZO-1α+ and ZO-1α− proteins are expressed in hermetic and leaky tight junctions, respectively. Two cis-acting distant exonic elements partly activate the 240 nucleotide-long α exon producing the ZO-1α+ isoform. However, the elements within and around the α exon and their respective factors involved in its splicing are unknown. To study the dynamic interaction between SRSF3 and its bioinformatically predicted target sites around the 3’ss upstream of the α exon during its activation, we performed EMSA, crosslinking, and in vivo splicing assays by ZO-1 minigene expression and siRNA-mediated silencing in transfected cells. Using V1 RNase, we probed the possible formation of a hairpin RNA structure between the intronic and proximal exonic SRSF3 binding sites. The hairpin sufficed for complex formations in the EMSA. The interaction of SRSF3 with the intronic site promoted the cooperative binding of SRSF3 to the exonic site. Finally, SRSF3 restored α exon activation in SRSF3 knockdown transfectants. Altogether, our results show that SRSF3–hairpin RNA interaction is crucial in the early recognition of 3’ss for α exon activation. It remains to be explored whether SRSF3 recruits or stabilizes the binding of other factors or brings separate splice sites into proximity

Impact of Conformations and Size on the Antileishmanial Activity of New Quinazoline Derivatives

There is an urgency of finding molecules available to treat Leishmaniasis, which is one of the significant issues of health in undeveloped countries. For that reason is needed to explore molecular diversity to find novel scaffolds. Fluorinated and adamantane derivatives exhibit a formidable starting point. They are proved to improve the antileishmanial activity when attached to molecules already active as we have shown in this paper. Particularly fluorinated methoxy and ethoxy derivatives can increase its volume depending on the number of fluorine, a unique behaviour that can be exploited for molecular drug design purposes